Wound Repair and Regeneration最新文献

Dermal fibrosis is a consequence of damage to skin and is accompanied by dysfunction and cosmetic disfigurement. Improved understanding of the pathological factors driving skin fibrosis is critical to development of therapeutic modalities. Here, we describe that the Wnt signalling antagonist SFRP2 is upregulated in organotypic keratinocyte cultures upon experimental reduced hydration, a model that simulates the aberrant epidermal barrier state characteristic of several skin pathologies, including those that manifest in development of fibrosis. Consistent with this, we find that SFRP2 is overexpressed in both the dermis and epidermis of human hypertrophic scar tissue and lesional tissue of a mouse scleroderma model. Knockdown of SFRP2 expression in human fibroblasts antagonises proliferation and myofibroblast differentiation, including deposition of type I collagen, suggesting that SFRP2 signalling in fibroblasts may contribute to propagation of fibrosis in hypertrophic scar, as well as in other clinical indications characterised by skin fibrosis.

Porcine models are frequently used for burn healing studies; however, factors including anatomic location and lack of standardised wound methods can impact the interpretation of wound data. The objectives of this study are to examine the influence of anatomical locations on the uniformity of burn creation and healing in porcine burn models. To optimise burn parameters on dorsal and ventral surfaces, ex vivo and in situ euthanized animals were first used to examine the location-dependence of the burn depth and contact time relationship. The location-dependent healing in vivo was then examined using burn and excisional wounds at dorsal, ventral, caudal and cranial locations. Lactate dehydrogenase (LDH) and H&E were used to assess burn depth and wound re-epithelialization. We found that burn depth on the ventral skin was significantly deeper than that of the dorsal skin at identical thermal conditions. Compared with burns created ex vivo, burns created in situ immediately post-mortem were significantly deeper in the ventral location. In live animals, 2 out of 12 burn wounds were fully re-epithelialized after 14 days in contrast to complete re-epithelialization of all excisional wounds. Among the burn wounds, those at the cranial-dorsal site exhibited faster healing than at the caudal-dorsal site. This study showed that anatomical location is an important consideration for the consistency of burn depth creation and healing. These data support symmetric localization of treatment and control for comparative assessment of burn healing in porcine models to prevent misinterpretation of results and increase the translatability of findings to humans.

Self-improving dystrophic epidermolysis bullosa (DEB) is a genodermatosis that is inherited autosomal dominantly or recessively, and its clinical symptoms may improve or subside spontaneously. Herein, we report a case of self-improving DEB with COL7A1 p.Gly2025Asp variant. The diagnosis was made through histopathological, electron microscopic examination, and genetic testing. The same variant is also noted on his father, who presents with dystrophic toenails without any blisters. This study highlights that idiopathic nail dystrophy could be linked to congenital or hereditary disease. Furthermore, we conducted a review of the literature on the characteristics of reported cases of self-improving DEB with a personal or family history of nail dystrophy. The results supported our findings that nail dystrophy may be the sole manifestation in some family members. We suggest that individuals suffering from idiopathic nail dystrophy may seek genetic counselling when planning pregnancy to early evaluate the potential risk of hereditary diseases.

The aim was to investigate methicillin-resistant Staphylococcus aureus (MRSA) incidence, conversion and outcomes in diabetic foot infections (DFIs). This is a pooled patient-level analysis of combined data sets from two randomised clinical trials including 219 patients admitted to the hospital with moderate or severe DFIs. Intraoperative bone and tissue cultures identified bacterial pathogens. We identified pathogens at index infections and subsequent re-infections. We identified MRSA conversion (MSSA to MRSA) in re-infections. MRSA incidence in index infections was 10.5%, with no difference between soft tissue infections (STIs) and osteomyelitis (OM). MRSA conversion occurred in 7.7% of the re-infections in patients who initially had MSSA in their cultures. Patients with re-infection were 2.2 times more likely to have MRSA compared to the first infection (10.5% vs. 25.8%, relative risk [RR] = 2.2, p = 0.001). Patients with MRSA had longer antibiotic treatment during the 1-year follow-up, compared to other pathogens (other 49.8 ± 34.7 days, MRSA 65.3 ± 41.5 days, p = 0.04). Furthermore, there were no differences in healing, time to heal, length of stay, re-infection, amputation, re-ulceration, re-admission, surgery after discharge and amputation after discharge compared to other pathogens. The incidence of MRSA at the index was 10.5% with no difference in STI and OM. MRSA incidence was 25.8% in re-infections. The RR of having MRSA was 2.2 times higher in re-infections. Patients with MRSA used more antibiotics during the 1-year follow-up. Furthermore, there were no differences in clinical outcomes compared to other bacterial pathogens.

