Wound Repair and Regeneration最新文献

Foot ulcers are amongst the most prevalent complications of diabetes, known for their delayed healing process. Recent research indicates that the transcription factor forkhead box M1 (FOXM1) plays a role in promoting diabetic ulcer repair. However, the precise mechanisms underlying FOXM1 functions in this context remain unclear. This study aimed to clarify the role of tripartite motif-containing protein 72 (TRIM72)-mediated endoplasmic reticulum stress in FOXM1 promotive effects. Immunohistochemistry revealed that FOXM1 expression was significantly reduced in the lesion tissues of diabetic foot ulcer patients. In vitro experiments revealed a decrease in FOXM1 expression in cultured dermal fibroblasts under high glucose conditions. Activating FOXM1 with a plasmid accelerated the proliferation, migration, and differentiation of dermal fibroblasts and mitigated endoplasmic reticulum stress under high glucose conditions. Additionally, ChIP and luciferase reporter gene assays confirmed that FOXM1 suppressed TRIM72 expression transcriptionally by binding to its promoter. Furthermore, high glucose induced ubiquitination of adenosine 5'-monophosphate-activated protein kinase alpha (AMPKα), whilst inactivation of AMPKα signalling reversed the aforementioned effects of FOXM1 on cells. Finally, the FOXM1-overexpressing plasmid was transfected in vivo, which promoted wound healing in a murine diabetic ulcer model. In conclusion, FOXM1 reduces endoplasmic reticulum stress by inhibiting TRIM72-mediated AMPKα ubiquitination, thereby accelerating the healing of diabetic ulcers.

Slough is not currently a recommended microbiology culture specimen. The aim of our work is to analyse the concordance of results between slough and swab samples for cultures. A single-centre, retrospective, cross-sectional study involving patients (n = 131) with hard to heal wounds was conducted from October 2022 to October 2023. Pairs of slough and swab samples were collected for microbiological analysis and subdivided depending on whether a relatively clean wound bed was obtained. Swab samples were collected using the Levine and deep pus methods, Cohen's κ coefficients calculated to evaluate concordance, and microbiological agreement analysed. Gram-stain results did not differ significantly between slough and swab samples (𝜒² = 329.287, p = 0.688; concordance, κ = 0.879, p < 0.001); microbiological agreement was 90.1%. Samples from 87 patients with relatively clean wound beds generated excellent concordance between slough and Levine technique (κ = 0.867, p < 0.001; microbiological agreement, 89.7%). In 44 patients with slough and deep pus swab where a relatively clean wound bed could not be obtained, Gram-stain also demonstrated excellent concordance (κ = 0.898, p < 0.001; microbiology agreement, 90.9%). Our data provide evidence that slough is a reliable wound specimen from hard to heal wounds for microbiology culture.

Diabetes mellitus (DM) is the leading cause of non-traumatic lower extremity amputations in the USA. After these amputations, patients exhibit reduced mobility and increased energy demands of walking. The best surgical practice is to preserve as much of a functional limb as possible, in part due to the fact that proximal amputations result in a greater increase in energy expenditure compared to more distal amputations. While differences in transfemoral, transtibial and partial foot amputation levels have been previously documented, no studies have directly compared transtibial and transmetatarsal amputees. The present study aimed to compare energy expenditure and patient-reported outcomes in patients with diabetes mellitus who have undergone transmetatrsal (TMA) and transtibial amputations (TTA). Thirty-nine DM participants with either unilateral TMA, unilateral TTA or no amputations (control group) participated in this observational study. Energy expenditure, heart rate (HR) and distance travelled during six-minute walk test (6MWT), the Foot and Ankle Ability Measure (FAAM) and the Patient-Reported Outcomes Measurement Information System (PROMIS-29) were measured at a single research visit. No significant differences between the three groups were detected in energy expenditure, HR or distance covered during 6MWT, as well as in PROMIS-29 or FAAM patient-reported outcomes. While the results of this study suggest no differences in functional and patient-reported outcomes between transmetatarsal and transtibial amputees, a larger sample size that would allow for control of comorbidities is needed.

