tag:theconversation.com,2011:/id/topics/tissue-engineering-6930/articlesTissue engineering – The Conversation2022-01-12T16:13:38Ztag:theconversation.com,2011:article/1738982022-01-12T16:13:38Z2022-01-12T16:13:38ZMilk without the cow: Cellular agriculture could be the future of farming, but dairy farmers need help<figure><img src="https://images.theconversation.com/files/440172/original/file-20220111-19-oqtgov.jpeg?ixlib=rb-1.1.0&rect=28%2C21%2C1249%2C935&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Dairy cows in the Fraser Valley, B.C.</span> <span class="attribution"><a class="source" href="https://www.evanbowness.ca/cell-ag">(Evan Bowness)</a>, <span class="license">Author provided</span></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/milk-without-the-cow--cellular-agriculture-could-be-the-future-of-farming--but-dairy-farmers-need-help" width="100%" height="400"></iframe>
<p>A new wave of cow-less dairy is hitting the market. In the United States, <a href="https://perfectday.com/">Perfect Day</a> is using genetically modified fungi to produce milk protein for ice cream at a commercial scale. And pre-commercial companies, like <a href="https://turtletree.com">TurtleTree</a> and <a href="https://www.bettermilknow.com">Better Milk</a>, are engineering mammary cells to produce human and cow milk in laboratories, although these remain in the early stages of development.</p>
<p>It might be some time before mammal-less dairy arrives in Canadian grocery stores. But these emerging technologies are part of the <a href="https://doi.org/10.3390/agriculture11111066">fourth agricultural revolution</a> that aims to improve food security, sustainability and agricultural working conditions. With these promises for wins on the horizon, should the diary sector be worried?</p>
<p>As researchers from the Food and Agriculture Institute at the University of the Fraser Valley, in British Columbia, we study food systems in transition. The Fraser Valley is home to 60 per cent of B.C.’s dairy farms, so we’re especially interested in the impacts cellular agriculture might have on the dairy system.</p>
<h2>Animal agriculture’s challenges</h2>
<p>Animal agriculture plays a big role in the global food system. The <a href="https://www.fao.org/animal-production/en/">Food and Agriculture Organization states</a> that animal agriculture provides roughly a third of global food protein, supports the livelihoods of over a billion people and contributes to soil fertility.</p>
<p>But animal agriculture is facing increased scrutiny, especially around environmental impacts and animal welfare issues. It is a significant source of greenhouse gas emissions, upwards of <a href="https://doi.org/10.3390/su13116276">16.5 per cent of global emissions</a>, by some estimates.</p>
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<img alt="Students sit near a hand sanitizer dispenser at a university." src="https://images.theconversation.com/files/440150/original/file-20220110-19-16z8l7l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/440150/original/file-20220110-19-16z8l7l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=747&fit=crop&dpr=1 600w, https://images.theconversation.com/files/440150/original/file-20220110-19-16z8l7l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=747&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/440150/original/file-20220110-19-16z8l7l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=747&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/440150/original/file-20220110-19-16z8l7l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=939&fit=crop&dpr=1 754w, https://images.theconversation.com/files/440150/original/file-20220110-19-16z8l7l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=939&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/440150/original/file-20220110-19-16z8l7l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=939&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">In 2009, the H1N1 virus, commonly called swine flu, triggered a pandemic and caused widespread illness around the world.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Darryl Dyck</span></span>
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<p>Animal agriculture is also vulnerable to extreme environmental conditions and climate change. Recent flooding in B.C. <a href="https://fvcurrent.com/article/dead-sumas-prairie-flood/">killed well over half a million farm animals</a> and threatened to contaminate the sensitive freshwater ecosystems of the Fraser Valley with <a href="https://www.nationalobserver.com/2021/11/19/latest-news/after-floods-oil-slicks-human-and-animal-waste">stored manure and agricultural chemicals</a>. And it’s a known <a href="https://www.unep.org/news-and-stories/press-release/unite-human-animal-and-environmental-health-prevent-next-pandemic-un">risk factor for zoonotic diseases and pandemics</a>, such <a href="https://ehp.niehs.nih.gov/doi/10.1289/ehp.117-a394">as H1N1 or the swine flu</a>.</p>
<p>One way to reduce the risks introduced by animal agriculture is to remove — or nearly remove — livestock from the food production equation. <a href="https://new-harvest.org/what-is-cellular-agriculture/">Cellular agriculture</a> uses cell cultures to produce animal products without raising livestock, hunting or fishing. While still in its early phases, this technology could help meet growing demand for animal protein, reduce environmental impacts and address animal welfare concerns.</p>
<h2>How does cellular agriculture work?</h2>
<p>Cellular agriculture makes biologically equivalent or near-equivalent foods to those produced with animals. This is different from plant-based meat and dairy alternatives, such as Beyond Burgers and oat milk, which use plant ingredients that approximate their non-vegetarian counterparts. </p>
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<a href="https://theconversation.com/plant-based-doesnt-always-mean-healthy-173303">Plant-based doesn’t always mean healthy</a>
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<p>One approach is to use advanced fermentation, where yeasts, fungi and bacteria are genetically modified to produce proteins. The approach is similar to brewing beer, but with highly specialized micro-organisms that follow instructions that have been added to their genetic code.</p>
<p>You may already be eating products created using this technology. Thirty years ago, the U.S. Food and Drug Administration approved the use of a <a href="https://www.washingtonpost.com/archive/politics/1990/03/24/fda-approves-bioengineered-cheese-enzyme/c4292eeb-1c74-45d2-94c3-b0eb09e4866c/">bioengineered form of rennet enzymes</a>, which is widely used in cheese making and replaces the original enzymes which were harvested from calf stomachs. </p>
<p>Today, vats of micro-organisms, genetically modified to carry the appropriate calf gene, supply rennet for about 70 per cent of cheese made in the U.S. It’s functionally identical to the original cheese-making enzymes, but it’s easier, less costly to produce and doesn’t rely on mammals.</p>
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<img alt="A worker walks between large stainless steel tanks in an industrial food site." src="https://images.theconversation.com/files/440144/original/file-20220110-27-1uz7t8k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/440144/original/file-20220110-27-1uz7t8k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/440144/original/file-20220110-27-1uz7t8k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/440144/original/file-20220110-27-1uz7t8k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/440144/original/file-20220110-27-1uz7t8k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/440144/original/file-20220110-27-1uz7t8k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/440144/original/file-20220110-27-1uz7t8k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Food scientists can use microorganisms to grow food ingredients in large vats, eliminating the need for livestock.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<p>Another approach, called tissue engineering, uses cells collected from an animal to grow meat, fish or even leather in a controlled environment. The tissues grow, but in a nutrient-rich broth called growth media in bioreactor tanks.</p>
<p>Examples include GOOD Meat’s cellular chicken nuggets, the <a href="https://doi.org/10.1038/s41587-021-00855-1">first commercially available cellular meat product</a>, and <a href="https://www.wildtypefoods.com/">WildType</a>’s cellular salmon, which is being grown in stainless steel tanks in San Francisco. </p>
<h2>What is at stake for dairy farmers?</h2>
<p>Dairy is an important food commodity in Canada. Over 18,000 farm operators are employed at the roughly 10,000 dairy farms across the country, which together produced 9.5 billion litres of milk and <a href="https://agriculture.canada.ca/en/canadas-agriculture-sectors/animal-industry/canadian-dairy-information-centre/canadas-dairy-industry-glance">earned farms over $7 billion in 2020</a>. </p>
<p>To meet consumer demand and guarantee a fair price to the farmers, the Canadian supply management system controls dairy production volumes and the number of producers at the provincial level using a quota system. Farmers essentially buy the right to sell dairy products. Dairy farms are capital intensive and farmers often carry large debt loads, making it a difficult industry to enter. </p>
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<img alt="Dairy cows stay dry inside a barn at night, with flood waters outside." src="https://images.theconversation.com/files/440149/original/file-20220110-13-1lhn3fk.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/440149/original/file-20220110-13-1lhn3fk.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=417&fit=crop&dpr=1 600w, https://images.theconversation.com/files/440149/original/file-20220110-13-1lhn3fk.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=417&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/440149/original/file-20220110-13-1lhn3fk.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=417&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/440149/original/file-20220110-13-1lhn3fk.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=524&fit=crop&dpr=1 754w, https://images.theconversation.com/files/440149/original/file-20220110-13-1lhn3fk.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=524&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/440149/original/file-20220110-13-1lhn3fk.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=524&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Flood waters rise outside a dairy barn near Agassiz, B.C., in November 2021.</span>
<span class="attribution"><span class="source">THE CANADIAN PRESS/Jonathan Hayward</span></span>
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<p>Livestock farmers in B.C. had an exceptionally challenging 2021. After a summer of <a href="https://www.cbc.ca/news/canada/british-columbia/b-c-livestock-owners-scramble-to-move-cattle-horses-caught-in-wildfire-risk-1.6107262">encroaching forest fires</a> and a <a href="https://www.cbc.ca/news/canada/british-columbia/bc-livestock-farmers-heat-wave-1.6130043">record-breaking heat dome</a>, the year ended with <a href="https://globalnews.ca/news/8483965/bc-flooded-farms-weather/">catastrophic floods followed by extreme cold</a>. Fraser Valley farmers were forced to dump 7.5 million litres of raw milk in November when shipping routes were destroyed by flooding, which also killed 428 dairy cows. </p>
<p><a href="https://theconversation.com/why-farmers-are-dumping-milk-down-the-drain-and-letting-produce-rot-in-fields-136567">Across the country, dairy farmers also dumped milk</a> early in the pandemic — more than <a href="https://globalnews.ca/news/8386413/canada-milk-price-increase-dairy-farmers-cdc/">30 million litres</a> in the year ending July 31, 2020, according to one analysis — when demand plummeted due to restaurant closures and other system shocks. </p>
