heparitin-sulfate and Diabetic-Foot

A novel heparan sulfate glycosaminoglycan mimetic product for local application to promote wound healing (CACIPLIQ) has recently become available. It is a biophysical therapeutic product comprising a polysaccharide as an innovative biomaterial to accomplish mechanical tissue engineering and skin regeneration in the site of ulceration. We present a series of 12 patients with type 2 diabetes (4 men and 8 women; age 53-87 years; diabetes duration 8-25 years) having chronic resistance to therapy for foot and lower extremity ulcerations. CACIPLIQ was locally applied twice per week after careful debridement. Complete ulcer healing was accomplished in all patients after a mean treatment duration of 4.92 months (range = 2-12 months). The product was very well tolerated. In conclusion, these results, although preliminary, are encouraging and suggest adequate efficacy and safety of the new product in difficult-to-heal foot and lower extremity ulcerations in type 2 diabetes.

Topics: Aged; Aged, 80 and over; Bandages; Diabetes Mellitus, Type 2; Diabetic Foot; Female; Heparitin Sulfate; Humans; Leg Ulcer; Male; Middle Aged; Treatment Outcome; Wound Healing

Diabetic foot ulcers represent a therapeutic problem of high clinical relevance. Reduced vascular supply, neuropathy and diminished expression of growth factors strongly contribute to wound healing impairment in diabetes. Secretoneurin, an angiogenic neuropeptide, has been shown to improve tissue perfusion in different animal models by increasing the amount of vessels in affected areas. Therefore, topical secretoneurin gene therapy was tested in a full thickness wound healing model in diabetic db/db mice. Secretoneurin significantly accelerated wound closure in these mice and immunohistochemistry revealed higher capillary and arteriole density in the wounded area compared to control mice. In-vitro, the mechanism of action of secretoneurin on human dermal microvascular endothelial cells was evaluated in normal and diabetic cells. Secretoneurin shows positive effects on in vitro angiogenesis, proliferation and apoptosis of these cells in a basic fibroblast growth factor dependent manner. A small molecular weight inhibitor revealed fibroblast growth factor receptor 3 as the main receptor for secretoneurin mediated effects. Additionally, we could identify heparan-sulfates as important co-factor of secretoneurin induced binding of basic fibroblast growth factor to human dermal endothelial cells. We suggest topical secretoneurin plasmid therapy as new tool for delayed wound healing in patients suffering from diabetes.

Topics: Administration, Topical; Animals; Cells, Cultured; Diabetic Foot; Fibroblast Growth Factor 2; Genetic Therapy; Heparitin Sulfate; Humans; Mice; Mice, Mutant Strains; Neuropeptides; Plasmids; Proteoglycans; Secretogranin II; Wound Healing