Wound Repair and Regeneration最新文献

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.

Diabetic foot ulcers (DFUs) are common and difficult to treat because the mechanisms behind unsuccessful responses to treatment are poorly understood. The goals of this study were to identify differences in healing and non-healing human DFUs using debrided tissue samples and to identify possible biomarkers of non-healing. First, DFU tissue samples collected over 12 weeks of treatment from 27 subjects (n = 12 healing and n = 15 non-healing) were analysed using a focused panel of 227 inflammation and wound healing-related human genes and 16S ribosomal RNA amplicon sequence to identify microbial species. Gene expression and correlation with microbial species differed between healing and non-healing DFUs. While no individual genes analysed at the initial time point could accurately predict healing outcome 12 weeks later, several 2-gene ratios were highly accurate. The ratio of C3AR1/CCL22 predicted healing outcome in the discovery cohort with an area under the receiver operator characteristic (ROC) curve (AUC) of 0.96. The AUC was 0.80 when tested on 74 unique samples collected at later time points from the discovery cohort, and the AUC was 0.69 when validated in a completely independent cohort of n = 51 subjects and using quantitative reverse transcription polymerase chain reaction (qRTPCR) as a more translational method of detection. The AUC increased to 0.75 when initial wound area was included. Overall, the results suggest that differences in inflammation contribute to differential healing outcomes in human chronic DFUs, and associated biomarkers may be used to predict healing outcome to guide treatment decisions.

Hard-to-heal arterial leg ulcers in older adults are a challenging and complex condition. In this quasi-experimental study, three treatment approaches were compared. The purpose was to investigate (1) the healing time of arterial leg ulcers in older adults (≥ 70 years) who underwent photobiomodulation, revascularisation, or conservative treatment; (2) the importance of factors associated with impaired healing; and (3) ulcer recurrence after healing with photobiomodulation. Participants who received photobiomodulation (n = 51) were frail older adults recruited from municipal home healthcare and matched with participants who received revascularisation (n = 71) or conservative treatment (n = 153). The latter two groups were retrieved from the Swedish Quality Registry RiksSår for ulcer treatment. Photobiomodulation was performed at wavelengths of 635 and 904 nm twice weekly. The results showed that the photobiomodulation group had a significantly shorter healing time (p < 0.001) and a higher proportion of healed ulcers; photobiomodulation 66.7%, revascularized 50.7% and conservatively treated group 41.2%. The median healing times for the photobiomodulation group were 135 days (confidence interval 95-175), compared to 252 (confidence interval 181-323) and 316 (confidence interval 192-440) in revascularized and conservatively treated groups, respectively. Neither ulcer duration nor other pretreatment factors exerted clinically relevant effects on healing time. In this study, recurrence within 24 months of healing with photobiomodulation was < 12%. In conclusion, photobiomodulation has the potential to heal hard-to-heal arterial ulcers markedly faster than revascularisation or conservative treatment. It could be a suitable treatment alternative for frail older adults, including those with previous substantial ulcer duration.