Search Results (123)

Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs) after light treatment at 450 nm were analyzed by kinetic assays on cell viability, proliferation, ATP quantification, migration assay, and apoptosis assay. Gene expression was evaluated by transcriptome analysis. Results: A biphasic effect was observed on HaCaTs, NHDFs, and HUVECs. Low-fluence (4.5 J/cm²) irradiation stimulated cell viability, proliferation, and migration. mRNA sequencing indicated involvement of transforming growth factor beta (TGF-β), ErbB, and vascular endothelial growth factor (VEGF) pathways. High-fluence (18 J/cm²) irradiation inhibited these cellular activities by downregulating DNA replication, the cell cycle, and mismatch repair pathways. Conclusions: HaCaTs, NHDFs, and HUVECs exhibited a dose-dependent pattern after BL irradiation. These findings broaden the view of PBM following BL irradiation of these three cell types, thereby promoting their potential application in wound healing and angiogenesis. Our data on low-fluence BL at 450 nm indicates clinical potential for a novel modality in wound therapy. Full article

Platelet-rich plasma (PRP) is widely applied in veterinary regenerative medicine due to its rich composition of growth factors that promote tissue repair. However, the direct pro-angiogenic function of canine PRP (cPRP) has not been thoroughly validated through controlled in vitro and in vivo experimentation. Human umbilical vein endothelial cells (HUVECs) were used to assess cell proliferation, migration, and tube formation after exposure to cPRP. In addition, a rabbit corneal micropocket assay was employed to evaluate in vivo angiogenic responses. Treatment with 20% cPRP significantly enhanced HUVEC proliferation and migration and induced robust tube formation. In the in vivo model, we observed dose-dependent neovascularization, with the earliest vascular sprouting seen on day 1 in the 40% group. Both models consistently demonstrated that cPRP stimulates vascular development in a concentration-dependent manner. This study provides novel evidence of cPRP’s capacity to induce neovascularization, supporting its therapeutic value for treating nonhealing wounds in dogs, especially in cases involving chronic inflammation, aging, or immune dysregulation. These findings offer a scientific foundation for the broader clinical application of cPRP in veterinary regenerative practice. Full article

Background and Objectives. Umbilical hernia is particularly common among patients with liver cirrhosis, affecting about 20% of this group, compared to 3–8.5% in healthy individuals. This increased prevalence is mainly due to weakened abdominal fascia, elevated intra-abdominal pressure, and malnutrition. The rapid progression of umbilical hernias often leads to complications such as skin necrosis, perforation, and strangulation. Historically, patients with liver cirrhosis and complicated umbilical hernia have faced high morbidity and mortality rates. However, recent advancements in perioperative management, especially in controlling ascites, have improved outcomes in elective treatments. Despite these advancements, managing patients with decompensated liver cirrhosis and complicated umbilical hernia in emergency settings remain a significant surgical challenge. Materials and Methods: We conducted a retrospective review of patients treated for complicated umbilical hernia at the University Medical Centre Ljubljana from 2015 to 2024, using prospectively collected data. This analysis involved implementing hernioplasty combined with incisional negative pressure wound therapy (iNPWT) as part of the surgical protocol. The primary endpoint of our study was the rate of local complications, while the secondary endpoints included the rate of systemic complications and 90-day mortality. Results: We treated 28 consecutive patients with complicated umbilical hernia and liver cirrhosis. Local wound complications were observed in three (10.7%) patients. Systemic complications developed in 10 patients (35.7%). The median duration of hospitalization was 8 days (range: 5–29), and no readmissions were recorded within the 30-day period. Two (7.1%) patients died within 90 days. Conclusions: Our experience indicates that iNPWT, when combined with surgical repair, can be safely utilized, yielding outcomes comparable to elective hernia repairs, even in emergency contexts. Further randomized controlled trials are necessary to validate these findings and optimize treatment protocols. Full article

