Programmed core-shell electrospun nanofibers to sequentially regulate osteogenesis-osteoclastogenesis balance for promoting immediate implant osseointegration
Programmed core-shell electrospun nanofibers to sequentially regulate osteogenesis-osteoclastogenesis balance for promoting immediate implant osseointegration
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DOI：
10.1016/j.actbio.2021.08.050
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发表时间：
2021-11-07
影响因子：
9.7
通讯作者：
Luo, En
中科院分区：
文献类型：
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作者：
Ji, Huanzhong;Wang, Yiyao;Luo, En
拔牙后即刻种植体骨整合的生物学由成骨细胞-破骨细胞相互作用的协调级联介导。本研究的目的是开发一种双释放系统，允许顺序释放P物质（SP），以促进骨再生和阿仑膦酸钠（ALN），以减少骨吸收，这将提高种植体骨整合。采用同轴静电纺丝技术制备了壳层为SP、核层为ALN的聚乳酸-羟基乙酸共聚物（PLGA）/明胶核壳纳米纤维。这种程序化的递送系统显示出顺序地释放SP和ALN以匹配骨愈合的时空特异性。迁移实验表明，SP-ALN双传递系统增加了骨髓间充质干细胞（BMSCs）的迁移。成骨/破骨细胞标志物的表达、茜素红染色、抗酒石酸酸性磷酸酶（TRAP）染色、F-actin染色和骨吸收实验表明，双传递系统可提供有利于成骨分化而不利于破骨细胞生成的微环境。采用大鼠即刻种植模型，通过显微CT和组织学分析，我们验证了SP-ALN双递送系统促进种植体周围的成骨特性和骨整合。这些发现表明，双递送系统与时间控制释放的SP和ALN的核-壳纳米纤维提供了一个有前途的战略，以促进立即种植体骨整合，通过有利的成骨。重要性声明即刻种植体植入可能面临困难，难以实现初次种植体稳定性和早期成骨。骨整合的初始阶段由成骨细胞/成骨细胞调节，导致协调的愈合过程。为了实现高效的骨再生，利用同轴静电纺丝技术制备了程序化的双传递系统。SP释放迅速，有利于骨髓基质细胞的迁移和成骨分化，而ALN的持续释放可减少骨吸收。大鼠即刻种植模型表明，SP-ALN双释药系统可通过调节成骨-破骨细胞平衡，促进种植体周围骨形成和骨整合。这项工作强调了SP和ALN的顺序双重递送具有实现即刻种植体放置的增强骨整合的有希望的潜力。(c)2021由Elsevier Ltd代表Acta Materialia Inc.发布。
The biology of immediate post-extraction implant osseointegration is mediated by a coordinated cascade of osteoblast-osteoclast interactions. The aim of this study was to develop a dual-delivery system that allowed sequential release of substance P (SP) to promote bone regeneration and alendronate (ALN) to reduce bone resorption, which will improve the implant osseointegration. We used coaxial electrospinning to fabricate the core-shell poly lactic-co-glycolic acid (PLGA)/gelatin nanofibers, which consists of SP in the shell and ALN in the core. This programmed delivery system was shown to release SP and ALN sequentially to match the spatio-temporal specificity of bone healing. The migration assay demonstrated that the SP-ALN dual-delivery system increased bone marrow mesenchymal stem cells (BMSCs) transmigration. Besides, the expression of osteogenic/osteoclastic markers, Alizarin Red staining, tartrate resistant acid phosphatase (TRAP) staining, F-actin staining and bone resorption experiment showed that the dual-delivery system can render a microenvironment favorable for osteogenic differentiation and adverse to osteoclastogenesis. Using a rat immediate implant model, we validated the promoted osteogenic property and osseointegration around the implants of SP-ALN dual-delivery system by micro-computed tomography (micro-CT) and histological analysis. These findings suggest that the dual-delivery system with time-controlled release of SP and ALN by core-shell nanofibers provides a promising strategy to facilitate immediate implant osseointegration through favorable osteogenesis. Statement of significance Immediate implant placement is potentially challenged by the difficulties in achieving primary implant stability and early osteogenesis. Initial period of osteointegration is regulated by osteoblastic/osteoclastic cells resulting in a coordinated healing process. To have an efficient bone regeneration, the coaxial electrospinning was used to fabricate a programmed dual-delivery system. The SP released rapidly and favored for BMSCs migration and osteogenic differentiation, while the sustained release of ALN can reduce the bone resorption. The rat immediate implant model indicated that the SP-ALN dual-delivery system could present the promoted peri-implant osteogenic property and osseointegration through modulating the osteogenesis-osteoclastogenesis balance. This work highlights the sequential dual delivery of SP and ALN has a promising potential of achieving enhanced osseointegration for immediate implant placement. (c) 2021 Published by Elsevier Ltd on behalf of Acta Materialia Inc.