中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (8): 2014-2022.doi: 10.12307/2026.079

• 材料生物相容性 material biocompatibility • 上一篇    下一篇

仿生功能涂层改善钛植入体与皮肤组织界面的整合

谭  婧1,李  莉2,王亮亮1,秦祥宇1   

  1. 1山西大同大学农学与生命科学学院,山西省大同市   037009;2大同市第五人民医院检验科,山西省大同市   037009
  • 收稿日期:2025-02-27 接受日期:2025-05-06 出版日期:2026-03-18 发布日期:2025-07-17
  • 通讯作者: 谭婧,博士,副教授,山西大同大学农学与生命科学学院,山西省大同市 037009
  • 作者简介:谭婧,女,1986年生,山西省大同市人,汉族,博士,副教授,主要从事钛基材料的生物效应研究。
  • 基金资助:
    国家自然科学基金项目(82001972),项目负责人:谭婧;山西省高等学校科技创新项目(2021L374),项目负责人:
    谭婧

Bionic functional coating improves the integration of titanium implants and skin tissue interface

Tan Jing1, Li Li2, Wang Liangliang1, Qin Xiangyu1   

  1. 1School of Agriculture and Life Science, Shanxi Datong University, Datong 037009, Shanxi Province, China; 2Department of Laboratory Medicine, Datong Fifth People’s Hospital, Datong 037009, Shanxi Province, China
  • Received:2025-02-27 Accepted:2025-05-06 Online:2026-03-18 Published:2025-07-17
  • Contact: Tan Jing, MD, Associate professor, School of Agriculture and Life Science, Shanxi Datong University, Datong 037009, Shanxi Province, China
  • About author:Tan Jing, MD, Associate professor, School of Agriculture and Life Science, Shanxi Datong University, Datong 037009, Shanxi Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82001972 (to TJ); Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi Province, No. 2021L374 (to TJ)

摘要:

文题释义:
固体结合肽:是通过噬菌体展示技术筛选出的、能够特异性识别并稳定结合固体表面的多肽,通常由10-20个氨基酸组成。固体结合肽通过静电作用、氢键或疏水相互作用等机制与固体表面结合,可用于材料表面改性,以改善材料的生物相容性、抗腐蚀性,并促进功能化(如细胞黏附、抗菌性能等),在生物医学和环境工程领域具有广泛应用潜力。
生物密封:是指经皮植入体(如人工关节、牙种植体或传感器等)植入人体后与周围软组织形成的一种紧密、稳定的界面封闭状态,这种封闭能够有效防止外界病原体侵入和体液渗漏,同时促进组织与植入体之间的整合。生物密封的形成依赖于植入体表面的生物相容性、微观结构设计及周围组织的愈合反应。良好的生物密封不仅能降低感染风险,还能提高植入体的长期稳定性和功能性,是经皮医疗器械成功应用的关键因素之一。

背景:经皮钛植入体的长期稳定性受限于皮肤-植入体界面动态整合机制缺失,表皮向下迁移导致的屏障功能衰退及继发感染等问题制约了其临床应用。尽管表面改性策略显著提升了钛材料的骨整合能力,但对皮肤组织界面的生物学调控仍存在挑战。
目的:开发一种基于钛亲和多肽的仿生功能涂层,改善钛植入体-皮肤组织界面整合。  
方法:通过酸碱两步法对纯钛片进行酸碱处理,随后浸泡于精氨酸-甘氨酸-天冬氨酸序列修饰的钛亲和多肽溶液中,在钛片表面制备仿生涂层。检测酸碱处理钛片、仿生涂层改性钛片表面的蛋白吸附与释放情况。将酸碱处理钛片、仿生涂层改性钛片分别与金黄色葡萄球菌共培养,扫描电镜观察黏附,活/死染色检测细菌存活情况。将酸碱处理钛片、仿生涂层改性钛片分别与小鼠成纤维细胞共培养,CCK-8法检测增殖,鬼笔环肽染色检测细胞黏附,划痕实验检测细胞迁移,免疫荧光染色检测Ⅰ型胶原蛋白和转化生长因子β表达,ELISA法检测细胞上清液中Ⅰ型和Ⅲ型胶原蛋白水平,qRT-PCR检测Ⅰ型胶原蛋白、Ⅲ型胶原蛋白、转化生长因子β、α平滑肌肌动蛋白和血管内皮生长因子mRNA表达。
结果与结论:①仿生涂层改性钛片在蛋白质吸附动力学方面展现出显著优势:与酸碱处理钛片相比,仿生涂层改性钛片表面在60 min内的蛋白质吸附率波动较小,并且在PBS中的蛋白质释放速率较为平稳,与蛋白质的结合更为牢固;②扫描电镜下可见两组钛片表面均黏附一定量细菌,并且细菌形态较为完整,呈球状,但活死染色显示仿生涂层改性钛片表面的细菌存活率较低;③小鼠成纤维细胞可在两组钛片表面增殖、黏附与铺展,其中仿生涂层改性钛片可促进小鼠成纤维细胞的迁移,免疫荧光染色显示两组钛片可促进Ⅰ型胶原蛋白和转化生长因子β的表达,ELISA检测显示仿生涂层改性钛片可延缓Ⅰ型胶原蛋白的过早沉积,qRT-PCR检测显示仿生涂层改性钛片可提升Ⅲ型胶原蛋白和转化生长因子β mRNA表达;④结果表明,仿生涂层改性可提高钛片表面蛋白质吸附与释放的稳定性、有效抑制细菌黏附与增殖、促进成纤维细胞迁移与创面修复相关因子的表达。
https://orcid.org/0009-0005-0969-2888 (谭婧) 

