To gain insight into the molecular mechanisms underlying cutaneous wound repair, we performed a large scale screen to identify novel injury-regulated genes. Here we show a strong up-regulation of the RNA and protein levels of the two Ca 2؉ -binding proteins S100A8 and S100A9 in the hyperthickened epidermis of acute murine and human wounds and of human ulcers. Furthermore, both genes were expressed by inflammatory cells in the wound. The increased expression of S100A8 and S100A9 in wound keratinocytes is most likely related to the activated state of the keratinocytes and not secondary to the inflammation of the skin, since we also found up-regulation of S100A8 and S100A9 in the epidermis of activin-overexpressing mice, which develop a hyperproliferative and abnormally differentiated epidermis in the absence of inflammation. Furthermore, S100A8 and S100A9 expression was found to be associated with partially differentiated keratinocytes in vitro. Using confocal microscopy, both proteins were shown to be at least partially associated with the keratin cytoskeleton. In addition, cultured keratinocytes efficiently secreted the S100A8/A9 dimer. These results together with previously published data suggest that S100A8 and S100A9 are novel players in wound repair, where they might be involved in the reorganization of the keratin cytoskeleton in the wounded epidermis, in the chemoattraction of inflammatory cells, and/or in the defense against microorganisms.After cutaneous injury, a series of biological events takes place that aims at the reconstruction of the damaged skin. Among them are the migration, proliferation, and differentiation of inflammatory, epithelial, and mesenchymal cells. These cells exert specific functions in a temporally and spatially coordinated manner such as the removal of irreversibly destructed tissue, the deposition of new extracellular matrix, and the reestablishment of the cutaneous barrier (1, 2). These processes are well described at the histological level, but little is known about their molecular basis.To gain insight into the molecular mechanisms that underlie the repair process, we performed a large scale subtractive hybridization screen to systematically identify genes that are differentially expressed in injured compared with normal skin. To minimize the risk of detecting differences in gene expression levels due to changes in cellular composition rather than to transcriptional regulation, we compared normal skin with early (24 h) wounds, because only minor changes in cell type composition occur during the initial wound healing period.One of the cDNA clones that we obtained encodes the murine S100A8 protein (also known as calgranulin A, MRP8, leukocyte protein L1, or cytokine CP-10). S100 proteins are intracellular Ca 2ϩ -binding and Ca 2ϩ -modulated proteins that form antiparallel noncovalently linked dimers in solution and play a role in various Ca 2ϩ -mediated cellular functions including cell growth and differentiation, energy metabolism, cytoskeletalmembrane interactions; some of th...

Cardiac ankyrin repeat protein (CARP) was identified by subtractive hybridization as one of a group of genes that are rapidly modulated by acute wounding of mouse skin. Quantitative RT-PCR showed that CARP was strongly induced during the first day after wounding (157.1-fold), and the high level persisted for up to 14 days. Immunohistochemistry and in situ hybridization revealed that CARP was expressed in skeletal muscle, vessel wall, hair follicle, inflammatory cells, and epidermis in the wound area. To examine the effects of CARP on wound healing, we developed an adenoviral CARP vector to treat subcutaneously implanted sponges in either rats or

Trends in the development of hemostatic agents are towards self-adhering pads. This study investigates a novel biomaterial made of a polyethylene glycol-coated collagen pad (PCC). The swelling and adherence of PCC were investigated in vitro, and the hemostatic and sealing ability was investigated in vivo. In vitro, the maximum swell of PCC submerged in human plasma for 24 h is 65%. The greatest swell was in thickness, averaging 24% to a mean thickness of 2.5 ± 0.19 mm (mean±SD) (N = 20). PCC withstood clinically relevant pressures when applied to a collagen casing washed with bile, lymph, urine, saline, and cerebrospinal fluid mixed at 33% and 67% with blood. In vivo, PCC provided complete hemostasis when applied to severe, arterial bleeds of actively ventilated pulmonary parenchyma at 3, 5, 8, and 10 min after application in a heparinized porcine pulmonary segmentectomy model. The mean rate of bleeding was 17.7 ± 8.6 ml/min. The lungs were ventilated at 15 ± 4 breaths per min and an airway pressure of 19 ± 2 cm H2O. PCC had no incidence of hematoma and an 11% incidence of intraoperative air leak (N = 36). These data are promising for future clinical application of a new versatile, self-adhering hemostatic sealing pad consisting of a polyethylene glycol-coated collagen.

PCC provided faster hemostasis than ORC in a vascular and hepatic surgical model with impaired coagulation.

No abstract