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14 pages, 3029 KiB  
Article
In Vitro Bioactivity and Cytotoxicity Assessment of Two Root Canal Sealers
by Yicheng Ye, Sepanta Hosseinpour, Juan Wen and Ove A. Peters
Materials 2025, 18(15), 3717; https://doi.org/10.3390/ma18153717 (registering DOI) - 7 Aug 2025
Abstract
The development of bioactive materials in endodontics has advanced tissue regeneration by enhancing the biological responses of periradicular tissues. Recently, calcium silicate-based sealers have gained attention for their superior biological properties, including biocompatibility, osteoconductivity, and cementogenic potential. This study aimed to evaluate the [...] Read more.
The development of bioactive materials in endodontics has advanced tissue regeneration by enhancing the biological responses of periradicular tissues. Recently, calcium silicate-based sealers have gained attention for their superior biological properties, including biocompatibility, osteoconductivity, and cementogenic potential. This study aimed to evaluate the cytotoxicity, biocompatibility, and bioactivity of EndoSequence BC Sealer (ES BC) and AH Plus Bioceramic Sealer (AHP BC) using human periodontal ligament stromal cells (hPDLSCs). Biocompatibility was assessed using MTT, Live/Dead, and wound healing assays. ES BC and AHP BC demonstrated significantly higher cell viability and proliferation compared to AH Plus used as a control. Gene expression analysis via real-time quantitative PCR demonstrated that ES BC, especially in set form, significantly upregulated osteogenic markers—alkaline phosphatase (2.49 ± 0.10, p < 0.01), runt-related transcription factor 2 (2.33 ± 0.13), and collagen type I alpha 1 chain (2.85 ± 0.40, p < 0.001)—more than cementogenic markers (cementum protein 1, cementum attachment protein, and cementum protein 23). This differential response may reflect the fibroblast-dominant nature of hPDLSCs, which contain limited cementoblast-like cells. This study supports the superior biocompatibility and regenerative capacity of ES BC and AHP BC compared to AH Plus. While in vitro models provide foundational insights, advanced ex vivo approaches are crucial for translating findings to clinical practice. Full article
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11 pages, 1581 KiB  
Article
Combining Topical Oxygen and Negative-Pressure Wound Therapy: New Insights from a Pilot Study on Chronic Wound Treatment
by Bartosz Molasy, Mateusz Frydrych, Rafał Kuchciński and Stanisław Głuszek
J. Clin. Med. 2025, 14(15), 5564; https://doi.org/10.3390/jcm14155564 - 7 Aug 2025
Abstract
Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed [...] Read more.
Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed to assess the clinical effectiveness of combined TOT and NPWT in chronic wound treatment and to explore the prognostic value of selected laboratory and thermographic markers. Methods: Eighteen patients with chronic wounds due to type 2 diabetes mellitus or chronic venous insufficiency were treated with either TOT alone (control group) or TOT combined with NPWT (intervention group). Wound characteristics, thermographic data, and laboratory parameters (NLR, MLR, PLR, CRP, and total protein) were collected at baseline and during therapy. The primary endpoints were the total treatment duration and complete wound closure. Statistical analyses were exploratory and used non-parametric tests, correlation analyses, and simple linear regression. Results: Ulcer duration was significantly associated with the wound surface area. Lower serum total protein levels correlated negatively with ulcer duration, wound size, and granulation tissue area. A significant reduction in treatment duration was observed in the intervention group compared to the controls. One strong correlation was found between MLR and peripheral wound temperature on day 7 in the control group. No significant group differences were observed in wound size or thermographic measures after one week of treatment. Conclusions: Combining TOT and NPWT may reduce treatment duration in chronic wound management. Selected laboratory and thermographic markers show promise as prognostic tools. These exploratory findings require confirmation in larger, randomized trials. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Wound Treatment)
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12 pages, 806 KiB  
Proceeding Paper
Enterococcus faecalis Biofilm: A Clinical and Environmental Hazard
by Bindu Sadanandan and Kavyasree Marabanahalli Yogendraiah
Med. Sci. Forum 2025, 35(1), 5; https://doi.org/10.3390/msf2025035005 - 5 Aug 2025
Abstract
This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange [...] Read more.
