Institute of Fundamental Technological Research

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.

Bone regeneration, Injectable hydrogel, Nano-risedronate, Controlled delivery, Nanotechnology

Oral drug delivery systems have innumerable advantages, despite their precedence, the delivery of lipophilic drugs belonging to biopharmaceutical class II and IV, which has challenges associated with their solubility and permeability, leading to the limitations of this route. To address these barriers, nanocarrier systems combined with biomaterials are considered one of the pre-eminent approaches. Therefore, in this study pH-responsive pullulan-based hydrogels were developed, which were loaded with curcumin nanocrystals, micelles and coarse curcumin. In-vitro characterization studies, including dynamic light scattering, Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance, scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, and X-ray diffraction supported the development of hydrogels. The swelling index showed that developed hydrogels have significant swelling at pH 7.4, as the optimized formulation shows a “q value” of 5.938% at higher pH and 2.382% at lower pH. Additionally, the nanocrystal-laden hydrogel showed 86.250% drug release at pH 7.4, and better release than micelles and coarse curcumin-laden hydrogel. Moreover, nanocrystals showed a 1-fold increase in the solubility of curcumin, enhanced physical stability, and 82.81% permeation as compared with formulations. Conclusively, the outcome of the studies distinctly revealed a promising approach for successfully developing Pu-g-MAA hydrogels and the inclusion of lipophilic drugs in them.

Nanocrystals, Micelles, Curcumin, Controlled release, pH sensitive, Hydrogels