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13 pages, 1677 KiB  
Article
A Single Tertiary-Care Center Case Series Using Vertical Rectus Abdominis Myocutaneous Flap in the Management of Complex Periprosthetic Joint Infection of the Hip
by Omar Salem, Jing Zhang, George Grammatopoulos, Simon Garceau and Hesham Abdelbary
Microorganisms 2025, 13(8), 1962; https://doi.org/10.3390/microorganisms13081962 - 21 Aug 2025
Viewed by 110
Abstract
Prosthetic joint infections (PJIs) pose significant challenges, often requiring multiple surgeries that lead to soft tissue loss, dead space, and fibrosis. Wound breakdown increases the risk of polymicrobial infection and treatment failure. The vertical rectus abdominis myocutaneous (VRAM) flap is a proven method [...] Read more.
Prosthetic joint infections (PJIs) pose significant challenges, often requiring multiple surgeries that lead to soft tissue loss, dead space, and fibrosis. Wound breakdown increases the risk of polymicrobial infection and treatment failure. The vertical rectus abdominis myocutaneous (VRAM) flap is a proven method for complex wound coverage, but its role in managing hip PJI is underexplored. This study evaluates outcomes of VRAM flap reconstruction in polymicrobial hip PJI. We retrospectively reviewed five patients who underwent VRAM flap reconstruction for polymicrobial hip PJI between December 2020 and December 2023. Primary outcomes included flap survival, infection control, and wound healing. Secondary outcomes were implant retention, postoperative complications, and functional status. At a mean follow-up of 28 months, four patients achieved wound healing and remained infection-free, while one had persistent sinus drainage but retained the implant. Flap survival was 100%, with no necrosis or failure. No major complications requiring reoperation occurred. Two patients developed deep collections, managed with ultrasound-guided drainage (Clavien-Dindo IIIa). Minor complications included donor-site dehiscence (three), flap dehiscence (one), edge necrosis (two), and hernias (two), all managed non-surgically (Clavien-Dindo I/II). All patients retained implants and remained ambulatory. VRAM flap reconstruction is a reliable option for managing complex polymicrobial hip PJI. Flap survival was excellent, and most patients achieved infection control. However, persistent infection and the need for suppressive antibiotics highlight the ongoing challenges in these cases. Full article
(This article belongs to the Special Issue Challenges of Biofilm-Associated Bone and Joint Infections)
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10 pages, 509 KiB  
Article
Transcriptional Regulation of CYP2E1: Promoter Methylation in In Vitro Models and Human Liver Disease Samples
by Nina Komaniecka, Mateusz Kurzawski, Sylwia Szeląg-Pieniek, Joanna Łapczuk-Romańska, Mariola Post, Urszula Adamiak-Giera and Marek Droździk
Genes 2025, 16(8), 990; https://doi.org/10.3390/genes16080990 - 21 Aug 2025
Viewed by 125
Abstract
Background/Objectives: DNA methylation is a critical epigenetic mechanism involved in gene expression regulation. This study examines promoter methylation of CYP2E1 in healthy liver, intestinal mucosa, as well as pathological liver samples, alongside in in vitro cell models. Methods: First, in tissue samples from [...] Read more.