中国组织工程研究杂志出版内容重点:生物材料;骨生物材料;口腔生物材料;纳米材料;缓释材料;材料相容性;组织工程

关键词: 经皮钛植入体, 钛亲和多肽, 仿生涂层, 表面改性, 生物密封, 界面整合, 抗菌性能, 组织修复

Abstract: BACKGROUND: The long-term stability of percutaneous titanium implants is compromised by the lack of dynamic integration mechanisms at the skin-implant interface. Persistent challenges include barrier function deterioration and secondary infections due to epidermal downgrowth, which severely restrict clinical utility. Although titanium surface modifications have significantly enhanced osseointegration, the biological regulation of the skin tissue interface is still challenging.
OBJECTIVE: To develop a biomimetic functional coating based on titanium-affinity peptide and improve titanium implant-skin tissue interface integration. 
METHODS: Pure titanium sheets were treated with acid and base by an acid-base two-step method, and then immersed in a titanium affinity peptide solution modified with arginine-glycine-aspartic acid sequence to prepare a bionic coating on the surface of titanium sheets. The protein adsorption and release on the surfaces of acid-base treated titanium sheets and bionic coating modified titanium sheets were detected. The acid-base treated titanium sheets and bionic coating modified titanium sheets were co-cultured with Staphylococcus aureus, respectively. The adhesion was observed by scanning electron microscopy. The bacterial survival was detected by live/dead staining. The acid-base treated titanium sheet and the biomimetic coating modified titanium sheet were co-cultured with mouse fibroblasts, respectively. The proliferation was detected by CCK-8 assay. Cell adhesion was detected by phalloidin staining. Cell migration was detected by scratch test. Type I collagen and transforming growth factor β expression levels were detected by immunofluorescence staining. Type I and type III collagen levels in cell supernatant were detected by ELISA. Type I collagen, type III collagen, transforming growth factor β, α-smooth muscle actin and vascular endothelial growth factor mRNA expression levels were detected by qRT-PCR.
RESULTS AND CONCLUSION: (1) The bionic coating modified titanium sheet showed significant advantages in protein adsorption kinetics: Compared with the acid-base treated titanium sheet, the protein adsorption rate on the surface of the bionic coating modified titanium sheet fluctuated less within 60 minutes, and the protein release rate in PBS was relatively stable, and the binding with protein was more firmly. (2) Scanning electron microscopy showed that a certain amount of bacteria adhered to the surfaces of both groups of titanium sheets, and the bacterial morphology was relatively complete and spherical, but live-dead staining showed that the bacterial survival rate on the surface of the bionic coating modified titanium sheet was lower. (3) Mouse fibroblasts could proliferate, adhere and spread on the surfaces of both groups of titanium sheets, among which the bionic coating modified titanium sheet could promote the migration of mouse fibroblasts. Immunofluorescence staining showed that the two groups of titanium sheets could promote the expression of type I collagen and transforming growth factor β. ELISA results showed that the bionic coating modified titanium sheet could delay the premature deposition of type I collagen. qRT-PCR results showed that the bionic coating modified titanium sheet could increase the mRNA expression of type III collagen and transforming growth factor β. (4) These findings show that bionic coating modification can improve the stability of protein adsorption and release on the surface of titanium sheets, effectively inhibit bacterial adhesion and proliferation, and promote the migration of fibroblasts and the expression of factors related to wound repair.

Key words: percutaneous titanium implant, titanium affinity peptide, bionic coating, surface modification, bio-sealing, interfacial integration, antimicrobial property, tissue repair

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