Objective: This study aimed to evaluate the photobiomodulatory (PBM) effects of low-power light-emitting diode (LED) irradiation on cultured human umbilical vein endothelial cells (HUVECs), focusing on changes in cellular metabolic activity and morphology. Materials and Methods: HUVECs were cultured and divided into three groups: control (no irradiation), red LED (655 nm), and blue LED (455 nm). Cells were irradiated once with a total energy dose of 4 J over 60 s. Cellular metabolic activity was assessed at 0, 1, 3, and 6 h post-irradiation using the WST-8 assay. Morphological changes were examined 3 h post-irradiation using rhodamine–phalloidin staining and confocal laser scanning microscopy. Results: Red LED irradiation significantly enhanced metabolic activity immediately and at 3 h post-irradiation compared to the control group. Blue LED irradiation showed a non-significant trend toward increased metabolic activity at 1 and 3 h. Morphometric analysis revealed increases in cell area, perimeter, and Feret diameter in both LED-irradiated groups, with more pronounced changes observed in the red LED group. Conclusions: Low-power red LED light (655 nm) effectively promotes metabolic activation and induces morphological changes in vascular endothelial cells, suggesting its potential application in angiogenesis and wound healing. Due to its safety and accessibility, LED-based PBM may serve as a promising therapeutic modality for soft tissue regeneration in both clinical and home-care settings. Full article

This study investigates the interplay between cellular senescence and inflammation in human umbilical vein endothelial cells (HUVECs). We employed RNA sequencing to analyze gene expression changes in HUVECs subjected to replicative- or radiation-stress-induced senescence, and we compared these profiles with those of cells under acute or chronic TNFα-mediated inflammation. Our findings reveal that both senescence types exhibited significant upregulation of genes associated with epithelial- (or endothelial) mesenchymal transition (EMT) and inflammatory pathways, indicating a shared molecular response. Notably, chronic inflammation led to a pronounced EMT signature, while acute inflammation primarily activated classical inflammatory responses. Experimental validation confirmed reduced proliferation and increased secretion of pro-inflammatory cytokines (IL-6 and IL-8) in senescent and chronically inflamed cells and substantiated the upregulation of EMT marker genes. Additionally, we observed impaired wound healing capacity in senescent and chronically inflamed cells, highlighting the functional consequences of these cellular states. Our study underscores the critical role of inflammation in exacerbating senescence-related changes, contributing to the understanding of age-related cardiovascular pathologies. These insights may inform future therapeutic strategies aimed at mitigating the effects of aging and inflammation on endothelial function and cardiovascular health. Full article

Background/Objectives: Laparoscopic surgery plays a central role in the management of abdominal trauma, particularly in patients with hemodynamic stability. Recently, single-port laparoscopic surgery (SPLS) has emerged as a technique that further reduces access-related trauma while preserving the benefits of conventional laparoscopy. Thus, this review aimed to examine the current landscape of SPLS in trauma care, summarizing available clinical data and highlighting practical considerations for its use. Despite the limited experience, early evidence suggests that SPLS can achieve diagnostic and therapeutic outcomes comparable to those achieved by multi-port approaches in selected cases. Particular attention is given to a hybrid method that combines intracorporeal assessment with extracorporeal small bowel examination and repair through a single umbilical incision. This technique offers a pragmatic balance between thorough exploration and minimal invasiveness. Methods: We searched PubMed, Scopus, Web of Science, and Google Scholar through December 2023 using the terms “single-port laparoscopy”, “single-incision laparoscopic surgery”, “trauma laparoscopy”, and related phrases. Case reports, case series, comparative studies, and reviews describing single-incision laparoscopic surgery in trauma were included in this narrative analysis. Results: SPLS may offer advantages in terms of postoperative pain, wound complications, and cosmetic outcomes, especially in younger patients. As familiarity with the approach increases and dedicated instrumentation becomes more accessible, its role in trauma protocols may expand. Conclusions: Further prospective research is needed to define long-term outcomes, refine patient selection, and integrate SPLS more systematically into trauma care protocols. Full article