Background/Objectives: DNA methylation is a critical epigenetic mechanism involved in gene expression regulation. This study examines promoter methylation of CYP2E1 in healthy liver, intestinal mucosa, as well as pathological liver samples, alongside in in vitro cell models. Methods: First, in tissue samples from the liver, duodenum, jejunum, and colon of healthy organ donors, CYP2E1 promoter methylation was quantified using the EpiTect Methyl II PCR System, while gene expression was determined by quantitative real-time PCR. Then, in vitro experiments were performed using HepG2 and Caco-2 cell lines. Cells were treated with 5-Aza-2′-deoxycytidine to induce demethylation, with subsequent analysis of CYP2E1 mRNA levels. Subsequently, promoter methylation was assessed via pyrosequencing, while gene expression was quantified using quantitative real-time PCR. Results: The analysis revealed statistically significant differences in the methylation patterns of the CYP2E1 promoter between healthy liver and gastrointestinal tissues. In cell lines, treatment with 5-Aza-2′-deoxycytidine resulted in increased CYP2E1 mRNA levels and demonstrated a strong negative correlation between promoter methylation and gene expression. However, in liver disease samples, differential methylation did not consistently translate into decreased CYP2E1 expression. Conclusions: Although in vitro experiments support a regulatory role of promoter methylation in controlling CYP2E1 expression, the clinical data indicate that additional factors may contribute to gene regulation in liver pathology. Full article
(This article belongs to the Section Epigenomics)
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21 pages, 6478 KiB  
Article
Localized Combination Therapy Using Collagen–Hydroxyapatite Bone Grafts for Simultaneous Bone Cancer Inhibition and Tissue Regeneration
by Alina Florentina Vladu, Madalina Georgiana Albu Kaya, Anton Ficai, Denisa Ficai, Raluca Tutuianu, Ludmila Motelica, Vasile Adrian Surdu, Ovidiu-Cristian Oprea, Roxana Doina Truşcă and Irina Titorencu
Polymers 2025, 17(16), 2239; https://doi.org/10.3390/polym17162239 - 18 Aug 2025
Viewed by 415
Abstract
The global burden of cancer continues to grow, with bone cancer—though rare—posing serious challenges in terms of treatment and post-surgical reconstruction. Autologous bone grafting remains the gold standard, yet limitations such as donor site morbidity drive the search for alternative solutions. Tissue engineering, [...] Read more.
The global burden of cancer continues to grow, with bone cancer—though rare—posing serious challenges in terms of treatment and post-surgical reconstruction. Autologous bone grafting remains the gold standard, yet limitations such as donor site morbidity drive the search for alternative solutions. Tissue engineering, combining biomaterials and therapeutic agents, offers promising avenues. This study focuses on the development of multifunctional scaffolds based on collagen and hydroxyapatite obtained by the freeze-drying technique and incorporating both synthetic (doxorubicin) and natural (caffeic acid) compounds for osteosarcoma treatment. These scaffolds aim to combine tumor inhibition with bone regeneration, addressing the dual need for local drug delivery and structural repair in bone cancer therapy. The characterization of these composite materials revealed that a spongious structure with interconnected pores and a homogeneous pore distribution, with pore sizes between 20 and 250 μm suitable for osteoblasts infiltration. The Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis-differential scanning calorimetry (TG-DSC) and X-ray diffraction (XRD) analyses confirmed the formation of hydroxyapatite inside the collagen matrix. LDH and XTT assays confirmed that the antitumoral scaffolds possess great potential for osteosarcoma treatment, showing that after 3 days of culturing, the extracts containing doxorubicin-7A, both alone and in combination with caffeic acid-9A, significantly reduced the viability of cell lines to below 7% and 20%, respectively. Full article
(This article belongs to the Special Issue Smart and Bio-Medical Polymers: 3rd Edition)
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18 pages, 7939 KiB  
Article
Peripheral Nerve Decellularisation Protocol for Allogeneic Transplantation: From Tissue Procurement to Banking
by Marco Govoni, Leonardo Vivarelli, Nicola Fazio, Federico Bolognesi, Viscardo Paolo Fabbri, Alessandra Maso, Elisa Storni, Giulia Querzoli, Deyanira Contartese, Stefania Pagani, Luca Cavazza, Marta Pluchino, Lucia De Franceschi, Gianluca Giavaresi and Dante Dallari
Int. J. Mol. Sci. 2025, 26(16), 7937; https://doi.org/10.3390/ijms26167937 - 17 Aug 2025
Viewed by 229
Abstract
Peripheral nerve injuries affect over one million individuals annually worldwide due to various causes such as trauma, metabolic disorders, and autoimmune diseases. While autologous nerve grafting remains the gold standard for treating large-gap nerve injuries, its limitations, including limited tissue availability, donor site [...] Read more.
