Development of injectable fucoidan and biological macromolecules hybrid hydrogels for intra-articular delivery of platelet-rich plasma

Platelet-rich plasma (PRP) is rich in growth factors and has commonly been utilized in the repair and regeneration of damaged articular cartilage. However, the major drawbacks of direct PRP injection are unstable biological fixation and fast or burst release of growth factors. Fucoidan is a heparinoid compound that can bind growth factors to control their release rate. Furthermore, fucoidan can reduce arthritis through suppressing inflammatory responses and thus it has been reported to prevent the progression of osteoarthritis, promote bone regeneration and accelerate healing of cartilage injury. Injectable hydrogels can be used to deliver cells and growth factors for an alternative, less invasive treatment of cartilage defects. In this study, hyaluronic acid (HA) and fucoidan (FD) was blended with gelatin (GLT) and the GLT/HA/FD hybrid was further cross-linked with genipin (GP) to prepare injectable GP-GLT/HA/FD hydrogels. The gelation rate was affected by the GP, GLT, HA and FD concentrations, as well as the pH values. The addition of HA and FD to GLT networks improved the mechanical strength of the hydrogels and facilitated the sustained release of PRP growth factors. The GP-GLT/HA/FD hydrogel showed adequate injectability, shape-persistent property and strong adhesive ability, and was more resistant to enzymatic degradation. The PRP-loaded GP-GLT/HA/FD hydrogel promoted cartilage regeneration in rabbits, which may lead to an advanced PRP therapy for enhancing cartilage repair.