The National Science Foundation (NSF) notes that the concept of
‘‘tissue engineering’’ was first coined in the 1980s at a time when the fields of cell biology and engineering rarely intersected.
Today, much of the most exciting tissue engineering research is fueled by growth in stem cell technologies, and this partnership continues to deliver new insights and opportunities for regenerative medicine. To highlight this exciting synergy, Cell
Stem Cell and Trends in Biotechnology (TIBTECH) have joined forces with a joint review feature on tissue engineering. Articles on advances and applications in creating high-fidelity tissue models span the pages of both journals, with an emphasis on stem cell approaches and technology.
A strong partnership between engineers and stem cell biologists has allowed researchers to start asking questions and developing solutions that were unthinkable only a few years ago. In particular, tissue engineering has made great strides in advancing regenerative medicine, with many different tissueengineered therapies recently entering clinical trials. Tissue engineered models have also contributed to advances in drug discovery and toxicological screening initiatives that could impact the way pharmaceuticals are evaluated prior to first-inhuman trials. Just as importantly, tissue-engineered constructs have allowed us to ask new questions about basic biology and gain novel insights into intricate organ systems, disease mechanisms, and the body’s own innate capacity for repair and regeneration. Historically, the inability to effectively investigate both living human tissue and critical species differences using animal models has often hampered advances in medicine. The articles in these issues of Cell Stem Cell and TIBTECH address some of these challenges and look to future approaches where high-fidelity engineered tissues augment the design of effective next-generation therapies.
The advent of new engineering tools, such as imaging techniques, computational approaches, and biofabrication, has overcome several of the limitations that previous generations of biologists faced and allows a better understanding of tissue systems and the design of more effective cell therapies.
An Article in Cell Stem Cell discusses new tools that explore essential components of the extracellular matrix of different organ systems, enabling improved design of decellularized matrix technologies for repair and regeneration. Taking this idea further, one central tenet of contemporary biotechnology is rational design: the deliberate creation of synthetic biochemical constructs, precisely engineered for specific purposes. A TIBTECH
Article proposes a strategy for characterizing novel peptides for cell adhesion and incorporating them into engineered tissues, and a Review describes how to use systems biology approaches to understand morphogenesis with an eye toward directing morphogenetic processes.
One of the oldest questions in tissue engineering is how to select platforms for promoting tissue growth while also faithfully recapitulating the desired biological environment. Older paradigms generally relied on biologically inert scaffolding, while scaffold-free, self-organizing methods including organoids have also become popular. New technologies have ushered in a flood of novel means beyond these traditional methods to create engineered tissues. A TIBTECH Opinion advocates for a synergistic ‘‘third strategy’’ as a middle ground between scaffolds and scaffold-free methods, made possible in part by advances in polymerization technology. Two Reviews in TIBTECH touch on the growing importance of functionalized substrates: one describes how new imaging techniques are improving our understanding of precisely which biomaterials to use for functionalized scaffolds and how cells interact with them, and the other details how a class of materials known as bioactive glasses are helping to solve the particularly tricky problem of engineered angiogenesis. A TIBTECH Feature Review, written by many of the founders and leading researchers in the emerging field of biofabrication, details more than a dozen biofabrication technologies and proposes a unifying metric for evaluating the performance of new methods in bioprinting and bioassembly.
On the path toward designing strategies for tissue regeneration, developing high-fidelity, tissue-engineered constructs may also offer basic biological insight into complex organ systems.
Cell Stem Cell features a Short Article on the design considerations that go into building engineered bone marrow proxies for investigating hematopoietic heterogeneity and hematopoietic disorders. Two articles in TIBTECH describe particular organs—the pancreas and the neurovascular system—and explain how advances in tissue engineering technologies have helped to create increasingly biologically realistic models of these organs. As the authors of these articles point out, the applications of these models range from better understanding the basic biology of how the organs work to using them for disease modeling or even transplantation in vivo .
Over the past decade, there have been many initiatives using tissue-engineered chips for disease modeling and drug development. Building strong tissue models can also help with developing personalized medicine platforms, and a TIBTECH Opinion argues that personalized cancer organoids are the most promising approach toward precision medicine strategies for tailored and more effective cancer screening. Over the past 6 years, there have been numerous high-profile initiatives using tissues and organs on chips as platforms for drug discovery to better predict drug toxicity and efficacy at earlier stages in the discovery process. The US NIH National Center for Advancing Translational Studies (NCATs) has funded over 30 projects to develop single and multi-organ tissue chips across multiple sites in collaboration with DARPA, the FDA, and industry partners. Other international initiatives, such as the Netherlands’ Organ-on-Chip
Initiative, are also committed to advancing these platforms for accelerated screening of drug candidates over the next decade. A Review in Cell Stem Cell highlights progress and forecasts future developments in tissue-chip technologies.
One particularly exciting frontier is the recent initiative to study
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tissues-on-chips on the International Space Station, where the environment can induce accelerated models of disease. To highlight some of the exciting technologies developed for tissues in space, TIBTECH is featuring a Short Article on culturing tissues in microgravity.
Even though work in a variety of tissue systems has shown promise in pre-clinical studies, some tissue systems are more prominently entering clinical trials as engineered therapies.
Cell
Stem Cell is featuring a couple of Reviews on such systems, covering engineered therapies for both musculoskeletal and vascular applications. Excitingly, Humacyte’s human avascular vessel graft, providing long-term vascular access for hemodialysis patients, is one of the first clinical technologies granted the
Regenerative Medicine Advanced Therapy (RMAT) designation as part of the 21 st
Century Cures Act. As safety and efficacy concerns have historically slowed human pluripotent stem cell
(hPSC) clinical translation, it is also exciting that there are currently clinical trials in progress involving bioengineered hPSC-derived approaches to treat macular degeneration, diabetes, and myocardial infarction. In Cell Stem Cell , a tissue engineer and clinician discusses the critical remaining challenges that preclude widespread clinical translation of engineered PSC-based therapies.
As the fields of stem cell technology and engineering firmly cement their marriage, we anticipate that tissue engineering itself will merge with additional fields to further address unmet regenerative needs. One example is the intersection of the fields of tissue engineering and physical rehabilitative sciences to birth the field of regenerative rehabilitation. In Cell Stem Cell , we feature an article from leaders in this emerging field on how this collaborative science can further improve tissue regeneration beyond the grasp of either field’s current limitations.
Finally, we hope that these exciting developments will continue to motivate bioengineers, clinicians, and interdisciplinary scientists to work together toward finding solutions to the world’s largest health concerns. In Cell Stem Cell , a tissue engineering pioneer highlights the importance of these interpersonal relationships, particularly mentoring the next generation, to ensure the continued progress of the field. As innovations and collaborations strengthen the marriage of stem cell technology and engineering, we can all benefit from what the next decade brings.
WEB RESOURCES
Humacyte, http://www.humacyte.com/press/humacyte-receives-fdaregenerative-medicine-advanced-therapy-rmat-expedited-reviewdesignation-humacyl-vascular-access-hemodialysis/
Netherlands Organ-on-Chip Initiative, https://www.nwo.nl/en/researchand-results/research-projects/i/42/29042.html
NIH NCATS How the Tissue Chip Program Works, https://ncats.nih.gov/ tissuechip/about/operations
NIH NCATS Tissue Chips in Space, https://ncats.nih.gov/tissuechip/ projects/space
NSF, https://www.nsf.gov/pubs/2004/nsf0450/start.htm
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