Cartilage Regeneration Units Based on Hydrogel Microcarriers for Injectable Cartilage Regeneration in an Autologous Goat Model

Despite numerous studies on tissue-engineered injectablecartilage,it is still difficult to realize stable cartilage formation in preclinicallarge animal models because of suboptimal biocompatibility, whichhinders further application in clinical settings. In this study, weproposed a novel concept of cartilage regeneration units (CRUs) basedon hydrogel microcarriers for injectable cartilage regeneration ingoats. To achieve this goal, hyaluronic acid (HA) was chosen as themicroparticle to integrate gelatin (GT) chemical modification anda freeze-drying technology to create biocompatible and biodegradableHA-GT microcarriers with suitable mechanical strength, uniform particlesize, a high swelling ratio, and cell adhesive ability. CRUs werethen prepared by seeding goat autologous chondrocytes on the HA-GTmicrocarriers and culturing in vitro. Compared withtraditional injectable cartilage methods, the proposed method formsrelatively mature cartilage microtissue in vitro andimproves the utilization rate of the culture space to facilitate nutrientexchange, which is necessary for mature and stable cartilage regeneration.Finally, these precultured CRUs were used to successfully regeneratemature cartilage in nude mice and in the nasal dorsum of autologousgoats for cartilage filling. This study provides support for the futureclinical application of injectable cartilage.