Search Results (122)

Adipose tissue micrografts (ATM) and dermis micrografts (DMG) have emerged as promising autologous therapies in regenerative wound care, leveraging mechanically disaggregated cell–matrix constructs to modulate the wound microenvironment and promote tissue repair. This scoping review systematically analyzed clinical studies investigating ATMs and DMGs in acute and chronic wounds. Eight studies, comprising randomized controlled trials, observational studies, and case series, were identified, involving diverse wound types such as burns, ulcers, surgical dehiscence, and posttraumatic defects. All interventions utilized mechanical disaggregation (Rigenera^® system) to produce micrografts, which were applied via perilesional injection, scaffold-assisted delivery, or topical administration. Outcomes consistently demonstrated accelerated re-epithelialization, enhanced angiogenesis, improved scar remodeling, and low complication rates. In select studies, micrografts were combined with platelet-rich fibrin or stromal vascular fraction, suggesting potential synergistic effects. While one randomized trial showed superior healing outcomes with DMGs over collagen scaffolds, others yielded mixed results, likely reflecting heterogeneity in methodology and outcome measures. Overall, the available clinical evidence supports the safety, feasibility, and biological activity of micrograft-based therapies. However, larger, standardized, and mechanistically driven studies are required to validate their efficacy and define optimal protocols across wound etiologies. Full article

Background/Objectives: This work aims to clarify whether the subtenon use of the sodium hyaluronate product Healaflow in filtrating surgery with PreserFlo MicroShunt positively influences the early postoperative course in terms of control of intraocular pressure, hypotony, and needling rate. Methods: A retrospective, randomized controlled, interventional, single-center trial was performed at the Ludwig Maximilians-University Munich from January 2024 to July 2024. Only patients with primary open angle glaucoma (POAG) were included. In all patients, a complete ophthalmological examination including best corrected visual acuity (BCVA), automated refraction, and Goldman tonometry was performed at 2 days, 1–4 and 5–8 weeks, and 3–4 and 5–6 months after surgery. Healaflow was injected underneath the tenon during filtrating surgery with PreserFlo MicroShunt in addition to mitomycin C (MMC). The Healaflow group was compared to a control group with POAG patients in which Healaflow was not used during surgery with PreserFlo MicroShunt and MMC. Results: A total of 45 eyes of 45 patients were included, with 20 eyes in the Healaflow group and 25 eyes in the control group. In both groups, a significant reduction in IOP and medication could be observed: complete surgical success (IOP ≥ 6 mm Hg and ≤17 mm Hg, without surgical complications or complete loss of vision) was reached in 88% of patients in the Healaflow group at the last follow-up. In 95% of patients in the control group, complete success could be observed. The success rates did not significantly differ between the two groups (p = 0.568). Hypotony rates were 35% in the Healaflow and 12% in the control group after two days (p = 0.083); the rates equalized after 1–4 weeks (p = 1). Needling rates were comparable between both groups (25% versus 20%, p = 0.731). Conclusions: PreserFlo MicroShunt implantation with MMC was equally effective in terms of reduction in IOP and medication in both scenarios with additional or without the use of Healaflow. Postoperative hypotony and needling rates did not significantly differ between the two groups. The additional effects of Healaflow on anti-scarring and maintaining space are likely too minimal to cause significant differences in IOP or medication when already treated with MMC. Full article

Background: Autologous fat grafting is increasingly used in daily clinical practice across various surgical fields, including the treatment of chronic wounds, scars, burns, and non-healing perianal fistulas. Recently, some studies have shown that non-enteric cutaneous fistulas can also benefit from adipose tissue injections, but the efficacy remains unclear. This study aims to systematically review the literature on fat grafting in the context of non-enteric cutaneous fistulas and to assess treatment outcomes. Methods: A comprehensive search of the PubMed/Medline database was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines up to January 2024 without restrictions on the time period or the language of publication. Results: Seven studies meeting the inclusion criteria were analyzed, encompassing 13 patients with non-healing cutaneous fistulas treated with injections of autologous fat. The mean age of the patients was 58 ± 3 years, of which 85% had comorbidities. Fat grafting resulted in complete healing in 92% of the cases, with a mean fistula persistence of 158 days before treatment. Treatment protocols varied among patients, including preparation of the fistulous tract, fat processing techniques, and suturing of the fistulous orifice. Conclusions: The results highlight the potential of autologous fat grafting in promoting tissue regeneration and healing of non-enteric cutaneous fistulas. Standardized protocols are essential to confirm and optimize treatment efficacy and, eventually, improve patient outcomes. Further research with a larger sample size and standardization is needed to confirm fat graft efficacy. Full article

