Abstract
Tissue remodeling is associated with both normal and abnormal processes including wound healing, fibrosis and cancer. In skin, abnormal remodeling causes permanent structural changes that can lead to hypertropic scarring and keloid formation. Normal remodeling, although fast and efficient in skin, is still imperfect, and a connective tissue scar remains at the wound site1. As a result, methods are needed to optimize tissue remodeling in vivo in all cases of wound repair. Since fibroblast-mediated contraction of engineered 3-D collagen based tissues (RAFTs) represents an in vitro model of the tissue contraction and collagen remodeling that occurs in vivo, RAFT tissue contraction studies combined with two-photon microscopy (TPM) studies are used to provide information on ways to improve tissue remodeling in vivo. In the RAFT models discussed here, tissue contraction is modulated either by application of exogenous growth factors or photodynamic therapy. During tissue contraction, TPM is used to image changes in Collagen Type I fibers in the RAFT skin models. Tissues are imaged at depth at day 15 after modulation. TPM signal analysis shows that RAFT tissues having the highest collagen density have the fastest rate of decay of fluorescent signal with depth.
Highlights
Wound healing is a biochemical and cellular reaction that is triggered by tissue damage
After 1-2 days, blood-born monocytes infiltrate into the wound site and differentiate into mature tissue macrophages, which are essential for proper wound healing
The artificial tissue model, RAFT, consists of a basic polymerized collagen gel made of Type I rat-tail collagen (RTTC; Collaborative, Bedford, MA) containing primary human dermal fibroblasts and U937 human tissue macrophages
Summary
Wound healing is a biochemical and cellular reaction that is triggered by tissue damage. Neutrophils infiltrate into the wound site, clear any initial bacteria, and release cytokines that begin to activate local fibroblasts and keratinocytes. After 1-2 days, blood-born monocytes infiltrate into the wound site and differentiate into mature tissue macrophages, which are essential for proper wound healing. After 3-5 days, these macrophages phagocytose any remaining neutrophils These macrophages release cytokines that act on other cells at the wound site and orchestrate wound healing through tissue debridement, matrix synthesis and angiogenesis. Reepithelialization is made easier by contraction of the underlying connective tissue, which brings the wound edges together. At this time, dermal fibroblasts at the wound edge begin to proliferate. Stimulating macrophage function within the wound itself using PDT could get around some of these issues
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