Chronic wounds in skin persist because the normal process of wound hea
ling is obstructed. Failures occur in the inflammation and proliferati
on phases of wound healing that reduce formation of granulation tissue
and prevent epithelial migration to close the wound, resulting mostly
from vascular insufficiencies of multiple etiologies. Microbial conta
mination of chronic wounds also contributes importantly to the persist
ence of venous stasis, diabetic, and decubitus ulcers. Although slow h
ealing can be stimulated by regular debridement and cleaning of chroni
c wounds, acceleration of epithelial closure has been demonstrated by
application of sheets of cultured allogeneic keratinocytes. These stud
ies have been extended by attachment of allogeneic keratinocytes to an
implantable collagen-based sponge that is populated with cultured all
ogeneic fibroblasts. Because chronic wounds have low vascular competen
ce and high probability for microbial contamination, skin substitutes
are irrigated topically with a solution of nutrients and antimicrobial
agents until epithelial engraftment. Initial case reports show that a
llogeneic epithelium can cover chronic wounds within seven to ten days
, protective epithelium forms within one month, and long-term wound cl
osure is accomplished, most probably by ingrowth of autologous epithel
ium. With this approach, cultured skin substitutes may be expected to
promote healing of chronic wounds that have sufficient vascular compet
ence to remain perfused. Together with surgical and non-surgical appro
aches to improvement of vascular function, cultured skin substitutes o
ffer an alternative therapy for accelerated closure of chronic wounds.