Abstract
In the inflammatory peri-implant microenvironment, excessive polarization of macrophages to the proinflammatory M1 phenotype can trigger the secretion of inflammatory cytokines, which promote bone resorption and impede osteogenesis around implants. The direct consequence of this process is the failure of prosthetic implants due to aseptic loosening. To reverse the inflammatory microenvironment and prevent prosthesis loosening, a mussel adhesion-inspired surface strategy was used for bioengineering of titanium implants with integrin-binding ability. In our design, a mussel-inspired catecholic peptide with tetravalent 3,4-dihydroxy-l-phenylalanine (DOPA) and Arg-Gly-Asp (RGD) sequences was synthesized. The peptide can easily anchor to the surface of medical titanium materials through a mussel adhesive mechanism. We found that peptide-decorated titanium implants could effectively inhibit peri-implant inflammation in a wear particle model and could promote the polarization of macrophages to a pro-healing M2 phenotype by interfering with integrin-α2β1 and integrin-αvβ3. Moreover, the peptide coating increased the adherence of osteoblasts and promoted osteogenesis on titanium implants even under inflammatory conditions. This work suggested that this biomimetic catecholic integrin-binding peptide can provide facile tactics for surface bioengineering of medical prostheses with improved interfacial osteogenesis under inflammatory conditions, which might contribute greatly to the prevention of prosthesis loosening and the improvement of clinical outcomes.