As the number of patients requiring organ transplants continues to rise exponentially, there is a dire need for therapeutics, with repair and regenerative properties, to assist in alleviating this medical crisis. Over the past decade, there has been a shift from conventional stem cell treatments towards the use of the secretome, the protein and factor secretions from cells. These components may possess novel druggable targets and hold the key to profoundly altering the field of regenerative medicine. Despite the progress in this field, clinical translation of secretome-containing products is limited by several challenges including but not limited to ensuring batch-to-batch consistency, the prevention of further heterogeneity, production of sufficient secretome quantities, product registration, good manufacturing practice protocols and the pharmacokinetic/pharmacodynamic profiles of all the components. Despite this, the secretome may hold the key to unlocking the regenerative blockage scientists have encountered for years. This review critically analyses the secretome derived from different cell sources and used in several tissues for tissue regeneration. Furthermore, it provides an overview of the current delivery strategies and the future perspectives for the secretome as a potential therapeutic. The success and possible shortcomings of the secretome are evaluated.

Burn injuries undergo a complex healing process in which progressive spreading of epithelial damage can lead to secondary complications such as wound infection, which is a major driver of mortality among burn patients. We recently reported that burning larval zebrafish triggers dysregulated keratinocyte dynamics compared to mechanical injury. Here, we investigate keratinocyte behaviour following burn injury and the subsequent potential for microbial colonisation of burn wounds over time. Real-time imaging, coupled with tracking of photoconverted cells, revealed that early keratinocyte motility contributes to the spread of epithelial damage beyond the initial site of burn injury and that increased epithelial damage was associated with wound colonisation by the fungal pathogen Candida albicans. Modulating osmotic balance by treating larval zebrafish with isotonic medium limited the spread of epithelial damage and reduced microbial colonisation of burn wounds. Using cultured human skin, we found that topical treatment with isotonic solution (saline) similarly prevented the spread of epithelial damage over time. These findings indicate that keratinocyte behaviour contributes to burn wound progression in larval zebrafish and links keratinocyte dynamics to microbial colonisation of burn wounded tissue.

Diabetes mellitus remains a global challenge to public health as it results in non-healing chronic ulcers of the lower limb. These wounds are challenging to heal, and despite the different treatments available to improve healing, there is still a high rate of failure and relapse, often necessitating amputation. Chronic diabetic ulcers do not follow an orderly progression through the wound healing process and are associated with a persistent inflammatory state characterised by the accumulation of pro-inflammatory macrophages, cytokines and proteases. Photobiomodulation has been successfully utilised in diabetic wound healing and involves illuminating wounds at specific wavelengths using predominantly light-emitting diodes or lasers. Photobiomodulation induces wound healing through diminishing inflammation and oxidative stress, among others. Research into the application of photobiomodulation for wound healing is current and ongoing and has drawn the attention of many researchers in the healthcare sector. This review focuses on the inflammatory pathway in diabetic wound healing and the influence photobiomodulation has on this pathway using different wavelengths.

Photobiomodulation (PBM) therapy is a continuously growing approach to stimulating healing and reducing inflammation and pain. However, its effects in the fields of regenerative medicine and tissue engineering are still under investigation. Studying PBM effects on the regenerative capacity of zebrafish can allow the application of novel clinical approaches where the impact of PBM will be cross-linked with the stem-cell therapeutic approaches. This study was done to establish an in-vivo experimental setup for studying the effects of laser and ultraviolet therapy on zebrafish caudal-fin regeneration and vascularization. Thirty zebrafish were randomly and equally allocated into three groups. The caudal-fins of all zebrafish were amputated under anaesthesia. In the first control group, the caudal-fin was only monitored until fully regenerated. In the second group, the amputated-fin was irradiated with ultraviolet. Finally, in the third group, the amputated-fin was irradiated with laser. Caudal-fin regeneration and vascularization were assessed at days 0, 3, 6, 9, 12, and 15 in all fish. In terms of regeneration, the results indicated that it is possible to discriminate the regenerative effect of laser with the experimental setup as laser therapy showed a statistically significant difference when compared to control-group. It was also found that regenerative stimulation of the group that received ultraviolet therapy showed significant difference when compared to the control group. In terms of vascularization, there was a statistically significant difference in all groups of the study, which may suggest that laser as well as ultraviolet have limited effects in terms of improving vascularization. This study presented a novel, simple and inexpensive method for the assessment of PBM effects on zebrafish. Laser and ultraviolet therapy appeared to act as regenerative stimulators for caudal-fin regeneration of zebrafish. However, laser therapy results were, to some extent, better than ultraviolet therapy. This novel in-vivo design of the experiment led to more rapid and reproducible results than in-vitro experiments.

