功能化脱细胞骨基质通过释放成骨肽促进骨再生,ACS Biomaterials Science & Engineering

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功能化脱细胞骨基质通过释放成骨肽促进骨再生
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2023-07-21 , DOI: 10.1021/acsbiomaterials.3c00413
Yutao Cui ₁ , Jingwei Wang ₁ , Yuhang Tian ₁ , Yi Fan ₁ , Shaorong Li ₁ , Gan Wang ₁ , Chuangang Peng ₁ , He Liu ₁ , Dankai Wu ₁

Affiliation

脱细胞骨基质（DCB）由于其与正常骨组织相似的生化、生物物理和机械特性，为治疗骨缺损提供了一种有前途的骨替代品。然而，脱细胞程序也大大降低了其成骨诱导活性。在这项研究中，将源自骨形态发生蛋白2指节表位的肽掺入热敏水凝胶泊洛沙姆407中，然后将负载肽的水凝胶填充到DCB的孔中，构建具有增强成骨功能的功能化支架。体外研究表明，功能化的 DCB 支架具有适当的机械性能和生物相容性，并表现出成骨肽的持续释放特性。这些性能极大地促进了骨髓间充质干细胞的细胞增殖和细胞铺展，并通过激活Smad/Runx2信号通路上调成骨相关基因的表达，从而促进成骨分化和细胞外基质矿化。进一步的体内研究表明，功能化的 DCB 支架可加速兔子严重径向缺损的修复，而不会诱导过度的移植物相关炎症反应。这些结果为治疗大节段骨缺损提供了一种具有临床意义的策略，所制备的成骨肽修饰复合DCB支架在骨再生方面具有巨大的应用潜力。

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Functionalized Decellularized Bone Matrix Promotes Bone Regeneration by Releasing Osteogenic Peptides

The decellularized bone matrix (DCB) provides a promising bone substitute for the treatment of bone defects because of its similar biochemical, biophysical, and mechanical properties to normal bone tissue. However, the decellularized procedure also greatly reduced its osteogenic induction activity. In this study, peptides derived from the knuckle epitope of bone morphogenetic protein-2 were incorporated into the thermo-sensitive hydrogel poloxamer 407, and the peptide-loaded hydrogel was then filled into the pores of DCB to construct a functionalized scaffold with enhanced osteogenesis. In vitro studies have shown that the functionalized DCB scaffold possessed appropriate mechanical properties and biocompatibility and exhibited a sustained release profile of osteogenic peptide. These performances critically facilitated cell proliferation and cell spreading of bone marrow mesenchymal stem cells and upregulated the expression of osteogenic-related genes by activating the Smad/Runx2 signaling pathway, thereby promoting osteogenic differentiation and extracellular matrix mineralization. Further in vivo studies demonstrated that the functionalized DCB scaffold accelerated the repair of critical radial defects in rabbits without inducing excessive graft-related inflammatory responses. These results suggest a clinically meaningful strategy for the treatment of large segmental bone defects, and the prepared osteogenic peptide modified composite DCB scaffold has great application potential for bone regeneration.

更新日期：2023-07-21

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