O-alg-THAM/gel hydrogels functionalized with engineered microspheres based on mesenchymal stem cell secretion recruit endogenous stem cells for cartilage repair

Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair.Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent,these approaches are still restricted by limited cell sources,excessive costs,risks of disease transmission and complex manufacturing practices.Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration.In this study,we propose an endogenous stem cell recruitment strategy for cartilage repair.Based on an injectable,adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement,the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair,providing new insights into in situ articular cartilage regeneration.

Bisphosphonate-based hydrogel mediates biomimetic negative feedback regulation of osteoclastic activity to promote bone regeneration

The intricate dynamic feedback mechanisms involved in bone homeostasis provide valuable inspiration for the design of smart biomaterial scaffolds to enhance in situ bone regeneration.In this work,we assembled a biomimetic hyaluronic acid nanocomposite hydrogel(HA-BP hydrogel)by coordination bonds with bisphosphonates(BPs),which are antiosteoclastic drugs.The HA-BP hydrogel exhibited expedited release of the loaded BP in response to an acidic environment.Our in vitro studies showed that the HA-BP hydrogel inhibits mature osteoclastic differentiation of macrophage-like RAW264.7 cells via the released BP.Furthermore,the HA-BP hydrogel can support the initial differentiation of primary macrophages to preosteoclasts,which are considered essential during bone regeneration,whereas further differentiation to mature osteoclasts is effectively inhibited by the HA-BP hydrogel via the released BP.The in vivo evaluation showed that the HA-BP hydrogel can enhance the in situ regeneration of bone.Our work demonstrates a promising strategy to design biomimetic biomaterial scaffolds capable of regulating bone homeostasis to promote bone regeneration.