Peripheral nerve injuries affect over one million individuals annually worldwide due to various causes such as trauma, metabolic disorders, and autoimmune diseases. While autologous nerve grafting remains the gold standard for treating large-gap nerve injuries, its limitations, including limited tissue availability, donor site morbidity, infection risk, and suboptimal functional recovery, have spurred interest in alternative approaches. Among these, allogeneic nerve grafting has emerged as a promising option, offering structural and functional advantages due to the native architecture of donor nerves. However, immune rejection due to histocompatibility antigens remains a significant challenge. Decellularisation protocols utilising mild detergents have shown the most promise in preserving the extracellular matrix’s structural and regenerative properties while mitigating immunogenicity. The study aimed to adapt and validate a decellularisation protocol for human nerves within our tissue bank, adhering to European and national regulatory guidelines. The protocol, based on the cleanroom-compliant method previously developed by our group, was optimised to reduce tissue handling time and ensure regulatory compliance. Decellularised sural nerves were assessed for extracellular matrix preservation and sterility using European (EU) Pharmacopoeia and European Directorate for the Quality of Medicines & HealthCare (EDQM) guidelines. The results demonstrated the feasibility of producing high-quality acellular nerve allografts (ANAs) that are suitable for peripheral nerve repair, paving the way for cost-effective and widely accessible grafting solutions. Full article
(This article belongs to the Special Issue Advances in Peripheral Nerve Regeneration)
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13 pages, 2845 KiB  
Article
Transplantation of Tissue from Native and Cryopreserved Pekin Duck Ovaries to Mulard Ducks with Study of Hormonal Changes After Grafting
by Kitti Buda, Barbara Vegi, Eva Kissne Varadi, Arpad Drobnyak, Eva Török, Zsuzsa Szabo, Bianka Babarczi, Istvan Lehoczky and Krisztina Liptoi
Animals 2025, 15(16), 2401; https://doi.org/10.3390/ani15162401 - 15 Aug 2025
Viewed by 146
Abstract
Orthotopic transplantation of ovarian tissue at one day of age is a promising solution for preserving female genetic material in avian species; using sterile recipients can ensure that all offspring are donor-derived. This study focuses on the suitability of the Mulard duck as [...] Read more.
Orthotopic transplantation of ovarian tissue at one day of age is a promising solution for preserving female genetic material in avian species; using sterile recipients can ensure that all offspring are donor-derived. This study focuses on the suitability of the Mulard duck as a sterile recipient for Pekin duck donors and provides an investigation of the hormonal background. Firstly, native Pekin ovarian tissue was grafted into Mulard duck recipients, resulting in a 40% adhesion rate and follicular development in 50% of the adhered grafts. Secondly, the transplantation of cryopreserved ovarian tissue resulted in a 66% adhesion rate, with 33% of the adhered grafts showing follicular development. Ovulation occurred in 16% of the recipients with adhered grafts, but the eggs did not move into the oviduct. Estrogen levels were elevated in the recipients with adherence but were lower than in the control Pekin group, while progesterone levels remained unchanged. Consequently, recipients received buserelin acetate, a GnRH analogue, to stimulate follicular and oviductal activity. In this group, graft adhesion occurred in 31% of animals, and primordial follicle development in 25%. The hormonal levels of the recipients with adhered ovaries were elevated, but the GnRH analogue treatment did not affect the ovulation process. We conclude that while the Mulard duck shows potential as a sterile recipient in ovarian transplantation, several questions remain unanswered regarding the adequacy of follicular maturation and ovulation. Full article
(This article belongs to the Section Animal Reproduction)
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10 pages, 518 KiB  
Article
A Novel Study of β1- and β2-Adrenergic Receptors Present on PBMCs, T Cells, Monocytes, and NK Cells by Radioligand Method: Quantitation and Correlations
by Mihail. M. Peklo, Ekaterina V. Smolyakova, Lyudmila N. Lipatova, Natal’ya M. Kashirina, Yurij S. Skoblov, Natal’ya A. Skoblova, Mihail A. Slinkin, Igor’ N. Rybalkin, Pavel N. Rutkevich, Olga K. Chusovitina, Elena V. Yanushevskaya, Kirill A. Zykov and Tat’yana N. Vlasik
Int. J. Mol. Sci. 2025, 26(16), 7894; https://doi.org/10.3390/ijms26167894 - 15 Aug 2025
Viewed by 220
Abstract
β-adrenoreceptor (ADRB) ligands are actively used in the therapy of bronchopulmonary and cardiovascular diseases. When using these drugs, it is important to assess changes in ADRB content in different tissues. In most cases, the direct measurement of ADRB content in lung and heart [...] Read more.
