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Cutaneous wound healing is a complex process that encompasses alterations in all aspects of the skin including the extracellular matrix (ECM). ECM consist of large structural proteins such as collagens and elastin as well as smaller proteins with mainly regulative properties called matricellular proteins. Matricellular proteins bind to structural proteins and their functions include but are not limited to interaction with cell surface receptors, cytokines, or protease and evoking a cellular response. The signaling initiated by matricellular proteins modulates differentiation and proliferation of cells having an impact on the tissue regeneration. In this review we give an overview of the matricellular proteins that have been found to be involved in cutaneous wound healing and summarize the information known to date about their functions in this process.

Thrombospondin-4 (THBS4) is a non-structural extracellular matrix molecule associated with tissue regeneration and a variety of pathological processes characterized by increased cell proliferation and migration. However, the mechanisms of how THBS4 regulates cell behavior as well as the pathways contributing to its effects have remained largely unexplored. In the present study we investigated the role of THBS4 in skin regeneration both in vitro and in vivo . We found that THBS4 expression was upregulated in the dermal compartment of healing skin wounds in humans as well as in mice. Application of recombinant THBS4 protein promoted cutaneous wound healing in mice and selectively stimulated migration of primary fibroblasts as well as proliferation of keratinocytes in vitro . By using a combined proteotranscriptomic pathway analysis approach we discovered that β-catenin acted as a hub for THBS4-dependent cell signaling and likely plays a key role in promoting its downstream effects. Our results suggest that THBS4 is an important contributor to wound healing and its incorporation into novel wound healing therapies may be a promising strategy for treatment of cutaneous wounds.

We describe a case of Lichtenberg Figures (LFs) following an electrical injury from a high-voltage switchgear in a 47 year-old electrician. LFs, also known as ferning pattern or keraunographic markings, are a pathognomonic skin sign for lightning strike injuries. Their true pathophysiology has remained a mystery and only once before described following an electical injury. The aim was to characterise the tissue response of LFs by performing untargeted non-labelled proteomics and immunohistochemistry on paraffin-embedded sections of skin biopsies taken from the area of LFs at presentation and at 3 months follow-up. Our results demonstrated an increase in dermal T-cells and greatly increased expression of the iron-binding glycoprotein lactoferrin by keratinocytes and lymphocytes. These changes in the LF-affected skin were associated with extravasation of red blood cells from dermal vessels. Our results provide an initial molecular and cellular insight into the tissue response associated with LFs.

Primary cilia (PC) are solitary, post-mitotic, microtubule-based, and membrane-covered protrusions that are found on almost every mammalian cell. PC are specialized cellular sensory organelles that transmit environmental information to the cell. Signaling through PC is involved in the regulation of a variety of cellular processes, including proliferation, differentiation, and migration. Conversely, defective, or abnormal PC signaling can contribute to the development of various pathological conditions. Our knowledge of the role of PC in organ development and function is largely based on ciliopathies, a family of genetic disorders with mutations affecting the structure and function of PC. In this review, we focus on the role of PC in their major signaling pathways active in skin cells, and their contribution to wound healing and scarring. To provide comprehensive insights into the current understanding of PC functions, we have collected data available in the literature, including evidence across cell types, tissues, and animal species. We conclude that PC are underappreciated subcellular organelles that significantly contribute to both physiological and pathological processes of the skin development and wound healing. Thus, PC assembly and disassembly and PC signaling may serve as attractive targets for antifibrotic and antiscarring therapies.

We aimed to investigate the learning needs of general practitioners and their preferences as regards the most appropriate teaching session for continuing medical education in wound management. A survey targeting general practitioners at the public health centres in the City of Helsinki. Twenty‐seven general practitioners participated in the study. The majority (74.1%) had received education in medical school, 40.7% from wound care nurses, and 40.7% from colleagues. Participants felt the most competent in wound diagnosis (59.3%) and etiological tests (55.6%) and requested training in these topics (74.1% and 74.1%). A peer‐led lecture (88.9%) was the most preferred technique, followed by lectures by wound care nurses (55.6%), an educational video (44.4%), a specialist‐led lecture (37.0%), an interactive wound product session (29.6%), and digital self‐study (29.6%). Wound diagnostics and etiological tests are recognised as crucial topics for continuing medical education. Peer‐led lectures were preferred over other techniques; however, we observed varying preferences regarding the most optimal technique. Based on our results, we propose a half‐day training including lectures, interactive and hands‐on activities, and reflection, led by a peer and a wound care nurse with supporting video materials. Future studies could assess its impact on learning outcomes and wound care quality.