This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article
(This article belongs to the Proceedings of The 4th International Electronic Conference on Antibiotics)
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8 pages, 1182 KiB  
Case Report
The First Schaalia (Formerly Actinomyces) Canis-Related Osteomyelitis Requiring Surgical Intervention
by Patrick Nugraha, Tzong-Yang Pan, Paul Di Giovine, Nigel Mann and William Murphy
Infect. Dis. Rep. 2025, 17(4), 94; https://doi.org/10.3390/idr17040094 - 4 Aug 2025
Viewed by 78
Abstract
Schaalia canis is a Gram-positive, facultatively anaerobic, rod-shaped bacterium originally isolated from the mucosa and skin of dogs. While it is a part of the normal canine oral flora, it has rarely been implicated in human disease, with only one prior case of [...] Read more.
Schaalia canis is a Gram-positive, facultatively anaerobic, rod-shaped bacterium originally isolated from the mucosa and skin of dogs. While it is a part of the normal canine oral flora, it has rarely been implicated in human disease, with only one prior case of cellulitis reported following a dog bite. Case Presentation: We present the case of a 57-year-old immunocompetent man who developed osteomyelitis of the left index finger following a delayed presentation after a dog bite. Despite initial conservative management with empirical oral antibiotics, the infection progressed, eventually requiring surgical debridement and the terminalisation of the finger at the proximal interphalangeal joint. Cultures from intraoperative bone specimens yielded the growth of Schaalia canis, with no other pathogenic organisms identified on the extended culture. Conclusions: This is the first documented case of Schaalia canis-associated osteomyelitis in a human and the first to necessitate a surgical intervention, expanding the known clinical spectrum of this organism. This case underscores the risks of delayed intervention in polymicrobial animal bite wounds and highlights the emerging role of Schaalia species as opportunistic zoonotic pathogens, particularly in the setting of deep, refractory infections. Full article
(This article belongs to the Section Bacterial Diseases)
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24 pages, 1951 KiB  
Review
Antioxidant Capacity and Therapeutic Applications of Honey: Health Benefits, Antimicrobial Activity and Food Processing Roles
by Ivana Tlak Gajger, Showket Ahmad Dar, Mohamed Morsi M. Ahmed, Magda M. Aly and Josipa Vlainić
Antioxidants 2025, 14(8), 959; https://doi.org/10.3390/antiox14080959 - 4 Aug 2025
Viewed by 127
Abstract
Honey is a natural product of honeybees that has been consumed for centuries due to its nutritional value and potential health benefits. Recent scientific research has focused on its antioxidant capacity, which is linked to a variety of bioactive compounds such as phenolic [...] Read more.
Honey is a natural product of honeybees that has been consumed for centuries due to its nutritional value and potential health benefits. Recent scientific research has focused on its antioxidant capacity, which is linked to a variety of bioactive compounds such as phenolic acids, enzymes (e.g., glucose oxidase, catalase), flavonoids, ascorbic acid, carotenoids, amino acids, and proteins. Together, these components work synergistically to neutralize free radicals, regulate antioxidant enzyme activity, and reduce oxidative stress. This review decisively outlines the antioxidant effects of honey and presents compelling clinical and experimental evidence supporting its critical role in preventing diseases associated with oxidative stress. Honey stands out for its extensive health benefits, which include robust protection against cardiovascular issues, notable anticancer and anti-inflammatory effects, enhanced glycemic control in diabetes, immune modulation, neuroprotection, and effective wound healing. As a recognized functional food and dietary supplement, honey is essential for the prevention and adjunct treatment of chronic diseases. However, it faces challenges due to variations in composition linked to climatic conditions, geographical and floral sources, as well as hive management practices. The limited number of large-scale clinical trials further underscores the need for more research. Future studies must focus on elucidating honey’s antioxidant mechanisms, standardizing its bioactive compounds, and examining its synergistic effects with other natural antioxidants to fully harness its potential. Full article
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19 pages, 349 KiB  
Review
Current Methods for Reliable Identification of Species in the Acinetobacter calcoaceticusAcinetobacter baumannii Complex
by Teodora Vasileva Marinova-Bulgaranova, Hristina Yotova Hitkova and Nikolay Kirilov Balgaranov
Microorganisms 2025, 13(8), 1819; https://doi.org/10.3390/microorganisms13081819 - 4 Aug 2025
Viewed by 184
Abstract
Acinetobacter baumannii is one of the most challenging nosocomial pathogens associated with a variety of hospital infections, such as ventilator-associated pneumonia, wound and urinary tract infections, meningitis, and sepsis, primarily in patients treated in critical care settings. Its classification as a high-priority pathogen [...] Read more.
