Tissue-specific composite hydrogel-loaded BMSCs inhibit apoptosis and promote meniscal repair.

The meniscus, as a weight-bearing tissue, will accelerate cartilage damage after injury and cause osteoarthritis. Currently, there is enthusiasm for using tissue engineering techniques to bionically fabricate grafts to replace meniscus. However, the high toughness and mechanical strength mediated by the specific arrangement of collagen-I fibers in the meniscus is an intractable challenge. Our study utilized decellularized meniscal extracellular matrix (mECM) in combination with GleMA to form a composite hydrogel for delivery of the BMSCs to regenerate the injured meniscus in situ. mECM has the same composition as the natural meniscus, and its retained bioactive factors can promote the differentiation of BMSCs to fibrocartilage to repair the meniscus and inhibit the meniscus cells' apoptosis. The presence of GelMA allows the hydrogel to adhere firmly to the defect, avoiding the risk of dislodging due to joint movement or gravity. In vitro cell culture, GelMA/mECM-loaded BMSCs retained essential glycosaminoglycans and collagen, and promoted the expression of cartilage markers, while down-regulating the expression of apoptosis-related markers. In a rat meniscal injury model, GelMA/mECM-loaded BMSCs inhibited further damage to the defective meniscus and avoided bone regrowth formation and articular cartilage destruction. In summary, the use of GelMA/mECM to deliver BMSCs for the treatment of meniscal injuries is a very promising strategy to be applied as an alternative treatment option to meniscal bionic graft implantation.