No abstract

Healing of cutaneous wounds requires a complex integrated network of repair mechanisms, including the action of newly recruited leukocytes. Using a skin repair model in adult humans, we investigated the role chemokines play in sequential infiltration of leukocyte subsets during wound healing. At day 1 after injury, the C-X-C chemokines IL-8 and growth-related oncogene alpha are maximally expressed in the superficial wound bed and are spatially and temporally associated with neutrophil infiltration. IL-8 and growth-related oncogene alpha profiles also correlate with keratinocyte migration and subsequently subside after wound closure at day 4. Macrophage infiltration reaches the highest levels at day 2 and is paralleled by monocyte chemoattractant protein-1 mRNA expression in both the basal layer of the proliferative epidermis at the wound margins and mononuclear cells in the wound area. Other monocyte-attracting chemokines such as monocyte chemoattractant protein-3, macrophage inflammatory protein-1alpha and -1beta, RANTES, and 1309 are undetectable. At day 4, perivascular focal lymphocyte accumulation correlates with strong focal expression of the C-X-C chemokines Mig and IP-10. Our results suggest that a dynamic set of chemokines contributes to the spatially and temporally different infiltration of leukocyte subsets and thus integrates the inflammatory and reparative processes during wound repair.

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters.

Groin wound infections pose a major problem in vascular surgery. Closed-incision negative pressure therapy (ciNPT) was especially designed for the management of incisions at risk of surgical site infections. The aim of this study was to investigate whether ciNPT is able to reduce the incidence of wound infections after vascular surgery. Data on 132 consecutive patients, scheduled for vascular surgery with a longitudinal femoral cutdown, were collected prospectively. All patients were randomised either to the ciNPT group (n = 64) or the control group (n = 68) with conventional dressing. In the ciNPT group, the foam dressing was applied intraoperatively and removed after 5 days. The control group received an absorbent dressing. All wounds were evaluated after 5 and 42 days. Infections were graded according the Szilagyi classification (I-III°). There were no significant differences between both groups considering patient characteristics. Indications for surgery were peripheral arterial disease in 95% (125/132) and aneurysm in 5% (7/132). The overall infection rates were 14% (9/64) in the ciNPT group and 28% (19/68) in the control group (P = 0·055). Early infections were observed in 6% (4/64) of the ciNPT group and 15% (10/68) of the control group (P = 0·125). ciNPT did not reduce infection rates associated with different risk factors for infection. While the experiences with the ciNPT device were encouraging, the study fails to provide evidence of the efficacy of the device to reduce groin wound infections after vascular surgery. It illustrates far more that larger multicentre studies are required and appear promising to provide further evidence for the use of ciNPT.