球体
材料科学
软骨发生
组织工程
自愈水凝胶
软骨
生物医学工程
间充质干细胞
细胞外基质
复合材料
纳米技术
细胞培养
化学
解剖
细胞生物学
高分子化学
医学
生物化学
遗传学
生物
作者
Nikolas Di Caprio,Matthew D. Davidson,Andrew C. Daly,Jason A. Burdick
标识
DOI:10.1002/adma.202312226
摘要
Abstract Many cell types require direct cell–cell interactions for differentiation and function; yet, this can be challenging to incorporate into 3‐dimensional (3D) structures for the engineering of tissues. Here, a new approach is introduced that combines aggregates of cells (spheroids) with similarly‐sized hydrogel particles (microgels) to form granular composites that are injectable, undergo interparticle crosslinking via light for initial stabilization, permit cell–cell contacts for cell signaling, and allow spheroid fusion and growth. One area where this is important is in cartilage tissue engineering, as cell–cell contacts are crucial to chondrogenesis and are missing in many tissue engineering approaches. To address this, granular composites are developed from adult porcine mesenchymal stromal cell (MSC) spheroids and hyaluronic acid microgels and simulations and experimental analyses are used to establish the importance of initial MSC spheroid to microgel volume ratios to balance mechanical support with tissue growth. Long‐term chondrogenic cultures of granular composites produce engineered cartilage tissue with extensive matrix deposition and mechanical properties within the range of cartilage, as well as integration with native tissue. Altogether, a new strategy of injectable granular composites is developed that leverages the benefits of cell–cell interactions through spheroids with the mechanical stabilization afforded with engineered hydrogels.
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