Wound Repair and Regeneration最新文献

ChatGPT can be used as an aid in education, research and clinical management. This study was conducted using the ChatGPT 4.0 program to develop artificial intelligence-supported wound care education material that can be read and understood by patients discharged after surgery. In this methodological study, while creating wound care education material, the education needs of the patients were determined first. Then, the education content was created in the ChatGPT 4 program. Expert opinion was taken for the clarity, applicability, accuracy and quality of the education content. The Turkish readability index of the education material was found to be 68.9 and easily understandable. The Automated Readability Index was found to be 9.29, the Simple Measure of Gobbledygook 7.89, the Flesch-Kincaid 8.07, the Flesch Reading Ease 59.0 and the Average Reading Level Consensus 9.99, which are frequently used in health literature. The PEMAT understandability and applicability score averages were determined 93.90 ± 6.11 (84-100) and 90.20 ± 8.66, respectively. The Global Quality Scale score average was found to be 4.40 ± 0.69. This study reveals that ChatGPT provides understandable, applicable, accurate and high-quality postoperative wound care education material.

Cutaneous wounds can be treated using skin substitutes, but they heal with scarring and absence of skin adnexal structures. We previously demonstrated hair follicle neogenesis in dermal-epidermal composites made of neonatal foreskin human keratinocytes and human dermal papilla cells grafted onto nude mice. A challenge to adapting this approach to graft large areas in humans is that dermal papilla cells lose trichogenicity when expanded in vitro. Herein, a peptide derived from a coiled-coil domain of multimerin-1, TSN6, was evaluated for its effects on graft characteristics and hair follicle formation. In a hair follicle reconstitution assay, TSN6 increased the number of hair fibres by 1.8-fold (p value < 0.05). Dermal-epidermal composites, constructed using late-passage human dermal papilla cells and incubated with TSN6 prior to grafting, retained 14 of 14 grafts for 10-12 weeks, whereas scrambled and vehicle groups kept only 9 of 12 and 13 of 16 grafts, respectively. Histological evaluation of skin grafts showed the presence of human hair follicles in 12 of 14 dermal-epidermal composites in the TSN6 group, 3 of 9 in the scrambled group and 6 of 13 in the vehicle group. The median number and interquartile range of hair follicles was 4.5 (1.8, 10.3) for the TSN6 group, 0 (0, 3.5) for the scrambled group and 0 (0, 3.3) for the vehicle group. TSN6 also increased epidermal thickness, showing a thickness of 127 ± 18 μm for the TSN6 group and 70 ± 28 μm and 94 ± 18 μm for the scrambled and vehicle groups, respectively. In summary, TSN6 increases epidermal thickness and promotes hair follicle neogenesis in a skin substitute.

To develop an international consensus on the timeframe for defining a hospital-acquired pressure injury (HAPI). The purpose of this study was to identify the time frames used internationally to report a HAPI and to obtain expert consensus on what time frame defines a HAPI. A Delphi survey was undertaken with 43 international experts from 11 countries. Three Delphi rounds were conducted over 9 months. A percentage level agreement/consensus was set at ≥ 70%. Items with < 70% were removed. This research highlighted a wide variation among international experts on the definition of a hospital-acquired pressure injury and the variation in the timeframe used in guidelines within healthcare organisations. Expert interpretations for defining a hospital-acquired pressure injury had 10 variations, ranging from zero hours on admission to 96 h after admission. After three Delphi rounds, a 100% agreement was reached by expert consensus. A hospital-acquired pressure injury was defined as occurring after the first 24 h following admission. Deep tissue injury/unstageable PIs were defined as occurring after 72 h. This study used expert consensus to define a hospital-acquired pressure injury. Previous inconsistencies in hospital-acquired pressure injury definitions have impacted incident reporting, hospital coding, and funding penalties imposed by some governments. A standard international definition will allow for international comparisons and local benchmarking of prevalence and incidence rates. Accurate benchmarking supports quality activities to improve patient outcomes. It is only at this time that this data will represent a definitive measure of quality and evidence-based practice.

