Citric acid fine-tuned silk fibroin/silver nanocomposite coating affords biomimetic, infection-defensive and pro-healing/osteo-angiogenic microenvironments for functional implant osseointegration

Prosthesis implant failures owing to recalcitrant bacterial infections and unsatisfactory biointegration remains a formidable challenge in orthopedic clinics. A fascinating solution is to develop advanced coating-functionalized implants to confer infection-free and pro-healing/osteo-angiogenic microenvironments amiable for establishing functional osteointegration. Inspired by the bone ECM-mimicking silk fibroin (SF) and the metabonegenic role of natural citrate in bone, herein we designed antimicrobial (nanosilver)-loaded, SF/citric acid (CA)-based biomimetic composite coatings (CA@Ag/SF) to furnish bioinert titanium with the abovementioned multifunctionalities. The key regards the ingenious synthesis of the CA@Ag/SF coating precursor by taking CA as a template/regulator for AgNPs nucleation and growth. Specifically, the reductive, metal-chelating functional groups of CA were leveraged to bind and reduce Ag+, while decorating and stabilizing the resulting AgNPs, thus producing uniform and monodispersed nanoparticles capped with CA "coronas" (CA@Ag). More attractively, the inclusion of CA into the Ag/SF system was found to also fine-tune the resultant coatings' surface topography and chemistry and Ag+-delivering behaviors, while conferring improved yet well-balanced antibacterial properties, osteocompatibility, and osteo/angiogenic functionalities that were unattainable in an Ag/SF control coating. Furthermore, in vivo implantation in rat femoral-condyle defects demonstrated that Ti implants decorated with CA@Ag/SF elicited drastically enhanced bone regeneration and rapid yet tight osseointegration, signifying great potential for clinical application. Our study has great potential for applications in harnessing CA and derivatives to optimize the performances of orthopedic biomaterials.