GelMA hydrogels reinforced by PCL@GelMA nanofibers and bioactive glass induce bone regeneration in critical size cranial defects

Abstract

Abstract Background The process of bone healing is complex and involves the participation of osteogenic stem cells, extracellular matrix, and angiogenesis. The advancement of bone regeneration materials provides a promising opportunity to tackle bone defects. This study introduces a composite hydrogel that can be injected and cured using UV light. Results Hydrogels comprise bioactive glass (BG) and PCL@GelMA coaxial nanofibers. The addition of BG and PCL@GelMA coaxial nanofibers improves the hydrogel’s mechanical capabilities (353.22 ± 36.13 kPa) and stability while decreasing its swelling (258.78 ± 17.56%) and hydration (72.07 ± 1.44%) characteristics. This hydrogel composite demonstrates exceptional biocompatibility and angiogenesis, enhances osteogenic development in bone marrow mesenchymal stem cells (BMSCs), and dramatically increases the expression of critical osteogenic markers such as ALP, RUNX2, and OPN. The composite hydrogel significantly improves bone regeneration (25.08 ± 1.08%) in non-healing calvaria defects and promotes the increased expression of both osteogenic marker (OPN) and angiogenic marker (CD31) in vivo. The expression of OPN and CD31 in the composite hydrogel was up to 5 and 1.87 times higher than that of the control group at 12 weeks. Conclusion We successfully prepared a novel injectable composite hydrogel, and the design of the composite hydrogels shows significant potential for enhancing biocompatibility, angiogenesis, and improving osteogenic and angiogenic marker expression, and has a beneficial effect on producing an optimal microenvironment that promotes bone repair.

Keywords

• GelMA
• Nanofiber
• Bioactive glass
• Organic-inorganic composite
• Bone regeneration