The aim of this study was to compare outcomes of moderate and severe foot infections in people with and without diabetes mellitus (DM). We retrospectively evaluated 382 patients (77% with DM and 23% non-DM). We collected demographic data, co-morbidities and one-year outcomes including healing, surgical interventions, number of surgeries, length of stay, re-infection and re-hospitalisation. DM patients required more surgeries (2.3 ± 2.2 vs. 1.7 ± 1.3, p = 0.01), but did not have a longer hospital length of stay during the index hospitalisation (DM 10.9 days ±9.2 vs. non-DM = 8.8 days ±5.8, p = 0.43). After the index hospitalisation, DM patients had increased rates of re-hospitalisation for any reason (63.3% vs. 35.2%, CI 1.9-5.2, OR 3.2, p < 0.01), re-infection at the index wound infection site (48% vs. 30.7%, CI 1.3-3.5, OR 2.1, p < 0.01), re-hospitalisation for a foot pathology (47.3% vs. 29.5%, CI 1.3-3.6, OR 2.1, p < 0.01), and longer times to ulcer healing (151.8 days ±108.8 vs. 108.8 ± 90.6 days, p = 0.04). Patients with DM admitted to hospital with foot infections have worse clinical outcomes during the index hospitalisation and are more likely to have re-infection and re-admission to hospital in the next year.

Diabetic foot ulcers are a common and severe complication of diabetes mellitus, and a risk factor for amputation. Because of the vessel insufficiency in diabetic foot ulcers (DFU), vascular endothelial growth factor (VEGF) that simulates angiogenesis is of interest to promote wound healing. This systematic review evaluates the last 16 years of in-vivo studies with VEGF stimulation as a treatment for DFU, developed based on the last published systematic article. A total of 961 articles were identified through databases in two phases. 947 articles were excluded by exclusion criteria, and four articles met our inclusion criteria and were included. The effects of VEGF on wound healing were analysed in all four studies. In three studies, the VEGF-treated wounds showed statistically faster healing than those not treated with VEGF. In one study, the VEGF-treated wounds revealed a positive trend toward faster healing. Furthermore, all four studies were in favor of using VEGF, but concluded that further research is needed. These studies showed a positive trend towards faster healing and was safe when using VEGF topically on humans. Furthermore, viral particles of VEGF seem to have a systematic effect when a dose exceeding 5.0 × 10⁹ vp pr wound. Future research in using VEGF on DFU should focus on VEGF's relevant dosage, release rate, and specific mechanism. This review inspires further research, and a consistent study design is prerequisite such that results are more homogenic and comparable. Much effort is needed to translate the results into our clinical practice.

