Pro-angiogenic thermosensitive injectable hydrogels for bone regeneration

Abstract

Hydrogels being similar to extracellular matrix (ECM) of tissues have very attractive features mitigating surgical treatments, and improving sustainable delivery of drugs and growth factors. Thermosensitive polymer solutions show excellent phase transition capacity from sol to gel when cooled or heated. Once low temperature processed polymer solutions are injected into the body, gelation formation occurs in-situ at tissue defects under the stimuli of body heat. In this project, we investigate thermosensitive chitosan matrixed hydrogel compositions in which hydroxyapatite and heparin are impregnated for bone repair and regeneration. Having similar properties to collagen, chitosan has a unique natural polysaccharide structure possessing good biocompatibility, biodegradability combined with the gelation capability makes it an ideal material to be used in tailor-making scaffolds for Tissue Engineering applications. Although chitosan-based thermoresponsive hydrogels have been clinically used for cartilage regeneration, there is limited research on their use in bone regeneration. The chitosan hydrogels with the impregnation of hydroxyapatite increase bioactivity and mechanical strength, and heparin inclusion induces vascularisation, ultimately helping bone regeneration. In this study, chitosanbased gels have been prepared with the varying amount of hydroxyapatite and heparin. These homogeneous composite gels have presented irreversible gelation behavior nearly at the body temperature accordingly the rheology tests (Tinitial gelation = ~31 °C). The initial gelation time of the solutions have been determined as ~ 10 min via test tube invert method. Injection performance of prepared solutions have been tested through the syringes with a range of scaled needles. The finest needle size in which the solutions could have a proper flow was a 21-gauge needle. The chemical structural properties of gels formed at 37 °C have been studied by Infrared and Raman spectroscopies. Morphological properties have also been fully evaluated. Biological properties to assess their biocompatibility and vascularisation potential have also been carried out. Results obtained to date are excellent confirming the great potential of thermosensitive gels to induce bone vascularisation