β-adrenoreceptor (ADRB) ligands are actively used in the therapy of bronchopulmonary and cardiovascular diseases. When using these drugs, it is important to assess changes in ADRB content in different tissues. In most cases, the direct measurement of ADRB content in lung and heart cells is not possible. ADRB2 content in peripheral blood lymphocytes (or mononuclear cells) was shown to correlate with that in myocardial cells. It has been suggested that blood lymphocytes can be used to monitor ADRB content in solid organs. However, the estimation of ADRB1 content in myocardium from its content in peripheral lymphocytes is not possible due to the low content of ADRB1 in lymphocytes. In the present study, we performed simultaneous determination of ADRB1 and ADRB2 both in the total population of PBMCs and in isolated subpopulations of monocytes, T-lymphocytes, and NK-cells from 23 healthy donors using the modified radioligand method. The highest amount of ADRB2 was detected in NK cells, followed by PBMCs, monocytes, and T cells. The content of these receptors in all blood cell subpopulations was significantly correlated with each other, suggesting the possibility of using PBMCs to monitor ADRB2 in solid organs. For the first time, ADRB1 was detected in monocytes and NK cells. Full article
(This article belongs to the Section Molecular Biology)
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21 pages, 1389 KiB  
Review
Hypoimmunogenic Human iPSCs for Repair and Regeneration in the CNS
by Haiwei Zhang, Hongxia Zhou, Xugang Xia, Qilin Cao and Ying Liu
Cells 2025, 14(16), 1248; https://doi.org/10.3390/cells14161248 - 13 Aug 2025
Viewed by 477
Abstract
Human induced pluripotent stem cells (iPSCs) can be genetically engineered to evade host immune recognition, rendering them hypoimmunogenic and suitable as “universal donor” cells for allogeneic transplantation. Such modifications enable the development of off-the-shelf iPSC-derived therapeutics that are immediately available for clinical use [...] Read more.
Human induced pluripotent stem cells (iPSCs) can be genetically engineered to evade host immune recognition, rendering them hypoimmunogenic and suitable as “universal donor” cells for allogeneic transplantation. Such modifications enable the development of off-the-shelf iPSC-derived therapeutics that are immediately available for clinical use without the need for patient-specific derivation or immunosuppression. This review focuses on recent developments in strategies for generating hypoimmunogenic human iPSCs, with particular emphasis on their applications in central nervous system (CNS) cell therapy and repair. We assess immunomodulatory factors based on their immune functions and potential roles in CNS development and disease, with the goal of identifying strategies to use these factors either individually, in combination, or alongside gene editing to reduce immune rejection without compromising neurogenesis or tissue repair. Full article
(This article belongs to the Special Issue Stem Cells and Beyond: Innovations in Tissue Repair and Regeneration)
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28 pages, 690 KiB  
Review
A Comprehensive Review of the Role of Rho-Kinase Inhibitors in Corneal Diseases
by Elizabeth Y. X. Leong, Jianbin Ding, Duoduo Wu, Blanche X. H. Lim, Andrea Ang, Evan Wong, Nigel Morlet, Jodhbir S. Mehta and Chris H. L. Lim
Life 2025, 15(8), 1283; https://doi.org/10.3390/life15081283 - 13 Aug 2025
Viewed by 516
Abstract
There is growing interest in the application of Rho-associated protein kinase (ROCK) inhibitors (ROCKI) to the treatment of corneal diseases. ROCK is a key regulator of several cellular processes in the cornea, including cytoskeletal organization, cell proliferation, migration, inflammation, and wound healing. ROCKI, [...] Read more.
