The repair process of bone tissue includes the early inflammatory response period and the late tissue repair period. It has been widely approved to be beneficial to the repair of bone injury by procedurally inhibiting the inflammatory response in the early stage and promoting bone regeneration in the late stage. In this study, the nano-hydroxyapatite/Poly(glycolide-co-caprolactone) (n-HA/PGCL) scaffold loaded with icariin was fabricated by fused deposition modeling technique, and the quercetin-loaded GelMA was further filled into the scaffold pores via light-curing methods to form a biphasic scaffold loaded with dual molecules (PHI + GQ scaffold). The releases of icariin and quercetin were sequential due to different degradation rates of GelMA and PGCL. In vitro, the scaffold not only scavenged reactive oxygen species production, but also promoted osteogenic differentiation of the MC-3T3-E1 cells. Furthermore, in vivo bone reconstruction of PHI + GQ scaffold was better than other groups by assessment of micro-CT data. In addition, the immunofluorescence staining of Arg-1 and iNOS indicated that PHI + GQ scaffold created an immune microenvironment conducive to bone repair due to the release of quercetin in the early stage, and HE and Masson staining suggested that PHI + GQ scaffold induced more new bone formation. These results demonstrated that the biphasic scaffold loaded with icariin and quercetin had both antioxidants in the early stage and osteogenesis properties in the late stage, obtaining satisfactory bone repair outcomes. Thus, the biphasic scaffold loaded with icariin and quercetin for sequential release could provide a promising solution for the restoration of bone defects and represent a potential strategy for bone regeneration.

中文翻译：

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一种增材制造的双相支架，用于通过抗氧化和成骨促进手术骨再生


骨组织的修复过程包括早期炎症反应期和晚期组织修复期。它已被广泛认为有利于骨损伤的修复，早期程序抑制炎症反应，晚期促进骨再生。本研究采用熔融沉积建模技术制备了负载淫羊藿苷的纳米羟基磷灰石/聚（乙交酚-共己内酯）（n-HA/PGCL）支架，并通过光固化方法将负载槲皮素的 GelMA 进一步填充到支架孔中，形成负载双分子的双相支架（PHI + GQ 支架）。由于 GelMA 和 PGCL 的降解速率不同，淫羊藿苷和槲皮素的释放是连续的。在体外，该支架不仅清除了活性氧的产生，还促进了 MC-3T3-E1 细胞的成骨分化。此外，通过评估 micro-CT 数据，PHI + GQ 支架的体内骨重建优于其他组。此外，Arg-1 和 iNOS 的免疫荧光染色表明，PHI + GQ 支架由于早期槲皮素的释放创造了有利于骨修复的免疫微环境，HE 和 Masson 染色表明 PHI + GQ 支架诱导了更多的新骨形成。这些结果表明，负载淫羊藿苷和槲皮素的双相支架在早期具有抗氧化性，在晚期具有成骨特性，获得了令人满意的骨修复效果。因此，负载淫羊藿苷和槲皮素顺序释放的双相支架可以为骨缺损的修复提供有前途的解决方案，并代表骨再生的潜在策略。