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- Alginate-nanohydroxyapatite hydrogel system: Optimizing the formulation for enhanced bone regenerationPublication . Barros, J.; Ferraz, Maria Pia; Azeredo, J.; Fernandes, M.H.; Gomes, P.S.; Monteiro, F.J.Ceramic/polymer-based biocomposites have emerged as potential biomaterials tofill, replace, repair or re-generate injured or diseased bone, due to their outstanding features in terms of biocompatibility, bioactivity,injectability, and biodegradability. However, these properties can be dependent on the amount of ceramiccomponent present in the polymer-based composite. Therefore, in the present study, the influence of nanohy-droxyapatite content (30 to 70 wt%) on alginate-based hydrogels was studied in order to evaluate the bestformulation for maximizing bone tissue regeneration. The composite system was characterized in terms ofphysic-chemical properties and biological response, within vitrocytocompatibility assessment with human os-teoblastic cells andex vivofunctional evaluation in embryonic chick segmental bone defects. The main mor-phological characteristics of the alginate network were not affected by the addition of nanohydroxyapatite.However, physic-chemical features, like water-swelling rate, stability at extreme pH values, apatite formation,and Ca2+release were nanoHA dose-dependent. Withinin vitrocytocompatibility assays it was observed thathydrogels with nanoHA 30% content enhanced osteoblastic cells proliferation and expression of osteogenictranscription factors, while those with higher concentrations (50 and 70%) decreased the osteogenic cell re-sponse.Ex vivodata underlined thein vitrofindings, revealing an enhanced collagenous deposition, trabecularbone formation and matrix mineralization with Alg-nanoHA30 composition, while compositions with highernanoHA content induced a diminished bone tissue response.The outcomes of this study indicate that nanohydroxyapatite concentration plays a major role in physic-chemical properties and biological response of the composite system and the optimization of the componentsratio must be met to maximize bone tissue regeneration.