Acinetobacter baumannii is one of the most challenging nosocomial pathogens associated with a variety of hospital infections, such as ventilator-associated pneumonia, wound and urinary tract infections, meningitis, and sepsis, primarily in patients treated in critical care settings. Its classification as a high-priority pathogen is due to the emergence of multidrug-resistant strains in healthcare environments and its tendency to spread clonally. A. baumannii belongs to the Acinetobacter calcoaceticusAcinetobacter baumannii (Acb) complex, a group of genotypically and phenotypically similar species. Differentiating between the species is important because of their distinct clinical significance. However, conventional phenotypic methods, both manual and automated, often fail to provide accurate species-level identification. This review aims to summarize current phenotypic and genotypic methods for the identification of species within the Acb complex, evaluating their strengths and limitations to offer guidance for their appropriate application in diagnostic settings and epidemiological investigations. Full article
18 pages, 914 KiB  
Article
Microvascular, Biochemical, and Clinical Impact of Hyperbaric Oxygen Therapy in Recalcitrant Diabetic Foot Ulcers
by Daniela Martins-Mendes, Raquel Costa, Ilda Rodrigues, Óscar Camacho, Pedro Barata Coelho, Vítor Paixão-Dias, Carla Luís, Ana Cláudia Pereira, Rúben Fernandes, Jorge Lima and Raquel Soares
Cells 2025, 14(15), 1196; https://doi.org/10.3390/cells14151196 - 4 Aug 2025
Viewed by 181
Abstract
Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study [...] Read more.
Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes—including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality—were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 ± 12 years; diabetes duration 18 ± 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p < 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-α). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies. Full article
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12 pages, 223 KiB  
Article
Improving Pain Management in Critically Ill Surgical Patients: The Impact of Clinical Supervision
by Telma Coelho, Diana Rodrigues and Cristina Barroso Pinto
Surgeries 2025, 6(3), 67; https://doi.org/10.3390/surgeries6030067 - 4 Aug 2025
Viewed by 111
Abstract
Background: Pain is a problem faced by critically ill surgical patients and has a major impact on their outcomes. Pain assessment is therefore essential for effective pain management, with a combination of pharmacological and non-pharmacological treatment. Clinical supervision, supported by models such as [...] Read more.