Intracerebral hemorrhage (ICH), a severe stroke subtype common in the elderly, often results in high morbidity and mortality, with limited treatment options for long-term recovery. While glial scar formation is increasingly recognized as key to central nervous system (CNS) repair, its role and characteristics in the aging brain post-ICH remain unclear. This study investigated glial scar formation after ICH (100 μL autologous blood injected into the right basal ganglia model) in aged Fischer 344 rats and assessed the effects of deferoxamine (DFX) treatment. Histological and immunohistochemical analyses were conducted on days 7, 28, and 60 post-ICH using cell-specific and iron-related markers, with DFX administered at 100 mg/kg daily for 14 days in separate groups. Over time, the lesion core showed increased hemosiderin accumulation and astrogliosis. By day 60, the area of astrogliosis corresponded to an area with persistent neuronal loss (DARPP-32-negative). Glial composition shifted from microglia dominance on day 28 to astrocyte predominance by day 60. DFX treatment reduced iron deposition, astrogliosis, and DARPP-32-negative regions while enhancing oligodendrocyte presence. Iron-related markers (HO-1, ferritin, Perls’ staining) and PDGFRβ-positive fibrotic cells were concentrated in the scar core. These findings provide novel insights into scar formation after ICH in aged rats and suggest DFX as a potential therapy to improve outcomes in elderly stroke patients. Full article

Background and Clinical Significance: Ocular cicatricial pemphigoid (OCP) is a rare autoimmune disease affecting the conjunctiva and oral mucosa. Chronic inflammation causes conjunctival scarring, leading to symblepharon, trichiasis, corneal damage, and possible blindness. Diagnosis is clinical, supported by biopsy and immunofluorescence. Treatment includes systemic corticosteroids, immunosuppressants, and biologics in refractory cases. Case Presentation: A 64-year-old male presented with ocular irritation, trichiasis, and counting fingers (CF) visual acuity in the left eye. Slit-lamp examination revealed conjunctival inflammation, corneal epithelial defect, and symblepharon in the left eye. Biopsy confirmed ocular cicatricial pemphigoid (OCP). He was treated with topical steroids, cyclosporine, subconjunctival injections, and systemic corticosteroids, followed by surgery, which improved BCVA to 0.10 logMAR. Two years later, disease progression resulted in severe inflammation and visual decline in both eyes. Systemic azathioprine and corticosteroids achieved partial control. Due to insufficient response, rituximab therapy was initiated, leading to significant reduction in inflammation and stabilization of disease. Right eye BCVA improved to 0.16 logMAR; the left remained at CF. The patient continues to receive rituximab during exacerbations and is under regular follow-up. Conclusions: Early diagnosis and timely systemic treatment are essential in preventing vision loss in OCP. In refractory cases, biologic agents like rituximab may offer effective disease control. Full article

Current treatment strategies for partial tendon tears often lack the capacity to promote true tissue regeneration and improve long-term clinical outcomes. This study tested the hypothesis that treatment of a partial defect in the rabbit common calcaneus tendon (CCT) with uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) enables regenerative healing without scar formation. A full-thickness, 3 mm defect was produced in the midsubstance of the right gastrocnemius tendon, a component of the CCT, in adult female New Zealand white rabbits. Animals received either an injection of 28.3 × 10⁶ UA-ADRCs in 0.5 mL Ringer’s lactated solution (RLS) or saline, or RLS or saline alone as sham treatment. Tendons were analyzed 4 or 12 weeks post-treatment using histology, immunohistochemistry and non-destructive biomechanical testing. UA-ADRC-treated tendons showed newly formed connective tissue consistent with tendon regeneration, whereas sham-treated tendons developed scar tissue. Biomechanical testing showed significantly higher percent relaxation in UA-ADRC-treated tendons compared to sham controls (p < 0.05), indicating greater viscoelasticity characteristic of healthy or well-integrated tissue. Together, these findings suggest that UA-ADRC therapy may provide a regenerative, structure-modifying treatment for partial tendon tears. Full article