Inflammatory cytokines are key indicators affecting the development of ulcers of lower limb. The causal role of inflammatory cytokines in ulcers of lower limb and whether this can be mediated by metabolites remain unknown. We conducted a two-step, two-sample Mendelian randomization (MR) study to investigate the causal effect of inflammatory cytokines on ulcers of lower limb and the mediating role of metabolites in the association between inflammatory cytokines and ulcers of lower limb. MR analysis identified seven inflammatory cytokines (CCL19, IL-12β, MCP4, MIP1a, SCF, sirtuin2, and TNFSF9) that promote ulcers of lower limb. Additionally, 56 metabolites were found to be associated with ulcers of lower limb. Mediation MR indicated that the causal effect of sirtuin2 on ulcers of lower limb (total effect Inverse Variance Weighted [IVW]: odds ratio [OR] = 1.162, 95% confidence interval [CI] [1.051, 1.285], p = 0.003) is largely mediated by 4-hydroxyphenylacetate (0.0185, 95% CI [-0.00278, 0.0397], accounting for 11.1% of the total effect).

Bacteria constitute the most abundant life form on earth, of which the majority exist in a protective biofilm state. Since the 1980s, we have learned much about the role of biofilm in human chronic infections, with associated global healthcare costs recently estimated at ~$386 billion. Chronic wound infection is a prominent biofilm-induced condition that is characterised by persistent inflammation and associated host tissue destruction, and clinical signs that are distinct from signs of acute wound infection. Biofilm also enables greater tolerance to antimicrobial agents in chronic wound infections compared with acute wound infections. Given the difficulty in eliminating wound biofilm, a multi-targeted strategy (namely biofilm-based wound care) involving debridement and antimicrobial therapies were introduced and have been practiced since the early 2000s. More recently, acknowledgement of the speed at which biofilm can develop and hence quickly interfere with wound healing has highlighted the need for an early anti-biofilm strategy to combat biofilm before it takes control and prevents wound healing. This strategy, referred to as wound hygiene, involves multiple tools in combination (debridement, cleansing, and antimicrobial dressings) to maximise success in biofilm removal and encourage wound healing. This review is intended to highlight the issues and challenges associated with biofilm-induced chronic infections, and specifically address the challenges in chronic wound management, and tools required to combat biofilm and encourage wound healing.

Deep dermal and full-thickness burns often result in scar sequelae such as contractures, hypertrophy, pain and itching following split-thickness skin grafting. Dermal substitutes are currently employed alongside split-thickness skin grafting to enhance clinical outcomes, though their indications remain a subject of ongoing debate. This systematic review aims to clarify the indications for the application of dermal substitutes in burn patients, in both acute and reconstructive settings. A comprehensive search across various databases was conducted. Studies (n = 190) assessing the indications and outcomes of dermal substitutes in acute burn patients and those requiring reconstructive surgery were included. Data extraction included the applied dermal substitute, age, total body surface area, wound depth, burn aetiology, anatomical site and exclusion criteria. The indications were derived from predetermined indications, i.e. inclusion and exclusion criteria and patient characteristics. The depth of the wound emerged as the primary indication for dermal substitute use. A one-stage approach is recommended for deep dermal to full-thickness wounds larger than 10 cm², while a two-stage approach is advised for wounds of this depth with limited donor sites or exposed bone or tendon. No definitive age or burn/scar location thresholds were identified, and careful consideration is advised for electrical and chemical burns. Contraindications include wound infections and allergies to matrix components. Limited data exist on use in patients with diabetes mellitus, chronic vascular disease, or immunocompromised status. This is the first review to address the indications for dermal substitutes in burn patients, providing valuable insights for the development of international evidence-based treatment guidelines.