钛植入体表面短效-长效复合抗菌促成骨涂层的构建及性能研究

钛因优异的机械性能与良好的生物相容性而被大量用于植入体，但其表面生物活性与抗菌性能的缺乏影响了服役性能。传统针对钛植入体的表面修饰技术往往功能单一，无法满足不同时期感染风险的威胁。因此，本项目拟研制同时具有短期和长期效用的复合抗菌促成骨涂层，以应对植入早期感染和迟发/晚期感染的不同需求。首先，利用贻贝仿生化学在钛材表面接枝具有抗菌肽和骨成长肽，构建短期有效的可降解分子刷涂层。其次，在钛材表面使用阳极氧化和水热法构建掺杂微量元素（锶）的钛纳米管，并在其中负载超声响应性的药物载体，实现锶的缓慢释放和抗菌药物/声敏剂的超声响应性作用，达到长期促成骨和抗感染的效果。最后，将短效-长效涂层复合：外层抗菌肽-促成骨肽分子刷在植入初期抵御细菌侵袭，并随着成骨细胞的粘附和成长而降解；内层钛纳米管持续释放锶促进骨整合，在迟发/晚期感染情况下利用外源超声激发管内包埋药物的释放/作用，达到长效抗感染的功能。

Titanium (Ti) is widely applied as implants in clinical practice owing to its excellent mechanical properties and good biocompatibility. However, the lack of surface bioactivity and antibacterial property has limited the service performance of pristine Ti implants. Conventional surface modification techniques generally endow Ti implants with single function, which cannot cope with the infection risks in different periods of implantation. Consequently, this proposal aims to design and prepare antibacterial and osteogenic dual-functional coatings with short and long-term acting characteristics, which could fulfil the different demands to fight against early postoperative, delayed and late infections. Firstly, to construct the short-acting biodegradable polymer brush coatings, antimicrobial peptides (AMP) and osteogenic growth peptides (OGP) are immobilized onto Ti surface via a facile mussel-inspired chemistry. Furthermore, anodic oxidation prepared titanium nanotube (TNT) array is doped with microelement (Sr) by hydrothermal method, and subsequently loaded with ultrasound responsive drug carriers or sonosensitizers. The sustainable release of Sr2+ is beneficial for osseointegration, and the antibacterial drugs/sonosensitizers could be released upon ultrasound irradiation when delayed or late infection occurs. At last, the two coatings are combined to generate the desired short and long-acting antibacterial and osteogenic coatings. The outer layer AMP and OGP brushes could prevent the bacteria contamination in the early postoperative stage and degrade along with the adhesion and proliferation of osteoblasts. On the other hand, the interior TNT layer loaded with ultrasound-responsive drugs acts as an ammunition depot ready to combat with delayed or late infections.