Our data show that cells from the growing margin of keloid scars have a higher production of collagen I and III compared with other lesional sites. Additionally, temporal extension of cell passage affects collagen production. Clinically these findings may influence selection and interpretation of extended cell passage and provide future direction for lesional site-specific therapy in keloid scars.

Chronic wounds, including diabetic and venous ulcers, represent disruption of normal healing processes resulting in a pathological state of nonhealing cutaneous inflammation. They place an increasingly significant economic burden on healthcare providers as their prevalence is rising in keeping with an aging population. Current treatment modalities are slow acting and resource intensive. Bioengineered skin substitutes from autogenic, allogenic, or xenogenic sources have emerged as a new and alternative therapeutic option. A range of such products is licensed for clinical use, which differ in terms of structure and cellular content. Placed directly onto a prepared wound bed, skin substitutes may stimulate or accelerate healing by promoting revascularization, cellular migration, and repopulation of wound fields through provision of an appropriate scaffold material to facilitate these processes. Products containing fetal or autologous cells also benefit from early release of bioactive molecules including growth factors and cytokines. To date, limited numbers of randomized controlled trials studying skin substitutes have been published but evidence from case series and case-control studies is encouraging. This review discusses chronic wound biology, the influence that skin substitutes can exert on this environment, the products currently available, and examines the evidence for their use in chronic wound management.

Background: Information Extraction (IE) is a component of text mining that facilitates knowledge discovery by automatically locating instances of interesting biomedical events from huge document collections. As events are usually centred on verbs and nominalised verbs, understanding the syntactic and semantic behaviour of these words is highly important. Corpora annotated with information concerning this behaviour can constitute a valuable resource in the training of IE components and resources.

Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting. There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone.

Non-unions pose complications in fracture management that can be treated using electrical stimulation (ES). Bone marrow mesenchymal stem cells (BMMSCs) are essential in fracture healing; however, the effect of different clinical ES waveforms on BMMSCs cellular activities remains unknown. We compared the effects of direct current (DC), capacitive coupling (CC), pulsed electromagnetic field (PEMF) and degenerate wave (DW) on cellular activities including cytotoxicity, proliferation, cell-kinetics and apoptosis by stimulating human-BMMSCs 3 hours a day, up to 5 days. In addition, migration and invasion were assessed using fluorescence microscopy and by quantifying gene and protein expression. We found that DW had the greatest proliferative and least apoptotic and cytotoxic effects compared to other waveforms. DC, DW and CC stimulations resulted in a higher number of cells in S phase and G2/M phase as shown by cell cycle analysis. CC and DW caused more cells to invade collagen and showed increased MMP-2 and MT1-MMP expression. DC increased cellular migration in a scratch-wound assay and all ES waveforms enhanced expression of migratory genes with DC having the greatest effect. All ES treated cells showed similar progenitor potential as determined by MSC differentiation assay. All above findings were shown to be statistically significant (p<0.05). We conclude that ES can influence BMMSCs activities, especially DW and CC, which show greater invasion and higher cell proliferation compared to other types of ES. Application of DW or CC to the fracture site may help in the recruitment of BMMSCs to the wound that may enhance rate of bone healing at the fracture site.

Cutaneous wounds establish endogenous "wound current" upon injury until re-epithelialization is complete. Keratinocyte proliferation, regulated partly by p53, is required for epidermal closure. SIVA1 promotes human double minute 2 homolog (HDM2)-mediated p53 regulation. However, the role of SIVA1 in wound healing is obscure. Here, we report that electrical stimulation (ES) accelerates wound healing by upregulating SIVA1 and its subsequent ability to modulate p53 activities. Cultured donut-shaped human skin explants, subjected to ES, exhibited better epidermal stratification, increased proliferation, and upregulation of gene and protein expression of HDM2/SIVA1, compared with non-ES-treated explants. ES significantly increased in vitro keratinocyte proliferation and phospho-p53-SIVA1 interaction; however, this showed stable expression of phospho-p53, which increased significantly in the absence of SIVA1. Here, HDM2 alone was unable to downregulate nuclear-accumulated phospho-p53, which was evident from decreased proliferation and increased sub-G1 population seen by flow cytometry. Further examination of the epidermis of human cutaneous wounds showed higher p53-SIVA1 coexpression and proliferation 7 days after injury in ES-treated wounds compared with control wounds. In summary, ES-inducible SIVA1 modulates p53 activities in proliferating keratinocytes, and exogenous ES affects p53/HDM2/SIVA1 axis leading to increased proliferation during re-epithelialization. This highlights ES as a potential strategy for enhancing cutaneous repair.

Dupuytren's disease (DD) is a fibroproliferative disorder characterized by aberrant proliferation of myofibroblasts, the source of which remains unknown. Recent studies indicate that circulating and tissue-resident mesenchymal stem cells (MSCs) can differentiate into myofibroblasts. Therefore, the aim of this study was to profile MSCs from phenotypically distinct DD sites including cord, nodule, skin overlying nodule (SON), and perinodular fat (PNF) compared with unaffected internal controls, that is, distant palmar fat (DPF) and transverse palmar fascia (Skoog's fibers) as well as external control carpal tunnel (CT) tissue including skin, fat, and fascia. Freshly isolated primary fibroblasts as well as cells grown up to passage 5 (P5) from DD (n=27) and CT (n=14) samples were analyzed for the presence of established MSC markers CD73, CD90, and CD105 and absence of hematopoietic marker CD34 using fluorescence-activated cell sorting, in-cell quantitative western blotting, immunohistochemistry, and immunocytochemistry. Freshly isolated cells from SON, PNF, and cord biopsies had a higher number of CD34(-)73(+)90(+)105(+) cells compared with Skoog's fibers and CT controls. P3 cells obtained from all DD biopsies compared with CT samples differentiated into osteocytes, adipocytes, and chondrocytes. P3 cord and nodule cells expressed intense α-smooth muscle actin staining compared with skin and fat cells. Stem cell markers including stem cell factor, MSC-homing marker CXCR4, and Wnt/β-catenin downregulator Dkk-1 were all upregulated in SON and PNF compared with CT skin and CT fat, respectively, as shown by real-time quantitative polymerase chain reaction. However, osteogenic marker OSF-1 had a significantly higher expression in the PNF (P=0.002) and cord (P=0.01) compared with the nodule. In conclusion, we have shown the presence of MSCs in specific DD tissue phenotypes compared with internal and external control tissue. These findings provide preliminary support for a potential alternative source of disease myofibroblasts originating from sites such as SON and PNF as opposed to palmar fascia alone.

An efficient and appropriate healing response in the skin postinjury is regulated by a fine balance of the quantity and quality of ECM proteins. A more complete understanding of ECM regulation of the cell fate and activities during cutaneous wound repair is vital for the development of novel treatment strategies for improvement of cutaneous healing.