Collagen fibril network and elastic system remodeling in a reconstructed skin transplanted on nude mice

Wound healing of deep and extensive bums can induce hypertrophic scar forma tion, which is a detrimental outcome for skin functionality. These scars ar e characterized by an impaired collagen fibril organization with fibril bun dles oriented parallel to each other, in contrast with a basket weave patte rn arrangement in normal skin. We prepared a reconstructed skin made of a c ollagen sponge seeded with human fibroblasts and keratinocytes and grown in vitro for 20 days. We transplanted it on the back of nude mice to assess w hether this reconstructed skin could prevent scar formation. After transpla ntation, murine blood vessels had revascularized one-third of the sponge th ickness on the fifth day and were observed underneath the epidermis at day 15. The reconstructed skin extracellular matrix was mostly made of human co llagen I, organized in loosely packed fibrils 5 days after transplantation, with a mean diameter of 45 nm. After 40-90 days, fibril bundles were arran ged in a basket weave pattern while their mean diameter increased to 56 nm, therefore exactly matching mouse skin papillary dermis organization. Inter estingly, we showed that an elastic system remodeling was started off in th is model. Indeed, human elastin deposits were organized in thin fibrils ori ented perpendicular to epidermis at day 90 whereas elastic system usually t ook years to be re-established in human scars. Our reconstructed skin model promoted in only 90 days the remodeling of an extracellular matrix nearly similar to normal dermis (i.e. collagen fibril diameter and arrangement, an d the partial reconstruction of the elastic system). (C) 2001 Elsevier Scie nce B.V./International Society of Matrix Biology. All rights reserved.