Natural micropatterned fish scales combing direct osteogenesis and osteoimmunomodulatory functions for enhancing bone regeneration

Surface topography of implants to remodel osteoimmune microenvironment and osteogenic differentiation by modulating macrophage polarization has been regarded as a valuable strategy for advanced bone materials developments. Fish scales, considered as fish waste, show rich anisotropic ridged micropatterns on the surface and similar components to natural bone. Here, we present a topography strategy enhancing bone regeneration using the Lateolabrax japonicus scales surface microtopography as physical cues to program cell behaviors. The anisotropic ridged micropatterned surfaces and mineralized collagen synergistically programmed cells directional arrangement and induced the M2-phenotype polarization of macrophage to modulate the osteoimmune microenvironment by promoting anti-inflammatory cytokines secretions. Furthermore, anisotropic surface topography and mineralized collagen synergistically precipitated osteogenic differentiation of marrow mesenchymal stem cells via Wnt/β-catenin pathway. In vivo, the implanted fish scales significantly increased M2/M1 macrophage ratio, up-regulated anti-inflammatory and pro-healing cytokines expressions, promoted osteogenesis and bone formation. In conclusion, Lateolabrax japonicus scales enriched with anisotropic ridged micropatterns and mineralized collagen components synergistically expedite osteogenic differentiation and bone regeneration via programming cell orientation and modulating osteoimmune microenvironment, which provided a novel candidate implant for bone repair and boosted sustainable utilization of bio-resources.