Background/Objectives: Dry eye disease (DED) is a multifactorial inflammatory disease that disrupts the ocular surface, causing tear film instability, epithelial damage, and chronic inflammation. Mesenchymal stem cell-derived exosomes (MSC-exos) are promising therapeutics with immunomodulatory and regenerative properties. This study investigates the therapeutic effects of umbilical cord MSC-derived exosomes (UCMSC-exos) in a severe dry eye model, induced by a surgical resection of the infra-orbital (ILG) and extra-orbital lacrimal gland (ELG) in rats. Methods: Clinical evaluations, including tear volume measurement, slit lamp biomicroscopy, fluorescein staining, and spectral domain optical coherence tomography (SD-OCT), were performed to assess corneal neovascularization, corneal abrasion, and epithelial/stromal thickness. Histopathological analysis, immunohistochemistry, and mRNA gene expression were conducted to evaluate corneal tissue changes and inflammatory marker expression. Results: The results show that the treatment group exhibited significantly reduced corneal neovascularization compared to the control group (p = 0.030). During the first month, the Exo group also had a significantly lower corneal fluorescein staining area (p = 0.032), suggesting accelerated wound healing. SD-OCT analysis revealed that the corneal epithelial thickness in the treatment group was closer to normal levels compared to the control group (p = 0.02 and p = 0.006, respectively). UCMSC-exos treatment also modulated the expression of α-SMA and apoptosis in the cornea. Additionally, the gene expression of inflammatory cytokines (IL-1β and TNF-α) were downregulated. Conclusions: These findings suggest that MSC-exosome therapy offers a novel, cell-free regenerative approach for managing severe DED, modulating inflammatory response. Full article

Mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) have shown great promise in promoting tissue repair, including skin wound healing, but challenges like rapid degradation and short retention have limited their clinical application. Hydrogels have emerged as effective carriers for sustained EV release. Three-dimensional printing enables the development of personalized skin substitutes tailored to the wound size and shape. This study aimed to develop 3D bioprinted gelatin–genipin hydrogels incorporating human umbilical cord MSC-sEVs (hUCMSC-sEVs) for future skin wound healing applications. Gelatin hydrogels (8% and 10% w/v) were crosslinked with 0.3% genipin (GECL) to improve stability. The hydrogels were evaluated for their suitability for extrusion-based 3D bioprinting and physicochemical properties, such as the swelling ratio, hydrophilicity, enzymatic degradation, and water vapor transmission rate (WVTR). Chemical characterization was performed using EDX, XRD, and FTIR. The hUCMSC-sEVs were isolated via centrifugation and tangential flow filtration (TFF) and characterized. The crosslinked hydrogels were successfully 3D bioprinted and demonstrated superior properties, including high hydrophilicity, a swelling ratio of ~500%, slower degradation, and optimal WVTR. hUCMSC-sEVs, ranging from 50 to 200 nm, were positive for surface and cytosolic markers. Adding 75 μg/mL of hUCMSC-EVs into 10% GECL hydrogels significantly improved the biocompatibility. These hydrogels offer ideal properties for 3D bioprinting and wound healing, demonstrating their potential as biomaterial scaffolds for skin tissue regeneration applications. Full article

Osteoarthritis (OA) is a chronic degenerative joint disease. Our previous study demonstrated that extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stem cells (HUCMSCs), which play a crucial role in regenerative medicine, have therapeutic effects on OA. Additionally, platelet-rich plasma (PRP) has been widely used in musculoskeletal diseases as it promotes wound healing, angiogenesis, and tissue remodeling; however, its efficacy as a stand-alone therapy remains controversial. Therefore, we investigated the therapeutic effects of combining stem cell-derived EVs with PRP in an OA model. HUCMSC-derived EVs treated with PRP were used as the experimental group, whereas HUCMSC-derived EVs cultured with serum-free (SF) or exosome-depleted fetal bovine serum (exo(-)FBS) and PRP served as controls. PRP-treated HUCMSCs maintained their surface antigen characteristics and potential to differentiate into adipocytes, osteoblasts, and chondrocytes. In the OA model, mice treated with HUCMSCs + 5% PRP-derived EVs showed significantly improved motor function compared to controls and were comparable to those treated with HUCMSCs +SF and +exo(-)FBS-derived EVs. Additionally, increased type II collagen and aggrecan and decreased IL-1β expression were observed in cartilage transplanted with various EVs. In conclusion, PRP enhances HUCMSC differentiation, whereas treatment with EVs improves OA outcomes, providing a promising strategy for future clinical applications. Full article