There is growing interest in the application of Rho-associated protein kinase (ROCK) inhibitors (ROCKI) to the treatment of corneal diseases. ROCK is a key regulator of several cellular processes in the cornea, including cytoskeletal organization, cell proliferation, migration, inflammation, and wound healing. ROCKI, such as ripasudil and netarsudil, enhances endothelial cell migration, and promotes repair in conditions characterized by endothelial dysfunction. These agents also exert anti-inflammatory, anti-angiogenic, and anti-fibrotic effects for wound healing. As such, ROCKI demonstrate promise as therapeutic options for conditions such as Fuchs’ endothelial corneal dystrophy, pseudophakic bullous keratopathy, and iridocorneal endothelial syndrome. Emerging data further supports ROCKI’s potential in managing corneal neovascularization and supporting recovery following cataract surgery and keratoplasty, reducing the need for donor tissue. This narrative review provides a comprehensive evaluation of ROCKI’s mechanism of action, pharmacological properties, safety profile, applications in corneal disease management, emerging clinical trials, and novel approaches. We emphasize both preclinical and clinical findings, highlight existing evidence gaps, and outline future research priorities. Full article
(This article belongs to the Section Physiology and Pathology)
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23 pages, 7940 KiB  
Article
A Novel Iodine–Dextrin Complex Exhibits No Acute or Subacute Toxicity and Enhances Azithromycin Efficacy in an LPS-Induced Sepsis Model
by Nailya Ibragimova, Arailym Aitynova, Seitzhan Turganbay, Marina Lyu, Alexander Ilin, Karina Vassilyeva, Diana Issayeva, Tamari Gapurkhaeva, Arkadiy Krasnoshtanov, Galina Ponomareva and Amir Azembayev
Pharmaceutics 2025, 17(8), 1040; https://doi.org/10.3390/pharmaceutics17081040 - 11 Aug 2025
Viewed by 378
Abstract
Background/Objectives: Our work was designed to study the physicochemical properties, safety profile, pharmacokinetics, and prophylactic efficacy of an original iodine–dextrin-based pharmaceutical formulation (PA), both alone and in combination with azithromycin (AZ), in a murine model of LPS-induced sepsis. Methods/Results: UV–vis and 1H-NMR [...] Read more.
Background/Objectives: Our work was designed to study the physicochemical properties, safety profile, pharmacokinetics, and prophylactic efficacy of an original iodine–dextrin-based pharmaceutical formulation (PA), both alone and in combination with azithromycin (AZ), in a murine model of LPS-induced sepsis. Methods/Results: UV–vis and 1H-NMR spectroscopy confirmed the formation of a stable iodine–dextrin complex, with triiodide anions stabilized by hydrogen bonding and donor–acceptor interactions. No clinical signs of acute toxicity were observed at doses up to 5000 mg/kg, and subacute administration (62.5 and 125 mg/kg) showed no adverse effects on hematological or biochemical parameters. A mild, non-pathological enlargement of thyrocytes and parallel increases in TSH, T3, and T4 levels were observed at 125 mg/kg, consistent with physiological adaptation to iodine. Pharmacokinetic analysis revealed high oral bioavailability (~92%), prolonged half-life (~21 h), and wide tissue distribution with low clearance. In the sepsis model, pretreatment with AZ+PA alleviated clinical symptoms, maintained body weight, and significantly improved hematological parameters, reducing WBCs and CRP levels. The combination also decreased plasma IL-6 and TNF-α concentrations more effectively than either agent alone, indicating a synergistic anti-inflammatory effect. Histological analysis confirmed that PA, particularly in combination with AZ, mitigated LPS-induced tissue injury in the liver, kidney, and lungs. Conclusions: These findings suggest that PA is a safe, bioavailable compound with immunomodulatory properties that enhance azithromycin’s protective effects during systemic inflammation. This supports its potential use as a prophylactic agent in clinical settings, such as preoperative immune modulation to prevent sepsis-related complications. Full article
