Bone regeneration involves complex physiological processes, which is generally regulated and controlled by multiple bioactive molecules. In situ controlled release of combined bioactive factors in a spatiotemporal sequence for adapting the demand of bone regeneration is a desired strategy. In this study, nanoparticle/hydrogel composite system was constructed by incorporating stromal cell derived factor-1α (SDF-1α) and chitosan/tripolyphosphate/hyaluronic acid/antimiRNA-138 nanoparticles (CTH/antimiR-138 NPs) in chitosan/β-sodium glycerol phosphate (CS/GP) hydrogel for rat critical-size calvarial bone regeneration. The fast release of SDF-1α promoted the migration of mesenchymal stem cells (MSCs) for 6 d, while the sustained release of antimiR-138 from the nanoparticle/hydrogel compound enhanced the osteogenic differentiation of MSCs over 21 d. 8 weeks after surgery, calvarial specimens were evaluated by microcomputed tomography (μ-CT), histological analysis and immunohistochemistry. Comparing with blank group and hydrogel group, hydrogels incorporated with SDF-1α and/or CTH/antimiR-138 NPs significantly enhanced bone regeneration (p < 0.05). In addition, the expression of collagen type-1 (COL-1), osteopontin (OPN) and osteocalcin (OCN) proteins were enhanced in the combined drug group (incorporated both SDF-1α and CTH/antimiR-138 NPs) in comparison to the hydrogel group. Our research indicated the in situ formation of NPs/hydrogel composite could provide temporal sequence-release of SDF-1α and CTH/antimiR-138 NPs for on-demand MSCs homing and cranial bone regeneration.

中文翻译：

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原位控制释放基质细胞衍生因子1α和antimiR-138用于按需颅骨再生

骨骼再生涉及复杂的生理过程，通常由多个生物活性分子调节和控制。以时空顺序原位控制释放组合生物活性因子以适应骨骼再生的需求是一种理想的策略。在这项研究中，通过将基质细胞衍生因子-1α（SDF-1α）和壳聚糖/三聚磷酸盐/透明质酸/ antimiRNA-138纳米颗粒（CTH / antimiR-138 NPs）掺入壳聚糖/β-钠中构建了纳米颗粒/水凝胶复合系统。磷酸甘油（CS / GP）水凝胶，用于大鼠临界大小颅盖骨的再生。SDF-1α的快速释放促进了间充质干细胞（MSCs）迁移6 d，而从纳米颗粒/水凝胶化合物中持续释放antimiR-138则在21 d内增强了MSCs的成骨分化。术后8周，通过显微计算机断层扫描（μ-CT），组织学分析和免疫组织化学对颅骨标本进行评估。与空白组和水凝胶组相比，掺有SDF-1α和/或CTH / antimiR-138 NP的水凝胶显着增强了骨再生（p <  0.05）。此外，与联合用药组（并入SDF-1α和CTH / antimiR-138 NPs）相比，联合用药组中1型胶原蛋白（COL-1），骨桥蛋白（OPN）和骨钙蛋白（OCN）的表达增强。水凝胶组。我们的研究表明，NPs /水凝胶复合物的原位形成可以为按需MSCs归巢和颅骨再生提供SDF-1α和CTH / antimiR-138 NP的时间序列释放。