Poly-Methacrylic Acid Cross-Linked with Collagen Accelerates Diabetic Wound Closure

Impaired blood vessel formation limits the healing of diabetic ulcers and leaves patients at high risk for amputation. Nonbiologic vascular regenerative materials made of methacrylic acid (MAA) copolymer, such as MAA-co-methyl methacrylate beads, have shown to enhance wound healing in a diabetic animal model, but their lack of biodegradability precludes their clinical implementation. Here, a new MAA-based gel was created by cross-linking polyMAA with collagen using carbodiimide chemistry. Using this gel on full-thickness wounds in diabetic db/db mice augmented vascularization of the wound bed, resulting in a faster closure compared to untreated or collagen-only treated wounds. After 21 days, almost all the wounds were closed and re-epithelialized in the polyMAA-collagen group compared to that in the other groups in which most wounds remained open. Histological and fluorescent gel tracking data suggested that the gel resorbed during the phase of tissue remodeling, likely because of the action of macrophages that colonized the gel. We expect the addition of the polyMAA to commercially available collagen-based dressing to be a good candidate to treat diabetic ulcers.