Progress and Prospect of Technical and Regulatory Challenges on Tissue-engineered Cartilage As Therapeutic Combination Product

Overview

Journal Bioact Mater

Specialty Biomedical Engineering

Date 2022 Jul 18

PMID 35846847

Authors

Xiaolei Guo

Yuan Ma

Yue Min

Jiayi Sun

Xinli Shi

Guobiao Gao

Lei Sun

Jiadao Wang

Affiliations

Soon will be listed here.

Abstract

Hyaline cartilage plays a critical role in maintaining joint function and pain. However, the lack of blood supply, nerves, and lymphatic vessels greatly limited the self-repair and regeneration of damaged cartilage, giving rise to various tricky issues in medicine. In the past 30 years, numerous treatment techniques and commercial products have been developed and practiced in the clinic for promoting defected cartilage repair and regeneration. Here, the current therapies and their relevant advantages and disadvantages will be summarized, particularly the tissue engineering strategies. Furthermore, the fabrication of tissue-engineered cartilage under research or in the clinic was discussed based on the traid of tissue engineering, that is the materials, seed cells, and bioactive factors. Finally, the commercialized cartilage repair products were listed and the regulatory issues and challenges of tissue-engineered cartilage repair products and clinical application would be reviewed.

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References

Hu J, Athanasiou K . A self-assembling process in articular cartilage tissue engineering. Tissue Eng. 2006; 12(4):969-79. DOI: 10.1089/ten.2006.12.969. View

Neves S, Teixeira L, Moroni L, Reis R, van Blitterswijk C, Alves N . Chitosan/poly(epsilon-caprolactone) blend scaffolds for cartilage repair. Biomaterials. 2010; 32(4):1068-79. DOI: 10.1016/j.biomaterials.2010.09.073. View

Cheng B, Tu T, Shi X, Liu Y, Zhao Y, Zhao Y . A novel construct with biomechanical flexibility for articular cartilage regeneration. Stem Cell Res Ther. 2019; 10(1):298. PMC: 6757433. DOI: 10.1186/s13287-019-1399-2. View

Funayama A, Niki Y, Matsumoto H, Maeno S, Yatabe T, Morioka H . Repair of full-thickness articular cartilage defects using injectable type II collagen gel embedded with cultured chondrocytes in a rabbit model. J Orthop Sci. 2008; 13(3):225-32. DOI: 10.1007/s00776-008-1220-z. View

Dattena M, Pilichi S, Rocca S, Mara L, Casu S, Masala G . Sheep embryonic stem-like cells transplanted in full-thickness cartilage defects. J Tissue Eng Regen Med. 2009; 3(3):175-87. DOI: 10.1002/term.151. View

Maas S, Breakefield X, Weaver A . Extracellular Vesicles: Unique Intercellular Delivery Vehicles. Trends Cell Biol. 2016; 27(3):172-188. PMC: 5318253. DOI: 10.1016/j.tcb.2016.11.003. View

Xu X, Shi D, Liu Y, Yao Y, Dai J, Xu Z . repair of full-thickness cartilage defect with human iPSC-derived mesenchymal progenitor cells in a rabbit model. Exp Ther Med. 2017; 14(1):239-245. PMC: 5488398. DOI: 10.3892/etm.2017.4474. View

Zhang W, Chen J, Tao J, Jiang Y, Hu C, Huang L . The use of type 1 collagen scaffold containing stromal cell-derived factor-1 to create a matrix environment conducive to partial-thickness cartilage defects repair. Biomaterials. 2012; 34(3):713-23. DOI: 10.1016/j.biomaterials.2012.10.027. View

Crawford D, Heveran C, Cannon Jr W, Foo L, Potter H . An autologous cartilage tissue implant NeoCart for treatment of grade III chondral injury to the distal femur: prospective clinical safety trial at 2 years. Am J Sports Med. 2009; 37(7):1334-43. DOI: 10.1177/0363546509333011. View

10.

Pattappa G, Johnstone B, Zellner J, Docheva D, Angele P . The Importance of Physioxia in Mesenchymal Stem Cell Chondrogenesis and the Mechanisms Controlling Its Response. Int J Mol Sci. 2019; 20(3). PMC: 6387316. DOI: 10.3390/ijms20030484. View

11.

Toh W, Lai R, Hui J, Lim S . MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment. Semin Cell Dev Biol. 2016; 67:56-64. DOI: 10.1016/j.semcdb.2016.11.008. View

12.

Dillon C, Rasch E, Gu Q, Hirsch R . Prevalence of knee osteoarthritis in the United States: arthritis data from the Third National Health and Nutrition Examination Survey 1991-94. J Rheumatol. 2006; 33(11):2271-9. View

13.

Silver I . Measurement of pH and ionic composition of pericellular sites. Philos Trans R Soc Lond B Biol Sci. 1975; 271(912):261-72. DOI: 10.1098/rstb.1975.0050. View

14.

Toh W, Lai R, Zhang B, Lim S . MSC exosome works through a protein-based mechanism of action. Biochem Soc Trans. 2018; 46(4):843-853. PMC: 6103455. DOI: 10.1042/BST20180079. View

15.

Schneider U, Rackwitz L, Andereya S, Siebenlist S, Fensky F, Reichert J . A prospective multicenter study on the outcome of type I collagen hydrogel-based autologous chondrocyte implantation (CaReS) for the repair of articular cartilage defects in the knee. Am J Sports Med. 2011; 39(12):2558-65. DOI: 10.1177/0363546511423369. View

16.

Nehrer S, Chiari C, Domayer S, Barkay H, Yayon A . Results of chondrocyte implantation with a fibrin-hyaluronan matrix: a preliminary study. Clin Orthop Relat Res. 2008; 466(8):1849-55. PMC: 2584266. DOI: 10.1007/s11999-008-0322-4. View

17.

Makris E, Gomoll A, Malizos K, Hu J, Athanasiou K . Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol. 2014; 11(1):21-34. PMC: 4629810. DOI: 10.1038/nrrheum.2014.157. View

18.

Krych A, Robertson C, Williams 3rd R . Return to athletic activity after osteochondral allograft transplantation in the knee. Am J Sports Med. 2012; 40(5):1053-9. DOI: 10.1177/0363546511435780. View

19.

Di Cave E, Versari P, Sciarretta F, Luzon D, Marcellini L . Biphasic bioresorbable scaffold (TruFit Plug) for the treatment of osteochondral lesions of talus: 6- to 8-year follow-up. Foot (Edinb). 2017; 33:48-52. DOI: 10.1016/j.foot.2017.05.005. View

20.

Iglesias-Lopez C, Agusti A, Obach M, Vallano A . Regulatory Framework for Advanced Therapy Medicinal Products in Europe and United States. Front Pharmacol. 2019; 10:921. PMC: 6728416. DOI: 10.3389/fphar.2019.00921. View