Biomimetic cryogel promotes the repair of osteoporotic bone defects through altering the ROS niche via down-regulating the ROMO1
Biomimetic cryogel promotes the repair of osteoporotic bone defects through altering the ROS niche via down-regulating the ROMO1
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DOI：
10.1016/j.ijbiomac.2023.128481
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发表时间：
2023-12-06
影响因子：
8.2
通讯作者：
Liao，Liqiong
中科院分区：
文献类型：
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作者：
Liu，Hai;Pan，Weilun;Liao，Liqiong
骨质疏松症是一种全身性骨骼疾病，由于骨密度和骨质量降低而易发生骨折，骨质疏松性骨折常发生延迟愈合或骨不连。因此，开发促进骨质疏松性骨折愈合的组织工程材料显得尤为重要。本研究将脱细胞细胞外基质(DECM)、甲基丙烯酸酯明胶(GelMA)和羧甲基壳聚糖(CMCs)通过单向冷冻、光和染料交联等方法制备成一系列仿生冷冻材料，用于骨质疏松性骨折的修复。从正常大鼠和骨质疏松大鼠中提取的dECM分别用于冷冻品的制备，分别命名为GC-Normal dECM和GC-OVX dECM。结果表明，GC-Normal dECM对体外培养的骨质疏松大鼠骨髓间充质干细胞(OVX-BMSCs)具有良好的促增殖作用，在体内外均能促进其向成骨细胞分化。RNA测序和进一步验证证实，GC-Normal dECM冷冻胶可以清除OVX-BMSCs中的细胞内活性氧(ROS)，通过下调活性氧调制物1(Romo1)的表达来促进骨质疏松性骨折的再生。结果表明，通过调节OVX-BMSCs的ROS生态位，仿生GC-Normal dECM冷冻胶有望成为修复骨质疏松性骨缺损的临床候选材料。
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)viaunidirectional 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 bothin vitroandin 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.