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

Abstract

Abstract Background Osteoporosis is a systemic bone disease prone to fractures due to decreased bone density and bone quality. The pathological environment of osteoporosis interferes with the normal process of fracture healing. The clinical regenerative repair materials specifically used for osteoporotic bone defects are not satisfactory, and the study of the mechanism of bone defect regeneration in the pathological environment of osteoporosis is helpful for the design of related materials.Methods In this study, the cryogels were prepared from decellularized extracellular matrix (dECM), methacrylate gelatin (GelMA), and carboxymethyl chitosan (CMCS) via unidirectional freezing, photocrosslinking, and genipin crosslinking. dECM extracted from normal or osteoporotic rats was applied for the preparation of the cryogels, named as GelMA-CMCS@Normal or GelMA-CMCS@OVX, respectively. The effects of different cryogels on BMSCs isolated from osteoporotic rats (OVX-BMSCs) were observed in vitro and in vivo.Results It was verified that the cryogels had excellent in vitro and in vivo biocompatibility. Furthermore, the GelMA-CMCS@Normal could effectively improve the proliferation of OVX-BMSCs, and promote the differentiation of OVX-BMSCs into osteoblasts in vitro and in vivo. RNA sequencing found that the OVX-BMSCs co-cultured with GelMA-CMCS@Normal cryogel exhibited down-regulated expression of reactive oxygen species modulator 1 (Romo1), which could activate the expression of nuclear factor erythroid 2-related factor 2 (Nfe2l2, NRF2). Further evidence showed that the reactive oxygen species (ROS) of the OVX-BMSCs were scavenged effectively after co-cultured with the GelMA-CMCS@Normal cryogel.Conclusions The results indicated that GelMA-CMCS@Normal cryogel was expected to be a clinical candidate for the repair of osteoporotic bone defects by regulating the ROS niche of OVX-BMSCs.Trial registration: Not applicable.