Nano-residronate loaded κ-carrageenan-based injectable hydrogels for bone tissue regeneration

Bone tissue possesses intrinsic regenerative capabilities to address deformities; however, its ability to repair defects caused by severe fractures, tumor resections, osteoporosis, joint arthroplasties, and surgical reconsiderations can be hindered. To address this limitation, bone tissue engineering has emerged as a promising approach for bone repair and regeneration, particularly for large-scale bone defects. In this study, an injectable hydrogel based on kappa-carrageenan-co-N-isopropyl acrylamide (κC-co-NIPAAM) was synthesized using free radical polymerization and the antisolvent evaporation technique. The κC-co-NIPAAM hydrogel's cross-linked structure was confirmed using Fourier transform infrared spectra (FTIR) and nuclear magnetic resonance (¹H NMR). The hydrogel's thermal stability and morphological behavior were assessed using thermogravimetric analysis (TGA) and scanning electron microscopy (SEM), respectively. Swelling and in vitro drug release studies were conducted at varying pH and temperatures, with minimal swelling and release observed at low pH (1.2) and 25 °C, while maximum swelling and release occurred at pH 7.4 and 37oC. Cytocompatibility analysis revealed that the κC-co-NIPAAM hydrogels were biocompatible, and hematoxylin and eosin (H&E) staining demonstrated their potential for tissue regeneration and enhanced bone repair compared to other experimental groups. Notably, digital x-ray examination using an in vivo bone defect model showed that the κC-co-NIPAAM hydrogel significantly improved bone regeneration, making it a promising candidate for bone defects.