The successful filling of bone defects remains challenging due to the incongruity between bone graft materials and the dynamic process of bone healing. Developing multifunctional materials matching the dynamic process of bone healing offers a viable solution to the current dilemma. Lines of evidence have shown that engineering osteoimmunomodulatory biomaterials can modulate the function of immune cells and thus promote bone regeneration. Herein, we utilized silk fibroin (SF) and polyglycolic acid (PGA) to create a PGA-SF core–shell fibrous scaffold, incorporating interleukin-4 (IL-4) and tricalcium phosphate (TCP) as a codelivery system (PGA/TCP-SF/IL-4), aiming to achieve an initial rapid release of IL-4 and sustained release of TCP. The PGA/TCP-SF/IL-4 scaffold mimicked the native bone structure and showed superior tenacity in the wetting regime. In vitro studies demonstrated that the PGA/TCP-SF/IL-4 scaffold significantly reduced the inflammatory response by upregulating the M2 macrophages, created a favorable microenvironment for osteogenesis, and facilitated osteogenic differentiation and mineralization. Implantation of the PGA/TCP-SF/IL-4 scaffold into the rat skull defect model notably increased the formation of new bones. IL-4 and TCP acted synergistically in attenuating inflammation and enhancing osteogenic differentiation. Overall, this multifunctional scaffold comprehensively considers the various demands in the bone defect region, which might have a significant potential for application in bone reconstruction.

中文翻译：

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从 PGA-SF 核壳静电纺丝支架中释放 IL-4 和 TCP 的双模式，通过协同免疫调节和成骨增强骨再生


由于骨移植材料与骨愈合的动态过程之间的不协调，骨缺损的成功填充仍然具有挑战性。开发与骨骼愈合的动态过程相匹配的多功能材料为当前的困境提供了一个可行的解决方案。证据表明，工程化骨免疫调节生物材料可以调节免疫细胞的功能，从而促进骨再生。在此，我们利用丝素蛋白 （SF） 和聚乙醇酸 （PGA） 创建了 PGA-SF 核壳纤维支架，结合了白细胞介素-4 （IL-4） 和磷酸三钙 （TCP） 作为共递送系统 （PGA/TCP-SF/IL-4），旨在实现 IL-4 的初始快速释放和 TCP 的持续释放。PGA/TCP-SF/IL-4 支架模拟天然骨骼结构，在润湿状态下表现出优异的韧性。体外研究表明，PGA/TCP-SF/IL-4 支架通过上调 M2 巨噬细胞显着降低炎症反应，为成骨创造有利的微环境，并促进成骨分化和矿化。将 PGA/TCP-SF/IL-4 支架植入大鼠颅骨缺损模型中，显著增加了新骨的形成。IL-4 和 TCP 在减轻炎症和增强成骨分化方面协同作用。总体而言，该多功能支架综合考虑了骨缺损区域的各种需求，在骨重建中可能具有重大应用潜力。