<h2>Planning a just transition</h2>
<p>We see animal-free dairy as possibly having some environmental and food security benefits, but with some trade-offs. </p>
<p>If cellular agriculture competes with conventional dairy in Canada, what would the impact be on dairy farmers? What would happen to the cows? To the farms? To the supply management system in general? </p>
<p>Addressing these questions is critical for developing policy that enables transitions to food systems with lower environmental and carbon footprints while ensuring harms and benefits are distributed equitably — what’s known as the j<a href="https://www.rncanengagenrcan.ca/en/collections/just-transition">ust transition</a>. </p>
<p>Much of our understanding of these just transitions comes from the energy sector, where coal mines have closed and oil production is declining as renewable energy becomes more available and less expensive, changing economies and forcing fossil fuel workers to find other work. </p>
<p>Canada recently developed a just transition <a href="https://www.canada.ca/en/environment-climate-change/services/climate-change/task-force-just-transition.html">task force</a> to look for ways to reduce the livelihood disruptions that come with phasing out coal. The federal government has also recently <a href="https://www.canada.ca/en/natural-resources-canada/news/2021/07/canada-launches-just-transition-engagement.html">initiated consultations</a> for just transition legislation that would direct resources to communities negatively impacted by the transition towards a low-carbon future.</p>
<p>Just transition policies for cellular agriculture could encourage farmers to transition into animal-free dairy production through infrastructure transition grants, support with licensing new technologies, biodiversity conservation and carbon credits for <a href="https://ipbes.net/glossary/land-sparing">land sparing</a>, sanctuary planning for current dairy farms and land back incentives to provide pathways for agriculture towards decolonization. </p>
<p>It’s unclear how soon Canadian dairy farmers will face competition from cellular agriculture, although some have suggested <a href="https://doi.org/10.1089/ind.2021.29240.ctu">U.S. beef and dairy sector revenues will decline nearly 90 per cent by 2035</a>. </p>
<p>Is it reasonable to expect Canadian dairy farmers will make way for cellular dairy? Or is up to policy-makers, industry leaders and food systems organizers to ensure this transition leads to a food system that is more sustainable, but also just?</p>
<p><em>Yadira Tejeda Saldana, research collaborations director at <a href="https://new-harvest.org/">New Harvest</a>, co-authored this article.</em></p><img src="https://counter.theconversation.com/content/173898/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Evan Bowness receives funding from the Social Sciences and Humanities Research Council (SSHRC) of Canada and Future Skills Centre Canada.</span></em></p><p class="fine-print"><em><span>Robert Newell receives funding from the Social Sciences and Humanities Research Council (SSHRC) of Canada and Future Skills Centre Canada.</span></em></p><p class="fine-print"><em><span>Sarah-Louise Ruder receives funding from the Social Sciences and Humanities Research Council (SSHRC) of Canada and Future Skills Centre Canada.</span></em></p>Technological changes on the horizon will likely disrupt the dairy industry as we know it — plans to mitigate the risks this transition poses to farmer livelihoods and animal welfare should start now.Evan Bowness, Postdoctoral Researcher, Food and Agriculture Institute, University of The Fraser ValleyRobert Newell, Associate Director, Food and Agriculture Institute, University of The Fraser ValleySarah-Louise Ruder, PhD Candidate at the Institute for Resources, Environment and Sustainability, University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1700762022-01-04T13:07:12Z2022-01-04T13:07:12ZThe promise of repairing bones and tendons with human-made materials<figure><img src="https://images.theconversation.com/files/438835/original/file-20211222-120394-wx89va.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C8093%2C5464&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Musculoskeletal injuries can cause severe pain and lead to greater problems. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/shot-of-a-young-woman-holding-her-shoulder-in-pain-royalty-free-image/1359197542?adppopup=true">PeopleImages/E+ via Getty Images</a></span></figcaption></figure><p><em>Brittany Taylor is a biomedical engineer and assistant professor who <a href="https://scholar.google.com/citations?user=KOS4i7AAAAAJ&hl=en">studies novel ways to improve bone and tendon healing</a> after injuries. She is exploring drug delivery systems and temporary artificial tissue replacements to promote healing of tendons and the interface with bones and muscle. Millions of musculoskeletal injuries each year cause pain and reduce people’s quality of life. Here, she answers questions about the <a href="https://www.bme.ufl.edu/dept-member/brittany-taylor-ph-d/">benefits of using composite materials</a> – biological materials like tissue from animals or synthetic materials – to improve repair outcomes. Many of the techniques are still in the experimental stages and have been tested in animal models.</em></p>
<h2>At least half a million bone grafts a year are performed in the United States. Why do doctors and patients need an alternative to using real bone in these surgeries?</h2>
<p>Musculoskeletal complications due to disease, traumatic injury or repetitive activity are major problems worldwide. Current treatments to repair these injuries rely on harvested or donated tissue. For example, doctors take bone from the iliac crest, the curved portion at the top of the hip, then mold it to fit the area needing the bone replacement. But donation sites for bone are limited, and there is a risk of tissue death where the bone is extracted. </p>
<p>When <a href="https://journals.lww.com/jaaos/fulltext/2005/01000/the_biology_of_bone_grafting.10.aspx?casa_token=MHJAoIBIQwMAAAAA:Yiq53pMIWz2_abzPfC-3eTTW3rzgf2QlI-AV_2HjIetqN6zzTS8LxAcT7CPah7BpTQZaoezJ031gOEd7suOVWplK">another patient or a cadaver provides bone for such repairs</a>, it can transmit disease. Harsh detergents and sterilization methods to remove any disease can also affect the bone’s strength.</p>
<p>The use of composite material <a href="https://scholar.google.com/citations?view_op=view_citation&hl=en&user=KOS4i7AAAAAJ&citation_for_view=KOS4i7AAAAAJ:IjCSPb-OGe4C">overcomes the risks and problems of real bone</a>. </p>
<h2>What kinds of materials work best to help injured bones regenerate?</h2>
<p>Composite materials that have a combination of metals, ceramics and polymers – human-made substances – appear to work best for bone regeneration. They <a href="https://www.researchgate.net/publication/288050539_Recent_Advances_in_Bone_Graft_Technologies">provide mechanical support and also a matrix</a> for tissue development. Biomaterials – engineered materials designed to interact with real body tissue – can regenerate tissues and help healing. </p>
<p>The biomaterial should be compatible with the body. It should not set off an immune response, and it should match tissue’s structural and mechanical properties. Biomaterials used for bone tissue engineering should be as tough as bone and allow for tissue to grow into the structure. Natural materials <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/jbm.b.33622">such as collagen from cows</a> or pigs can also be integrated into the bone scaffold to promote bone repair. </p>
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<figcaption><span class="caption">This short video from the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health introduces nonscientists to the process of tissue engineering for healing.</span></figcaption>
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<h2>You study tendons and their limited ability to regenerate when torn. Why don’t tendons heal themselves easily?</h2>
<p>Tendons do not regenerate well because they have low cellularity – fewer clusters of cells than other parts of the body – and fewer blood vessels. Tendons also form scar tissue as they heal and therefore have limited functionality. Surgically repaired tendons can also easily retear, which reduces a person’s quality of life and lead to prolonged complications. Therefore, researchers are working on tissue engineering strategies to augment healing.</p>
<h2>What kind of engineered materials can help tendons heal?</h2>
<p>Tendons are fibrous tissues that transmit energy loads from muscles to bones. They are “highly aligned,” which means they orient along the direction of the load they transmit. Any engineered biomaterial that replaces a tendon should mimic its mechanical force and allow cells to attach and grow on them, as real tendons do. Therefore, polymer-based biomaterials are the best materials to engineer tendon tissue. Engineers make the experimental polymers with techniques such as electrospinning, which uses an electric field to draw a nanosized polymer strand from a solution, making nanofibers. </p>
<p>Nanofibers can be combined with other materials to engineer tendons, as they have a large surface area-to-volume ratio and are porous. Cells easily adhere to these materials.</p>
<h2>You have worked on developing stronger scaffolds that act like real bone in the body. What do scaffolds do, and why do they need to be made stronger?</h2>
<p>Biomaterial scaffolds for tissue engineering are similar to scaffolding used in construction: a temporary framework that supports the structure and provides a platform for the builders to climb and place materials in their appropriate location. Once the construction is complete, the scaffolding is removed and the newly built structure remains.</p>
<p>The same process works in the human body. Cells attach to the scaffold, proliferate and migrate throughout the scaffold. As the cells “climb” they start to deposit biological factors that promote tissue formation.</p>
<p>The scaffold degrades over time as the new tissue regenerates. Mechanical supports can be added to the scaffolds to make them stronger. My colleagues and I included ceramic posts made out of naturally occurring bone mineral, hydroxyapatite, in the three-dimensional composite bone scaffold for load-bearing applications. The posts were similar to beams added to a structure.</p>
<h2>As a Black scientist, you have advocated for <a href="https://scholar.google.com/citations?view_op=view_citation&hl=en&user=KOS4i7AAAAAJ&citation_for_view=KOS4i7AAAAAJ:5nxA0vEk-isC">good mentors</a> to help other scientists of color.</h2>
<p>I have had to overcome several societal and academic challenges. As a Black first-generation college graduate and female biomedical engineer, I am underrepresented at every level of academia. The obstacles I conquered and the knowledge I gained along this journey contribute to the diverse perspective I bring to the field as a culturally competent educator, well-rounded scientist and strong mentor.</p>
<p>My vision for diversifying scientific research is to continually influence members of the next generation as they work their way through their studies. I mentor scientists, transparently share my experiences and encourage trainees from all backgrounds.</p>
<p>I strongly believe a significant part of being successful in academia is the ability to mentor and be mentored throughout the academic pipeline. I am grateful for the many mentors throughout my journey who opened doors for new opportunities and provided access to the necessary spaces to get me to where I am now. And I am committed to doing the same for others.</p>
