Advances in Wound Care

Oral mucosal wound healing is not completely understood, and effective therapies are lacking. This study explores the potential of an adipose-derived stem cell (ADSC) exosome sheet in enhancing intraoral wound healing in rats.

An ADSC exosome sheet derived from Tisseel and rat adipose tissue (ADSC-exo) was applied to 16 rats with 6 mm full-thickness mucosal hard palate wounds. Eight wounds received ADSC-exo with a superficial occlusive dressing (ADSC-exo group), and eight received only an occlusive dressing (control group). Wound closure was monitored on days 0, 2, 4, 7, and 10, with dressings changed every 2 days. On day 10, rats were sacrificed, and wounds (n = 8 per group) were collected for immunohistochemical analysis. In vitro, four ADSC-exosome concentrations (0, 4.5 × 10¹¹, 9 × 10¹¹, and 18 × 10¹¹ exosomes/mL; n = 4 per group) were applied to rat oral mucosal fibroblasts to assess migration speed.

ADSC-exo accelerated wound closure (18% ± 5% vs. 35% ± 9% of initial wound area; p = 0.002) and fibroblast migration (for 18 × 10¹¹ exosomes/mL at 24 h: 29.7% ± 3% vs. 62.2% ± 4% of initial gap area; p < 0.0001) compared with the control. ADSC-exo promoted reepithelialization (87% ± 14% vs. 21% ± 6%; p < 0.0001), proliferation (34 ± 12 vs. 18 ± 7 Ki67+/high-power field [HPF]; p = 0.004), and neovascularization (28 ± 9 vs. 11 ± 5 CD31+/HPF; p = 0.0002) while reducing inflammation (4 ± 1 vs. 13 ± 9 CD68+/HPF; p < 0.0001) and increasing M2 macrophages (9.2 ± 2 vs. 4.2 ± 3 CD163+/HPF; p = 0.0008). ADSC-exo increased Transforming Growth Factor beta 1 (TGF-β1) (1.3 ± 0.3 vs. 0.9 ± 0.2; p = 0.006), Smad3 (0.9 ± 0.02 vs. 0.7 ± 0.1; p = 0.006), and collagen I (1.5 ± 0.9 vs. 0.5 ± 0.3; p = 0.005) while downregulating caspase-3 (0.7 ± 0.3 vs. 1.1 ± 0.2; p = 0.003) and Bax (0.9 ± 0.2 vs. 1.4 ± 0.1; p < 0.0001).

This is the first study to demonstrate the pro-wound healing effects of an ADSC exosome sheet on intraoral wounds. This paves the way for future research and clinical applications of ADSC exosomes in mucosal wound healing.

Application of an ADSC-exo to rat mucosal wounds significantly improved wound healing. Mechanistically, these effects may be linked to upregulated activity of the TGF-β/Smad pathway.

To analyze global trends in pressure ulcer (PU) burden, focusing on microbial infections, antimicrobial resistance (AMR), and climate change from 1990 to 2021, and to forecast location-specific disease burdens through 2035.

: This is a cross-sectional study on PU globally from 1990 to 2021. This analysis assessed incidence and disability-adjusted life-years (DALYs) of PU by age, sex, and location, focusing on the relationship between PU burden and microbial infections, AMR, and climate factors.

Incidence and DALYs of PU increased from 1990 to 2021, while the corresponding age-standardized rate (ASR) declined or remained steady. ASR of incidence was highest in high sociodemographic index (SDI) areas and lowest in those with low SDI, while ASR of DALYs showed the opposite pattern. PU burden positively correlated with microbial infections and AMR in skin and subcutaneous infections (p < 0.05), and its increase was also associated with high temperature and humidity. Regardless of age, males bear a greater disease burden. However, with aging, females gradually surpass males in disease burden.

This study offers decision-makers insights into PU burden, contributing factors, and forecasts, supporting informed policies to mitigate its impact.

PU poses a rising global challenge with persistent disease burden, especially in low-SDI and low-income regions. Microbial infections, AMR, and climate factors are associated with increased burden. Targeted policies and enhanced epidemiological understanding are crucial for effective prevention and control.

Fibroblasts (FBs) are the cytological basis of keloid (KD) formation. This study aimed to identify the key pathogenic target cell subpopulation involved in KD recurrence.

Single-cell RNA sequencing data were retrieved from public databases, revealing distinct gene expression patterns in FB subpopulations. Flow cytometry (FCM) was used to identify the surface molecular phenotypes of FBs that affect KD recurrence. Simultaneously, logistic regression analysis was performed to assess the predictive value of changes in FB subpopulation percentages for clinical KD recurrence.

