Department of Materials Science and Engineering, Monash Institute of Medical Engineering, Monash University, Clayton, VIC, 3800, Australia.
Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Biomaterials. 2021 Dec;279:121214. doi: 10.1016/j.biomaterials.2021.121214. Epub 2021 Oct 21.
Injectable hydrogels have been employed extensively as versatile materials for cartilage regeneration due to their excellent biocompatibility, tunable structure, and ability to accommodate bioactive factors, as well as their ability to be locally delivered via minimally invasive injection to fill irregular defects. More recently, in vitro and in vivo studies have revealed that processing these materials to produce cell-laden microgels can enhance cell-cell and cell-matrix interactions and boost nutrient and metabolite exchange. Moreover, these studies have demonstrated gene expression profiles and matrix regeneration that are superior compared to conventional injectable bulk hydrogels. As cell-laden microgels and their application in cartilage repair are moving closer to clinical translation, this review aims to present an overview of the recent developments in this field. Here we focus on the currently used biomaterials and crosslinking strategies, the innovative fabrication techniques being used for the production of microgels, the cell sources used, the signals used for induction of chondrogenic differentiation and the resultant biological responses, and the ability to create three-dimensional, functional cartilage tissues. In addition, this review also covers the current clinical approaches for repairing cartilage as well as specific challenges faced when attempting the regeneration of damaged cartilage tissue. New findings related to the macroporous nature of the structures formed by the assembled microgel building blocks and the novel use of microgels in 3D printing for cartilage tissue engineering are also highlighted. Finally, we outline the challenges and future opportunities for employing cell-laden microgels in clinical applications.
可注射水凝胶由于其优异的生物相容性、可调的结构和容纳生物活性因子的能力，以及通过微创注射局部给药以填充不规则缺陷的能力，已被广泛用作软骨再生的多功能材料。最近，体外和体内研究表明，将这些材料加工成含有细胞的微凝胶可以增强细胞-细胞和细胞-基质相互作用，并促进营养物质和代谢物的交换。此外，这些研究表明，与传统的可注射块状水凝胶相比，这些微凝胶具有优越的基因表达谱和基质再生。由于负载细胞的微凝胶及其在软骨修复中的应用越来越接近临床转化，本综述旨在概述该领域的最新进展。在这里，我们重点介绍了目前使用的生物材料和交联策略、用于生产微凝胶的创新制造技术、使用的细胞来源、用于诱导软骨分化的信号以及产生的生物学反应，以及创建三维功能软骨组织的能力。此外，本综述还涵盖了目前修复软骨的临床方法以及在尝试再生受损软骨组织时面临的具体挑战。还强调了与组装微凝胶构建块形成的结构的大孔性质以及微凝胶在 3D 打印用于软骨组织工程中的新用途相关的新发现。最后，我们概述了在临床应用中使用负载细胞的微凝胶面临的挑战和未来机遇。
