Chitosan hydrogels functionalized with either unfractionated heparin or bemiparin improve diabetic wound healing

• Functionalized hydrogels improved diabetes-associated impaired wound healing. • Bemiparin showed a greater capacity for collagen maturation and contributes to the stabilization of neoformed scar tissue. • Chitosan hydrogels promote the progression of the reparative process and induce the formation of stable scar tissue. • Quality of scar tissue at 21 days is clearly better and this would lead us, to a lower recurrence of ulcers. Diabetes mellitus causes severe impairment in the cutaneous wound healing process, which has led to extensive research striving to establish new treatments. In this work, we describe the effects of chitosan hydrogels functionalized with either unfractionated heparin or bemiparin (a low molecular weight heparin, LMWH) as topical treatments in an experimental diabetic wound healing model. Although wound morphometry showed similar values at the end of the study, microscopic analyses revealed impaired healing in diabetic animals in terms of inflammation and tissue formation. However, both types of loaded hydrogels accelerated inflammation resolution and improved the epithelialization process, while showing a neodermal thickness similar to that of nondiabetic animals. Immunohistochemistry analyses revealed an intermediate response in macrophage evolution between diabetic and nondiabetic controls in the treated groups, as well as enhanced collagenization and myofibroblast progression patterns. However, these changes were not accompanied by differences among groups in collagen I, III and TGF-β1 gene expression. Functionalized hydrogels improved diabetes-associated impaired wound healing, thus promoting the progression of the process and inducing the formation of high-quality cicatricial tissue. Although the beneficial healing effect observed after topical treatment with chitosan hydrogels loaded with bemiparin or unfractionated heparin was similar, the chitosan hydrogel loaded with bemiparin is the preferred choice as it exhibited high-quality tissue in the neoformed dermal tissue.