<p>[<em>The Conversation’s science, health and technology editors pick their favorite stories.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-favorite">Weekly on Wednesdays</a>.]</p><img src="https://counter.theconversation.com/content/170076/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brittany Taylor receives funding from the University of Florida and Burroughs Wellcome Fund.</span></em></p>A biomedical engineer explains how human-made materials inserted in the body hold hope to repair painful injuries more efficiently than bone grafts.Brittany Taylor, Assistant Professor of Biomedical Engineering, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1734842021-12-21T13:43:21Z2021-12-21T13:43:21ZMechanical forces in a beating heart affect its cells’ DNA, with implications for development and disease<figure><img src="https://images.theconversation.com/files/436506/original/file-20211208-23-3udfl3.png?ixlib=rb-1.1.0&rect=0%2C0%2C764%2C459&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Contracting heart cells exert forces on their genetic material that affect how they develop.</span> <span class="attribution"><a class="source" href="https://doi.org/10.1038/s41551-021-00823-9">Benjamin Seelbinder</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>Sometimes cells can forget what type of cell they are and stop functioning correctly. This commonly happens in <a href="https://doi.org/10.1016/j.devcel.2015.12.001">cancer</a>, in which mature cells lose aspects of their identity and become more susceptible to begin dividing uncontrollably.</p>
<p>Heart conditions like <a href="https://www.mayoclinic.org/diseases-conditions/cardiomyopathy/symptoms-causes/syc-20370709">cardiomyopathy</a>, a disease that makes it harder to pump blood, affect the shape and function of affected heart cells. These changes can also occur in the nucleus of the cell, which houses genetic material that tells a cell how to function.</p>
<p>Because certain changes to nuclear structure can be early warning signals for heart problems, monitoring for such changes could help clinicians diagnose and treat disease before it gets worse. Researchers know that certain <a href="https://dx.doi.org/10.1172%2FJCI87491">changes in the physical forces exerted on heart cells</a>, including from their own contraction, can lead the cells to lose their heart cell identity and function poorly. But exactly how these physical forces work to change heart cell identity was unclear. </p>
<p>In <a href="https://doi.org/10.1038/s41551-021-00823-9">a 2021 study</a> my colleagues and I published in the journal Nature Biomedical Engineering, we found that mechanical forces can reorganize the genetic material inside the nucleus of heart cells and affect how they develop and function. Better understanding of how cells claim and maintain their identities may help advance treatments to repair heart damage from cardiovascular disease and create new prosthetic tissues.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/AONaH_oi3wQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Heart cells in a petri dish change the structure of their nuclei with each beat.</span></figcaption>
</figure>
<h2>Pushing cell development in another direction</h2>
<p>Early in human development, the external pressures surrounding immature cells influence what type of cell they eventually become when they <a href="https://doi.org/10.1016/j.cell.2006.06.044">differentiate</a>, or fully mature. These external forces also help maintain <a href="https://doi.org/10.1146/annurev-bioeng-071114-040829">tissue health as people age</a>. </p>
<p>During differentiation, cells move around and restructure a mixture of proteins and DNA called <a href="https://www.genome.gov/genetics-glossary/Chromatin">chromatin</a> that’s located in their nuclei. Cells use chromatin as a way to package and organize their genetic code. Knowing that external physical pressures can affect how cells mature, <a href="https://www.colorado.edu/lab/neulab/">my research lab</a> and I wanted to explore how mechanical forces can reorganize chromatin and what that might tell us about how heart cells develop and sometimes stop working.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/438277/original/file-20211217-27-ca80jb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of chromosome unwinding to show chromatin, histones and DNA" src="https://images.theconversation.com/files/438277/original/file-20211217-27-ca80jb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/438277/original/file-20211217-27-ca80jb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=515&fit=crop&dpr=1 600w, https://images.theconversation.com/files/438277/original/file-20211217-27-ca80jb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=515&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/438277/original/file-20211217-27-ca80jb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=515&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/438277/original/file-20211217-27-ca80jb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=648&fit=crop&dpr=1 754w, https://images.theconversation.com/files/438277/original/file-20211217-27-ca80jb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=648&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/438277/original/file-20211217-27-ca80jb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=648&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Chromatin consists of DNA tightly coiled around proteins called histones.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/chromation-biological-diagram-vector-royalty-free-illustration/1205309579">VectorMine/iStock via Getty Images Plus</a></span>
</figcaption>
</figure>
<p>To do this, we looked at adult heart cells as they contracted under a microscope to see how their nuclei change shape. We then compared these images with the nuclei of embryonic heart cells as they normally change during early development. We found that areas in the nucleus with high tension tended to organize chromatin into specific shapes known to influence cell behavior. When we changed the tension in those areas of the nucleus, we were able to prevent cells from developing into normal heart cells. This meant that tension may play a key role in guiding heart cells on how to develop.</p>
<p>We then examined how mechanical stress changed the chromatin structure of heart cells from patients with cardiovascular disease and mice with reduced heart performance. Compared with healthy cells, heart cells from both patients and mice lost their chromatin organization and identity as heart cells. This meant that mechanical tension could influence how well mature cells function and their likelihood of developing into cardiovascular disease.</p>
<h2>Mechanical forces matter in medicine</h2>
<p>While our study explores the role that chromatic reorganization plays in early development, additional research is needed to understand exactly what triggers cells to develop into specific cell types. Further insight into how the mechanical environment surrounding a cell affects how it matures will help researchers better understand the process of human development.</p>
<p>Understanding what triggers a collection of cells to transition to a fully functional organ may also help researchers learn how to mimic these developmental processes and create new prosthetic devices. For example, accounting for the mechanical forces that affect how well <a href="https://doi.org/10.1038/nm1394">tissue grafts for failing hearts</a> and <a href="https://doi.org/10.1073/pnas.1402723111">muscles</a> work may help biomedical engineers design even more effective artificial implants. It may also set the stage for more <a href="https://doi.org/10.1038/s41573-020-0079-3">organ-on-chip models</a> that can be used instead of animals to screen potential drugs.</p><img src="https://counter.theconversation.com/content/173484/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Corey Neu receives funding from the National Institutes of Health, National Science Foundation, and the Department of Defense. </span></em></p>Heart disease can change the genetic structure of heart cells. Understanding the role that mechanical forces play in these changes could lead to improvements in artificial tissue design.Corey Neu, Professor of Mechanical and Biomedical Engineering, University of Colorado BoulderLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1235522019-09-18T20:16:50Z2019-09-18T20:16:50ZReimagining eggshells and other everyday items to grow human tissues and organs<figure><img src="https://images.theconversation.com/files/292895/original/file-20190917-19035-15ppsex.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Are eggshells the next supermaterial for tissue engineers?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/shell-eggs-background-372870151?src=j4WJ6byIaOZePa3yDgQQxw-1-26">icepkman/Shutterstock.com</a></span></figcaption></figure><p>Imagine you wanted to grow a blood vessel or kidney or liver outside the body. How would you get all the cells to stick together and form the correct three-dimensional structure?</p>
<p>That is just one of the many challenges of tissue engineering, a field with the broad goal of repairing or improving tissues that are damaged due to degeneration, disease, trauma or aging. Often, it can be quite cumbersome and expensive to develop new combinations of engineered materials and molecules that support the creation of artificial tissues outside of the human body. </p>
<p>But as humans go about our daily lives, there is a diverse range of natural and man-made materials that are overlooked in tissue engineering. Recent successes use materials like tofu, eggshells and paper for a range of therapies including conditions that involve our <a href="https://doi.org/10.1016/j.biotechadv.2017.07.012">heart valves</a>, <a href="http://doi.org/10.1039/C9BM00230H">bones</a>, <a href="https://doi.org/10.1016/j.jclepro.2016.12.036">cartilage</a> and <a href="https://doi.org/10.1088/1758-5090/aa68ed">nerves</a>.</p>
<p><a href="https://scholar.google.com/citations?user=kPzJ-qgAAAAJ&hl=en">We are engineers</a> and focus on developing functional biomaterials to repair and regenerate tissues. Because there aren’t enough tissues to transplant or implant in all the patients who need it, one of the strategies we use is to take unconventional approaches and utilize materials from nature or everyday life. Why? Because we want to make engineering tissues and organs simple, accessible and inexpensive so that our materials can be used by people in countries that have fewer resources as well as the ones with access to the best equipment and resources. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/293030/original/file-20190918-187967-1hovf4r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/293030/original/file-20190918-187967-1hovf4r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/293030/original/file-20190918-187967-1hovf4r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=465&fit=crop&dpr=1 600w, https://images.theconversation.com/files/293030/original/file-20190918-187967-1hovf4r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=465&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/293030/original/file-20190918-187967-1hovf4r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=465&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/293030/original/file-20190918-187967-1hovf4r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=585&fit=crop&dpr=1 754w, https://images.theconversation.com/files/293030/original/file-20190918-187967-1hovf4r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=585&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/293030/original/file-20190918-187967-1hovf4r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=585&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Gulden Camci-Unal works with student Xinchen Wu on origami-inspired 3D paper scaffoldings to culture cells for cardiovascular, cardiac and bone tissue engineering.</span>
<span class="attribution"><span class="source">Edwin Aguirre for UMass Lowell</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>The unconventional approach and why it works</h2>
