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通过局部递送普乐沙福和基质细胞衍生因子-1α实现干细胞归巢以改善钛植入物周围的骨再生

Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants.

作者信息

Karlsson Johan, Harmankaya Necati, Palmquist Anders, Atefyekta Saba, Omar Omar, Tengvall Pentti, Andersson Martin

机构信息

Department Of Chemistry and Chemical Engineering, Applied Chemistry, Chalmers University of Technology, Gothenburg, Sweden.

Department Of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden.

出版信息

J Biomed Mater Res A. 2016 Oct;104(10):2466-75. doi: 10.1002/jbm.a.35786. Epub 2016 Jun 6.

Abstract

Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1α/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1α, from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1α were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2466-2475, 2016.

摘要

早期愈合事件的触发,包括祖细胞的募集,已被认为可促进骨再生。在种植牙学中,局部药物释放技术可能提供一种有吸引力的促进组织再生的方法。在本研究中,我们针对趋化性的SDF-1α/CXCR4轴,例如该轴负责干细胞归巢至创伤部位。这是通过从孔径为7.5 nm的介孔二氧化钛薄膜涂层钛植入物局部递送普乐沙福(一种CXCR4拮抗剂)和/或SDF-1α来实现的。体外药物递送实验表明,介孔涂层具有高药物负载能力和控释性能。随后在大鼠胫骨上进行的体内研究表明,当局部递送普乐沙福和SDF-1α时,在骨-植入物锚固以及沿植入物表面的骨形成方面具有有益效果。最显著的效果是发现药物组合显著改善了骨的机械锚固。这些观察结果表明,能够局部递送药物以增强祖细胞局部募集的钛植入物具有促进骨整合的能力。这种方法可能为新型植入治疗的开发提供一种潜在策略。© 2016威利期刊公司。《生物医学材料研究杂志》A部分:第104A卷:2466 - 2475页,2016年。

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