Abstract
Lately, cellular-based cartilage joint therapies have gradually gained more attention, which leads to next generation bioengineering approaches in the development of cell-based medicinal products for human use in cartilage repair. The greatest hurdles of chondrocyte-based cartilage bioengineering are: (i) preferring the cell source; (ii) differentiation and expansion processes; (iii) the time necessary for chondrocyte expansion pre-implantation; and (iv) fixing the chondrocyte count in accordance with the lesion surface area of the patient in question. The chondrocyte presents itself to be the focal starting material for research and development of bioengineered cartilage-based medicinal products which promise the regeneration and restoration of non-orthopedic cartilage joint defects. Even though chondrocytes seem to be the first choice, inevitable complications related to proliferation, dedifferentation and redifferentiation are probable. Detailed studies are a necessity to fully investigate detailed culturing conditions, the chondrogenic strains of well-defined phenotypes and evaluation of the methods to be used in biomaterial production. Despite a majority of the current methods which aid amelioration of joint functionality, they are insufficient in fully restoring the natural structure and composition of the joint cartilage. Hence current studies have trended towards gene therapy, mesenchymal stem cells and tissue engineering practices. There are many studies addressing the outcomes of chondrocytes in the clinical scene, and many vital biomaterials have been developed for structuring the bioengineered cartilage. This study aims to convey to the audience the practical significance of chondrocyte-based clinical applications.
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The authors have no conflicts of interest to declare. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for profit sectors. Pelin Kilic, Damla Alkaya and Cansu Grucan performed the literature search and data analysis, and all authors had the idea for the article and thereafter drafted and critically revised the work.
Appendix 1
Appendix 1
A list of some cell-based, tissue engineered autologous chondrocyte therapies which are either on the market, were reluctant to reach the market or were withdrawn (Huang et al. 2016; Atilla et al. 2018)
Product proprietary name | Active composition | Current regulatory status |
|---|---|---|
Biocart II | Autologous chondrocytes (passage number unknown) | No progress after Phase II clinical studies |
Bioseed-C | Autologous chondrocytes (passage number unknown) | Open to access only in some European countries |
Cartipatch | Autologous chondrocytes (up to passage 3) | Phase III clinical studies ceased |
Chondrosphere | Autologous chondrocytes (passage number unknown) | Phase III clinical studies expected to finish in 2020 |
Hyalograft C | Autologous chondrocytes (up to passage 3) | Withdrawn from the market |
MACI | Autologous chondrocytes (passages 1-3) | Too high price margin, manufacturing plant shut down due to reluctancy in the cover of expenditures |
NeoCart | Autologous chondrocytes (passage number unknown) | Phase III clinical studies completed in 2017 |
NOVOCART 3D | Autologous chondrocytes (passage 1) | Phase III clinical studies expected to finish in 2019 |
RevaFlex | Allogeneic, juvenile chondrocytes (passage number unknown) | Phase III clinical studies expected to finish in 2019 |
CaReS | Autologous chondrocytes (primary culture) | Delivered to Turkey, Iran and China but no access due to the high price margin |
INSTRUCT | Autologous chondrocytes (primary culture) + bone marrow cells | Phase II clinical studies completed in 2014 |
ChondroCelect | Autologous chondrocytes containing specific marker proteins | Withdrawn from the market upon request of the authorization holder |
Spherox | Autologous chondrocyte spheroids | On the market |
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Alkaya, D., Gurcan, C., Kilic, P. et al. Where is human-based cellular pharmaceutical R&D taking us in cartilage regeneration?. 3 Biotech 10, 161 (2020). https://doi.org/10.1007/s13205-020-2134-5
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DOI: https://doi.org/10.1007/s13205-020-2134-5