(This article belongs to the Section Biopharmaceutics)
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15 pages, 356 KiB  
Systematic Review
Buccal Mucosa Graft in Urological Surgery: A State-of-the-Art Review and Expert Opinion
by Simone Botti, Tommaso Ceccato, Marco Cassaro, Giangiacomo Sanna, Lorenzo Trevisiol and Tommaso Cai
Uro 2025, 5(3), 16; https://doi.org/10.3390/uro5030016 - 8 Aug 2025
Viewed by 405
Abstract
Background/Objectives: Buccal mucosa graft (BMG) is increasingly utilized in reconstructive urological surgeries due to its versatility, robust integration, histological characteristics and low morbidity at the donor site. Initially employed in urethral surgery, BMG use has expanded to complex ureteral and penile reconstructive procedures. [...] Read more.
Background/Objectives: Buccal mucosa graft (BMG) is increasingly utilized in reconstructive urological surgeries due to its versatility, robust integration, histological characteristics and low morbidity at the donor site. Initially employed in urethral surgery, BMG use has expanded to complex ureteral and penile reconstructive procedures. This narrative review examines BMG applications in various urological surgeries, comparing its outcomes to other graft types, with a focus on surgical techniques and patient outcomes. Methods: A narrative review was conducted using PubMed and Scopus to identify relevant studies published over the last three decades on the use of BMG in urological reconstructive surgery. Articles in English addressing BMG harvesting, applications and functional outcomes were analyzed. Results: BMG has demonstrated high success rates in every field of its application, especially in urethral reconstruction with an 83–91% efficacy rate in intermediate follow-up. Studies have also reported positive outcomes in complex ureteral and penile curvature surgeries, with patient satisfaction rates reaching up to 85%. Conclusions: BMG is an adaptable tissue graft for urological reconstructive surgeries, offering favorable outcomes with minimal morbidity. Although the current results are encouraging, larger prospective studies with standardized protocols are necessary to fully validate its long-term efficacy and optimize treatment approaches for complex urological reconstructions. Full article
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30 pages, 13403 KiB  
Article
Baicalein-Loaded Chitosan Films for Local Treatment of Oral Infections
by Magdalena Paczkowska-Walendowska, Anna Rył, Jakub Kwiatek, Natalia Rosiak, Kamil Szarzyński, Weronika Wawrzyniak, Julia Ziółkowska, Weronika Kuderska, Kaja Kręcka, Anna Marciniak, Tomasz M. Karpiński, Tomasz Plech, Andrzej Miklaszewski, Piotr Owczarz and Judyta Cielecka-Piontek
Polymers 2025, 17(16), 2167; https://doi.org/10.3390/polym17162167 - 8 Aug 2025
Viewed by 531
Abstract
Oral infections and tissue defects remain significant clinical challenges, often requiring localized, sustained, and multifunctional therapeutic solutions. In this study, baicalein-loaded chitosan films were developed and comprehensively characterized as novel biomaterials for oral and maxillofacial applications. Using a 32 factorial design, nine [...] Read more.