Biomimetic peptides represent a growing class of active ingredients in modern cosmeceuticals, designed to mimic the function of the naturally occurring peptides involved in skin homeostasis, repair, and regeneration. Among them, acetyl hexapeptide-8 (AH-8), often referred to as a “botox-like” peptide, has received considerable attention for its potential to dynamically reduce wrinkles through the modulation of neuromuscular activity. AH-8 is widely used in topical formulations intended for anti-aging effects, scar treatment, and skin rejuvenation. This review provides a comprehensive overview of the structure and proposed mechanisms of action of AH-8, with particular focus on its efficacy and skin penetration properties. Due to its hydrophilic nature and relatively large molecular size, AH-8 faces limited permeability through the lipophilic stratum corneum, making effective dermal delivery challenging. Formulation strategies such as oil-in-water (O/W) and multiple water-in-oil-in-water (W/O/W) emulsions have been explored to enhance its delivery, but the ability of AH-8 to reach neuromuscular junctions remains uncertain. Preclinical and clinical studies indicate that AH-8 may reduce wrinkle depth, improve skin elasticity, and enhance hydration. However, the precise biological mechanisms underlying these effects—particularly the peptide’s ability to inhibit muscle contraction when applied topically—remain incompletely understood. In some studies, AH-8 has also shown beneficial effects in scar remodeling and sebum regulation. Despite promising cosmetic outcomes, AH-8’s low skin penetration limits its bioavailability and therapeutic potential. This review emphasizes the need for further research on formulation science and delivery systems, which are essential for optimizing the effectiveness of peptide-based cosmeceuticals and validating their use as non-invasive alternatives to injectable treatments. Full article

Tendon ruptures have recently reached incidences of 18–35 cases/100,000 and often lead to adhesion formation during healing. Furthermore, scar formation may result in inferior biomechanics and often leads to re-ruptures. To address these problems, we cultivated rabbit adipose-derived stem cells in a co-culture with rabbit Achilles tenocytes and harvested their secretome. Following a cell-free approach, we incorporated such secretome into an electrospun tube via emulsion electrospinning. These novel implants were characterized by SEM, the WCA, and FTIR. Then, they were implanted in the rabbit Achilles tendon full transection model with an additional injection of secretome, and the adhesion extent as well as the biomechanics of extracted tendons were assessed three weeks postoperatively. The fiber thickness was around 3–5 μm, the pore size 11–13 μm, and the tube wall thickness approximately 265 μm. The WCA indicated slightly hydrophilic surfaces in the secretome-containing layer, with values of 80–90°. In vivo experiments revealed a significant reduction in adhesion formation (−22%) when secretome-treated tendons were compared to DegraPol^® (DP) tube-treated tendons (no secretome). Furthermore, the cross-sectional area was significantly smaller in secretome-treated tendons compared to DP tube-treated ones (−32%). The peak load and stiffness of secretome-treated tendons were not significantly different from native tendons, while tendons treated with pure DP tubes exhibited significantly lower values. We concluded that secretome treatment supports tendon healing, with anti-adhesion effects and improved biomechanics at 3 weeks, making this approach interesting for clinical application. Full article

This study assessed the impact of implanting mononuclear stem cells and Wharton’s Jelly (WJ), either separately or together, on left ventricular dysfunction following myocardial infarction in Wistar rats. Functional and histopathological parameters were analyzed, and a rat model of left anterior descending coronary artery ligation was used. Treatments included an intramyocardial injection of 0.9% sodium chloride (control, n = 14), decellularized WJ (n = 12), bone marrow-derived mononuclear cells (BMMC) (n = 12), and bone marrow-derived mononuclear cells (BMMC) combined with WJ (n = 15). Echocardiography assessed the left ventricular function and ejection fraction over four weeks. Histological and immunohistochemical analyses with anti-factor VIII evaluated angiogenesis and collagen types I and III. The results showed no statistically significant effect on ventricular remodeling 30 days post-acute myocardial infarction (AMI). Moreover, the infarct area was significantly smaller in the BMMC + WJ group compared to the control group, suggesting a potential benefit in reducing myocardial scarring. BMMC + WJ therapy demonstrated potential for functional improvement and infarct size reduction 30 days post-infarction. Further studies are needed to confirm its therapeutic benefits. Full article

