Dextrin hydrogel loaded with a macroporous Bonelike® scaffold and dental pulp stem cells for critical-sized defect repair

• Published in: Materialia 2023-08, Vol.30, p.101859, Article 101859
• Main Authors: Machado, Alexandra, Pereira, Isabel, Pereira, José Eduardo, Maltez, Luís, Brandão, Ana, Alvites, Rui, Sousa, Ana Catarina, Branquinho, Mariana, Caseiro, Ana Rita, Pedrosa, Sílvia Santos, Maurício, Ana Colette, Pires, Isabel, Prada, Justina, Santos, José Domingos, Gama, Miguel
• Format: Article
• Language: English
• Subjects: Bone regeneration; Dental pulp; Dextrin; Hydrogel; Injectable; Stem cells
• ISSN: 2589-1529; 2589-1529
• DOI: 10.1016/j.mtla.2023.101859

Regeneration of severe bone defects remains a challenge. A formulation of synthetic glass-reinforced hydroxyapatite bone substitute, Bonelike® Poro (BL®P), 250–500 µm-diameter, with a dextrin-based hydrogel (HG), further loaded with human dental pulp stem cells (hDPSCs) with osteogenic differentiation ability, was tested for the management of critical-sized defects in an ovine model. Morphology, calcium release, and mechanical strength of HG + BL®P were analyzed. Then, BL®P, HG + BL®P, and 106 hDPSCs-loaded HG + BL®P were implanted in ovine critical-sized 14 mm-diameter calvaria defects. Bone samples were collected after 3 and 6 weeks for histological and micro-CT analysis. BL®P exhibits a suitable porous size for cell ingrowth, from the nm (>200 nm) to the µm (5 µm) range. The addition of BL®P granules to the HG resulted in increased compressive elastic modulus and ultimate tensile strength. The mildly acidic nature of the HG contributed to a faster dissolution of granules. In vivo results confirmed the HG suitability as a carrier, providing better defect filling, easy handling, and injectability of BL®P without compromising new bone formation nor biocompatibility. The HG + BL®P formulations can successfully regenerate critical-sized defects; however, addition of hDPSCs did not significantly enhance new bone formation under these conditions. Granular BL®P provides an effective alternative to autologous grafts. The HG acts as a biocompatible carrier of granular bone substitutes and cells, conferring injectability and cohesivity. Dextrin-based hydrogel works as a carrier of dental pulp stem cells and confers injectability and cohesivity to a granular synthetic bone substitute sized ∅ 250–500 µm. This hydrogel is an advanced three-dimensional carrier rather than a simple sticky binder. [Display omitted]