An extracellular matrix-inspired self-healing composite hydrogel for enhanced platelet-rich plasma-mediated chronic diabetic wound treatment

Abstract

Diabetes is generally accompanied by difficult-to-heal wounds, which often lead to permanent disability and even death of patients. Because of the abundance of a variety of growth factors, platelet rich plasma (PRP) has been proven to have great clinical potential for diabetic wound treatment. However, how to suppress the explosive release of its active components while realizing adaptability to different wounds remains important for PRP therapy. Here, an injectable, self-healing, and non-specific tissue-adhesive hydrogel formed by oxidized chondroitin sulfate and carboxymethyl chitosan was designed as an encapsulation and delivery platform for PRP. With a dynamic cross-linking structural design, the hydrogel can meet the clinical demands of irregular wounds with controllable gelation and viscoelasticity. Inhibition of PRP enzymolysis as well as sustained release of its growth factors is realized with the hydrogel, enhancing cell proliferation and migration in vitro. Notably, greatly accelerated healing of full thickness wounds of diabetic skins is enabled by promoting the formation of granulation tissues, collagen deposition and angiogenesis as well as reducing inflammation in vivo. This self-healing and extracellular matrix-mimicking hydrogel provides powerful assistance to PRP therapy, enabling its promising applications for the repair and regeneration of diabetic wounds.