Although a myocardial infarction occurs roughly every minute in the U.S. alone, medical research has yet to unlock the key to fully enabling post-hypoxic myocardial regeneration. Thymosin beta-4 (TB4), a short, secreted peptide, was shown to possess a beneficial impact regarding myocardial cell survival, coronary re-growth and progenitor cell activation following myocardial infarction in adult mammals. It equally reduces scarring, however, the precise mechanisms through which the peptide assists this phenomenon have not been properly elucidated. Accordingly, the primary aim of our study was to identify novel molecular contributors responsible for the positive impact of TB4 during the remodeling processes of the infarcted heart. We performed miRNA profiling on adult mice hearts following permanent coronary ligation with or without systemic TB4 injection and searched for targets and novel mechanisms through which TB4 may mitigate pathological scarring in the heart. Our results revealed a significant increase in miR139-5p expression and identified ROCK1 as a potential target protein aligned. Real-time PCR, Western blot and immunostaining on adult mouse hearts and human cardiac cells revealed the peptide indirectly or directly modulates ROCK1 protein levels both in vivo and in vitro. We equally discovered TB4 may reverse or inhibit fibroblast/myofibroblast transformation and the potential downstream mechanisms by which TB4 alters cellular responses through ROCK1 are cell type specific. Given the beneficial effects of ROCK1 inhibition in various cardiac pathologies, we propose a potential utilization for TB4 as a ROCK1 inhibitor in the future. Full article

Background/Objectives: Polysaccharides are complex molecules with a wide range of biological activities that can be used in various biomedical applications. In this work, the antiulcer effect and influence on the level of pro- and anti-inflammatory cytokines of Solanum tuberosum L. polysaccharide (STP) were studied. Methods: The antiulcer effect of STP was studied in the Okabe chronic peptic ulcer model by evaluating the influence of STP on the ulcer index in Wistar rats, comparing it to omeprazole and ranitidine. Dose-effect analysis was also carried out. The level of pro- and anti-inflammatory cytokines was studied using ELISA kits. Results: After treatment in the polysaccharide groups, ulcer healing is observed in 60–80% of cases, in the omeprazole group in 50%, and in the ranitidine group in 25%. STP intravenous injections lead to the formation of a more differentiated mucous membrane; no coarse scar tissue is formed, which is typical for control and comparison drugs. Glycan causes a significant acceleration of the healing of experimental peptic ulcers in rats. STP appears to modulate pro- and anti-inflammatory cytokines. On the fourth and tenth days, a significant decrease in the levels of pro-inflammatory cytokines IL-1b and IFN-γ was noted in the polysaccharide group compared to the control group, while the level of anti-inflammatory cytokine IL-4 significantly increased. Conclusions: Intravenous administration of STP leads to the restoration of functionality and effective tissue regeneration. The antiulcer activity of STP is based on the regulation of the pro- and anti-inflammatory balance. Full article

Myocardial infarction (MI) is a cardiovascular disease (CVD) with high morbidity and mortality worldwide, which is a serious threat to human life and health. Inflammatory and immune responses are initiated immediately after MI, and unbalanced inflammation post-MI can lead to cardiac dysfunction, scarring, and ventricular remodeling, emphasizing the critical need for an effective inflammation-regulating treatment. With the development of novel therapies, the drug delivery system specific to inflammatory cells offers significant potential. In this review, we introduce immune cells and fibroblasts involved in the development of MI and summarize the newly developed delivery systems related to the use of injectable hydrogels, cardiac patches, nanoparticles, and extracellular vesicles (EVs). Finally, we highlight the recent trends in the use of inflammatory cell-targeting drug delivery systems involving different strategies that facilitate the effective treatment of MI. Full article

