Zinc finger-inspired peptide-metal-phenolic nanointerface enhances bone-implant integration under bacterial infection microenvironment through immune modulation and osteogenesis promotion

Orthopedic and dental implantations under bacterial infection microenvironment face significant challenges in achieving high-quality bone-implant integration. Designing implant coatings that incorporate both immune defense and anti-inflammation is difficult in conventional single-functional coatings. We introduce a multifunctional nanointerface using a zinc finger-inspired peptide-metal-phenolic nanocoating, designed to enhance implant osseointegration under such conditions. Abaloparatide (ABL), a second-generation anabolic drug for treating osteoporosis, can be integrated into the design of a zinc-phenolic network constructed on the implant surface (ABL@ZnTA). Importantly, the phenolic-coordinated Zn2+ ions in ABL@ZnTA can act as zinc finger motif to co-stabilize the configuration of ABL through multiple molecular interactions, enabling high bioactivity, high loading capacity (1.36 times), and long-term release (>7 days) of ABL. Our results showed that ABL@ZnTA can modulate macrophage polarization from the pro-inflammatory M1 towards the anti-inflammatory M2 phenotype, promoting immune osteogenesis with increased OCN, ALP, and SOD 1 expression. Furthermore, the ABL@ZnTA significantly reduces inflammatory fibrous tissue encapsulation and enhances the long-term stability of the implants, indicated by enhanced binding strength (6 times) and functional connectivity (1.5−3 times) in the rat bone defect model infected by S. aureus. Overall, our research offers a nano-enabled synergistic strategy that balances infection defense and osteogenesis promotion in orthopedic and dental implantations.

A biologically stable, self-catalytic DNAzyme machine encapsulated by metal-phenolic nanoshells for multiple microRNA imaging

DNAzyme machines play critical roles in the fields of cell imaging, disease diagnosis, and cancer therapy. However, the applications of DNAzyme machines are limited by the nucleases-induced degradation,non-specific binding of proteins, and insufficient provision of cofactors. Herein, protected DNAzyme machines with different cofactor designs(referred to as Pro Ds) were nanoengineered by the construction of multifunctional metal-phenolic nanoshells to deactivate the interferential proteins, including nucleases and non-specific binding proteins. Moreover, the nanoshells not only facilitate the cellular internalization of Pro Ds but provide specific metal ions acting as cofactors of the designed DNAzymes. Cellular imaging results demonstrated that Pro Ds could effectively and simultaneously monitor multiple tumor-related micro RNAs in living cells. This facile and rapid strategy that encapsulates DNAzyme machines into the protective metal-phenolic nanoshells is anticipated to extend to a wide range of functional nucleic acidsbased biomedical applications.

Collagen-based materials in reproductive medicine and engineered reproductive tissues

Collagen,the main component of mammal skin,has been traditionally used in leather manufacturing for thousands of years due to its diverse physicochemical properties.Collagen is the most abundant protein in mammals and the main component of the extracellular matrix(ECM).The properties of collagen also make it an ideal building block for the engineering of materials for a range of biomedical applications.Reproductive medicine,especially human fertility preservation strategies and reproductive organ regeneration,has attracted significant attention in recent years as it is key in resolving the growing social concern over aging populations worldwide.Collagen-based biomaterials such as collagen hydrogels,decellularized ECM(dECM),and bioengineering techniques including collagen-based 3D bio-printing have facilitated the engineering of reproductive tissues.This review summarizes the recent progress in apply-ing collagen-based biomaterials in reproductive.Furthermore,we discuss the prospects of collagen-based materials for engineering artificial reproductive tissues,hormone replacement therapy,and reproductive organ reconstruction,aiming to inspire new thoughts and advancements in engineered reproductive tissues research.