Recent studies showcased the regenerative potential of Platelet-Rich Fibrin (PRF) combined with Adipose-Derived Stem Cells (ASC). PRF enhances cellular proliferation through sustained growth factor secretion which are continuously released to surrounding cells. However, its regulatory mechanisms remain unclear. ASC were isolated from liposuction and abdominoplasty samples of healthy donors, characterised via flow-cytometry and cultured for 7 days. Four cell culture conditions were tested: (1) 10% PRF extract (PRFe), (2) 10% Platelet-Low Plasma (PLP), (3) 10% Foetal Bovine Serum (FBS) and (4) basal medium as control. Cell viability and proliferation were assessed using AlamarBlue and PicoGreen assays, as well as live-dead staining. Enzyme-Linked Immunosorbent Assays quantified growth factor concentrations, while multiplex qPCR and immunocytochemical staining analysed gene and protein expression on days 1 and 7. PRFe-supplemented cultures showed the highest viability and proliferation, significantly surpassing other groups at day 7 (p < 0.05). Supernatant analysis revealed significantly elevated TGF-β1 and PDGF-AA/BB levels in PRFe cultures at day 7 (p of at least < 0.05). Multiplex qPCR indicated increased expression of proliferation and pluripotency markers (NANOG, JUN, SOX2, RPS6KA4; p < 0.05) and fibrillar collagen (COL1A; p < 0.05) in the PRFe group. These findings demonstrate that PRFe significantly enhances ASC proliferation and regenerative potential. Elevated levels of TGF-1, PDGF-AA/BB and to a lesser extend VEGF in PRFe cultures suggest that its benefits in regenerative medicine may be linked to these cytokines' upregulation. These results underscore PRFe's potential as a key supplement for optimising ASC-based therapies in tissue regeneration.

Wound healing is an essential and complex biological mechanism to repair barrier breaches in the human body, but it results in scar formation. The extent of scar formation is associated with the depth of injury. Stromal cells play a vital role in wound healing and scar formation, but the role of the subcutaneous tissue in human skin wound healing remains largely unknown. In order to dissect the role of dermal fibroblasts, adipose stromal cells, and adipocytes in superficial and deep skin wound healing, we created a human tissue-engineered skin model and assessed healing outcomes in vitro. Three different reconstructed skin models were created, with dermal fibroblasts, adipose stromal cells, or adipocytes in the wound bed underneath a standardised biopsy punch wound. The superficial skin wound model with only dermal fibroblasts in the wound bed was completely healed within 14 days. The engineered 'deep' wounds with adipocytes in the wound bed showed delayed wound closure with reduced Ki67 proliferating keratinocytes and reduced basement membrane collagen IV deposition. This was accompanied by increased wound contraction and α-SMA protein expression underneath the newly formed epidermis, indicative of early scar formation. The 'deep' wound model with adipose stromal cells but without adipocytes showed improved re-epithelialisation but still healed with increased α-SMA protein expression. Furthermore, decreased leptin was observed in the supernatant of the 'deep' wound model. The superficial and deep wound models presented here can be used to test future therapies to improve wound closure which will lead to improved scar formation.

The vasa vasorum of the superficial collecting lymph vessel (VCL) has been reported to show morphological changes in lymphedematous limbs. This study aimed to develop a pathophysiological severity staging of the superficial collecting lymph vessels (SCLs) based on VCL morphology. A retrospective review was conducted using the medical charts of lower extremity lymphedema patients who underwent video-capillaroscopy (VC) during lymphaticovenular anastomosis (LVA). Intraoperative SCLs were evaluated using VC at 175× and 620× magnifications. The VCL stage was determined based on VCL morphology observed under VC. D2-40 (podoplanin) staining was assessed with a score of 0 for negative, 1 for mildly positive, and 2 for strongly positive. Red blood cell (RBC) movement was scored as 1 for movement and 0 for no movement. A total of 32 patients with 104 SCLs were evaluated. The distribution of VCL stages was as follows: Stage 0 in 4 SCLs (3.8%), Stage 1 in 16 SCLs (15.4%), Stage 2 in 18 SCLs (17.3%), Stage 3 in 36 SCLs (34.6%), Stage 4 in 20 SCLs (19.2%), and Stage 5 in 10 SCLs (9.6%). A significant difference was observed in the prevalence of lymphosclerosis grade according to the VCL stage (p = 0.002). Among the VCL stages (Stage 1 vs. 2 vs. 3 vs. 4 vs. 5), a higher VCL stage was significantly associated with lower positivity to D2-40 staining of the SCL (p < 0.001), as well as with lower positivity to RBC movement in both the main VCL (p < 0.001) and the branch VCL (p < 0.001). These findings indicate that the progression of the VCL stage is associated with pathologic changes in the SCLs and physiological deterioration of the VCLs, highlighting the significance of the VCLs in the progression of lymphedema.

