July 1, 2017 (Vol. 37, No. 13)
The Ideal of Tissue Engineering Is Becoming More of a Reality
Common trends are emerging among experts in the field of tissue engineering, and many of the trends rely heavily on the use of 3D-printed tissue scaffolds, especially those that “resemble the spatial and physical features of the biology they seek to repair/replace,” according to Anthony Weiss, Ph.D., the Sir Samuel McCaughey Chair in Biochemistry and a professor of Biochemistry and Molecular Biotechnology School of Life and Environmental Science at the University of Sydney. These engineered tissue constructs are now demonstrating improved drug delivery upon transplantation,1 and contain cells that can communicate better via built-in vasculature systems.2 Additionally, advances in T-cell engineering have allowed researchers to guide differentiation in T cells from hematopoietic stem and progenitor cells (HSPCs).3 Two recent papers have also highlighted innovation in protein-delivery techniques.4,5
Martin James Stoddart, Ph.D., principal scientist at the AO Research Institute in Davos, Switzerland, cites several advances: the use of microRNA for diagnosis and therapy, use of CRISPR/Cas9 for in vivo and in vitro editing, and the potential approval of the cell and gene therapy Invossa (tonogenchoncel-L), an investigational agent featuring ex vivo gene delivery via a retroviral transduction. TissueGene, Invossa’s manufacturer, touts the drug as the “First Cell-Mediated Gene Therapy for Degenerative Osteoarthritis.”6
GEN editors asked other experts in the field to identify the top trends that are occurring in tissue engineering. The other leaders in the field that GEN spoke to include Manuela E. Gomes, Ph.D., principal investigator of the 3B’s Research Group at the University of Minho; Wei Liu, M.D., Ph.D., professor of plastic surgery at the Shanghai Jiao Tong University School of Medicine and associate director of the Shanghai Tissue Engineering Center and Shanghai Institute of Plastic and Reconstructive Surgery in China; and Gerjo van Osch, Ph.D., professor at the Erasmus MC, University Medical Center in Rotterdam in the Netherlands and head of the connective tissue cells and repair group in the department of orthopedics.
GEN: What are the top trends in the field of tissue engineering?
Dr. Gomes: During the past year, I have identified the following as top advances in our field:
- 3D bioprinting
Microfabricated tissue-engineered models for cancer and other diseases
- Personalized/precision regenerative medicine approaches
- Diagnostic and theranostic tools for monitoring and real-time control of tissue engineering systems
- Remote actuation of tissue-engineered constructs.
Concerning areas/topics that seems to be more intensely emerging in Portugal/Europe, I would say that there has been a major focus on developing personalized medicines, including tissue engineering. [This encompasses] the development of patient custom-made scaffolds using 3D-printing technologies. This area, in my opinion, is expected to grow a lot and expand [in the fields of] genetics, pharmacology, and regenerative medicine.
Dr. Weiss: I suggest the following helicopter-view advances:
- Demand for more robust biology as a driver of tissue engineering
- Increased emphasis on relevance to clinical outcomes
- The use of more natural materials
- Less compartmentalization of technology (e.g., a demand that cells function in the context of their environment).
Emerging in my part of the world, there is a greater emphasis on innovation in tissue engineering, which means making heroes of researchers who are serial inventors, company founders, and [those who] successfully translate technology [from the benchtop] into the clinic.
Dr. Liu: I would recommend the following advances in the field during the past year:
- Clinical application of engineered tissue or regenerative materials
- 3D printing for cell-contained tissue and organs
- Intelligent biomaterials for tissue regeneration and stem-cell differentiation
- Automatic cell expansion and tissue culture bioreactors
- Engineered tissue chips and their applications.
Dr. van Osch: A predictive computational framework for direct reprogramming between human cell types [has been described in the literature].7
Selection of factors for transdifferentiation of one cell type to another is a trial-and-error process that is time-consuming and expensive. An algorithm derived by this team can predict with great accuracy the factors needed for reprogramming, thus enabling the generation of large number of human cell types in the lab by cell reprogramming.
3D printing is everywhere these days and, it is advancing. Generation of engineered vascularized tissue remains a challenge, however. In a newer study, Jennifer Lewis’ research group built on their earlier work and generated vascularized tissue of about 1 cm in thickness, thus, taking a step forward in tissue engineering and repair.8
Also, 3D-printed ovaria have shown to be functional in a study with mice.9 A bioprosthetic ovary was created using 3D-printed microporous scaffolds, restoring ovarian function in sterilized mice.
Connected to this, the microrobotics field and its use in tissue engineering has evolved. Micro-sized smart building blocks containing cells or drugs will be elements to build tissues.
There has also been increased attention to the paracrine effects of mesenchymal stem cells via extracellular vesicles, but also via transfer of mitochondria. There are many articles coming out on this; this discovery could have clinical applications soon.
Lastly, we have seen the derivation and differentiation of haploid human embryonic stem cells.10 These cells may provide a novel tool to understand human development. Further, it may serve as a powerful tool for genetic screening to study the loss-of-function mutation. These stem cells have potential in transplantation and cell-based therapies [because they provide] a better genetic match.
1. F.T. Moutos et al., “Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing,” Proc. Natl. Acad. Sci. U.S.A. 113 (31) E4513–E4522, doi: 10.1073/pnas.1601639113.
2. B. Zhang et al., “Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis”, Nat. Materials 15, 669–678 (2016), doi:10.1038/nmat4570.
3. S. Shukla et al., “Progenitor T-cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1”, Nat. Methods 14(5), 531-538 (May 2017), doi: 10.1038/nmeth.4258. Epub Apr 10, 2017.
4. M.M. Pakulska, S. Miersch, and M.S. Shoichet, “Designer protein delivery: from natural occurring to engineered affinity controlled release systems”, Science 351(6279):aac4750, doi: 10.1126/science.aac4750.
5. M.M. Pakulska, C.H. Tator, and M.S. Shoichet, “Local delivery of chondroitinase ABC with or without stromal cell-derived factor 1 promotes functional repair in the injured rat spinal cord”, Biomaterials (accepted April 2017).
6. TissueGene, “TissueGene to Highlight Invossa, the World’s First Cell-Mediated Gene Therapy for Degenerative Osteoarthritis, at JP Morgan Healthcare Conference”, Press Release, accessed June 12, 2017.
7. O.J.L. Rackham et al., “A predictive computational framework for direct reprogramming between human cell types”, Nat. Genetics 48, 331–335 (2016), doi:10.1038/ng.3487.
8. D.B. Kolesky et al., “Three-dimensional bioprinting of thick vascularized tissue”, Proc. Natl. Acad. Sci. U.S.A. 113 (12), 3179–3184, doi: 10.1073/pnas.1521342113.
9. M.M. Laronda et al., “A Bioprosthetic Ovary Created Using 3D Printed Microporous Scaffolds Restores Ovarian Function in Sterilized Mice”, Nat. Commun. 8, 15261 (May 16, 2017).
10. I. Sagi et al., “Derivation and differentiation of haploid human embryonic stem cells”, Nature 532, 107–111 (April 7, 2016), doi:10.1038/nature17408.