Exosome-Functionalized Ti6Al4V Scaffolds Promoting Osseointegration by Modulating Endogenous Osteogenesis and Osteoimmunity.

Abstract

Periprosthetic bone defects are the most serious problem of revision total hip arthroplasty, which can easily lead to insufficient osteointegration between the prosthesis and host bone. Bone marrow mesenchymal stem cells (BMSCs) and a moderate inflammatory response at the prosthesis-bone interface play an important role in osteointegration. Here, we developed microarc oxide titanium implant loaded engineered exosomes (S-Exos) to promote osseointegration at the prosthesis-bone interface. First, Smurf1-shRNA was transferred into the BMSCs using a viral vector to prepare S-Exos, which were subsequently immobilized to the microarc oxide titanium implant surface with positively charged polyethyleneimine. The immobilized S-Exos could be slowly and uniformly released and subsequently phagocytosed by BMSCs and macrophages. Once the S-Exos were phagocytosed, they could simultaneously activate the BMP/Smad signaling pathway in the BMSCs and promote macrophage M2 polarization, both of which enhance osseointegration. Specifically, this S-Exos coating exhibits a dual effect of promoting osseointegration, including the osseointegration of BMSCs by activating the BMP/Smad signaling pathway and the macrophage M2 polarization promoting osseointegration. In summary, the construction of S-Exos modified microarc oxide titanium implants could provide a new method for promoting osteointegration between the prosthesis and host bone in revision total hip arthroplasty.