Zhang Bingjun, Li Jia, He Lei, Huang Hao, Weng Jie
Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, 610031, P. R. China; State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.
Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, 610031, P. R. China.
Acta Biomater. 2020 Sep 15;114:431-448. doi: 10.1016/j.actbio.2020.07.024. Epub 2020 Jul 15.
In view of the fact that titanium (Ti)-based implants still face the problem of loosening and failure of the implants caused by the slow biological response, the low osseointegration rate and the implant bacterial infection in clinical application, we designed a cancellous bone-like biomimetic Ti scaffold using the template accumulated by sugar spheres as a pore-forming agent. And based on a modified surface mineralization process and mussel-like adhesion mechanism, a silicon-doped calcium phosphate composite coating (Van-pBNPs/pep@pSiCaP) with Vancomycin (Van)-loaded polydopamine (pDA)-modified albumin nanoparticles (Van-pBNPs) and cell adhesion peptides (GFOGER) was constructed on the surface of Ti scaffold for mimicking the extracellular matrix (ECM) microenvironment of natural bone matrix to induce greater tissue regeneration. The in vitro study demonstrated that this porous Ti scaffold with functional bio-surface could distinctly facilitate cell early adhesion and spreading, and activate the expression of α2β1 integrin receptor on the cell membrane through promoting the formation of focal adhesions (FAs) in bone marrow stromal cells (BMSCs), thus mediating greater osteogenic cell differentiation. And it could also effectively inhibit the adhesion and growth of Staphylococcus epidermidis, exhibiting good antibacterial properties. Moreover, the Van-pBNPs/pep@pSiCaP-Ti scaffolds showed enhanced in vivo bone-forming ability due to the contributions of bioactive chemical components and the natural cancellous bone-like macrostructure. This work offers a promising structural and functional bio-inspired strategy for designing metal implants with desirable ability of osteoinduction synergistically with antibacterial efficacy for promoting bone regeneration and infection prevention simultaneously. STATEMENT OF SIGNIFICANCE: This manuscript describes a new method for making porous Ti scaffolds with a natural cancellous bone-like structure. Besides, a functional bio-surface was constructed on the bionic structure, mimicking some of the functions of the collagen-rich organic matrix and inorganic CaP nanocrystallites of native ECM of bone in chemical components and biological activities. This interconnected inter-pore opening structure encouraged the migration of cells among open macro-pores within the scaffold. In addition, the functionalized surface not only improved early cell adhesion, spreading, stimulated greater osteogenic differentiation of bone-forming cells, but also endowed the scaffold with excellent antibacterial effect. The biomimetic metal implant with multiple biomedical functions designed in this study has a great clinical application potential. This study represents a feasible method for the preparation of biomimetic structure of metal implants and the improvement of their surface biological activity.
鉴于钛(Ti)基植入物在临床应用中仍面临因生物反应缓慢、骨整合率低和植入物细菌感染导致的植入物松动和失效问题,我们以糖球堆积模板为造孔剂设计了一种松质骨样仿生钛支架。并基于改进的表面矿化过程和类贻贝粘附机制,在钛支架表面构建了一种硅掺杂磷酸钙复合涂层(Van-pBNPs/pep@pSiCaP),该涂层含有负载万古霉素(Van)的聚多巴胺(pDA)修饰的白蛋白纳米颗粒(Van-pBNPs)和细胞粘附肽(GFOGER),用于模拟天然骨基质的细胞外基质(ECM)微环境,以诱导更大程度的组织再生。体外研究表明,这种具有功能性生物表面的多孔钛支架能够显著促进细胞早期粘附和铺展,并通过促进骨髓基质细胞(BMSCs)中粘着斑(FAs)的形成来激活细胞膜上α2β1整合素受体的表达,从而介导更大程度的成骨细胞分化。并且它还能有效抑制表皮葡萄球菌的粘附和生长,表现出良好的抗菌性能。此外,由于生物活性化学成分和天然松质骨样宏观结构的作用,Van-pBNPs/pep@pSiCaP-Ti支架在体内显示出增强的骨形成能力。这项工作为设计具有理想骨诱导能力并协同抗菌功效以同时促进骨再生和预防感染的金属植入物提供了一种有前景的结构和功能仿生策略。重要性声明:本手稿描述了一种制造具有天然松质骨样结构的多孔钛支架的新方法。此外,在仿生结构上构建了功能性生物表面,在化学成分和生物活性方面模拟了富含胶原蛋白的有机基质和骨天然ECM的无机CaP纳米微晶的一些功能。这种相互连接的孔间开口结构促进了细胞在支架内开放大孔之间的迁移。此外,功能化表面不仅改善了细胞早期粘附、铺展,刺激了成骨细胞更大程度的成骨分化,还赋予了支架优异的抗菌效果。本研究设计的具有多种生物医学功能的仿生金属植入物具有巨大的临床应用潜力。这项研究代表了一种制备金属植入物仿生结构并改善其表面生物活性的可行方法。