Wound healing is often hindered by hyperglycemia, chronic inflammation and ageing. Despite extensive research on the pathophysiology of hard-to-heal wounds, wound healing remains complex and poses challenges in treatment and management. Current wound treatments and care mostly target a single pathology, such as infection, while most hard-to-heal wounds are multifactorial. Therefore, exploring the factors that do not rely on a single pathology is crucial to fill the gap in current wound management. Despite containing more comprehensive information than commonly used wound tissue samples, cells in the wound fluid have not drawn much attention because of collection difficulties. This study aimed to use single-cell RNA sequencing (scRNA-seq) of cells from wound fluid to identify specific biomarkers for hard-to-heal wounds, with the hypothesis that common biomarkers among various wound models can be potentially applied to complex hard-to-heal wounds in clinical settings. Three representative delayed wound models, aged, diabetic and lipopolysaccharide-induced inflammatory wound models, were compared with normal young mice to explore commonly shared genes that exist in different pathological delayed wound healing models. The shared upregulation of cell cycle and cellular senescence-related genes such as Rpl11, Rpl26, Rps3, Rps15, Rps 20, Rps26, Ccl2, Cdk2ap2 and Ccnd3 and the downregulation of immune response regulation genes such as Tnfaip3, Junb, Il1r2, Plaur, Il1rn, Il1a, Cxcl2, Cd14, S100a8 and S100a9 in all delayed healing wound models were found in most immune cell subgroups, especially the macrophage subgroup. The results of this study suggested cellular senescence of cells in wound fluid could be related to hard-to-heal wounds.

Hair follicle stem cells (HFSCs) are crucial for maintaining cutaneous functions under various pathological conditions, including wounds. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) interacts with its receptor, fibroblast growth factor-inducible 14 (Fn14), and plays a role in the development and tissue repair of skin diseases. This study aims to elucidate the effects of TWEAK/Fn14 signalling on HFSCs and the associated mechanisms. The expressions of HFSC markers, including K19, integrin β1 and K15, were analysed via immunohistochemistry in normal and Fn14-deficient mouse skin. Primary HFSCs were cultured in vitro and then treated with TWEAK or a chemokine (CXC motif) (CXCR) 4 inhibitor. The phenotype markers and secreted cytokines of HFSCs were assessed via immunofluorescence analysis, Western blotting and real-time polymerase chain reaction. Our results showed that both Fn14 and CXCR4 were highly expressed in hair follicles. Fn14 deficiency led to a decrease in the expression levels of K19 and CD34. Exogenous TWEAK enhanced the expression of K15, K19, integrin β1, tumour necrosis factor receptor type 2 and CXCR4 in cultured HFSCs. Additionally, TWEAK induced the proliferation, migration and cytokine production in HFSCs. Furthermore, the Wnt/β-catenin signalling pathway was upregulated in HFSCs upon TWEAK stimulation, and inhibitors of β-catenin or CXCR4 suppressed the effects of TWEAK on the differentiation and secretory functions of HFSCs. In conclusion, TWEAK/Fn14 interaction regulates the expression of differentiation markers and secretory functions of HFSCs in vitro. Wnt/β-catenin signalling or CXCR4 activation mediates the effects of TWEAK on HFSCs. Targeting the Fn14-Wnt/β-catenin-CXCR4 signalling axis may offer a potential approach for managing HFSC-related skin diseases, such as wounds.

Diabetic foot ulcers (DFUs) are a serious clinical problem, leading to high rates of morbidity, disability, amputations, and mortality. Many DFUs fail to heal completely and a major challenge includes identifying non-healers early in treatment. However, effective predictive biomarkers for DFUs have not yet been validated. The goal of this study was to validate if two previously identified, objective and quantitative tissue biomarkers, c-Myc and phosphorylated glucocorticoid receptor (p-GR), could predict complete healing at week 12 in a multicenter observational cohort study of individuals with open DFUs, conducted by the NIDDK Diabetic Foot Consortium (DFC). Wound tissue collected at the initial visit was analysed for c-Myc and p-GR biomarkers by immunohistochemistry, quantifying their nuclear presence in full thickness epidermis and correlating with week 12 clinical outcomes. The primary analyses included AUC comparisons to assess the biomarkers' predictive capability for wound healing. Other analyses included descriptive measures and t-tests to evaluate the difference between biomarker quantification among healers and non-healers. Of 140 DFUs enrolled, 107 participants completed biomarker and clinical outcome data for analysis. The distributions of baseline c-Myc and p-GR between healed and not-healed DFUs by week 12 were not significantly different (p > 0.05). Although the two biomarkers did not yield significant predictability (ΔAUC = -0.006, 95% CI (-0.02, 0.01) and ΔAUC = -0.0002, 95% CI (-0.01, 0.01), p > 0.025) for each of c-Myc and p-GR respectively, this first DFC clinical study using a national consortium of DFU centres successfully created a unique resource of wound-related biomaterials coupled with the clinical outcomes, providing a platform for further biomarker discovery and validation.