The aim of this study was to identify the competencies and challenges in the care of chronic wounds experienced by general practitioners. An online survey study targeted at primary care general practitioners in the City of Helsinki. The survey was created using REDCap and sent via email to the participants. Data were analysed with descriptive statistics. Thirty‐two participated in the study. A third considered the primary diagnostics difficult (N = 9/31, 29.0%). The determination of the appropriate urgency (N = 17/31, 54.9%), specialty of referral (N = 12/31, 38.7%), compression therapy (N = 16/31, 51.6%), offloading (N = 14/31, 45.2%) and the nutritional support (N = 19, 61.3%) were challenging. Over half felt that insufficient resources (N = 15/27, 55.6%), pressure and time constraints (N = 19/27, 70.4%) complicate the care. The majority (N = 15/27, 55.6%) considered the role of a general practitioner to be crucial, but (N = 16/27, 59.3%) felt that improving wound care within primary care would yield better outcomes. General practitioners consider themselves skilled in wound aetiology diagnostics but not in treatment, where they estimated their skills as weak. Inadequate resources hinder the treatment of chronic wounds, and over half of respondents were unsatisfied with current care. Establishing primary care centres specialising in wound care could improve treatment.

Olfactomedin-4 (OLFM4) is an olfactomedin-domain-containing glycoprotein, which regulates cell adhesion, proliferation, gastrointestinal inflammation, innate immunity and cancer metastasis. In the present study we investigated its role in skin regeneration. We found that OLFM4 expression is transiently upregulated in the proliferative phase of cutaneous wound healing in humans as well as in mice. Moreover, a significant increase in OLFM4 expression was detected in the skin of lesional psoriasis, a chronic inflammatory disease characterized by keratinocyte hyperproliferation. In vitro experiments demonstrated that OLFM4 selectively stimulated keratinocyte proliferation and increased both keratinocyte and fibroblast migration. Using proteotranscriptomic pathway analysis we revealed that transcription factors POU5F1/OCT4 and ESR1 acted as hubs for OLFM4-induced signalling in keratinocytes. In vivo experiments utilizing mouse splinted full-thickness cutaneous wound healing model showed that application of recombinant OLFM4 protein can significantly improve wound healing efficacy. Taken together, our results suggest that OLFM4 acts as a transiently upregulated inflammatory signal that promotes wound healing by regulating both dermal and epidermal cell compartments of the skin.

Background Cellular grafts used for skin repair require rapid integration with the host tissue to remain viable and especially to nourish the epidermal cells. Here, we evaluated the responses in the split-thickness skin grafts (STSGs) grafted on three differently treated wound beds: directly on excised wound bed (EX), on an artificial dermal template (DT) and on granulation tissue (GT) induced by cellulose sponge. Methods In ten burn patients, after excision, a test area was divided into three sections: One transplanted with STSG instantaneously and two sections had a pre-treatment for 2 weeks with either DT or a cellulose sponge inducing granulation tissue formation and thereafter grafted with STSGs. Results One week after grafting, the STSGs on GT demonstrated most endothelial CD31 + staining, largest average vessel diameters as well as most CD163 + staining of M2-like macrophages and most MIB1 + proliferating epidermal cells, suggesting an active regenerative environment. STSGs on DT had smallest vessel diameters and the least CD163 + macrophages. STSGs on EX had the least CD31 + cells and the least MIB1 + proliferating cells. After 3 months, this reactivity in STSGs had subsided, except increased dermal cell proliferation was observed in STSGs on EX. Conclusions Results show that pre-treatment of wound bed and induction of granulation tissue formation can accelerate host–graft interaction by stimulating graft vasculature and inducing cell proliferation.

Because molecular memories of past inflammatory events can persist in epidermal cells, we evaluated the long-term epidermal protein expression landscapes after dermal regeneration and in psoriatic inflammation. We first characterized the effects of two dermal regeneration strategies on transplants of indicator split-thickness skin grafts (STSGs) in ten adult patients with deep burns covering more than 20% of their body surface area. After fascial excision, three adjacent areas within the wound were randomized to receive a permanent dermal matrix, a temporary granulation-tissue-inducing dressing or no dermal component as control. Control areas were covered with STSG immediately, and treated areas after two-weeks of dermis formation. Epidermis-dermis-targeted proteomics of one-year-follow-up samples were performed for protein expression profiling. Epidermal expression of axonemal dynein heavy chain 10 (DNAH10) was increased 20-fold in samples having had regenerating dermis vs control. Given the dermal inflammatory component found in our dermal regeneration samples as well as in early psoriatic lesions, we hypothesized that DNAH10 protein expression also would be affected in psoriatic skin samples. We discovered increased DNAH10 expression in inflammatory lesions when compared to unaffected skin. Our results associate DNAH10 expression with cell proliferation and inflammation as well as with the epidermal memory resulting from the previous regenerative signals of dermis. This study (ISRCTN14499986) was funded by the Finnish Ministry of Defense and by government subsidies for medical research.