Background/Objectives: This study aimed to explore the therapeutic potential of umbilical mesenchymal stem cell-derived apoptotic vesicles (UMSC-apoVs) in a 5-Fluorouracil (5-FU)-induced impairment in skin wound healing. Methods: UMSC-apoVs were isolated from UMSCs using differential centrifugation after the induction of apoptosis. A murine model was established by administering 5-FU via intravenous tail injection, followed by full-thickness skin wound creation. Mice received local injections of UMSC-apoVs at the lesion site. Wound healing was evaluated based on wound closure rates, histological analysis, and in vivo/in vitro functional assays. Rotenone (Rot)-pretreated UMSC-apoVs were used to explore the role of mitochondrial transfer between skin mesenchymal stem cells (SMSCs) and UMSC-apoVs in wound healing. Results: UMSC-apoVs significantly accelerated wound healing in 5-FU-treated mice, as demonstrated by enhanced wound closure rates and histological findings of reduced inflammatory infiltration and increased collagen deposition. UMSC-apoVs transferred mitochondria to SMSCs, enhancing viability, proliferation, and migration while reducing reactive oxygen species (ROS) production in SMSCs. Rot pretreatment inhibited the therapeutic effects of UMSC-apoVs on wound healing by inducing mitochondrial dysfunction in UMSC-apoVs. Conclusions: Our findings indicate that UMSC-apoVs improve 5-FU-induced impaired skin wound healing by facilitating mitochondrial transfer, suggesting a novel therapeutic strategy for alleviating chemotherapy-induced impairment in wound healing. Full article

Background: Ischemic heart disease remains the leading cause of death worldwide, with coronary microvascular dysfunction (CMD) as a key complication after ST-elevation myocardial infarction (STEMI). Endothelial dysfunction contributes to CMD, impairing vascular tone and increasing inflammation. While angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) aid vascular health, their efficacy may improve with therapeutic ultrasound, which enhances drug delivery and endothelial response. This study explores the combined effects of ultrasound and pharmacological treatment on the ACE axis and inflammation in endothelial and renal cells. Methods: Human umbilical vein endothelial cells (HUVECs) and human renal proximal tubular epithelial cell line RPTEC/TERT1 were treated with captopril, losartan, and dexamethasone, alone or combined with low-frequency ultrasound (LFU). Cell viability and wound-healing assays assessed cellular function, while nitric oxide (NO) and reactive oxygen species (ROS) assays were used to evaluate redox signaling. Gene expression related to the ACE axis, inflammation, and vascular and renal cell function was analyzed via qPCR. Results: Captopril and losartan combined with LFU improved endothelial cell viability, wound healing, and NO production at various concentrations, whereas only losartan with LFU enhanced cell viability and wound healing in renal cells. Dexamethasone with LFU increased ROS levels and had variable effects on RPTEC/TERT1 cell survival. Gene expression analysis showed that LFU alone reduced pro-inflammatory markers VCAM-1, ICAM-1, and PTGS2 in captopril-treated HUVECs and similarly affected CYP4F2 in losartan-treated HUVECs. LFU also decreased PTGS2 expression at higher dexamethasone concentrations. In RPTEC/TERT1 cells, LFU alone did not impact SGLT2 or GGT1 expression, but captopril with LFU downregulated GGT1, and dexamethasone with LFU upregulated SGLT2 at higher concentrations. Conclusions: This study demonstrates that LFU enhances the effects of RAS inhibitors by promoting NO synthesis and reducing oxidative stress, while its combination with dexamethasone may have variable, potentially cytotoxic effects on renal cells. Gene expression patterns suggest LFU’s anti-inflammatory potential and its role in modulating drug efficacy. Full article

Diabetic wounds are therapeutically challenging because of the complex and adverse microenvironment that impedes healing. Unlike conventional wound dressings, hydrogels provide antibacterial, anti-inflammatory, and repair-promoting functions. In this study, we developed a light-responsive and injectable chitosan methacryloyl (CSMA) hydrogel, incorporating soy isoflavones (SIs) and gold nanoparticles (AuNPs). Transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and proton nuclear magnetic resonance (1H NMR) spectroscopy analyses confirmed the successful synthesis of the CSMA/SI/AuNP hydrogels. In vitro experiments demonstrated that this hydrogel exhibited exceptional biocompatibility and enhanced the migration of human umbilical vein endothelial cells (p < 0.05), thereby underscoring its potential for promoting angiogenesis. In vivo studies have indicated that hydrogels significantly enhance the rate of wound healing (p < 0.001). Moreover, they facilitate angiogenesis (p < 0.01) and diminish the inflammatory response at the wound site (p < 0.05). Additionally, hydrogels promote collagen deposition and the regeneration of skin appendages. These findings substantiate the hydrogel’s therapeutic potential for diabetic wound care, highlighting its promise for regenerative medicine. CSMA/SI/AuNP represents a significant advancement in diabetic wound treatment, addressing key challenges in wound healing by offering a multifaceted therapeutic approach with broad clinical implications for enhancing patient outcomes in chronic wound management. Full article

