TY - JOUR
T1 - Optimization of 3D autologous chondrocyte-seeded polyglycolic acid scaffolds to mimic human ear cartilage
AU - Melgar-Lesmes, Pedro
AU - Bosch, Oriol
AU - Zubajlo, Rebecca
AU - Molins, Gemma
AU - Comfort, Sofia
AU - Luque-Saavedra, Ainara
AU - López-Moya, Mario
AU - García-Polite, Fernando
AU - Parri Ferrandis, Francisco José
AU - Rogers, Carolyn
AU - Gelabertó, Agata
AU - Martorell, Jordi
AU - Edelman, Elazer R.
AU - Balcells, Mercedes
N1 - Funding Information:
We acknowledge support provided by the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology for providing access to multiphoton microscopy used for this study. M. B. was supported in part by Fundació Empreses IQS, by La Caixa Foundation, by the Asociación Española de Microtia and the MIT-Spain program, and by two grants from the Spanish Ministry of Economy, SAF2013-43302-R and SAF2017-84773-C2-1-R. E. R. E. and this work was supported in part by a grant (R01 HL 161069) from the National Institutes of Health. P. M.-L. was supported by the Ministerio de Ciencia, Innovación y Universidades (grant PID2021-123426OB-I00) co-funded by the European Regional Development Fund (ERDF)-“A way to make Europe”, and the Ramón y Cajal Program 2018 (Ministerio de Ciencia, Innovación y Universidades, Reference: RYC2018-023971-I). The Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by the Instituto de Salud Carlos III. A. G. acknowledges the support from Regenear and the Asociación Española de Microtia.
Publisher Copyright:
© 2023 The Royal Society of Chemistry.
PY - 2023/5/16
Y1 - 2023/5/16
N2 - Auricular reconstruction in children with microtia is one of the more complex procedures in plastic surgery. Obtaining sufficient native material to build an ear requires harvesting large fragments of rib cartilage in children. Herein, we investigated how to optimize autologous chondrocyte isolation, expansion and re-implantation using polyglycolic acid (PGA) scaffolds for generating enough cartilage to recapitulate a whole ear starting from a small ear biopsy. Ear chondrocytes isolated from human microtia subjects grew slower than microtia rib or healthy ear chondrocytes and displayed a phenotypic shift due to the passage number. Rabbit ear chondrocytes co-cultured with mesenchymal stem cells (MSC) at a 50 : 50 ratio recapitulated the cartilage biological properties in vitro. However, PGA scaffolds with different proportions of rabbit chondrocytes and MSC did not grow substantially in two months when subcutaneously implanted in immunosuppressed mice. In contrast, rabbit chondrocyte-seeded PGA scaffolds implanted in immunocompetent rabbits formed a cartilage 10 times larger than the original PGA scaffold. This cartilage mimicked the biofunctional and mechanical properties of an ear cartilage. These results indicate that autologous chondrocyte-seeded PGA scaffolds fabricated following our optimized procedure have immense potential as a solution for obtaining enough cartilage for auricular reconstruction and opens new avenues to redefine autologous cartilage replacement.
AB - Auricular reconstruction in children with microtia is one of the more complex procedures in plastic surgery. Obtaining sufficient native material to build an ear requires harvesting large fragments of rib cartilage in children. Herein, we investigated how to optimize autologous chondrocyte isolation, expansion and re-implantation using polyglycolic acid (PGA) scaffolds for generating enough cartilage to recapitulate a whole ear starting from a small ear biopsy. Ear chondrocytes isolated from human microtia subjects grew slower than microtia rib or healthy ear chondrocytes and displayed a phenotypic shift due to the passage number. Rabbit ear chondrocytes co-cultured with mesenchymal stem cells (MSC) at a 50 : 50 ratio recapitulated the cartilage biological properties in vitro. However, PGA scaffolds with different proportions of rabbit chondrocytes and MSC did not grow substantially in two months when subcutaneously implanted in immunosuppressed mice. In contrast, rabbit chondrocyte-seeded PGA scaffolds implanted in immunocompetent rabbits formed a cartilage 10 times larger than the original PGA scaffold. This cartilage mimicked the biofunctional and mechanical properties of an ear cartilage. These results indicate that autologous chondrocyte-seeded PGA scaffolds fabricated following our optimized procedure have immense potential as a solution for obtaining enough cartilage for auricular reconstruction and opens new avenues to redefine autologous cartilage replacement.
UR - http://www.scopus.com/inward/record.url?scp=85152662762&partnerID=8YFLogxK
U2 - 10.1039/d3bm00035d
DO - 10.1039/d3bm00035d
M3 - Article
C2 - 37022673
AN - SCOPUS:85152662762
SN - 2047-4830
VL - 11
SP - 3695
EP - 3708
JO - Biomaterials Science
JF - Biomaterials Science
IS - 10
ER -
