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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.
- Anti-sessile bacterial and cytocompatibility properties of CHX-loaded nanohydroxyapatitePublication . Barros, J.; Grenho, Liliana; Fernandes, M.H.; Manuel, C.M.; Melo, L.F.; Nunes, O.C.; Monteiro, F.J.; Ferraz, Maria PiaNanohydroxyapatite possesses exceptional biocompatibility and bioactivity regarding bone cells and tissues, justifying its use as a coating material or as a bone substitute. Unfortunately, this feature may also encourage bacterial adhesion and biofilm formation. Surface functionalization with antimicrobials is a promising strategy to reduce the likelihood of bacterial infestation and colonization on medical devices. Chlorhexidine digluconate is a common and effective antimicrobial agent used for a wide range of medical applications. The purpose of this work was the development of a nanoHA biomaterial loaded with CHX to prevent surface bacterial accumulation and, simultaneously, with good cytocompatibility, for application in the medical field. CHX (5-1500 mg/L) was loaded onto nanoHA discs and the materials were evaluated for CHX adsorption and release profile, physic-chemical features, antibacterial activity against Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis, and cytocompatibility toward L929 fibroblasts. Results showed that the adsorption of CHX on nanoHA surface occurred by electrostatic interactions between the cationic group of CHX and the phosphate group of nanoHA. The release of CHX from CHX-loaded nanoHA showed a fast initial rate followed by a slower kinetics release, due to constraints caused by dilution and diffusion-limiting processes. NanoHA.50 to nanoHA.1500 showed strong anti-sessile activity, inhibiting bacterial adhesion and the biofilm formation. CHX-nanoHA caused a dose- and time-dependent inhibitory effect on the proliferation of fibroblasts for nanoHA.100 to nanoHA.1500. Cellular behavior on nanoHA.5 and nanoHA.50 was similar to control. Therefore, CHX-loaded nanoHA surfaces appear as a promising alternative to prevention of devices-related infections.