Three Birds, One Stone: An Osteo-Microenvironment Stage-Regulative Scaffold for Bone Defect Repair through Modulating Early Osteo-Immunomodulation, Middle Neovascularization, and Later Osteogenesis,Advanced Science

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Three Birds, One Stone: An Osteo-Microenvironment Stage-Regulative Scaffold for Bone Defect Repair through Modulating Early Osteo-Immunomodulation, Middle Neovascularization, and Later Osteogenesis
Advanced Science ( IF 14.3 ) Pub Date : 2023-12-07 , DOI: 10.1002/advs.202306428
Yuhao Yuan _{1,

2} , Yan Xu _{3,

4} , Yiyang Mao _{1,

3} , Hongbin Liu ₁ , Minning Ou ₁ , Zhangyuan Lin ₁ , Ruibo Zhao ₁ , Haitao Long ₁ , Liang Cheng ₁ , Buhua Sun ₁ , Shushan Zhao ₁ , Ming Zeng ₁ , Bangbao Lu ₁ , Hongbin Lu _{2,

3,

4} , Yong Zhu ₁ , Can Chen _{1,

2,

3}

Affiliation

In order to repair critical-sized bone defects, various polylactic acid-glycolic acid (PLGA)-based hybrid scaffolds are successfully developed as bone substitutes. However, the byproducts of these PLGA-based scaffolds are known to acidify the implanted site, inducing tiresome acidic inflammation. Moreover, these degradation productions cannot offer an osteo-friendly microenvironment at the implanted site, matching natural bone healing. Herein, inspired by bone microenvironment atlas of natural bone-healing process, an osteo-microenvironment stage-regulative scaffold (P80/D10/M10) is fabricated by incorporating self-developed decellularized bone matrix microparticles (DBM-MPs) and multifunctional magnesium hydroxide nanoparticles (MH-NPs) into PLGA with an optimized proportion using low-temperature rapid prototyping (LT-RP) 3D-printing technology. The cell experiments show that this P80/D10/M10 exhibits excellent properties in mechanics, biocompatibility, and biodegradability, meanwhile superior stimulations in osteo-immunomodulation, angiogenesis, and osteogenesis. Additionally, the animal experiments determined that this P80/D10/M10 can offer an osteo-friendly microenvironment in a stage-matched pattern for enhanced bone regeneration, namely, optimization of early inflammation, middle neovascularization, and later bone formation. Furthermore, transcriptomic analysis suggested that the in vivo performance of P80/D10/M10 on bone defect repair is mostly attributed to regulating artery development, bone development, and bone remodeling. Overall, this study reveals that the osteo-microenvironment stage-regulative scaffold provides a promising treatment for bone defect repair.

中文翻译：

三鸟一石：通过调节早期骨免疫调节、中期新生血管和后期成骨来修复骨缺损的骨微环境阶段调节支架

为了修复临界尺寸的骨缺损，各种基于聚乳酸-乙醇酸（PLGA）的混合支架被成功开发为骨替代品。然而，已知这些基于 PLGA 的支架的副产品会使植入部位酸化，从而引发令人厌烦的酸性炎症。此外，这些降解产物无法在植入部位提供与自然骨愈合相匹配的骨友好微环境。在此，受自然骨愈合过程骨微环境图谱的启发，通过结合自主研发的脱细胞骨基质微粒（DBM-MPs）和多功能氢氧化镁纳米颗粒，制备了骨微环境阶段调节支架（P80/D10/M10）使用低温快速原型 (LT-RP) 3D 打印技术，以优化的比例将 (MH-NP) 转化为 PLGA。细胞实验表明，P80/D10/M10在力学、生物相容性和生物降解性方面表现出优异的性能，同时在骨免疫调节、血管生成和成骨方面具有优异的刺激作用。此外，动物实验确定P80/D10/M10可以以阶段匹配的模式提供有利于骨的微环境，以增强骨再生，即优化早期炎症、中期新生血管和后期骨形成。此外，转录组分析表明，P80/D10/M10在体内对骨缺损修复的作用主要归因于调节动脉发育、骨发育和骨重塑。总的来说，这项研究表明骨微环境阶段调节支架为骨缺损修复提供了一种有前景的治疗方法。

更新日期：2023-12-07

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