<p>In the <a href="http://faculty.uml.edu/Gulden_CamciUnal/Research/Research.aspx">Camci-Unal Research Group</a> one of our goals is to look at the items we see or throw out every day and <a href="https://marlin-prod.literatumonline.com/pb-assets/journals/trends/biotechnology/TIBTEC_1826.pdf">reimagine how they might be useful for growing three-dimensional tissues</a> in the lab that could later be transplanted into people.</p>
<p>For instance, eggshells might appear as just leftover waste after cooking an omelet. But in our lab, we repurpose eggshells to fabricate tissue templates, also known as scaffolds, that promote the growth of bone cells and help them harden faster. Eggshells have minerals that contain carbonate which is also present in the bone. Because some of the components of eggshell resemble bone, they can be used to make tissue templates that replicate the biology of these tissues. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/293032/original/file-20190918-187951-2c2lnq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/293032/original/file-20190918-187951-2c2lnq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/293032/original/file-20190918-187951-2c2lnq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=454&fit=crop&dpr=1 600w, https://images.theconversation.com/files/293032/original/file-20190918-187951-2c2lnq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=454&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/293032/original/file-20190918-187951-2c2lnq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=454&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/293032/original/file-20190918-187951-2c2lnq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=571&fit=crop&dpr=1 754w, https://images.theconversation.com/files/293032/original/file-20190918-187951-2c2lnq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=571&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/293032/original/file-20190918-187951-2c2lnq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=571&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Gulden Camci-Unal has found that microscopic eggshell particles incorporated into hydrogels used to grow bone cells in the laboratory enhance the cells’ ability to harden.</span>
<span class="attribution"><span class="source">Edwin Aguirre for UMass Lowell)</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>We also use nontraditional and inexpensive materials like paper to help grow tissues. Using paper, we make origami-inspired scaffolds, also known as three-dimensional frames or templates, for repairing muscle, bone and cartilage. </p>
<p>Unconventional use of abundant common materials like <a href="http://doi.org/10.1002/adhm.201601225">plant</a> <a href="http://doi.org/10.1371/journal.pone.0157894">parts</a>, <a href="http://doi.org/10.1016/j.biomaterials.2018.11.011">ice</a> <a href="http://doi.org/10.1039/C7TB02852K">and tofu</a> have shown promise in improving tissue regrowth and functions. Some of <a href="https://doi.org/10.1038/srep27693">these materials even help transport nutrients</a> <a href="http://doi.org/10.1002/jbm.b.33706">or cellular signals</a> and <a href="https://doi.org/10.1038/srep27693">others support the cells’ ability to move, attach,</a> <a href="https://doi.org/10.1002/adhm.201500709">grow, reproduce and differentiate</a> <a href="https://doi.org/10.1039/C9BM00230H">into specialized cells</a>. </p>
<p>A major advantage of using these materials is they can be modified biologically, chemically and physically to look and work like specific tissues found in the human body. For example, paper is flexible, textiles are porous and <a href="http://doi.org/10.1016/j.biotechadv.2017.07.012">apple pomace</a>, the material left after juicing, <a href="https://doi.org/10.1016/j.jclepro.2016.12.036">contains fibers</a> useful for building human tissue. In tissue engineering, we like to use materials that mimic biological tissues because they integrate seamlessly with the parts of our body. </p>
<h2>Taking a deeper dive</h2>
<p>With more research and emphasis on these common materials, we can better understand their potential deficiencies and other special properties and address specific questions: How does the material interact with the human body? Is it safe for the long term? What tests do we need to run to study these aspects? Can the technology be scaled or mass-produced?</p>
<p>Answering these questions helps us to gauge the future prospects of an unconventional material. It also enables us to advance cost-effective and sustainable tissue scaffolds and platforms that address global biomedical challenges. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/292894/original/file-20190917-19040-vmwln2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/292894/original/file-20190917-19040-vmwln2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=723&fit=crop&dpr=1 600w, https://images.theconversation.com/files/292894/original/file-20190917-19040-vmwln2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=723&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/292894/original/file-20190917-19040-vmwln2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=723&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/292894/original/file-20190917-19040-vmwln2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=909&fit=crop&dpr=1 754w, https://images.theconversation.com/files/292894/original/file-20190917-19040-vmwln2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=909&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/292894/original/file-20190917-19040-vmwln2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=909&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">This figure shows a tissue engineering approach that incorporates native biological molecules and unconventional materials to culture a viable and implantable scaffold in the body.</span>
<span class="attribution"><span class="source">Nguyen and Camci-Unal/Trends in Biotechnology</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Affordable tissue technology</h2>
<p>To tackle health inequities, bioengineers must consider the important differences in resources for underdeveloped regions which might not have well-equipped facilities like in the U.S. or other developed countries. </p>
<p>Our lab wants to change the access to tissue engineering technologies and make our science available to individuals of different parts of the world. Using unconventional materials that are cheap and widely available increases the likelihood that these technologies will be widely adopted.</p>
<p>When you take notes, get a household plant, change clothes, put ice in your coffee, crack an egg or throw away an apple core, reimagine these items in tissue engineering. It could be a mold for a patient’s heart valve, a model to study cancer or a rare disease, a wound dressing or a scaffold to heal someone’s fractured bone. There are still many more innovations to discover, and the possibilities are endless.</p><img src="https://counter.theconversation.com/content/123552/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gulden Camci-Unal receives funding from the American Heart Association, Defense Health Agency, and US Army.</span></em></p><p class="fine-print"><em><span>Michelle A. Nguyen receives funding from Urban Massachusetts Louis Stokes Alliance for Minority Participation (UMLSAMP) by the National Science Foundation (NSF).</span></em></p>Bioengineers who are trying to grow replacement human tissues and organs are at the forefront of biomedicine. But you may be surprised by some of the materials they are using for this endeavor.Gulden Camci-Unal, Assistant Professor of Chemical Engineering, UMass LowellMichelle A Nguyen, Biomedical Engineering Student, UMass LowellLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1177272019-07-05T12:22:07Z2019-07-05T12:22:07ZSo far cultured meat has been burgers – the next big challenge is animal-free steaks<figure><img src="https://images.theconversation.com/files/282365/original/file-20190702-126382-pchbd2.jpg?ixlib=rb-1.1.0&rect=479%2C455%2C4501%2C3038&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Meat of the future might be quite different from meat of the past.</span> <span class="attribution"><a class="source" href="https://www.loc.gov/pictures/item/2004671592/">Stanley Kubrick, photographer, LOOK Magazine Photograph Collection, Library of Congress, Prints & Photographs Division, LC-USZ6-2352.</a>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>The meat you eat, if you’re a carnivore, comes from animal muscles. But animals are composed of a lot more than just muscle. They have organs and bones that most Americans do not consume. They require food, water, space and social connections. They produce waste.</p>
<p>Farmers spend a lot of energy and resources to grow complex organisms, creating waste in the process, only to focus on the profitable cuts of meat they can harvest.</p>
<p>It would be easier, more humane, less wasteful, to <a href="https://vimeo.com/78403188">produce just the parts people want</a>. And with cell biology and tissue engineering, it is possible to grow just muscle and fat tissue. It’s called cultured meat. Scientists provide cells with the same inputs they need to grow, just outside an animal: nutrients, oxygen, moisture and molecular signals from their cell neighbors.</p>
<p>So far researchers have <a href="https://youtu.be/slslQLZL2EI">cultivated bunches of cells</a> that can be turned into processed meat like a burger or a sausage. This cultured meat technology is still in the early phases of research and development, as prototypes are scaled-up and fine-tuned to prepare for the challenges of commercialization. But already bioengineers are taking on the next tougher challenge: growing structured cuts of meat like a steak or a chicken cutlet.</p>
<h2>What meat’s made of</h2>
<p>If you look at a piece of raw meat under the microscope, you can see what you’re eating on the cellular level. Each bite is a matrix of muscle and fat cells, interlaced with blood vessels and enrobed by connective tissue.</p>
<p>The muscle cells are full of proteins and nutrients and the fat cells are full of, well, fats. These two cell types contribute to most of the taste and mouth-feel a carnivore experiences when biting into a burger or steak. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/279615/original/file-20190614-158945-158jkci.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/279615/original/file-20190614-158945-158jkci.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/279615/original/file-20190614-158945-158jkci.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=677&fit=crop&dpr=1 600w, https://images.theconversation.com/files/279615/original/file-20190614-158945-158jkci.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=677&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/279615/original/file-20190614-158945-158jkci.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=677&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/279615/original/file-20190614-158945-158jkci.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=850&fit=crop&dpr=1 754w, https://images.theconversation.com/files/279615/original/file-20190614-158945-158jkci.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=850&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/279615/original/file-20190614-158945-158jkci.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=850&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Section of turkey stained to show cellular-level organization skeletal muscle tissue – also known as meat.</span>
<span class="attribution"><span class="source">Natalie Rubio</span></span>
</figcaption>
</figure>
<p>The blood vessels supply an animal’s tissue with nutrients and oxygen while it’s alive; after slaughter, the blood adds a unique, metallic, umami nuance to the meat.</p>
