Tough, in-situ thermogelling, injectable hydrogels for biomedical applications

Injectable hydrogels are extensively used in drug delivery and tissue engineering to administer drugs, genes, growth factors and live cells. We report a method to produce tough, in-situ thermogelling, non-toxic, injectable hydrogels made of chitosan and hyaluronic acid co-crosslinked with β-glycerophophate and genipin. The gels are highly homogeneous and form within 32 min, i.e., faster than gels crosslinked with either genipin or β-glycerophophate. The shear strength of co-crosslinked hydrogels is 3.5 kPa, higher than any chitosan-based gel reported. Chondrocytes and nucleus pulposus cells thrive inside the gels and produce large amounts of collagen II. Injection in rats shows that the gels form in-vivo within a short time and remain well localized for more than one week while the rats remain healthy and active. The excellent mechanical properties, fast in-situ gelation, good biocompatibility and the ability to encapsulate live cells at physiological conditions make these hydrogels ideal for tissue engineering, especially cartilage regeneration.