Bone-Inspired Tube Filling Decellularized Matrix of Toad Cartilage Provided an Osteoinductive Microenvironment for Mesenchymal Stem Cells to Facilitate the Radius Defect Repair of Rabbit
Bone-Inspired Tube Filling Decellularized Matrix of Toad Cartilage Provided an Osteoinductive Microenvironment for Mesenchymal Stem Cells to Facilitate the Radius Defect Repair of Rabbit
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仿骨管填充蟾蜍软骨脱细胞基质为间充质干细胞提供骨诱导微环境，促进兔桡骨缺损修复
DOI：
10.1002/biot.202000004
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发表时间：
2020
影响因子：
4.7
通讯作者：
Zhao Ying-Zheng
中科院分区：
文献类型：
--
作者：
Xu He-Lin;Yang Wai-Geng;Chen Pian-Pian;Chen Rui;Xue Peng-Peng;Wang Li-Fen;Yuan Jian-Dong;Yao Qing;Chen Bin;Zhao Ying-Zheng
蟾蜍骨不仅含有丰富的软骨样基质，而且免疫原性低。推测脱细胞蟾蜍骨基质（dBECM）可能为间充质干细胞（MSCs）提供更有利的骨诱导微环境，促进骨缺损的修复。在此，首先由羟基磷灰石（HA）和聚（γ-谷氨酸）（PGA）制成中空的骨激发管，然后将MSC/dBECM水凝胶均匀填充到其中心腔，构建仿生骨（dBECM + MSC-PGA + HA）。体外划痕实验和transwell实验表明，dBECM水凝胶不仅能有效地促进MSCs的迁移和增殖，而且能诱导其向成骨细胞分化。此外，皮下注射dBECM水凝胶后，炎症性巨噬细胞在大鼠皮肤浸润较少，表明其炎症攻击的可能性较低。将dBECM + MSCs − PGA + HA植入兔桡骨临界缺损后，X线和CT影像显示皮质有效再生，20周时髓腔再通完成。此外，在植入dBECM + MSCs − PGA + HA后，缺损中胶原蛋白II和OCN的表达明显增加。dBECM + MSCs − PGA + HA支架的治疗机制与增强的血管生成高度相关。总的来说，仿生dBECM + MSC − PGA + HA支架可能是提高桡骨缺损愈合效率的有前途的策略。
Toad bone not only contains the rich cartilage‐like matrix but also presents low immunogenicity. It is inferred that decellularized toad bone matrix (dBECM) may provide the more profitable osteoinductive microenvironment for mesenchymal stem cells (MSCs) to promote the repair of bone defects. Herein, a hollow bone‐inspired tube is first made from hydroxyapatite (HA) and poly (γ‐glutamic acid) (PGA), and then MSCs/dBECM hydrogel is uniformly filled to its central cavity, constructing a biomimetic bone (dBECM + MSCs − PGA + HA). In vitro scratch and transwell experiments show that dBECM hydrogel not only effectively promotes migration and proliferation of MSCs but also induces their osteogenic differentiation. Moreover, the less inflammatory macrophages infiltrate at rat skin after subcutaneously injecting dBECM hydrogel, indicating its low potential for inflammatory attack. After implanting dBECM + MSCs − PGA + HA to critical radius defect of rabbit, X‐ray and CT imaging shows that the cortex is effectively regenerated and the medullary cavity recanalization is completed at 20 weeks. Moreover, the expression of Collagen‐II and OCN are obviously increased in the defect after implanting dBECM + MSCs − PGA + HA. The therapeutic mechanism of dBECM + MSCs − PGA + HA scaffold are highly associated with the enhanced angiogenesis. Collectively, the biomimetic dBECM + MSCs − PGA + HA scaffold may be a promising strategy to improve radius defect healing efficiency.