Treatment of calcaneal fractures in patients with diabetes mellitus (DM) is challenging. The purpose of this study was to compare post-operative outcomes after open reduction and internal fixation (ORIF) for calcaneus fracture in patients with complicated DM, uncomplicated DM, and patients without DM. A commercially available de-identified database was queried for all calcaneus fracture diagnoses undergoing ORIF from 2010 to 2021. The patients were separated into three groups for analysis: patients without DM (10,951, 82.6%), uncomplicated DM (1,500, 11.3%) and complicated DM (802, 6.1%). At 1 year, post-operative adverse events were assessed among the three groups. The odds of adverse event(s) for each group were compared between the three groups with and without characteristic matching. In the unmatched cohorts, patients with complicated DM, when compared with patients without DM and patients with uncomplicated DM, had significantly higher rates of all adverse events with exception of DVT. Rates of CNA were significantly higher in patients with complicated DM compared with no DM (OR 107.7 (CI 24.83-467.6) p < 0.0001) and uncomplicated DM (OR 44.26 (CI 3.86-507.93) p = 0.0002). After matching, non-union, AKI, sepsis, surgical site infection, and wound disruption were higher in patients with complicated DM compared with patients without DM. There were no significant differences in the three groups with regard to reoperation, DVT, MI, pneumonia, or below the knee amputation. Patients with DM who underwent ORIF for calcaneus fracture experienced higher rates of post-operative adverse events compared with those patients without DM.

Recognising the need for objective imaging-based technologies to assess wound healing in clinical studies, the suction blister wound model offers an easily accessible wound model that creates reproducible epidermal wounds that heal without scarring. This study provides a comprehensive methodology for implementing and evaluating photography-based imaging techniques utilising the suction blister wound model. Our method encompasses a protocol for capturing consistent, high-quality photographs and procedures for quantifying these images via a visual wound healing score and a computer-assisted colour analysis of wound exudation and wound redness. We employed this methodology on 16 suction blister wounds used as controls in a clinical phase-1 trial. Our method enabled us to discern and quantify subtle differences between individual wounds concerning healing progress, erythema and wound exudation. The wound healing score exhibited a high inter-rater agreement. There was a robust correlation between the spectrophotometer-measured erythema index and photography-based wound redness, as well as between dressing protein content and photography-based dressing yellowness. In conclusion, this study equips researchers conducting clinical wound studies with reproducible methods that may support future wound research and aid in the development of new treatments.

Skin injuries can have unexpected surfaces, leading to uneven wound surfaces and inadequate dressing contact with these irregular surfaces. This can decrease the dressing's haemostatic action and increase the healing period. This study recommends the use of sticky and flexible cryogel coverings to promote faster haemostasis and efficiently handle uneven skin wounds. Alginate cryogels have a fast haemostatic effect and shape flexibility due to their macroporous structure. The material demonstrates potent antibacterial characteristics and enhances skin adherence by adding grafted chitosan with gallic acid. In irregular defect wound models, cryogels can cling closely to uneven damage surfaces due to their amorphous nature. Furthermore, their macroporous structure allows for quick haemostasis by quickly absorbing blood and wound exudate. After giving the dressing a thorough rinse, its adhesive strength reduces and it is simple to remove without causing any damage to the wound. Cryogel demonstrated faster haemostasis than gauze in a wound model on a rat tail, indicating that it has considerable potential for use as a wound dressing in the biomedical area.

Flaps are mainly used to repair wounds in the clinical setting but can sometimes experience ischaemic necrosis postoperatively. This study investigated whether donepezil, an acetylcholinesterase inhibitor, can enhance the survival rate of flaps. We randomly allocated 36 rats into control, low-dose (3 mg/kg/day), and high-dose (5 mg/kg/day) groups. On Postoperative day 7, we assessed flap viability and calculated the mean area of viable flap. After euthanizing the rats, we employed immunological and molecular biology techniques to examine the changes in flap tissue vascularization, apoptosis, autophagy, and inflammation. Donepezil enhanced the expression of hypoxia-inducible factor and vascular endothelial growth factor to facilitate angiogenesis. In addition, it elevated the expression of LC3B, p62, and beclin to stimulate autophagy. Furthermore, it increased the expression of Bcl-2 while reducing the expression of Bax, thus inhibiting apoptosis. Finally, it had anti-inflammatory effects by reducing the levels of IL-1β, IL-6, and TNF-α. The results suggest that donepezil can enhance the viability of randomly generated skin flaps by upregulating HIF-1α/VEGF signalling pathway, facilitating vascularization, inducing autophagy, suppressing cell apoptosis, and mitigating inflammation within the flap tissue.