<p>The connective tissue, composed of proteins like collagen and elastin, organizes the muscle fibers into aligned bundles, oriented in the direction of contraction. This connective tissue changes during cooking and adds texture – and gristle – to meat.</p>
<p>The challenge for cellular agriculture researchers is to emulate this complexity of meat from the bottom up. We can grow muscle and fat cells in a petri dish – but blood vessels and connective tissue don’t spontaneously generate as they do in an animal. How can we engineer biomaterials and bioreactors to provide nutrient diffusion and induce organization so we end up with a thick, structured cut of meat?</p>
<h2>Cultured-meat burgers are the first step</h2>
<p>To create any cultured meat, researchers take small – think marble-sized – amounts of tissue from a cow, pig or chicken and isolate individual cells. Then, bioengineers like me put the cells in plastic flasks and give them nutrients, oxygen and moisture while housing them at body temperature. The cells are happy and can divide exponentially, creating more and more cells. </p>
<p>When grown on plastic, the cells will continue to divide until they exist on all of the available surface area. This results in a crowded layer that’s one cell thick. Once the cells stop dividing, they start to mature. Muscle cells fuse together to create long muscle fibers and fat cells begin to produce lipids. Researchers can combine a bunch of these cells together to create processed meat products, like burgers, hot dogs and sausages.</p>
<p>Animal cells alone can replicate most of the meat experience. But without blood vessels and connective tissue, you don’t end up with an organized, three-dimensional tissue – and that’s what you need for structured cuts of meat, like steak, chicken breast and bacon. </p>
<p>To overcome this challenge, scientists can use biomaterials to replicate the structure and function of blood vessels (for nutrient and oxygen transfer) and connective tissue (for organization and texture). This area of research is called <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/scaffolds-for-tissue-engineering">scaffold development</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/282551/original/file-20190703-126400-8iv3fh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/282551/original/file-20190703-126400-8iv3fh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/282551/original/file-20190703-126400-8iv3fh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=473&fit=crop&dpr=1 600w, https://images.theconversation.com/files/282551/original/file-20190703-126400-8iv3fh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=473&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/282551/original/file-20190703-126400-8iv3fh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=473&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/282551/original/file-20190703-126400-8iv3fh.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=594&fit=crop&dpr=1 754w, https://images.theconversation.com/files/282551/original/file-20190703-126400-8iv3fh.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=594&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/282551/original/file-20190703-126400-8iv3fh.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=594&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Providing some structure for cells to grow on will get cultured meat from hamburger to steaks.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/high-angle-rear-view-female-butcher-242663623">Tyler Olson/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Scaffolds are the secret ingredient for steaks</h2>
<p>The concept of scaffolds originates in the field of <a href="https://doi.org/10.1016/B978-008045154-1.50021-6">tissue engineering for medical applications</a>. Scientists combine cells and scaffolds to produce functional biomaterials for research, toxicology screening or <a href="https://www.sciencedaily.com/releases/2019/06/190607193705.htm">implants</a>.</p>
<p>These biomaterials can take different forms – films, gels, sponges – depending on what properties are desired in the resulting tissue. For example, you could <a href="https://technobleak.com/regenerative-artificial-skin-new-technology-booming-worldwide/">grow skin cells on a flat collagen film</a> to create a skin graft to help burn victims or <a href="https://www.sciencedaily.com/releases/2019/05/190516155338.htm">bone cells in a hydroxyapatite sponge</a> for bone regeneration.</p>
<p>For medical applications, scaffolds generally need to be safe for implantation, must not induce a response from the body’s immune system, be degradable and capable of supporting cell growth. </p>
<p>For food applications, the design considerations of scaffolds are different. They should still support cell growth, but it’s also important that they are inexpensive, edible and environmentally friendly to produce. Some common biomaterials for food applications include cellulose from plants, a carbohydrate called chitosan from mushrooms and a carbohydrate called alginate from algae.</p>
<p>Here’s one “recipe” for cultured meat that I’ve worked on in the lab. First, create an appropriate scaffold. Isolate chitosan from mushrooms and dissolve it in water to create a viscous gel. Put the gel in a tube and expose one end to a cold substance, like dry ice or liquid nitrogen. The whole tube of gel will slowly freeze, starting at the cold end. The frozen gel can then be freeze-dried by a vacuum pulling on the gel at very low temperatures, ultimately creating a dry sponge-like material. The <a href="https://doi.org/10.1021/acsbiomaterials.8b01261">directional freezing process creates a sponge</a> with small, long, aligned pores resembling a bundle of straws – and also muscle tissue.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/282536/original/file-20190703-126400-19y7moh.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/282536/original/file-20190703-126400-19y7moh.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/282536/original/file-20190703-126400-19y7moh.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=116&fit=crop&dpr=1 600w, https://images.theconversation.com/files/282536/original/file-20190703-126400-19y7moh.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=116&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/282536/original/file-20190703-126400-19y7moh.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=116&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/282536/original/file-20190703-126400-19y7moh.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=146&fit=crop&dpr=1 754w, https://images.theconversation.com/files/282536/original/file-20190703-126400-19y7moh.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=146&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/282536/original/file-20190703-126400-19y7moh.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=146&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The simplified process for creating a chitosan sponge with aligned pores.</span>
<span class="attribution"><span class="source">Natalie Rubio</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Then, instead of growing meat on flat plastic, you can transfer the cells to this three-dimensional sponge to provide more surface area for growing thicker tissue. The pores can also help distribute nutrients and oxygen throughout the tissue. So far with this technique, my lab has been able to produce small bits of meat less than a centimeter square – a little small for a cookout but a strong start.</p>
<p>Other scaffold possibilities include growing cells within alginate-based fibers, gels or sponges. Or technicians can rinse plant cells off of plants in a process called decellularization and <a href="https://medium.com/neodotlife/meat-on-a-leaf-glenn-gaudette-9b2765a861f0">repopulate the cellulose framework that’s left behind with animal cells</a>.</p>
<p>Once researchers find materials and methods that work really well, we’ll work on creating larger batches. At that point, it’ll be a game of scaling up the process and bringing down the cost so cultured meat products can be cost-competitive with farmed meat products.</p>
<p>It’s always exciting to see startup companies debut their cultured meatballs, sausages and burgers. But I’m looking ahead to what’s next. With a bit more research, time, funding and luck, the cultured meat menu 2.0 will include the steak and pork chops many carnivores know and love.</p><img src="https://counter.theconversation.com/content/117727/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Natalie R. Rubio is funded by New Harvest and is an advisor for Bond Pet Foods.</span></em></p>It’s relatively easy to grow a bunch of animal cells to turn into a burger. But to grow a steak made of cultured meat is a trickier task. Bioengineers must create organized, three-dimensional tissues.Natalie R. Rubio, Cellular Agriculture PhD Candidate, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1113042019-02-11T12:23:17Z2019-02-11T12:23:17ZOur artificial cornea breakthrough could lead to self-assembling organs<figure><img src="https://images.theconversation.com/files/257930/original/file-20190208-174890-oepsu9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/human-eye-macro-272614787?src=4yNas__-xFXfzIjXTSoYMQ-1-33">Michal Vitek/Shutterstock</a></span></figcaption></figure><p>For every person in the world who receives a cornea transplant, there are <a href="https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2474372">69 others</a> who still need one. That leaves about 12.5m people with limited sight because there aren’t enough eye donors. But what if we could grow new corneas in the lab? </p>
<p>Over the last decade, scientists <a href="http://stm.sciencemag.org/content/2/46/46ra61.editor-summary">have been testing</a> artificial corneas made from synthetic collagen gel. One of the difficulties is in getting the gel to take the right curved shape to fit the eye and focus light so the patient can see again.</p>
<p>My colleagues and I <a href="https://onlinelibrary.wiley.com/doi/10.1002/adfm.201807334">recently found</a> a way to make gel containing live corneal cells self-assemble into the correct pattern, like a piece of paper that folds itself into an origami design. The same principle could one day be exploited to produce other human organs, potentially helping millions more people in need of transplants.</p>
<p>The live cells that we added to the collagen acted like micro-actuators, microscopic engines exerting a contracting pull force. Each cell’s force is tiny but together they can shape a one inch-wide block of tissue into a cornea-like structure.</p>
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<p>We <a href="https://pubs.rsc.org/en/content/articlelanding/2014/bm/c4bm00121d#!divAbstract">previously showed</a> that collagen gels containing corneal cells contracted less when certain molecules (called peptide amphiphiles) were added. From this observation, we were able to design the gel mixture to contract by different amounts in different places to adopt a specific shape.</p>
<p>In this particular case, we created a circular shape divided into two rings, with peptide amphiphiles located either in the outer ring or in the centre. In both cases, one part contracted more than the other and this difference caused the gel to progressively curve over five days until it reached a cornea-like shape.</p>
<p>It might be possible to use this technique to create other artficial tissues from organs that normally contain cells that are able to contract. Heart, skin, muscle and blood vessel tissues could be theoretically reproduced using this technology.</p>
<p>First, the contracting cells have to be combined with the bio-material of interest. Then it is just a matter of understanding which parts have to contract less than others and positioning the peptide amphiphiles within well-defined areas within the bio-material to make it self-assemble into the desired shape.</p>
