A microenvironment responsive polyetheretherketone implant with antibacterial and osteoimmunomodulatory properties facilitates osseointegration. Bioactive materials Failure of intraosseous prostheses is primarily attributed to implant loosening and infections. Current primary therapeutic modalities, such as antibiotics and local debridement, not only face challenges in thoroughly eliminating obstinate adhered bacteria but also encounter difficulties in ameliorating undue inflammatory reactions and regenerating impaired peri-implant bone tissues. Polyetheretherketone (PEEK) has excellent mechanical and physicochemical characteristics and has been used extensively as a medical biomaterial. However, the limited bactericidal and osseointegrative activities of bioinert PEEK restrict its clinical application. Herein, a microenvironment responsive coating with immobilised immunomodulatory magnesium ions (Mg) and disinfectant cerium oxide nanoparticles (CNPs) is designed via ion coordination mediated by polydopamine (PDA) and electrospinning based on collagen structure-bionic silk fibroin (SF). By utilising the pH responsiveness of SF, CNPs exhibit potent antibacterial effects in an acidic environment (pH 5.0) caused by local bacterial infection. Due to the chelation interaction with PDA and the constraint of SF, Mg is slowly released, ameliorating the local immune microenvironment and boosting osteogenesis by upregulating M2 phenotype macrophages. Bioinformatics analysis indicates that the inflammation is suppressed via the NF-κB signaling pathway. Overall, this SF-based coating maximizes the synergistic effect of CNPs and Mg, offering enhanced antibacterial and osteoimmunomodulatory bioactivity for successful implantation. 10.1016/j.bioactmat.2024.09.017

An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats. Hasani-Sadrabadi Mohammad Mahdi,Sarrion Patricia,Pouraghaei Sevda,Chau Yee,Ansari Sahar,Li Song,Aghaloo Tara,Moshaverinia Alireza Science translational medicine Cell-laden hydrogels are widely used in tissue engineering and regenerative medicine. However, many of these hydrogels are not optimized for use in the oral environment, where they are exposed to blood and saliva. To address these challenges, we engineered an alginate-based adhesive, photocrosslinkable, and osteoconductive hydrogel biomaterial (AdhHG) with tunable mechanical properties. The engineered hydrogel was used as an injectable mesenchymal stem cell (MSC) delivery vehicle for craniofacial bone tissue engineering applications. Subcutaneous implantation in mice confirmed the biodegradability, biocompatibility, and osteoconductivity of the hydrogel. In a well-established rat peri-implantitis model, application of the adhesive hydrogel encapsulating gingival mesenchymal stem cells (GMSCs) resulted in complete bone regeneration around ailing dental implants with peri-implant bone loss. Together, we have developed a distinct bioinspired adhesive hydrogel with tunable mechanical properties and biodegradability that effectively delivers patient-derived dental-derived MSCs. The hydrogel is photocrosslinkable and, due to the presence of MSC aggregates and hydroxyapatite microparticles, promotes bone regeneration for craniofacial tissue engineering applications. 10.1126/scitranslmed.aay6853

Osteoimmunity-Regulating Biomimetically Hierarchical Scaffold for Augmented Bone Regeneration. Advanced materials (Deerfield Beach, Fla.) Engineering a proper immune response following biomaterial implantation is essential to bone tissue regeneration. Herein, a biomimetically hierarchical scaffold composed of deferoxamine@poly(ε-caprolactone) nanoparticles (DFO@PCL NPs), manganese carbonyl (MnCO) nanosheets, gelatin methacryloyl hydrogel, and a polylactide/hydroxyapatite (HA) matrix is fabricated to augment bone repair by facilitating the balance of the immune system and bone metabolism. First, a 3D printed stiff scaffold with a well-organized gradient structure mimics the cortical and cancellous bone tissues; meanwhile, an inside infusion of a soft hydrogel further endows the scaffold with characteristics of the extracellular matrix. A Fenton-like reaction between MnCO and endogenous hydrogen peroxide generated at the implant-tissue site triggers continuous release of carbon monoxide and Mn , thus significantly lessening inflammatory response by upregulating the M2 phenotype of macrophages, which also secretes vascular endothelial growth factor to induce vascular formation. Through activating the hypoxia-inducible factor-1α pathway, Mn and DFO@PCL NP further promote angiogenesis. Moreover, DFO inhibits osteoclast differentiation and synergistically collaborates with the osteoinductive activity of HA. Based on amounts of data in vitro and in vivo, strong immunomodulatory, intensive angiogenic, weak osteoclastogenic, and superior osteogenic abilities of such an osteoimmunity-regulating scaffold present a profound effect on improving bone regeneration, which puts forward a worthy base and positive enlightenment for large-scale bone defect repair. 10.1002/adma.202202044