3 years ago

Covalent Incorporation of Heparin Improves Chondrogenesis in Photocurable Gelatin-Methacryloyl Hydrogels

Covalent Incorporation of Heparin Improves Chondrogenesis in Photocurable Gelatin-Methacryloyl Hydrogels
Khoon S. Lim, Brooke L. Farrugia, Gabriella C. J. Brown, Gary J. Hooper, Tim B. F. Woodfield
Multicomponent gelatin-methacryloyl (GelMA) hydrogels are regularly adopted for cartilage tissue engineering (TE) applications, where optimizing chemical modifications for preserving biofunctionality is often overlooked. This study investigates the biological effect of two different modification methods, methacrylation and thiolation, to copolymerize GelMA and heparin. The native bioactivity of methacrylated heparin (HepMA) and thiolated heparin (HepSH) is evaluated via thromboplastin time and heparan sulfate-deficient myeloid cell-line proliferation assay, demonstrating that thiolation is superior for preserving anticoagulation and growth factor signaling capacity. Furthermore, incorporating either HepMA or HepSH in chondrocyte-laden GelMA hydrogels, cultured for 5 weeks under chondrogenic conditions, promotes cell viability and chondrocyte phenotype. However, only GelMA-HepSH hydrogels yield significantly greater differentiation and matrix deposition in vitro compared to GelMA. This study demonstrates that thiol-ene chemistry offers a favorable strategy for incorporating bioactives into gelatin hydrogels as compared to methacrylation while furthermore highlighting GelMA-HepSH hydrogels as candidates for cartilage TE applications. Covalent incorporation of heparin into cell-laden gelatin methacryloyl hydrogels significantly improves cartilage tissue formation. Thiolation is observed to be a more attractive chemical modification strategy that preserves heparin bioactivity compared to the almost ubiquitous application of methacrylation copolymerization protocols.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mabi.201700158

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