Biomimetic cryogel promotes the repair of osteoporotic bone defects through altering the ROS niche via down-regulating the ROMO1

Osteoporosis is a systemic bone disease that is prone to fractures due to decreased bone density and bone quality, and delayed union or nonunion often occurs in osteoporotic fractures. Therefore, it is particularly important to develop tissue engineering materials to promote osteoporotic fracture healing. In this study, a series of biomimetic cryogels prepared from the decellularized extracellular matrix (dECM), methacrylate gelatin (GelMA), and carboxymethyl chitosan (CMCS) via unidirectional freezing, photo- and genipin crosslinking were applied for the regeneration of osteoporotic fractures. Specifically, dECM extracted from normal or osteoporotic rats was applied for the preparation of the cryogels, named as GC-Normal dECM or GC-OVX dECM, respectively. It was verified that the GC-Normal dECM demonstrated superior performance in promoting the proliferation of BMSCs isolated from osteoporotic rats (OVX-BMSCs), and the differentiation of OVX-BMSCs into osteoblasts both in vitro and in vivo. RNA sequencing and further verifications confirmed that GC-Normal dECM cryogel could scavenge the intracellular reactive oxygen species (ROS) in OVX-BMSCs to accelerate the regeneration of osteoporotic fracture by down-regulating the reactive oxygen species modulator 1 (Romo1). The results indicated that by regulating the ROS niche of OVX-BMSCs, biomimetic the GC-Normal dECM cryogel was expected to be a clinical candidate for repairing osteoporotic bone defects.