Background: Pain is a problem faced by critically ill surgical patients and has a major impact on their outcomes. Pain assessment is therefore essential for effective pain management, with a combination of pharmacological and non-pharmacological treatment. Clinical supervision, supported by models such as SafeCare, can improve professional development, safety and the quality of care in intensive care units. Objectives: This study aimed to: (1) assess current pain assessment practices in a polyvalent Intensive Care Unit (ICU) in the Porto district; (2) identify nurses’ training needs regarding the Clinical Supervision-Sensitive Indicator—Pain; and (3) evaluate the impact of clinical supervision sessions on pain assessment practices. Methods: A quantitative, quasi-experimental, cross-sectional study with a pre- and post-intervention design was conducted. Based on the SafeCare model, it included a situational diagnosis, 6 clinical supervision sessions (February 2023), and outcome evaluation via nursing record audits (November 2022 and May 2023) in 31 total critical ill patients. Pain was assessed using standardised tools, in line with institutional protocols. Data was analysed using Software Statistical Package for the Social Sciences v25.0. Results: Pain was highly prevalent in the first 24 h, decreasing during hospitalisation. Generalised acute abdominal pain predominated, with mild to moderate intensity, and was exacerbated by wound care and mobilisation/positioning. Pain management combined pharmacological and non-pharmacological treatment. There was an improvement in all the parameters of the pain indicator post-intervention. Conclusions: Despite routine assessments, gaps remained in reassessing pain post-analgesia and during invasive procedures. Targeted clinical supervision and ongoing training proved effective in improving compliance with protocols and supporting safer, more consistent pain management. Full article
10 pages, 277 KiB  
Systematic Review
Autologous Fat Grafting for the Treatment of Non-Enteric Cutaneous Fistulas: A Systematic Literature Review
by Francesca Bonomi, Ettore Limido, Yves Harder, Ken Galetti and Marco De Monti
Surg. Tech. Dev. 2025, 14(3), 26; https://doi.org/10.3390/std14030026 - 4 Aug 2025
Viewed by 137
Abstract
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, [...] Read more.
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
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20 pages, 11379 KiB  
Article
Silk Fibroin–Alginate Aerogel Beads Produced by Supercritical CO2 Drying: A Dual-Function Conformable and Haemostatic Dressing
by Maria Rosaria Sellitto, Domenico Larobina, Chiara De Soricellis, Chiara Amante, Giovanni Falcone, Paola Russo, Beatriz G. Bernardes, Ana Leite Oliveira and Pasquale Del Gaudio
Gels 2025, 11(8), 603; https://doi.org/10.3390/gels11080603 - 2 Aug 2025
Viewed by 276
Abstract
Infection control and bleeding management in deep wounds remain urgent and unmet clinical challenges that demand innovative, multifunctional, and sustainable solutions. Unlike previously reported sodium alginate and silk fibroin-based gel formulations, the present work introduces a dual-functional system combining antimicrobial and haemostatic activity [...] Read more.
Infection control and bleeding management in deep wounds remain urgent and unmet clinical challenges that demand innovative, multifunctional, and sustainable solutions. Unlike previously reported sodium alginate and silk fibroin-based gel formulations, the present work introduces a dual-functional system combining antimicrobial and haemostatic activity in the form of conformable aerogel beads. This dual-functional formulation is designed to absorb exudate, promote clotting, and provide localized antimicrobial action, all essential for accelerating wound repair in high-risk scenarios within a single biocompatible system. Aerogel beads were obtained by supercritical drying of a silk fibroin–sodium alginate blend, resulting in highly porous, spherical structures measuring 3–4 mm in diameter. The formulations demonstrated efficient ciprofloxacin encapsulation (42.75–49.05%) and sustained drug release for up to 12 h. Fluid absorption reached up to four times their weight in simulated wound fluid and was accompanied by significantly enhanced blood clotting, outperforming a commercial haemostatic dressing. These findings highlight the potential of silk-based aerogel beads as a multifunctional wound healing platform that combines localized antimicrobial delivery, efficient fluid and exudate management, biodegradability, and superior haemostatic performance in a single formulation. This work also shows for the first time how the prilling encapsulation technique with supercritical drying is able to successfully produce silk fibroin and sodium alginate composite aerogel beads. Full article
(This article belongs to the Special Issue Aerogels and Composites Aerogels)
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23 pages, 5771 KiB  
Article
Photobiomodulation of 450 nm Blue Light on Human Keratinocytes, Fibroblasts, and Endothelial Cells: An In Vitro and Transcriptomic Study on Cells Involved in Wound Healing and Angiogenesis
by Jingbo Shao, Sophie Clément, Christoph Reissfelder, Patrick Téoule, Norbert Gretz, Feng Guo, Sabina Hajizada, Stefanie Uhlig, Katharina Mößinger, Carolina de la Torre, Carsten Sticht, Vugar Yagublu and Michael Keese
Biomedicines 2025, 13(8), 1876; https://doi.org/10.3390/biomedicines13081876 - 1 Aug 2025
Viewed by 191
Abstract
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 [...] Read more.