Various types of wounds represent a persistent healthcare burden that demands innovative and effective therapeutic solutions. Innovative approaches have emerged that focus on skin regeneration with minimal side effects. One such method is cell-free therapy that utilizes the secretome of human mesenchymal stem cells (hMSCs) as a promising alternative to traditional cell-based therapies, leveraging a complex mixture of bioactive molecules, including growth factors, cytokines, and extracellular vesicles, to accelerate tissue regeneration. This systematic review synthesizes the findings of 35 studies evaluating the impact of hMSC-derived secretomes on wound healing, with a focus on their regenerative, immunomodulatory, and angiogenic effects. The influence of MSC sources (adipose tissue, bone marrow, umbilical cord) and culture conditions on secretome composition and efficacy in the cutaneous wound healing process is examined, highlighting their therapeutic potential in regenerative medicine. This review also explores emerging preclinical and clinical applications, highlighting promising results, such as enhanced fibroblast proliferation, reduced inflammation, and improved extracellular matrix remodeling. In addition, advances in secretome-based biomaterials, including hydrogels and scaffolds, which optimize therapeutic delivery and efficacy are discussed. Despite the growing body of evidence supporting the safety and efficacy of secretomes, challenges remain regarding standardization, large-scale production, and clinical validation. This review highlights the potential of MSC-derived secretomes as a next-generation cell-free approach for wound healing and regenerative medicine. Full article

PDRN, polydeoxyribonucleotide, which is used as a tissue-regeneration material, is present in human cells under physiological conditions and stimulates regeneration and metabolic activity. PDRN can be used as a biomaterial for several types of regeneration, including wound healing, to promote cell growth and growth-factor production. The aims of this study were to determine the effect of PDRN derived from human placenta-derived mesenchymal stem cells (hPD-MSCs) on cellular regeneration through A2A receptor signaling and to investigate its therapeutic effects in a mouse model of wound healing. Human PDRN (UNIPlax) was extracted from hPD-MSCs fragmented via a sonication system and evaluated for its effect on the migration of HaCaT cells in an in vitro system and in a wound-healing mouse model in vivo. Compared with the sham treatment, UNIPlax treatment significantly increased the migration of injured HaCaT cells (p < 0.05). Additionally, the tube formation of human umbilical vein endothelial cells (HUVECs) was greater than that of the sham group (p < 0.05), and the effects of this treatment were mediated through the A2A receptor. Furthermore, UNIPlax treatment led to a decrease in wound size; in addition, the area of granulation and the rate of collagen formation at the wound site were significantly greater than those in the sham group in the wound-healing mouse model (p < 0.001). We also confirmed that UNIPlax promoted tissue regeneration and the expression of VEGF through the A2A receptor. Taken together, these findings indicate that UNIPlax has potential for regeneration of damaged tissues, including during wound healing. Full article

This case report outlines the intricate clinical management of a 5-month-old infant with recurrent bacterial infections and a non-healing umbilical ulcer following the surgical excision of a urachal remnant. The infant’s medical history was significant for delayed umbilical cord detachment and multiple surgical site infections. The initial surgical approach included the excision of the residual urachus, wound debridement, and abdominal wall reinforcement using a collagen matrix combined with local flap closure. Despite an apparently uneventful postoperative course, the wound experienced dehiscence and failed to heal. As part of the diagnostic workup, genetic testing was conducted, revealing an autosomal dominant mutation in the RAC2 gene, which impairs neutrophil function. Given the urgent need for wound closure prior to hematopoietic stem cell transplantation (HSCT), further debridement and sessions of negative pressure therapy were performed, alongside attempted repair with acellular dermal regeneration matrices, which ultimately proved to be ineffective. Ultimately, HSCT was undertaken despite the infectious associated risks, resulting in spontaneous wound healing without requiring further surgical interventions. This case highlights the challenges of coordinating medical, surgical, and hematological treatments in such complex cases, necessitating effective communication and collaboration among multidisciplinary teams to optimize patient outcomes. Full article