Oral infections and tissue defects remain significant clinical challenges, often requiring localized, sustained, and multifunctional therapeutic solutions. In this study, baicalein-loaded chitosan films were developed and comprehensively characterized as novel biomaterials for oral and maxillofacial applications. Using a 32 factorial design, nine film formulations were prepared via solvent casting, varying chitosan molecular weight and composition. Physicochemical and structural analyses (microscopy, SEM, FTIR, and XRPD) confirmed uniform drug distribution and matrix compatibility. Mechanical testing and dissolution studies demonstrated zero-order baicalein release kinetics, with controlled, sustained delivery influenced by chitosan content and molecular weight. The optimal formulation (F5: CS MMW 2%, Gel 2%) combined favorable mechanical integrity, drug release, and potent antioxidant and anti-inflammatory activities. Further evaluation on 3D anatomical models simulating bone and soft tissue defects highlighted excellent membrane adaptability, stability, and ease of handling under conditions mimicking clinical surgery. The films acted as effective barriers in guided tissue regeneration and donor site protection, with improved surgical visibility due to their baicalein-induced coloration. Biocompatibility assays confirmed the safety of the materials, while antibacterial testing demonstrated activity against Streptococcus mutans. These results support the potential of baicalein-loaded chitosan films as multifunctional membranes for regenerative dentistry, periodontal therapy, and peri-implant care. The modular formulation design provides a platform for future integration of additional bioactive agents, paving the way for personalized, advanced wound healing solutions. Full article
(This article belongs to the Section Biobased and Biodegradable Polymers)
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20 pages, 704 KiB  
Review
Clinical Applications of Corneal Cells Derived from Induced Pluripotent Stem Cells
by Yixin Luan, Aytan Musayeva, Jina Kim, Debbie Le Blon, Bert van den Bogerd, Mor M. Dickman, Vanessa L. S. LaPointe, Sorcha Ni Dhubhghaill and Silke Oellerich
Biomolecules 2025, 15(8), 1139; https://doi.org/10.3390/biom15081139 - 7 Aug 2025
Viewed by 580
Abstract
Corneal diseases are among the leading causes of blindness worldwide and the standard treatment is the transplantation of corneal donor tissue. Treatment for cornea-related visual impairment and blindness is, however, often constrained by the global shortage of suitable donor grafts. To alleviate the [...] Read more.
Corneal diseases are among the leading causes of blindness worldwide and the standard treatment is the transplantation of corneal donor tissue. Treatment for cornea-related visual impairment and blindness is, however, often constrained by the global shortage of suitable donor grafts. To alleviate the shortage of corneal donor tissue, new treatment options have been explored in the last decade. The discovery of induced pluripotent stem cells (iPSCs), which has revolutionized regenerative medicine, offers immense potential for corneal repair and regeneration. Using iPSCs can provide a renewable source for generating various corneal cell types, including corneal epithelial cells, stromal keratocytes, and corneal endothelial cells. To document the recent progress towards the clinical application of iPSC-derived corneal cells, this review summarizes the latest advancements in iPSC-derived corneal cell therapies, ranging from differentiation protocols and preclinical studies to the first clinical trials, and discusses the challenges for successful translation to the clinic. Full article
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24 pages, 1115 KiB  
Review
Stem Cell-Derived Corneal Epithelium: Engineering Barrier Function for Ocular Surface Repair
by Emily Elizabeth Fresenko, Jian-Xing Ma, Matthew Giegengack, Atalie Carina Thompson, Anthony Atala, Andrew J. W. Huang and Yuanyuan Zhang
Int. J. Mol. Sci. 2025, 26(15), 7501; https://doi.org/10.3390/ijms26157501 - 3 Aug 2025
Viewed by 410
Abstract
The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation [...] Read more.
