Spatiotemporal Immunomodulation Using Biomimetic Scaffold Promotes Endochondral Ossification-Mediated Bone Healing.
Spatiotemporal Immunomodulation Using Biomimetic Scaffold Promotes Endochondral Ossification-Mediated Bone Healing.
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DOI：
10.1002/advs.202100143
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Liu Y;Yang Z;Wang L;Sun L;Kim BYS;Jiang W;Yuan Y;Liu C
生物材料通过膜内骨化（IO）促进直接成骨愈合，在治疗骨缺损中发挥重要作用。然而，大多数身体的骨通过软骨内骨化（EO）经由软骨中间体形成，这是一个尚未被工程支架很好地模仿的过程，因此限制了它们在治疗大段骨缺损中的临床实用性。在这里，通过将皮质类固醇地塞米松包埋在仿生重组人骨形态发生蛋白（rhBMP）负载的多孔介孔玻璃支架内并调节其释放动力学，通过软骨内骨化实现了显著程度的异位骨形成。通过调节免疫抑制性巨噬细胞表型的募集和极化，支架通过激活间充质干细胞中的Hif-3α信号通路促进快速软骨形成，这上调下游软骨形成基因的表达。抑制HIF-3α信号转导可逆转软骨内骨化表型。总之，这些结果揭示了使用免疫调节仿生支架促进发育骨生长过程的策略，从而为开发能够诱导天然组织再生的生物材料提供了新的机会。制备时空地塞米松包埋、rhBMP-2负载的多孔介孔玻璃支架，以精确调节发育性软骨内骨化。地塞米松的初始释放可以有效介导软骨内阶段之前涉及M2/M1 ≈ 1的炎症反应，并通过激活Hif-3α信号通路并通过软骨细胞肥大、血管生成和成骨来促进随后rhBMP-2诱导的软骨内成骨。
Biomaterials play an important role in treating bone defects by promoting direct osteogenic healing through intramembranous ossification (IO). However, majority of the body's bones form via cartilaginous intermediates by endochondral ossification (EO), a process that has not been well mimicked by engineered scaffolds, thus limiting their clinical utility in treating large segmental bone defects. Here, by entrapping corticosteroid dexamethasone within biomimetic recombinant human bone morphogenetic protein (rhBMP)‐loaded porous mesoporous bioglass scaffolds and regulating their release kinetics, significant degree of ectopic bone formation through endochondral ossification is achieved. By regulating the recruitment and polarization of immune suppressive macrophage phenotypes, the scaffold promotes rapid chondrogenesis by activating Hif‐3α signaling pathway in mesenchymal stem cells, which upregulates the expression of downstream chondrogenic genes. Inhibition of Hif‐3α signaling reverses the endochondral ossification phenotype. Together, these results reveal a strategy to facilitate developmental bone growth process using immune modulating biomimetic scaffolds, thus providing new opportunities for developing biomaterials capable of inducing natural tissue regeneration. A spatiotemporal dexamethasone‐entrapped, rhBMP‐2‐loaded porous mesoporous bioglass scaffold is fabricated to precisely regulate developmental endochondral ossification. The initial release of dexamethasone can effectively mediate the inflammatory response involving M2/M1 ≈ 1 before endochondral stage, and further promotes later rhBMP‐2‐induced endochondral ossification via rapid chondrogenesis by activating Hif‐3α signaling pathway and ensuing ossification by hypertrophy of chondrocytes, angiogenesis, and osteogenesis.
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影响因子：
16.6
作者：
Petersen A;Princ A;Korus G;Ellinghaus A;Leemhuis H;Herrera A;Klaumünzer A;Schreivogel S;Woloszyk A;Schmidt-Bleek K;Geissler S;Heschel I;Duda GN
通讯作者：
Duda GN
皮下软骨内骨形成过程中巨噬细胞与软骨模板的相互作用
影响因子：
3.9
作者：
Huang, Jing;Zhou, Yi;Wang, Yan;Cai, Xinjie;Wang, Yining
通讯作者：
Wang, Yining
β-磷酸三钙通过 BMP2 信号通路刺激巨噬细胞诱导骨髓 MSC 成骨分化
影响因子：
14
作者：
Chen, Zetao;Wu, Chengtie;Xiao, Yin
通讯作者：
Xiao, Yin
DOI：
10.1083/jcb.138.5.1159
发表时间：
1997-09-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Camper L;Heinegârd D;Lundgren-Akerlund E
通讯作者：
Lundgren-Akerlund E
影响因子：
6.2
作者：
Alexander, Kylie A.;Chang, Ming K.;Pettit, Allison R.
通讯作者：
Pettit, Allison R.