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Purpose: Poultry by-products can contribute as an innovative natural source for the development of composites based on polymers and minerals aiming at bone regeneration. The objective of this study was the physicochemical and biological characterization of collagen-based hydrogels crosslinked with ultraviolet (UV)-riboflavin. Methods: Pure hydrogels of 100% collagen (G1) or hybrid hydrogels, 90% collagen:10% apatite (G2), 90% collagen:10% nanokeratin (G3), and 90% collagen:5% apatite:5% nanokeratin (G4) were characterized by scanning electron microscope, Fourier-transform infrared spectroscopy, differential scanning calorimetry, swelling degree and quali-quantitative histological analysis. Ectopic implantation in subcutaneous tissue in mice at one, three and nine weeks allowed to assess the inflammation (neutrophils, lymphocytes, macrophages, and giant cells) and repair (neovascularization, and connective tissue) to determine biocompatibility and the integrity of biomaterials to score their biodegradability. Histomorphometry on critical size defects in rat calvaria at one and three months evaluated the percentage of bone, connective tissue, and biomaterials in all groups. Results: The hydrogels presented porous microstructure, water absorption and physicochemical characteristics compatible with their polymeric and/or mineral composition. All materials exhibited biocompatibility, biodegradability, and low osteoconductivity. G2 showed greater density of new bone and biomaterial than the G1, G3 and G4. Conclusions: The collagen-apatite group formulation suggests potential for development as osteopromoting membrane.

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