<p>This concept could also be given a boost by advances in <a href="https://theconversation.com/3d-printers-a-revolutionary-frontier-for-medicine-83031">3D printing</a>, which is already being used to develop new ways of producing various artificial organs. Although the technology is still being optimised, we’ve recently seen major breakthroughs in cell printing that could eventually lead to 3D printed <a href="https://www.ft.com/content/67e3ab88-f56f-11e7-a4c9-bbdefa4f210b">livers</a>, <a href="https://www.gla.ac.uk/news/archiveofnews/2017/september/headline_548468_en.html">bones</a>and even <a href="https://www.popularmechanics.com/science/health/a22029280/3d-printed-flesh-heart-biolife4d/">hearts</a>.</p>
<p>My colleagues, led by Professor Che Connon, have already managed to 3D print a <a href="https://www.sciencedirect.com/science/article/pii/S0014483518302124">full artificial cornea</a>. Eventually, 3D printers may be able to reproduce far more complex biological structures by building them up layer by layer. For instance, to create the multiple chambers of a heart, bio-ink containing heart cells from a patient would by printed onto a biodegradable scaffold that can later be removed by heat to leave a fully biological heart ready for transplantation.</p>
<p>But it’s also possible to take this technology one step further with the invention of <a href="https://theconversation.com/explainer-what-is-4d-printing-35696">4D printing</a>, the printing of structures that can self-assemble by folding after the manufacturing process is done, just like our corneas. Printing biological structures that can <a href="https://www.sciencedirect.com/science/article/pii/S1369702117302250">arrange themselves</a> into an even more complex shape would mean you wouldn’t need to produce scaffolds to print the cells on, or remove them afterwards. The accuracy of the printing process would be extremely useful in precisely positioning the peptide-based molecules that make the cells contract within the bio-material. </p>
<p>Full 4D printing of complete organs might still be relatively far into the future. But in the meantime, we can also look at how the technology could help develop new, more efficient smart materials. The process could be used to create <a href="https://theconversation.com/shape-shifting-materials-could-be-crucial-in-tight-spaces-such-as-inside-our-bodies-66622">shape-changing stents</a> to keep clogged blood vessels open. A closed stent could easily be injected into the bloodstream and then made to open up by the contracting force of cells at a site of injury, avoiding the need for surgery.</p>
<p>In general, the range of possible applications of bio-responsive, self-folding materials is vast. In the meantime, our team will continue to work with self-curving corneas, exploring them as improved substitutes of the corneal tissue. Our hope is that this technology will gradually expand what we can achieve with bio-synthetic organs and tissues, bringing hope to the millions of people waiting for transplants.</p><img src="https://counter.theconversation.com/content/111304/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martina Miotto received a PhD scholarship from Newcastle University. She has co-founded a pre-spin out company, CellulaREvolution.</span></em></p>We developed the world’s first self-curving artificial cornea.Martina Miotto, Post-Doctoral Researcher in Tissue Engineering, Newcastle UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/627592016-08-09T22:57:52Z2016-08-09T22:57:52ZBiohybrid robots built from living tissue start to take shape<figure><img src="https://images.theconversation.com/files/133577/original/image-20160809-11006-q4ewto.JPG?ixlib=rb-1.1.0&rect=737%2C419%2C3825%2C2545&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Biohybrid sea slug, reporting for duty.</span> <span class="attribution"><span class="source">Dr. Andrew Horchler</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>Think of a traditional robot and you probably imagine something made from metal and plastic. Such “nuts-and-bolts” robots are made of hard materials. As robots take on more roles beyond the lab, such rigid systems can present safety risks to the people they interact with. For example, if an industrial robot swings into a person, there is the risk of bruises or bone damage. </p>
<p>Researchers are increasingly looking for solutions to make robots softer or more compliant – less like rigid machines, more like animals. With traditional actuators – such as motors – this can mean using <a href="http://dx.doi.org/10.1109/BIOROB.2006.1639201">air muscles</a> or adding springs in parallel with motors. For example, on a <a href="http://biorobots.case.edu/projects/whegs/usar-whegs/">Whegs robot</a>, having a spring between a motor and the wheel leg (Wheg) means that if the robot runs into something (like a person), the spring absorbs some of the energy so the person isn’t hurt. The bumper on a Roomba vacuuming robot is another example; it’s spring-loaded so the Roomba doesn’t damage the things it bumps into.</p>
<p>But there’s a growing area of research that’s taking a different approach. By combining robotics with tissue engineering, we’re starting to build robots powered by living muscle tissue or cells. These devices can be stimulated electrically or with light to make the cells contract to bend their skeletons, causing the robot to swim or crawl. The resulting biobots can move around and are soft like animals. They’re safer around people and typically less harmful to the environment they work in than a traditional robot might be. And since, like animals, they need nutrients to power their muscles, not batteries, biohybrid robots tend to be lighter too.</p>
<figure class="align-center zoomable">
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<figcaption>
<span class="caption">Tissue-engineered biobots on titanium molds.</span>
<span class="attribution"><span class="source">Karaghen Hudson and Sung-Jin Park</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
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<h2>Building a biobot</h2>
<p>Researchers fabricate biobots by growing living cells, usually from heart or skeletal muscle of rats or chickens, on scaffolds that are nontoxic to the cells. If the substrate is a polymer, the device created is a biohybrid robot – a hybrid between natural and human-made materials.</p>
<p>If you just place cells on a molded skeleton without any guidance, they wind up in random orientations. That means when researchers apply electricity to make them move, the cells’ contraction forces will be applied in all directions, making the device inefficient at best.</p>
<p>So to better harness the cells’ power, researchers turn to micropatterning. We stamp or print microscale lines on the skeleton made of substances that the cells prefer to attach to. These lines guide the cells so that as they grow, they align along the printed pattern. With the cells all lined up, researchers can direct how their contraction force is applied to the substrate. So rather than just a mess of firing cells, they can all work in unison to move a leg or fin of the device.</p>
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<a href="https://images.theconversation.com/files/133573/original/image-20160809-5131-12xdbn0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/133573/original/image-20160809-5131-12xdbn0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/133573/original/image-20160809-5131-12xdbn0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=398&fit=crop&dpr=1 600w, https://images.theconversation.com/files/133573/original/image-20160809-5131-12xdbn0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=398&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/133573/original/image-20160809-5131-12xdbn0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=398&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/133573/original/image-20160809-5131-12xdbn0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/133573/original/image-20160809-5131-12xdbn0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/133573/original/image-20160809-5131-12xdbn0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Tissue-engineered soft robotic ray that’s controlled with light.</span>
<span class="attribution"><span class="source">Karaghen Hudson and Michael Rosnach</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
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<h2>Biohybrid robots inspired by animals</h2>
<p>Beyond a wide array of biohybrid robots, researchers have even created some completely organic robots using natural materials, like the collagen in skin, rather than polymers for the body of the device. <a href="http://dx.doi.org/10.1088/1748-3190/11/3/036012">Some can crawl or swim</a> when stimulated by an electric field. Some take inspiration from <a href="http://dx.doi.org/10.1021/ac0507800">medical tissue engineering techniques</a> and use <a href="http://dx.doi.org/10.1038/srep00857">long rectangular arms</a> (or cantilevers) to pull themselves forward.</p>
<p>Others have taken their cues from nature, creating biologically inspired biohybrids. For example, a group led by researchers at California Institute of Technology developed a biohybrid robot <a href="http://dx.doi.org/10.1038/nbt.2269">inspired by jellyfish</a>. This device, which they call a medusoid, has arms arranged in a circle. Each arm is micropatterned with protein lines so that cells grow in patterns similar to the muscles in a living jellyfish. When the cells contract, the arms bend inwards, propelling the biohybrid robot forward in nutrient-rich liquid.</p>
<p>More recently, researchers have demonstrated how to steer their biohybrid creations. A group at Harvard used genetically modified heart cells to make a <a href="http://dx.doi.org/10.1126/science.aaf4292">biologically inspired manta ray-shaped robot</a> swim. The heart cells were altered to contract in response to specific frequencies of light – one side of the ray had cells that would respond to one frequency, the other side’s cells responded to another.</p>
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<p>When the researchers shone light on the front of the robot, the cells there contracted and sent electrical signals to the cells further along the manta ray’s body. The contraction would propagate down the robot’s body, moving the device forward. The researchers could make the robot turn to the right or left by varying the frequency of the light they used. If they shone more light of the frequency the cells on one side would respond to, the contractions on that side of the manta ray would be stronger, allowing the researchers to steer the robot’s movement.</p>
<h2>Toughening up the biobots</h2>
<p>While exciting developments have been made in the field of biohybrid robotics, there’s still significant work to be done to get the devices out of the lab. Devices currently have limited lifespans and low force outputs, limiting their speed and ability to complete tasks. Robots made from mammalian or avian cells are very picky about their environmental conditions. For example, the ambient temperature must be near biological body temperature and the cells require regular feeding with nutrient-rich liquid. One possible remedy is to package the devices so that the muscle is protected from the external environment and constantly bathed in nutrients.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/133582/original/image-20160809-5131-n8kji7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/133582/original/image-20160809-5131-n8kji7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/133582/original/image-20160809-5131-n8kji7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=593&fit=crop&dpr=1 600w, https://images.theconversation.com/files/133582/original/image-20160809-5131-n8kji7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=593&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/133582/original/image-20160809-5131-n8kji7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=593&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/133582/original/image-20160809-5131-n8kji7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=745&fit=crop&dpr=1 754w, https://images.theconversation.com/files/133582/original/image-20160809-5131-n8kji7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=745&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/133582/original/image-20160809-5131-n8kji7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=745&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The sea slug <em>Aplysia californica</em>.</span>