Lymphadenectomy for vulvar carcinoma is characterized by many complications. Studies have demonstrated the diagnostic accuracy of sentinel lymph node biopsy (SLNB) as a valid alternative to lymphadenectomy in the early stages of vulvar squamous cell carcinoma (VSCC). Objective: To evaluate the feasibility, safety, and accuracy, as well as the oncological outcomes of SLNB following scar injection; in addition, to assess the role of a repeat sentinel node procedure in patients with local vulvar recurrence after primary treatment. Materials and Methods: A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science, Pub Med, and Cochrane Library) from 2010 to August 2024. Only scientific publications in English were included. Risk of bias assessment was performed. Results: Five articles were included in the study: four retrospective and one prospective observational studies. All patients’ characteristics, including type of surgery, postoperative morbidities, adjuvant therapy, and recurrence, as well as SLN detection and oncological outcomes, have been reported. Four studies compared the scar-injection group (cases) with the tumor-injection group (controls); only one study described the SLNB after vulvar recurrence (second procedure), comparing it with SLNB during primary vulvar surgery (first procedure). Conclusions: SLNB is a feasible and safe option in patients who have had previous excision of the vulvar tumor and in patients with a recurrence of VSCC who are not able or willing to undergo lymphadenectomy. Moreover, it accurately reflects the nodal status in these patients. Full article

Introduction: After myocardial infarction (MI), the heart undergoes necrosis, inflammation, scar formation, and remodeling. While restoring blood flow is crucial, it can cause ischemia-reperfusion (IR) injury, driven by reactive oxygen species (ROSs), which exacerbate cell death and tissue damage. This study introduces a mathematical model capturing key post-MI dynamics, including inflammatory responses, IR injury, cardiac remodeling, and stem cell therapy. The model uses nonlinear ordinary differential equations to simulate these processes under varying conditions, offering a predictive tool to understand MI pathophysiology better and optimize treatments. Methods: After myocardial infarction (MI), left ventricular remodeling progresses through three distinct yet interconnected phases. The first phase captures the immediate dynamics following MI, prior to any medical intervention. This stage is mathematically modeled using the system of ordinary differential equations: The second and third stages of the remodeling process account for the system dynamics of medical treatments, including oxygen restoration and subsequent stem cell injection at the injury site. Results: We simulate heart tissue and immune cell dynamics over 30 days for mild and severe MI using the novel mathematical model under medical treatment. The treatment involves no intervention until 2 h post-MI, followed by oxygen restoration and stem cell injection at day 7, which is shown experimentallyand numerically to be optimal. The simulation incorporates a baseline ROS threshold ($R_c$) where subcritical ROS levels do not cause cell damage. Conclusion: This study presents a novel mathematical model that extends a previously published framework by incorporating three clinically relevant parameters: oxygen restoration rate ($\omega$), patient risk factors ($\gamma$), and neutrophil recruitment profile ($\delta$). The model accounts for post-MI inflammatory dynamics, ROS-mediated ischemia-reperfusion (IR) injury, cardiac remodeling, and stem cell therapy. The model’s sensitivity highlights critical clinical insights: while oxygen restoration is vital, excessive rates may exacerbate ROS-driven IR injury. Additionally, heightened patient risk factors (e.g., smoking, obesity) and immunodeficiency significantly impact tissue damage and recovery. This predictive tool offers valuable insights into MI pathology and aids in optimizing treatment strategies to mitigate IR injury and improve post-MI outcomes. Full article

Polydeoxyribonucleotides (PDRNs) and polynucleotides (PNs) are similar DNA-derived biopolymers that have garnered significant scientific attention since the 1990s for their potential applications in wound healing and skin rejuvenation. These biopolymers exhibit a broad molecular weight (MW) range, typically spanning from 50 to 1500 kDa. However, recent studies have expanded this range to encompass fragments as small as 1 kDa and as large as 10,000 kDa. Clinically, PDRN/PN formulations, commercially available in various galenic forms (gels, creams, serums, masks, and injectables), have demonstrated promising effects in significantly promoting skin regeneration, reducing inflammation, improving skin texture, preventing scar formation, and mitigating wrinkles. Importantly, despite their widespread use in cosmetology and aesthetic dermatology, the interchangeable use of the terms “PDRN” and “PN” in the scientific literature (to describe polymers of varying lengths) has led to considerable confusion within the medical and scientific communities. To specifically address this PDRN/PN ambiguity, this narrative review proposes a standardized structure-based nomenclature for these DNA-derived polymers, the “Marques Polynucleotide Cutoff”, set at 1500 kDa. Thus, we propose that the term “PDRN” should be exclusively reserved for small- and medium-chain polymers (MW < 1500 kDa), while the term “PN” should specifically be used to denote longer-chain polymers (MW ≥ 1500 kDa). In a broader perspective, this classification is based on the distinct physicochemical properties and therapeutic effects of these DNA fragments of various MWs, which are comprehensively discussed in the present review. Full article