Survival of Apligraf in Acute Human Wounds

Abstract

Apligraf consists of bovine collagen dermis seeded with allogeneic male fibroblasts and keratinocytes. It is been shown to promote healing, but the length of persistence and pathological features have not been characterized previously in acute wounds. Forty-eight deep dermal wounds were created and Apligraf, a split-skin graft (SSG), or a dressing was applied. Biopsies of wounds were taken for immunohistochemical analysis and polymerase chain reaction was performed to detect the Y chromosome from Apligraf cells in 14 female wounds. Male allogeneic DNA was detected in wounds for the first 4 weeks. All subsequent time points were negative apart from one biopsy at 6 weeks. The wounds took 4-9 weeks to heal, with the Apligraf exhibiting no features of engraftment. This was in contrast to the rapid healing seen in the SSG control group. Histology revealed a more intense cellular infiltrate, but less vascularization below Apligraf compared with controls. Evidence of an epidermal-mesenchymal interaction was observed. This is the first article to elucidate the survival of Apligraf allogeneic cells in acute wounds in immunocompetent human subjects for up to 6 weeks and demonstrates that in the management of acute surgical wounds, Apligraf has a role only as a temporary biological dressing.

A review of tissue-engineered skin bioconstructs available for skin reconstruction

“…There are reports of host immunogenic tolerance to allogeneic fibroblasts (Coulomb et al 1998) and their survival in the host up to three weeks (Morimoto et al 2005). Long-term preservation of allogeneic fibroblasts and their proliferation up to two months in the host without signs of immune rejection have also been reported (Sher et al 1983;Bell et al 1984;Eaglstein et al 1999;Hebda & Dohar 1999;Sandulache et al 2003;Griffiths et al 2004). However, porcine studies could not confirm allogeneic fibroblast survival beyond a 7-day time point ), nor could some clinical studies when allogeneic fibroblasts were transplanted onto burn wounds (Kolokol'chikova et al 2001).…”

“…Although this product does not cause immunological rejection, allogeneic cells of the construct do not survive after one to two months in vivo (Eaglstein et al 1999;Griffiths et al 2004). Hence, Apligraf, which was marketed initially as an organotypic skin substitute, can only be considered as a temporary bioactive dressing.…”

Distinct phenotype and therapeutic potential of gingival fibroblasts

“…Cryopreserved dermal substitutes appear to promote the same degree of re-epithelialization as native living substitutes (144). Several studies have indicated that allogeneic fibroblasts do not persist, at least in acute wounds (145). It is probable, therefore, that all these products serve more as biological dressings than as tissue replacements.…”

Facilitating Healing of Granulating Wounds: Dressings, Dermal Substitutes, and Other Methods

“…Apligraf is considered a temporary dressing because the allogenic cells survive less than 2 months in vivo [58]. Disadvantages of Apligraf are that it cannot be used for fullthickness wounds, the shelf life is only 5 days, and it requires delicate handling.…”