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通过缓解缺氧微环境和释放生物活性离子来增强钛植入物的免疫调节和骨再生。

Enhancing immune modulation and bone regeneration on titanium implants by alleviating the hypoxic microenvironment and releasing bioactive ions.

机构信息

Shenzhen Key Laboratory for Innovative Technology in Orthopedic Trauma, Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, PR China.

Medical Research Institute, Department of Orthopedics, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, PR China; Hebei Key Laboratory of Biomaterials and Smart Theranostics, School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, PR China.

出版信息

Colloids Surf B Biointerfaces. 2024 Apr;236:113805. doi: 10.1016/j.colsurfb.2024.113805. Epub 2024 Feb 17.

DOI:10.1016/j.colsurfb.2024.113805
PMID:38422666
Abstract

Bone implantation inevitably causes damage to surrounding vasculature, resulting in a hypoxic microenvironment that hinders bone regeneration. Although titanium (Ti)-based devices are widely used as bone implants, their inherent bioinert surface leads to poor osteointegration. Herein, a strontium peroxide (SrO)-decorated Ti implant, Ti_P@SrO, was constructed through coating with poly-L-lactic acid (PLLA) to alleviate the hypoxic microenvironment and transform the bioinert surface of the implant into a bioactive surface. PLLA degradation resulted in an acidic microenvironment and the release of SrO nanoparticles. The acidic microenvironment then accelerated the decomposition of SrO, resulting in the release of O and Sr ions. O released from Ti_P@SrO can alleviate the hypoxic microenvironment, thus enhancing cell proliferation in an O-insufficient microenvironment. Furthermore, under hypoxic and normal microenvironments, Ti_P@SrO enhanced alkaline phosphatase activity and bone-related gene expression in C3H10T1/2 cells with the continuous release of Sr ions. Meanwhile, Ti_P@SrO suppressed M1 polarization and promoted M2 polarization of bone marrow-derived monocytes under hypoxic and normal conditions. Furthermore, in a rat implantation model, the implant enhanced new bone formation and improved osteointegration after modification with SrO. In summary, the newly designed O- and Sr ion-releasing Ti implants are promising for applications in bone defects.

摘要

骨植入物不可避免地会对周围的脉管系统造成损伤,导致缺氧的微环境,从而阻碍骨再生。尽管钛(Ti)基设备广泛用作骨植入物,但它们固有的生物惰性表面导致骨整合不良。在此,通过聚 L-乳酸(PLLA)涂层构建了过氧锶(SrO)修饰的 Ti 植入物 Ti_P@SrO,以减轻缺氧微环境并将植入物的生物惰性表面转化为生物活性表面。PLLA 降解导致酸性微环境和 SrO 纳米粒子的释放。然后,酸性微环境加速 SrO 的分解,导致 O 和 Sr 离子的释放。Ti_P@SrO 释放的 O 可以缓解缺氧微环境,从而增强 O 不足微环境中的细胞增殖。此外,在缺氧和正常微环境下,Ti_P@SrO 通过持续释放 Sr 离子,增强 C3H10T1/2 细胞中碱性磷酸酶活性和与骨相关的基因表达。同时,Ti_P@SrO 在缺氧和正常条件下抑制骨髓来源单核细胞的 M1 极化并促进 M2 极化。此外,在大鼠植入模型中,经 SrO 修饰后,植入物增强了新骨形成并改善了骨整合。总之,新设计的 O 和 Sr 离子释放 Ti 植入物有望应用于骨缺损。

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