Suppressed Wound Healing Research Articles

Monocyte/macrophage androgen receptor suppresses cutaneous wound healing in mice by enhancing local TNF-α expression

Cutaneous wounds heal more slowly in elderly males than in elderly females, suggesting a role for sex hormones in the healing process. Indeed, androgen/androgen receptor (AR) signaling has been shown to inhibit cutaneous wound healing. AR is expressed in several cell types in healing skin, including keratinocytes, dermal fibroblasts, and infiltrating macrophages, but the exact role of androgen/AR signaling in these different cell types remains unclear. To address this question, we generated and studied cutaneous wound healing in cell-specific AR knockout (ARKO) mice. General and myeloid-specific ARKO mice exhibited accelerated wound healing compared with WT mice, whereas keratinocyte- and fibroblast-specific ARKO mice did not. Importantly, the rate of wound healing in the general ARKO mice was dependent on AR and not serum androgen levels. Interestingly, although dispensable for wound closure, keratinocyte AR promoted re-epithelialization, while fibroblast AR suppressed it. Further analysis indicated that AR suppressed wound healing by enhancing the inflammatory response through a localized increase in TNF-alpha expression. Furthermore, AR enhanced local TNF-alpha expression via multiple mechanisms, including increasing the inflammatory monocyte population, enhancing monocyte chemotaxis by upregulating CCR2 expression, and enhancing TNF-alpha expression in macrophages. Finally, targeting AR by topical application of a compound (ASC-J9) that degrades AR protein resulted in accelerated healing, suggesting a potential new therapeutic approach that may lead to better treatment of wound healing.

Evaluation of the Healing Potential of Schrebera swietenioides in the Dexamethasone-Suppressed Wound Healing in Rodents

The wound healing potential of the aqueous, alcoholic extracts, and the butanolic fraction of the alcoholic extract obtained from the bark of Schrebera swietenioides were evaluated in the dexamethasone suppressed wound healing model. The work was conducted on rodents using incision, excision, and dead space wound models. The extracts of S swietenioides enhanced the breaking strength of incision wounds significantly (P < .05). Faster epithelization and contraction of excision wounds were observed in the treated groups (P < .05). Dead space wound model demonstrated an increase in breaking strength of granulation tissue and weight of dried granulation tissue after treatment with the extracts.The extracts attenuated the effect of dexamethasone on healing.The total RNA isolated from the granulation tissues of the extract-treated animals was significantly higher than in both dexamethasone and normal groups, (P < 0.05). It was observed that the DNA was intact in all the groups. These findings suggest that dexamethasone suppresses wound healing, possibly through an inappropriate transcription rather than causing DNA damage.The S swietenioides extracts have the capacity to reverse this effect.

Effect of chitosan acetate bandage on wound healing in infected and noninfected wounds in mice

HemCon bandage is an engineered chitosan acetate preparation designed as a hemostatic dressing, and is under investigation as a topical antimicrobial dressing. We studied its effects on healing of excisional wounds that were or were not infected with Staphylococcus aureus, in normal mice or mice previously pretreated with cyclophosphamide (CY). CY significantly suppressed wound healing in both the early and later stages, while S. aureus alone significantly stimulated wound healing in the early stages by preventing the initial wound expansion. CY plus S. aureus showed an advantage in early stages by preventing expansion, but a significant slowing of wound healing in later stages. In order to study the conflicting clamping and stimulating effects of chitosan acetate bandage on normal wounds, we removed the bandage from wounds at times after application ranging from 1 hour to 9 days. Three days application gave the earliest wound closure, and all application times gave a faster healing slope after removal compared with control wounds. Chitosan acetate bandage reduced the number of inflammatory cells in the wound at days 2 and 4, and had an overall beneficial effect on wound healing especially during the early period where its antimicrobial effect is most important.

Effects of Membrane Adhesion Barriers on Wound Healing Reaction after Glaucoma Filtration Surgery: A Comparative Study with Interceed and Seprafilm

To evaluate and compare the effectiveness of two adhesion barriers, Interceed and Seprafilm, on wound heal ing reaction after glaucoma filtration surgery. Full-thickness filtration surgery was carried out on three groups, each containing four rabbits. Interceed and Seprafilm prepared in 3 x 4 mm dimensions was put on and around scleral opening in Groups 1 and 2, respectively. All groups received tobramycin and dexamethasone drops tid for 14 days. Intraocular pressure (IOP), anterior chamber depth, and bleb appearance were checked on the first, third, seventh, and 14th days. The rabbits were killed on the 14th day and the trabeculectomy area with overlying conjunctiva was excised. The samples were fixed wi th 10% formalin, buried in paraffin, and stained with hematoxylin and eosin. The surgical site and surrounding subconjunctival area were evaluated histopathologically for cell counts (fibroblast, lymphocyte, eosinophil, and macrophage), presence of edema and foreign body reaction, and potency of the fistula tract. Mean IOP at the first and third day examinations was significantly different between groups, but there was no statistically significant difference among the groups with respect to IOP, anterior chamber depth, or bleb appearance at the seventh and 14th days. The groups were similar with respect to number of fibroblasts, eosinophils, and neutrophils. Number of macrophages was significantly increased in Groups 1 and 2 and number of vessels was significantly decreased in Group 1. Neither of these two adhesion-preventing substances seems to suppress wound healing reaction after glaucoma filtration surgery. However, a diminished wound healing reaction was expected wi th a decreased number of vessels, such as in Group 1. Increased number of macrophages in both groups may result in a decreased level of some inflammatory mediators.

Thrombospondin-1 suppresses wound healing and granulation tissue formation in the skin of transgenic mice.

The function of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in tissue repair has remained controversial. We established transgenic mice with targeted overexpression of TSP-1 in the skin, using a keratin 14 expression cassette. TSP-1 transgenic mice were healthy and fertile, and did not show any major abnormalities of normal skin vascularity, cutaneous vascular architecture, or microvascular permeability. However, healing of full-thickness skin wounds was greatly delayed in TSP-1 transgenic mice and was associated with reduced granulation tissue formation and highly diminished wound angiogenesis. Moreover, TSP-1 potently inhibited fibroblast migration in vivo and in vitro. These findings demonstrate that TSP-1 preferentially interfered with wound healing-associated angiogenesis, rather than with the angiogenesis associated with normal development and skin homeostasis, and suggest that therapeutic application of angiogenesis inhibitors might potentially be associated with impaired wound vascularization and tissue repair.