<span class="attribution"><span class="source">Jeff Gill</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Another option is to use more robust cells as actuators. Here at Case Western Reserve University, we’ve recently begun to investigate this possibility by turning to the hardy marine sea slug <em>Aplysia californica</em>. Since <em>A. californica</em> lives in the intertidal region, it can experience big changes in temperature and environmental salinity over the course of a day. When the tide goes out, the sea slugs can get trapped in tide pools. As the sun beats down, water can evaporate and the temperature will rise. Conversely in the event of rain, the saltiness of the surrounding water can decrease. When the tide eventually comes in, the sea slugs are freed from the tidal pools. Sea slugs have evolved very hardy cells to endure this changeable habitat. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/133579/original/image-20160809-18037-1eyplpd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/133579/original/image-20160809-18037-1eyplpd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/133579/original/image-20160809-18037-1eyplpd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/133579/original/image-20160809-18037-1eyplpd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/133579/original/image-20160809-18037-1eyplpd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/133579/original/image-20160809-18037-1eyplpd.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/133579/original/image-20160809-18037-1eyplpd.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/133579/original/image-20160809-18037-1eyplpd.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Sea turtle-inspired biohybrid robot, powered by muscle from the sea slug.</span>
<span class="attribution"><span class="source">Dr. Andrew Horchler</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>We’ve been able to <a href="http://dx.doi.org/10.1007/978-3-319-42417-0_33">use <em>Aplysia</em> tissue to actuate a biohybrid robot</a>, suggesting that we can manufacture tougher biobots using these resilient tissues. The devices are large enough to carry a small payload – approximately 1.5 inches long and one inch wide.</p>
<p>A further challenge in developing biobots is that currently the devices lack any sort of on-board control system. Instead, engineers control them via external electrical fields or light. In order to develop completely autonomous biohybrid devices, we’ll need controllers that interface directly with the muscle and provide sensory inputs to the biohybrid robot itself. One possibility is to use neurons or clusters of neurons called ganglia as organic controllers.</p>
<p>That’s another reason we’re excited about using <em>Aplysia</em> in our lab. This sea slug has been a model system for <a href="https://www.routledge.com/Model-Systems-and-the-Neurobiology-of-Associative-Learning-A-Festschrift/Steinmetz-Gluck-Solomon/p/book/9780415650229">neurobiology research for decades</a>. A great deal is already known about the relationships between its neural system and its muscles – opening the possibility that we could use its neurons as organic controllers that could tell the robot which way to move and help it perform tasks, such as finding toxins or following a light.</p>
<p>While the field is still in its infancy, researchers envision many intriguing applications for biohybrid robots. For example, our tiny devices using slug tissue could be released as swarms into water supplies or the ocean to seek out toxins or leaking pipes. Due to the biocompatibility of the devices, if they break down or are eaten by wildlife these environmental sensors theoretically wouldn’t pose the same threat to the environment traditional nuts-and-bolts robots would.</p>
<p>One day, devices could be fabricated from human cells and used for medical applications. Biobots could provide targeted drug delivery, clean up clots or serve as compliant actuatable stents. By using organic substrates rather than polymers, such stents could be used to strengthen weak blood vessels to prevent aneurysms – and over time the device would be remodeled and integrated into the body. Beyond the small-scale biohybrid robots currently being developed, ongoing research in tissue engineering, such as attempts to grow vascular systems, may open the possibility of growing large-scale robots actuated by muscle.</p><img src="https://counter.theconversation.com/content/62759/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Victoria Webster receives funding from the National Science Foundation and the National Institute of Health.</span></em></p>To do the jobs “nuts-and-bolts” robots aren’t good at, engineers are creating soft living machines powered by muscle cells.Victoria Webster-Wood, Ph.D. Candidate in Mechanical and Aerospace Engineering, Case Western Reserve UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/581832016-05-04T12:53:17Z2016-05-04T12:53:17ZTesting drugs on animals could soon be a thing of the past<figure><img src="https://images.theconversation.com/files/119962/original/image-20160425-22378-68rq6i.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Rats are commonly used in animal testing</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-68440837/stock-photo-rat-in-laboratory-tests-on-animal-experiments.html?src=9XOxfxI_HlUB--6P27QedA-1-25">FikMik</a></span></figcaption></figure><p>Before a drug can be tested on humans, it has to be tested on animals. The drugs regulators <a href="http://www.efpia.eu/topics/innovation/animal-welfare">demand it</a>. Nobody – including researchers – likes testing on animals, which is why the race is on to find <a href="http://www.neavs.org/alternatives/in-testing">alternatives</a>. </p>
<p>For this reason – as well as the fact that animal models are often unable to correctly predict how a drug will react in humans – scientists are actively considering alternatives. Fortunately, rapid progress is being made in a number of areas which may soon, hopefully, render animal testing obsolete.</p>
<p>One promising alternative to animal testing is computer models. This “<a href="http://www.oapublishinglondon.com/article/1119"><em>in silico</em></a>” technique simulates the workings of human biology to predict how a new drug will behave in the body, where it will end up – and even what side effects might occur. </p>
<p>This helps researchers refine drug structures before they are tested in animals. It can reduce the number of animals that are tested on by weeding out compounds that are overly toxic or not likely to be effective. Almost all pharmaceutical companies now routinely use computer models in drug development as the database of background knowledge of how drugs interact with biological systems has expanded significantly in recent years. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/119964/original/image-20160425-22383-1f49c7c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/119964/original/image-20160425-22383-1f49c7c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/119964/original/image-20160425-22383-1f49c7c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/119964/original/image-20160425-22383-1f49c7c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/119964/original/image-20160425-22383-1f49c7c.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/119964/original/image-20160425-22383-1f49c7c.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/119964/original/image-20160425-22383-1f49c7c.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It can take up to 12 years and £1.15 billion for a drug to be ready for use.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/en/pic.mhtml?irgwc=1&utm_campaign=Pixabay&tpl=44814-43068&utm_medium=Affiliate&id=298303490&utm_source=44814">VonaUA</a></span>
</figcaption>
</figure>
<p>Another alternative to animal testing is <a href="http://mpkb.org/home/patients/assessing_literature/in_vitro_studies">“<em>in vitro</em>” testing</a>. These are biological and chemical mimics that recreate particular parts of the body. They include mimics of the <a href="http://www.scientificamerican.com/article/brain-in-a-dish-could-replace-toxic-animal-tests/">brain</a>, heart, lungs and a variety of other body systems. Although these systems may look nothing like the original organ, they will consist of cells or molecules that have been made in the lab and behave in a similar way to those found in actual biological systems. For example, the surface of the skin can be recreated to measure how fast drugs get through and how much can be delivered by this route. </p>
<p>These in vitro studies have become so advanced that it’s now possible to predict how drugs will behave in almost any part of the body or any disease state. This has been achieved through an accumulation of knowledge about the science behind each disease, from how the body behaves in a healthy situation to how it changes when unwell and then how drugs can cure the disease. </p>
<p>Using clinical data available for existing drugs allows scientists to compare real-life results with their mimics to prove their suitability before they are validated as a potential alternative.</p>
<p>Once the test system has been validated using known drugs, it can be used to analyse potential new drugs. Basically, once a new test method has proven effective it can begin the process of approval as a legal alternative for testing a specific property of a drug. In the EU these test methods are organised through EURL-ECVAM (the European Union Reference Laboratory for alternatives to animal testing), an organisation based in northern Italy.</p>
<h2>We’re getting there</h2>
<p>These alternatives to animal studies still need refining. Although they are used in some laboratories today, they can only help narrow down potential drug candidates or confirm results already obtained from animals. Unfortunately, at this time it is not possible to recreate all of the intricacies of the human body. The models we use are often overly simplified. This can sometimes make it hard to predict everything we need to know about a drug and we can miss out on noticing the more subtle biological interactions. </p>
<p>In some situations these simplified systems can work well, especially when ranking a series of potential drugs against each other, or looking for one particular interaction.</p>
