Bilayered bioengineered skin substitute (Apligraf®) -: A review of its use in the treatment of venous leg ulcers and diabetic foot ulcers

The bilayered bioengineered skin substitute (BBSS) [Apligraf(R)] is used for the treatment of venous leg ulcers and diabetic foot ulcers. It has an epidermal layer formed from human keratinocytes and a dermal layer composed of human fibroblasts in a bovine type I collagen matrix. BBSS does not contain any antigen-presenting cells such as Langerhans cells, dermal dendritic cells, endothelial cells or leucocytes. In clinical trials, there was no evidence of clinical rejection and immunological tests indicated no humoral or cellular response to the keratinocytes or fibroblasts of BBSS. Further clinical trials are required to identify the exact mechanism of action of BBSS in chronic wounds. BBSS plus compression therapy was well tolerated and was superior in efficacy to compression therapy alone in a multicentre, randomised trial in patients with venous leg ulcers. At 6 months' follow-up, complete wound healing occurred in 63 versus 49% of patients and the median time to wound closure was 61 versus 181 days. In a subgroup of patients with hard-to-heal ulcers (>1 year's duration), wound healing was achieved in significantly more patients (47 vs 19%) and the median time to wound healing was significantly shorter (181 days vs not attained). In a multicentre, randomised trial, BBSS was well tolerated and effective in patients with full-thickness neuropathic diabetic foot ulcers. Ulcer healing occurred in significantly more patients (56 vs 38%) and the median time to wound healing was shorter (65 vs 90 days) with BBSS than with saline-moistened gauze at 12 weeks' follow-up. Patients in both groups also received standard diabetic foot care. The cost effectiveness of BBSS in patients with chronic ulcers has yet to be examined in well designed, prospective clinical trials. However, according to a modelled analysis incorporating data from a multicentre randomised trial, BBSS was cost effective in patients with hard-to-heal venous leg ulcers. The average annual medical cost of managing patients with ulcers of >1 year's duration was estimated to be $US20 041 per patient treated with BBSS plus compression therapy and $US27 493 per patient treated with compression therapy alone (1996 costs). Conclusions: Clinical trials have shown that BBSS in conjunction with standard compression therapy was effective and well tolerated in patients with venous leg ulcers, especially patients with ulcers of >6 months' duration or that extended to the subcutaneous tissue. In addition, BBSS in conjunction with standard diabetic foot care was effective and well tolerated in patients with full-thickness neuropathic diabetic foot ulcers. BBSS represents a useful adjuvant to standard ulcer therapy in patients with venous leg ulcers or full-thickness neuropathic diabetic foot ulcers that do not respond to conventional ulcer therapy.