PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis ina Temporal Manner

Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its role during osteogenesis to be controversial.Regarding the differential functions of this pathway during 3 stages of bone healing,we hypothesized that temporal inhibition of PDGF-BB/PDGFR-βpathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells,toward osteogenic lineage,which leads to improved bone regeneration.We first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked extracellular regulated protein kinase 1/2 pathway,which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis.This study offered updated understanding of the use of PDGFR-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.

A trilogy antimicrobial strategy for multiple infections of orthopedic implants throughout their life cycle

Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles.However,ordinary antimicrobial treatments usually failed to combat multiple waves of infections during arthroplasty and prosthesis revisions etc.As these incidents could easily introduce new microbial pathogens in/onto the implants.Herein,we demonstrate that an antimicrobial trilogy strategy incorporating a sophisticated multilayered coating system leveraging multiple ion exchange mechanisms and fine nanotopography tuning,could effectively eradicate bacterial infection at various stages of implantation.Early stage bacteriostatic effect was realized via nano-topological structure of top mineral coating.Antibacterial effect at intermediate stage was mediated by sustained release of zinc ions from doped CaP coating.Strong antibacterial potency was validated at 4 weeks post implantation via an implanted model in vivo.Finally,the underlying zinc titanate fiber network enabled a long-term contact and release effect of residual zinc,which maintained a strong antibacterial ability against both Staphylococcus aureus and Escherichia coli even after the removal of top layer coating.Moreover,sustained release of Sr2+and Zn2+during CaP coating degradation substantially promoted implant osseointegration even under an infectious environment by showing more peri-implant new bone formation and substantially improved bone-implant bonding strength.