<p>We are now in an incredibly exciting period of scientific progress. It is imaginable that all the information needed to understand how drugs behave can be determined without the need for animal testing. And it’s entirely plausible that in the next decade or two, animal testing will no longer be needed in the pharmaceutical industry.</p><img src="https://counter.theconversation.com/content/58183/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Laura Waters does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Why are animals still being used in drug development and what are the alternatives that could end their use altogether?Laura Waters, Principal Enterprise Fellow, University of HuddersfieldLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/438942015-09-14T10:14:13Z2015-09-14T10:14:13ZStem cells could help mend a broken heart, but they’ve got to mature<figure><img src="https://images.theconversation.com/files/94437/original/image-20150910-27328-16adew0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Heart cells showing damage after a heart attack.</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:MI_with_contraction_bands_very_high_mag.jpg">Nephron</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Heart disease is the <a href="http://www.cdc.gov/heartdisease/facts.htm">number one cause of death</a> in the US. The most common type is coronary heart disease, which occurs when there’s a buildup of plaque within the heart’s blood vessels. <a href="http://www.nhlbi.nih.gov/health/health-topics/topics/hdw/causes">Smoking, diabetes, obesity and high blood pressure</a> can all contribute. When there’s a complete blockage – a heart attack – a large portion of the heart muscle dies. The heart responds by creating scar tissue, eventually leading to heart failure – the heart muscle just can’t pump enough blood to the rest of the body.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=479&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=479&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=479&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=602&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=602&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94438/original/image-20150910-27340-2zsjmz.PNG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=602&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Blood vessels are blocked with plaque in atherosclerosis.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Coronary_heart_disease-atherosclerosis.PNG">NIH: National Heart, Lung and Blood Institute</a></span>
</figcaption>
</figure>
<p>Currently, the only treatment options for damaged heart muscle are <a href="http://heartsurgery.templehealth.org/content/heart_failure_surgery_transplantation.htm">surgery</a>, if possible, and for the worst cases, a whole heart transplantation. But there’s a <a href="http://www.organdonor.gov/about/data.html">huge shortage of organs</a> for transplantation, and for this reason, we need to find new strategies to treat heart disease.</p>
<p><a href="http://stemcells.nih.gov/info/basics/pages/basics1.aspx">Stem cells</a> have great potential to fill this void. They’re a unique type of cell that starts out unspecialized but can multiply and turn into specialized cells of the adult body – for instance, brain cells or heart muscle cells, officially called cardiomyocytes.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/94560/original/image-20150911-1566-d4g9rs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94560/original/image-20150911-1566-d4g9rs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/94560/original/image-20150911-1566-d4g9rs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94560/original/image-20150911-1566-d4g9rs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94560/original/image-20150911-1566-d4g9rs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94560/original/image-20150911-1566-d4g9rs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94560/original/image-20150911-1566-d4g9rs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94560/original/image-20150911-1566-d4g9rs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A colony of induced pluripotent stem cells under the microscope.</span>
<span class="attribution"><span class="source">Ashley Fong</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Stem cells may be useful in tissue engineering therapies; researchers <a href="http://dx.doi.org/10.1016/j.biomaterials.2013.12.052">build tissues from them in the lab</a> to transplant and replace damaged muscle. They could potentially be used in cellular therapies; researchers inject the heart cells into the heart and <a href="http://dx.doi.org/10.1038/nature13233">allow for regeneration</a>. Right now, one <a href="http://capricor.com/clinical-trials/caduceus/">ongoing clinical trial</a> injects a heart attack patient’s own heart stem cells back into the patient’s heart to decrease scar size and promote heart regeneration. In addition, stem cells can also be used as a drug-screening platform in order to find new drugs to treat heart disease.</p>
<p>These options rely on turning stem cells into heart muscle cells – but even once they differentiate, the <a href="http://doi.org/10.1089/scd.2012.0490">heart cells remain immature</a>. They’re not fully developed, having characteristics you’d find in a fetus, not an adult. To advance these possible therapies, we need ways to take these heart muscle cells one step further, to maturity. I’m studying how the heart’s natural environment affects that maturation process. I focus on how the extracellular matrix, or scaffold, of the heart affects maturation. The overall goal is to find a way to create from stem cells fully functioning, mature heart cells that can be safely and effectively used for transplantation therapies and drug screening applications.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/QrNOHKjA2q4?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The author explains her research as part of the UC Grad Slam 2015 at 29:23.</span></figcaption>
</figure>
<h2>Adult cells to stem cells to immature heart cells</h2>
<p>There are <a href="http://stemcells.nih.gov/info/basics/pages/basics1.aspx">many kinds of naturally occurring stem cells</a>, but I work with a type that can be made from the adult body. For example, I can take your regular skin cell or blood cell and <a href="http://dx.doi.org/10.1016/j.cell.2007.11.019%20show">transform it in the lab</a> into a stem cell by using viruses to introduce stem cell genes into it. The official name for what I wind up with after three or four weeks is “induced pluripotent stem cells.”</p>
<p>This new stem cell has the unique ability to replicate and turn into almost any cell of the adult body. Since they can be made from a patient’s own cells, the induced pluripotent stem cells retain the patient’s specific genetic information. That’s a big benefit when transplanting the cells – there’s no need for immunosuppression to avoid rejection of the new tissue by the patient’s body. It also allows a patient’s specific disease to be modeled in the lab, in hopes of finding a customized drug or therapy for this individual’s particular disease. This situation is sometimes called a “clinical trial in a dish.”</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94530/original/image-20150911-1572-7zb9to.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The author feeding her cells in the lab.</span>
<span class="attribution"><span class="source">Kimberly Lim</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>After years of hard work, I was finally successful at manipulating the stem cells into heart muscle cells in the lab. I had to find the perfect stem cell line and protocol to use, which required lots of trial and error. It was very exciting to finally see the beating heart muscle cells in my petri dish!</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/AONaH_oi3wQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Immature cardiomyocytes beating spontaneously in a petri dish.</span></figcaption>
</figure>
<p>But the cells’ ability to beat on their own actually demonstrates that they’re immature, and thus shouldn’t be used in treatment and drug screening. They spontaneously beat inappropriately. They don’t have the proper machinery to contract with the necessary force. These actions could have dangerous consequences if we were to rely on immature cells in a patient’s heart. Mature cardiomyocytes beat in response to a signal from the heart’s pacemaker cells, avoiding the safety risk of arrhythmia. And mature cells are strong enough to pump blood throughout the body. </p>
<p>So I need to figure out how to mature these cells. </p>
<h2>Scaffold provides more than just structure</h2>
<p>Within heart tissue, a scaffold surrounds the cells and provides structural support. The tissue is like a brick wall; the bricks are the cells and the mortar is the scaffold of proteins that holds everything together. Just as crucially, in a healthy heart, the scaffold sends signals to the heart cells to behave a specific way that allows them to survive and function normally.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94558/original/image-20150911-1544-1r1cux5.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Cut-up pieces of cow heart with the cells removed, leaving behind the scaffold.</span>
<span class="attribution"><span class="source">Ashley Fong</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>I obtain the heart scaffold by extracting it from cow hearts. I use detergents to remove the heart cells, similar to how laundry detergent removes dirt from clothes. Once all the cells are removed, only the scaffold remains. It’s made up of a network of fibers consisting of collagen, fibrinogen, elastin and other types of extracellular matrix proteins. After a few more steps, I get the scaffold into the form of a 3D gel – now it has a texture similar to Jello, which I can shape.</p>
<p>When I put my human stem cell-derived heart muscle cell into the adult heart scaffold, it matures. The process works by increasing the amount of some important proteins, including those that handle calcium. That improves calcium signaling, which is essential for the cell to contract.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94559/original/image-20150911-1569-7llxph.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The tissue scaffold with the heart muscle cells inside.</span>
<span class="attribution"><span class="source">Ashley Fong</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>I also discovered that the most maturation occurs when the cells are grown in a 3D scaffold, rather than a 2D scaffold in a traditional flat petri dish. This finding supports the idea that placing the cells in an environment more like their natural habitat can instruct them to develop and mature. We still don’t know how the scaffold actually issues its instructions to the cardiomyocytes to mature, but for now we’re glad it seems to work. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=457&fit=crop&dpr=1 600w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=457&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=457&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=574&fit=crop&dpr=1 754w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=574&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/94528/original/image-20150911-1572-1v86pow.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=574&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Mature heart muscle cells glowing green with blue nuclei.</span>
<span class="attribution"><span class="source">Ashley Fong</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>We’re another step closer to being able to use mature stem cell-derived cardiomyocytes in new advanced treatment options to cure heart disease. I’m working on just a small sliver of the type of research that’s needed to get stem cells ready to be used to treat diseases. Stem cell research gives patients and their families hope, but cures won’t happen overnight. Even when we’re not seeing immediate results, stem cell research needs continued support so we researchers can develop the cures we so desperately need.</p><img src="https://counter.theconversation.com/content/43894/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ashley Fong receives funding from the California Institute for Regenerative Medicine, National Science Foundation and National Institute for Health.</span></em></p>Stem cells hold great promise for treating heart disease. But it’s not so simple to get from stem cell to fully functioning adult heart cell, even in the lab.Ashley Fong, PhD Student in Molecular Biology & Biochemistry, University of California, IrvineLicensed as Creative Commons – attribution, no derivatives.