Bio-clickable mussel-inspired peptides improve titanium-based material osseointegration synergistically with immunopolarization-regulation.
Bio-clickable mussel-inspired peptides improve titanium-based material osseointegration synergistically with immunopolarization-regulation.
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生物可点击的贻贝肽可与免疫极化调节协同改善钛基材料的骨整合
DOI：
10.1016/j.bioactmat.2021.10.003
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发表时间：
2022-03
影响因子：
18.9
通讯作者：
Shi Q
中科院分区：
文献类型：
--
作者：
Sun J;Huang Y;Zhao H;Niu J;Ling X;Zhu C;Wang L;Yang H;Yang Z;Pan G;Shi Q
在骨质疏松情况下，成骨缓慢、骨吸收过度和慢性炎症使得生物惰性钛（Ti）种植体与周围骨组织的骨整合变得困难，常常导致假体松动、骨塌陷和种植体失败。在这项研究中，我们首先设计了可点击的贻贝肽（DOPA-N3），并通过强大的儿茶酚-TiO2配位相互作用将其接枝到钛材料的表面。然后，通过生物正交反应将两个二苄基环辛炔（DBCO）封端的生物活性肽RGD和BMP-2生物活性结构域（BMP-2）点击到DOPA-N3涂层的Ti材料表面上。我们表征了钛基底的表面形貌和生物相容性，并通过将 BMP-2/RGD 的理想比例调整为 3:1 来优化钛表面的成骨能力。在体外，双功能化钛基质对间充质干细胞（MSC）的粘附和成骨具有良好的促进作用，具有显着的免疫极化调节作用，可将巨噬细胞转变为替代（M2）表型并抑制炎症，并增强骨质疏松大鼠的骨整合和机械稳定性。综上所述，我们的生物正交反应仿生表面修饰策略为解决钛基种植体的生物惯性和临床并发症提供了一种方便可行的方法，有利于钛种植体的长期成功，特别是在骨质疏松或炎症条件下。将贻贝启发的粘附和生物正交反应相结合，用 RGD 肽和 BMP-2 肽对钛基植入物进行表面修饰。双功能化钛基植入物可以通过促进骨髓间充质干细胞粘附和骨分化来增强成骨和骨整合，并调节骨质疏松大鼠的巨噬细胞极化。一种可点击的贻贝肽和两种 DBCO 封端的生物活性肽，可通过强大的儿茶酚/TiO2 配位相互作用和点击化学反应轻松装饰钛假体。双功能化钛基表面可以通过合理调整BMP-2和RGD肽的接枝比例来提高细胞锚定和成骨性。双功能化钛基表面协同实现 M2 转变和有效的骨整合炎症抑制。
Upon the osteoporotic condition, sluggish osteogenesis, excessive bone resorption, and chronic inflammation make the osseointegration of bioinert titanium (Ti) implants with surrounding bone tissues difficult, often lead to prosthesis loosening, bone collapse, and implant failure. In this study, we firstly designed clickable mussel-inspired peptides (DOPA-N3) and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions. Then, two dibenzylcyclooctyne (DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain (BMP-2) were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction. We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1. In vitro, the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells (MSCs), and conspicuous immunopolarization-regulation to shift macrophages to alternative (M2) phenotypes and inhibit inflammation, as well as enhancement of osseointegration and mechanical stability in osteoporotic rats. In summary, our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants, which was conducive to the long-term success of Ti implants, especially in the osteoporotic or inflammatory conditions. Mussel-inspired adhesion and bio-orthogonal reactions are combined for surface modification of Ti-based implants with RGD peptide and BMP-2 peptide. Dual-functionalized Ti-based implants can enhance osteogenesis and osseointegration through promoting BMSCs adhesion and osteodifferentiation, as well as modulate macrophage polarization in the osteoporotic rats. A clickable mussel-inspired peptide and two DBCO-capped bioactive peptides for facile decoration of Ti prostheses via robust catechol/TiO2 coordinative interactions and click chemical reaction. Dual functionalized Ti-based surface can improve cell anchoring and osteogenicitity by rationally adjusting the grafting ratio of BMP-2 and RGD peptides. Dual functionalized Ti-based surface synergistically achieve M2 shifting and efficient inflammation inhibition for osseointegration.
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DOI：
10.5037/jomr.2017.8201
发表时间：
2017-04
期刊：
Journal of oral & maxillofacial research
影响因子：
--
作者：
Haimov H;Yosupov N;Pinchasov G;Juodzbalys G
通讯作者：
Juodzbalys G
巨噬细胞和骨炎症
影响因子：
6.6
作者：
Gu Q;Yang H;Shi Q
通讯作者：
Shi Q
DOI：
10.1016/j.ijom.2012.07.018
发表时间：
2013-04-01
影响因子：
2.4
作者：
Jacobi-Gresser, E.;Huesker, K.;Schuett, S.
通讯作者：
Schuett, S.
影响因子：
14
作者：
Chen, Junjian;Hu, Guansong;Wang, Yingjun
通讯作者：
Wang, Yingjun
影响因子：
9.7
作者：
Bilem, I.;Chevallier, P.;Laroche, G.
通讯作者：
Laroche, G.