Increase in wound breaking strength in rats in the presence of positively charged dextran beads correlates with an increase in endogenous transforming growth factor‐β1 and its receptor TGF‐βRI in close proximity to the wound

Abstract

We have previously shown that positively charged beads (DEAE A25) increase wound breaking strength in linear incisions in rats and nonhuman primates at days 10-14 post-wounding. The increased wound strength may result in part from a stimulation of cells adjacent to the DEAE A25 beads to produce growth factors important for wound healing. In this report, we investigate this hypothesis by comparing the relative expression levels of transforming growth factor-beta1 and its receptor transforming growth factor-beta receptor type I in DEAE A25-treated and contralateral untreated rat linear incisions. DEAE A25-treated incisions were stronger than untreated control wounds at 3 days post-wounding, and the difference in breaking strength reached statistical significance at days 5, 7 and 10. Immunohistochemical analysis revealed a significant increase in transforming growth factor-beta1 and transforming growth factor-beta receptor type I expression in DEAE A25-treated incisions, up to 7 days post-wounding, as compared to untreated control wounds. FACS analysis revealed that macrophage cell lines exposed to DEAE A25 in vitro upregulate transforming growth factor-beta1 and transforming growth factor-beta receptor type I expression by 2-3 fold. Therefore, the increase in expression of transforming growth factor-beta1 and transforming growth factor-beta receptor type I in DEAE A25-treated incisions may be due to an increase in the concentration of macrophages adjacent to DEAE A25 beads, as well as the stimulation of individual macrophages to produce greater amounts of transforming growth factor-beta1 and transforming growth factor-beta receptor type I. This study also supports the significance of transforming growth factor-beta1 in wound healing.

Immobilization Modulates Macrophage Accumulation in Tendon-Bone Healing

“…Because studies by us [17,19,[24][25][26] and others [15,23] have shown a scar tissue interface forms between tendon and bone rather than reformation of a normal insertion site, we therefore hypothesized the presence of abundant macrophages plays an important role in this scar formation. In other experimental models, the presence of macrophages and overexpression of transforming growth factor-b has been linked to states of chronic inflammation and tissue fibrosis [5,7,8,16,18,21,28]. In contrast, embryonic wounds heal in the absence of an inflammatory cell infiltrate with recapitulation of normal, scar-less tissue morphology.…”

“…Macrophages expressing the ED1 antigen are recruited from circulating blood monocytes, accumulate in the first few days after surgery, and have a phagocytic function in débriding the wound environment, whereas macrophages expressing the ED2 antigen are derived from the local tissue environment, have maximum accumulation by 28 days, and have an anabolic role in tissue healing [22]. One of the principal functions of macrophages is secretion of growth factors and cytokines responsible for fibroblast mitogenesis and proliferation [5,8,13,31], extracellular matrix and collagen synthesis [13,22], and angiogenesis [8,11,13]. However, excessive levels of cytokines such as transforming growth factor b may result in excessive scar formation at the healing tendon-bone interface.…”

TNF-α Suppresses α-Smooth Muscle Actin Expression in Human Dermal Fibroblasts: An Implication for Abnormal Wound Healing

“…Several studies have demonstrated that TGF-β1 increases tensile strength during wound healing (Mustoe et al, 1987;Connors et al, 2000;Korenkov et al, 2005). For example, Mustoe et al (1987) found that TGF-β1 improved both the breaking strength and the rate of healing in rats' incisional wounds.…”

Thrombin Production and Human Neutrophil Elastase Sequestration by Modified Cellulosic Dressings and Their Electrokinetic Analysis

“…, interactions of inflammatory proteases with fibrin to name one example [83]. More work on the tunable functional features of dressings such as mixed charged materials, which promote both hemostasis and attract growth factor-containing macrophages, may lead to improved dressings [84]. In addition revisiting the mechanism of action of controlled release molecules like oleic acid which has been found to both accelerate wound closure and inhibit inflammatory proteases like elastase, presents an emblematic approach to improving wound healing materials [32,85].…”