Regulation of MSC and macrophage functions in bone healing by peptide LL-37-loaded silk fibroin nanoparticles on a titanium surface.

Titanium-based materials have been long regarded as effective bone implants for clinical use, yet the corresponding osteointegration ability needs to be optimized. This challenge can be overcome by fabricating titanium (Ti) materials with physiological functions. In this study, peptide LL-37-loaded silk fibroin nanoparticles (SFNPs) were immobilized on a titanium surface to facilitate osteointegration by regulating the physiological functions of mesenchymal stem cells (MSCs) and macrophages. According to our results, the cell viability, recruitment and paracrine responses of MSCs and macrophages were improved by the modified Ti samples. MSC differentiation was promoted by the macrophages incubated on the modified Ti samples, and the phenotype switch of macrophages was also modulated by the MSCs incubated on the modified Ti samples. In vivo studies proved that the modified Ti implant induced MSC and macrophage recruitments to injury sites and the inflammatory response was positively regulated. Moreover, better bone formation was achieved around the modified Ti implant 28 days after surgery. This suggested that the immobilization of peptide LL-37-loaded SFNPs on a titanium surface improves osteointegration via the regulation of physiological functions of MSCs and macrophages.