Wound Repair and Regeneration最新文献

Chronic venous insufficiency and venous leg ulcers remain a major challenge in wound care, with profound effects on patient health and quality of life. This prospective observational study compared clinical outcomes and patient-reported quality of life following conservative or surgical treatment of venous leg ulcers at Miguel Servet University Hospital, Spain, between 2017 and 2021. Fifty-two patients completed baseline and follow-up assessments with the 36-Item Short Form Health Survey and the Charing Cross Venous Ulcer Questionnaire. Conservative therapy was associated with a significantly shorter mean estimated time to healing compared with surgical treatment (average 21.5 vs. 34.1 weeks, p = 0.019) and greater ulcer area reduction (97% vs. 78.9%, p = 0.034) than surgical treatment with skin grafting and autologous fat transfer. Although complete closure rates were higher in the conservative group (66.7% vs. 47.4%), the difference was not statistically significant. Quality of life improvements were greater in the conservative group, with significant gains in bodily pain, general health, vitality and emotional well-being. Multivariate analysis identified smaller ulcer size, fewer comorbidities and conservative treatment as independent predictors of quality of life improvement. Surgical intervention yielded modest benefits, limited to vitality. These findings demonstrate that improvements in quality of life are closely tied to ulcer healing rather than treatment modality. The study underscores the efficacy of compression therapy and highlights the importance of patient-reported outcomes as essential endpoints in the evaluation of venous leg ulcer management.

Diabetes-related lower extremity amputations (LEAs) are a significant global issue, exacerbated by the rising prevalence of diabetes and peripheral artery disease (PAD). Traditional revascularization techniques often fail in patients with severe vascular damage or comorbidities. Tibial Osteodistraction angiogenesis (ODA) represents a novel approach, leveraging angiogenesis to improve perfusion and wound healing. A systematic review was conducted across four databases. Inclusion criteria focused on studies evaluating ODA in diabetic foot ulcers and chronic ischemic wounds. Outcomes analysed included amputation rates, wound healing, mortality, and safety metrics. Eighteen studies (n = 3000 treated with ODA) were included, with subjects aged 35-87. Diabetes prevalence was 87.8%. ODA demonstrated high limb salvage rates (92%-100%) and wound healing rates (58%-100%). Pooled analysis revealed amputation rates of 2% and mortality rates of 4%. Angiogenic cytokine levels increased post-procedure, suggesting enhanced angiogenesis. Complications were minimal, with a 3% pin-site infection rate and 4% major adverse limb events. ODA offers a promising addition for patients with limb-threatening ischemia, achieving significant improvements in perfusion, wound healing, and limb salvage. Despite study heterogeneity and limitations, ODA's angiogenic benefits warrant further research through randomised clinical trials to validate its efficacy and broaden clinical adoption.

Recombinant human platelet-derived growth factor BB (rhPDGF-BB), is the only growth factor approved by the US Food and Drug Administration (FDA) for tissue regeneration and rejuvenation indications. It has received four FDA approvals for both soft tissue (e.g., skin) and hard tissue regeneration/rejuvenation. Regranex gel, 0.01% rhPDGF-BB, is the only growth factor approved by the FDA for the promotion of skin wound healing. While the safety of one and two 15 g tubes of Regranex, generally sufficient for up to 60 daily applications onto open skin wounds, has never been questioned, a decade after its introduction in 1997, a boxed warning regarding rates of cancer mortality was placed on its label for daily use of three or more tubes. This was based on a mathematical calculation on incomplete data from an insurance claims database which was subsequently invalidated with the addition of three more years of data. Removal of this warning from the label required another decade and several very large propensity-matched database studies including over 13,000 patients. These studies provided incontrovertible proof that up to 140 daily applications (≥ 4 tubes) of rhPDGF-BB onto open skin wounds are safe, with no increased risk of either cancer development or cancer mortality. Removing a boxed warning is an arduous task that requires extensive and robust evidence; less than 4% of box warnings are removed once placed. Thus, the successful removal of the boxed warning from the Regranex label should reassure both prescribers and patients of the product's safety.

Tissue regeneration is critical, particularly in obesity, where abnormal lipid expansion poses significant challenges. Traditional biomaterials struggle to address the complex wound microenvironment caused by impaired lipid metabolism. There is growing interest in enhancing lipolysis by converting the white adipocytes into brown-like adipocytes to improve overall adipose tissue health, but translating these findings into humans is challenging due to the specificity of targeted signalling pathways. In this study, a combination of browning agents was utilised for the development of specialised biomaterials that can parallelly activate angiogenesis and localised browning to promote faster soft tissue regeneration. The combinatorial effects of apigenin and resveratrol-integrated collagen biomatrix were analyzed. Our findings indicate that the engineered AR collagen biomatrix promotes rapid tissue regeneration compared to biomaterials incorporating individual bioactives by enhancing cell attachment, site-specific thermogenesis within subcutaneous fat, and angiogenesis. In an in vivo DIO-C57BL/6 mouse model, tissue repair was observed within 8 days when treated with AR collagen biomatrix, characterized by distinct neo-epidermal formation, new blood vessel growth, increased collagen deposition, and a significant thermogenic transformation of subcutaneous adipose tissue. This research contributes to the development of novel strategies for addressing impaired wound healing associated with metabolic disorders and offers promise for the advancement of biomaterials for clinical use in wound management.

Human skin is the outermost complex ecosystem that hosts numerous microbial communities. The reciprocal communication between these microbial inhabitants and host cells plays pivotal roles in maintaining skin homeostasis. While current research primarily focuses on the functions of skin microbiota in chronic wounds, the mechanisms by which skin microbiota affect acute wounds such as burn wounds need further exploration. Until recently, an increasing body of evidence has proven the indispensable role of skin microbiota in burn wound healing, suggesting that targeting skin microbiota maybe a highly promising therapeutic approach in treating burns. This review aims to summarize current research findings, with a focus on discussing the dynamic alterations of skin microbiota following burns and its profound impact on the wound healing process. Additionally, we delve into strategies for maintaining microbial homeostasis to facilitate effective healing of burn wounds, offering new perspectives for research and practice in related fields.

Impaired lower extremity wound healing due to diabetes presents a significant societal burden, as 25% of diabetic wounds lead to major amputations. While TGF-β has been extensively studied in diabetic wound healing, the role of βII spectrin (SPTBN1), a known adapter of SMAD3 in the canonical TGF-β signalling pathway, remains unexplored. Single-cell RNA sequencing analysis revealed an increase in SPTBN1 expression in endothelial cells from non-diabetic skin to diabetic skin and ulcers. We found that silencing SPTBN1 in human umbilical vein endothelial cells (HUVECs) suppressed endothelial sprouting and tube formation. Based on these findings, we hypothesised that SPTBN1 regulates diabetic wound healing by modulating angiogenesis. To test this, we created Sptbn1 endothelial-specific conditional knockout (Sptbn1^ECKO) mice and used the well-established streptozocin-induced diabetic excisional dorsal wound model. Interestingly, while Sptbn1^ECKO mice showed delayed wound healing, the delay was not due to impaired angiogenesis, but rather due to excessive inflammation. Inflammation persisted in Sptbn1^ECKO mice when it resolved in controls, as evidenced by higher numbers of neutrophils, inflammatory monocytes and greater iNOS staining intensity in the wound beds. Additionally, Sptbn1^ECKO wounds had significantly less granulation tissue and fewer fibroblasts in the regenerative phase. Collectively, these findings suggest that βII spectrin in endothelial cells is a potential therapeutic target in chronic diabetic wound healing.