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
(This article belongs to the Section Cell Biology and Pathology)
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10 pages, 1973 KiB  
Communication
Pro-Angiogenic Effects of Canine Platelet-Rich Plasma: In Vitro and In Vivo Evidence
by Seong-Won An and Young-Sam Kwon
Animals 2025, 15(15), 2260; https://doi.org/10.3390/ani15152260 - 1 Aug 2025
Viewed by 149
Abstract
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 [...] Read more.
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
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21 pages, 3146 KiB  
Article
TnP as a Multifaceted Therapeutic Peptide with System-Wide Regulatory Capacity
by Geonildo Rodrigo Disner, Emma Wincent, Carla Lima and Monica Lopes-Ferreira
Pharmaceuticals 2025, 18(8), 1146; https://doi.org/10.3390/ph18081146 - 1 Aug 2025
Viewed by 196
Abstract
Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling [...] Read more.
Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article
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15 pages, 2399 KiB  
Review
Cyclodextrin-Based Supramolecular Hydrogels in Tissue Engineering and Regenerative Medicine
by Jiamin Lin, Yuanyuan Chen and Xuemei Wang
Molecules 2025, 30(15), 3225; https://doi.org/10.3390/molecules30153225 - 31 Jul 2025
Viewed by 324
Abstract
Cyclodextrins (CDs), cyclic oligosaccharides formed by α-1,4-glycosidic-bonded D-glucopyranose units, feature unique hydrophobic cavities and hydrophilic exteriors that enable molecular encapsulation via host–guest interactions. CDs form supramolecular host–guest complexes with diverse molecular entities, establishing their fundamental role in supramolecular chemistry. This review examines fabrication [...] Read more.
Cyclodextrins (CDs), cyclic oligosaccharides formed by α-1,4-glycosidic-bonded D-glucopyranose units, feature unique hydrophobic cavities and hydrophilic exteriors that enable molecular encapsulation via host–guest interactions. CDs form supramolecular host–guest complexes with diverse molecular entities, establishing their fundamental role in supramolecular chemistry. This review examines fabrication strategies for CD-based supramolecular hydrogels and their applications in tissue engineering and regenerative medicine, with focused analysis on wound healing, corneal regeneration, and bone repair. We critically analyze CD–guest molecular interaction mechanisms and innovative therapeutic implementations, highlighting the significant potential of CD hydrogels for tissue regeneration while addressing clinical translation challenges and future directions. Full article
(This article belongs to the Special Issue Cyclodextrin Chemistry and Toxicology III)
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18 pages, 1625 KiB  
Review
The Potential of Functional Hydrogels in Burns Treatment
by Nathalie S. Ringrose, Ricardo W. J. Balk, Susan Gibbs, Paul P. M. van Zuijlen and H. Ibrahim Korkmaz
Gels 2025, 11(8), 595; https://doi.org/10.3390/gels11080595 - 31 Jul 2025
Viewed by 154
Abstract
Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, [...] Read more.
Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, and integration with host tissue. Functional hydrogels are being explored as alternatives due to properties such as high water content, biodegradability, adhesiveness, antimicrobial activity, and support for angiogenesis. Unlike standard templates, hydrogels can adapt to irregular wound shapes as in burn wounds and reach deeper tissue layers, supporting moisture retention, cell migration, and controlled drug delivery. These features may improve the wound environment and support healing in burns of varying severity. This review outlines recent developments in functional hydrogel technologies and compares them to current clinical treatments for burn care. Emphasis is placed on the structural and biological features that influence performance, including material composition, bioactivity, and integration capacity. Through an exploration of key mechanisms of action and clinical applications, this review highlights the benefits and challenges associated with hydrogel technology, providing insights into its future role in burn care. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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