Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopaedic Surgery, University of Otago Christchurch, Christchurch8011, New Zealand.
Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.
Macromol Biosci. 2017 Dec;17(12). doi: 10.1002/mabi.201700158. Epub 2017 Oct 25.
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.
多组分明胶甲基丙烯酰基（GelMA）水凝胶常用于软骨组织工程（TE）应用，其中优化化学修饰以保持生物功能性经常被忽视。本研究调查了两种不同修饰方法，甲基丙烯酰化和巯基化，共聚明胶和肝素的生物学效应。通过凝血酶原时间和硫酸乙酰肝素缺陷髓系细胞系增殖试验评估了甲基化肝素（HepMA）和巯基化肝素（HepSH）的天然生物活性，表明巯基化在保持抗凝和生长因子信号转导能力方面更具优势。此外，在软骨细胞负载的 GelMA 水凝胶中加入 HepMA 或 HepSH，在软骨形成条件下培养 5 周，可促进细胞活力和软骨细胞表型。然而，只有 GelMA-HepSH 水凝胶在体外产生的分化和基质沉积显著大于 GelMA。本研究表明，与甲基丙烯酰化相比，硫醇-烯化学为将生物活性物质掺入明胶水凝胶提供了一种有利的策略，同时进一步强调了 GelMA-HepSH 水凝胶作为软骨 TE 应用的候选物。
