Alginate-nanohydroxyapatite hydrogel system: Optimizing the formulation for enhanced bone regeneration

• Published in: Materials Science & Engineering C 2019-12, Vol.105, p.109985-109985, Article 109985
• Main Authors: Barros, J., Ferraz, M.P., Azeredo, J., Fernandes, M.H., Gomes, P.S., Monteiro, F.J.
• Format: Article
• Language: English
• Subjects: Alginate; Alginates; Alginates - pharmacology; Alginic acid; Animals; Apatite; Biocompatibility; Biodegradability; Biodegradation; Biological activity; Biological properties; Biomaterials; Biomedical materials; Bone biomaterials; Bone composition; Bone growth; Bone matrix; Bone Regeneration - drug effects; Bones; Calcium; Calcium - analysis; Calcium ions; Cancellous bone; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Chemical properties; Chick Embryo; Collagen; Composite; Composite materials; Composition; Durapatite - pharmacology; Evaluation; Extreme values; Gene Expression Regulation - drug effects; Humans; Hydrogel; Hydrogels; Hydrogels - pharmacology; Hydrogen-Ion Concentration; Injectability; Ions; Materials science; Mesenchymal Stem Cells; Mineralization; Nanohydroxyapatite; Nanoparticles - chemistry; Optimization; Organic chemistry; Osteoblasts; Osteoblasts - cytology; Osteoblasts - drug effects; Osteogenesis; Osteogenesis - drug effects; Osteogenic activity; Physical characteristics; Polymers; Regeneration; Regeneration (physiology); Solubility; Spectroscopy, Fourier Transform Infrared; Static Electricity; Tissue engineering; Tissues; Transcription factors; Water - chemistry
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.109985

Ceramic/polymer-based biocomposites have emerged as potential biomaterials to fill, replace, repair or regenerate 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 ceramic component present in the polymer-based composite. Therefore, in the present study, the influence of nanohydroxyapatite content (30 to 70 wt%) on alginate-based hydrogels was studied in order to evaluate the best formulation for maximizing bone tissue regeneration. The composite system was characterized in terms of physic-chemical properties and biological response, with in vitro cytocompatibility assessment with human osteoblastic cells and ex vivo functional evaluation in embryonic chick segmental bone defects. The main morphological 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. Within in vitro cytocompatibility assays it was observed that hydrogels with nanoHA 30% content enhanced osteoblastic cells proliferation and expression of osteogenic transcription factors, while those with higher concentrations (50 and 70%) decreased the osteogenic cell response. Ex vivo data underlined the in vitro findings, revealing an enhanced collagenous deposition, trabecular bone formation and matrix mineralization with Alg-nanoHA30 composition, while compositions with higher nanoHA 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 components ratio must be met to maximize bone tissue regeneration. [Display omitted] •Physic-chemical properties of the composite were nanoHA dose-dependent•Alg-nanoHA30 hydrogel enhanced the hMSCs proliferation and osteogenic activation•Alg-nanoHA30 induced osteogenesis with higher expression of Runx2, Col1a1, and BGLAP•Alg-nanoHA30 enhanced the collagenous deposition and trabecular bone formation•The components ratio optimization must be met to maximize bone tissue regeneration