The percentage of keloid fibroblasts was significantly greater than that in normal tissues. Through further clustering analysis of the FB population, we obtained four subpopulations, FB1–FB4, in which the percentages of FB1 subpopulation were increased, and functional enrichment analysis suggested that the FB1 subpopulation may play a greater role in extracellular matrix collagen oversynthesis in KD. In addition, the gene expression of CD26 (DPP4), CD117 (c-KIT), and CD34 in the FB1 subpopulation was significantly higher than that in FB2–4 subpopulations. Moreover, the percentage of CD26+/CD117+/CD34+ cell subpopulations in the FCM data of patients with KD recurrence was significantly increased. Regression analysis confirmed that the CD26+/CD117+/CD34+ FB subpopulation was a risk factor for relapse.

We demonstrated that the molecular phenotypic and functional heterogeneity of FBs influences KD recurrence.

We identified key pathogenic FB subpopulations that may affect KD development, which can be used as potential markers to predict recurrence and provide potential target cell populations for future clinical treatment.

Wound healing is a complex, tightly regulated process involving a range of enzymes, growth factors, and cytokines that coordinate cellular activities essential for tissue repair and wound closure. However, in cases of extensive or severe injury, the intrinsic repair mechanisms are often insufficient, underscoring the need for advanced therapeutic strategies to accelerate healing and minimize scar formation.

Electrically conductive hydrogels (ECHs), combining the advantageous properties of hydrogels with the physiological and electrochemical characteristics of conductive materials, present a safer and more convenient alternative to traditional electrode-based electrical stimulation (ES) for treating chronic and nonhealing wounds. This review summarizes the various types of ECHs and their functional roles in facilitating wound healing.

Understanding the mechanisms by which ECHs interact with electrical signals in the skin, along with precise control of the synergy between these signals and other functional properties, is critical for achieving optimal wound healing outcomes.

Future development of ECHs should focus on elucidating underlying mechanisms, standardizing ES parameters, validating efficacy in clinically relevant animal models, and integrating multifunctional systems. Additionally, material design must be optimized for biocompatibility, adaptability, and scalability to facilitate clinical translation in chronic and nonhealing wound treatment.

Burn wound injuries are a global health challenge, affecting millions annually and resulting in significant morbidity, mortality, and economic burden. The urgent need for accessible and cost-effective therapeutic alternatives, especially for underserved populations, has driven interest in novel approaches such as noninvasive splenic stimulation using pulsed-focused ultrasound (pFUS). This technique targets systemic inflammation, a key factor in delayed wound healing, offering a potential shift in burn care management.

Preclinical studies have shown that pFUS applied to the spleen can accelerate wound healing by activating the cholinergic anti-inflammatory pathway, promoting pro-angiogenic and anti-inflammatory responses. While current treatments—including biologics, antioxidants, and growth factors—have limitations, pFUS presents a noninvasive alternative. One interventional study and ongoing clinical trials are now investigating its application in burn wound care, marking an important step toward clinical translation.

Despite encouraging results, research on splenic stimulation for wound healing remains limited. The small number of studies highlights the need for further investigation into the underlying mechanisms, optimal treatment parameters, and potential risks. Additionally, the scalability and cost-effectiveness of pFUS in diverse clinical settings require thorough evaluation.

Ongoing clinical trials will provide critical data on the efficacy and safety of splenic pFUS in burn patients. Future research should focus on expanding clinical studies, refining stimulation protocols, and exploring its broader application in tissue repair. If validated, this approach could offer a cost-effective, noninvasive treatment, particularly valuable in socioeconomically challenged regions.

Skin lipids are essential for various skin functions including maintaining barrier integrity, regulating hydration, and providing protection against microbes and inflammatory irritants. Along with skin health, the role of lipids in the etiology of macroangiopathic diseases, such as atherosclerosis of arteries, is well recognized.

In diabetes, lipid dysregulation is evident and may contribute to the diverse complications of the disease. Diabetic vasculopathy primarily reflects the dysfunction and deterioration of existing blood vessels, as their preservation is key in preventing the progression of vascular disease and reducing the need for compensatory angiogenesis. In the peripheral diabetic skin of the limbs, diabetic vasculopathy runs alongside peripheral neuropathy. Although a causative link between the two is plausible, direct evidence in support of such claim is scanty.

Diabetic skin is known to be compromised in many ways, including weakened barrier functionality and diabetes-induced alterations in the extracellular matrix, likely stemming from chronic inflammation, which may directly affect vascular integrity and nerve health. Both, in the compromised skin and within wounds, microbial pathogens and their enzymes may metabolize host lipids, driving inflammatory reactions and exacerbating the pathogenesis of diabetic vasculopathy and related neuropathy.

This review focuses on lipid mediators such as sphingolipids, resolvins, oxidized low-density lipoproteins and their specific downstream signaling pathways to obtain a comprehensive understanding of diabetic complications relevant to wound healing. Through lipid-based strategies, this review hopes to inspire the development and utilization of individualized, precision-based approaches to manage diabetic vasculopathy and neuropathy.