Applications: Wound Healing

Wounds in healthy people ordinarily heal without problems and do not require special medication unless they are infected. On the other hand, large groups of patients suffer from chronic wounds which heal very slowly or not at all. Among them are diabetics, or patients with venous or pressure ulcers. It was found recently that MALP-2 stimulates wound closure in an animal model using obese, diabetic mice. MALP-2 accomplishes accelerated wound closure in these animals by enhancing the inflammatory phase of wound healing.

This is brought about by first stimulating the release of chemokines from skin fibroblasts and keratinocytes. Chemokines are proteins which attract macrophages and other leukocytes to the wound. When the macrophages arrive in the wound, they are stimulated by MALP-2 to release a cocktail of growth factors and other mediators required for optimal wound healing. A phase 1 clinical trial has been carried out after approval by the ethics committee and showed that MALP-2 was well tolerated in doses which are expected to be effective. Moreover, MALP-2 was active in patients with diabetes.

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A cryosection through the skin of an obese mouse which has been treated with MALP-2 13 days earlier. The wound edge is shown at the left, the epidermis at the top. Note the thick fat layer showing as round "empty" areas to the right.

The red stain is caused by antibodies against CD31, an antigen specific for endothelial cells. See the many newly formed blood vessels at the wound edge. Untreated wounds show a much less pronounced neovascularization.