The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells with functional barrier properties for corneal reconstruction and in vitro pharmacotoxicity testing. In this review, we delineate the current limitations of corneal transplantation, the advantages of stem cell-based approaches, and recent advances in generating engineered corneal epithelium. Finally, we address remaining technical challenges and propose future research directions aimed at clinical translation. Full article
(This article belongs to the Special Issue Enhancing Stem Cell Grafting in Tissue Regeneration and Repair)
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17 pages, 1097 KiB  
Article
Mapping Perfusion and Predicting Success: Infrared Thermography-Guided Perforator Flaps for Lower Limb Defects
by Abdalah Abu-Baker, Andrada-Elena Ţigăran, Teodora Timofan, Daniela-Elena Ion, Daniela-Elena Gheoca-Mutu, Adelaida Avino, Cristina-Nicoleta Marina, Adrian Daniel Tulin, Laura Raducu and Radu-Cristian Jecan
Medicina 2025, 61(8), 1410; https://doi.org/10.3390/medicina61081410 - 3 Aug 2025
Viewed by 288
Abstract
Background and Objectives: Lower limb defects often present significant reconstructive challenges due to limited soft tissue availability and exposure of critical structures. Perforator-based flaps offer reliable solutions, with minimal donor site morbidity. This study aimed to evaluate the efficacy of infrared thermography [...] Read more.
Background and Objectives: Lower limb defects often present significant reconstructive challenges due to limited soft tissue availability and exposure of critical structures. Perforator-based flaps offer reliable solutions, with minimal donor site morbidity. This study aimed to evaluate the efficacy of infrared thermography (IRT) in preoperative planning and postoperative monitoring of perforator-based flaps, assessing its accuracy in identifying perforators, predicting complications, and optimizing outcomes. Materials and Methods: A prospective observational study was conducted on 76 patients undergoing lower limb reconstruction with fascio-cutaneous perforator flaps between 2022 and 2024. Perforator mapping was performed concurrently with IRT and Doppler ultrasonography (D-US), with intraoperative confirmation. Flap design variables and systemic parameters were recorded. Postoperative monitoring employed thermal imaging on days 1 and 7. Outcomes were correlated with thermal, anatomical, and systemic factors using statistical analyses, including t-tests and Pearson correlation. Results: IRT showed high sensitivity (97.4%) and positive predictive value (96.8%) for perforator detection. A total of nine minor complications occurred, predominantly in patients with diabetes mellitus and/or elevated glycemia (p = 0.05). Larger flap-to-defect ratios (A/C and B/C) correlated with increased complications in propeller flaps, while smaller ratios posed risks for V-Y and Keystone flaps. Thermal analysis indicated significantly lower flap temperatures and greater temperature gradients in flaps with complications by postoperative day 7 (p < 0.05). CRP levels correlated with glycemia and white blood cell counts, highlighting systemic inflammation’s impact on outcomes. Conclusions: IRT proves to be a reliable, non-invasive method for perforator localization and flap monitoring, enhancing surgical planning and early complication detection. Combined with D-US, it improves perforator selection and perfusion assessment. Thermographic parameters, systemic factors, and flap design metrics collectively predict flap viability. Integration of IRT into surgical workflows offers a cost-effective tool for optimizing reconstructive outcomes in lower limb surgery. Full article
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13 pages, 1189 KiB  
Article
The Role of Biodegradable Temporizing Matrix in Paediatric Reconstructive Surgery
by Aikaterini Bini, Michael Ndukwe, Christina Lipede, Ramesh Vidyadharan, Yvonne Wilson and Andrea Jester
J. Clin. Med. 2025, 14(15), 5427; https://doi.org/10.3390/jcm14155427 - 1 Aug 2025
Viewed by 534
Abstract
Introduction: Biodegradable Temporizing Matrix (BTM) is a new synthetic dermal substitute suitable for wound closure and tissue regeneration. The data in paediatric population remain limited. The study purpose is to review the indications for BTM application in paediatric patients, evaluate the short-term and [...] Read more.
Introduction: Biodegradable Temporizing Matrix (BTM) is a new synthetic dermal substitute suitable for wound closure and tissue regeneration. The data in paediatric population remain limited. The study purpose is to review the indications for BTM application in paediatric patients, evaluate the short-term and long-term results, including complications and functional outcomes, as well as to share some unique observations regarding the use of BTM in paediatric population. Patients and Methods: Patients undergoing reconstructive surgery and BTM application during the last three years were included. Data collected included patient demographics, primary diagnosis, previous surgical management, post-operative complications and final outcomes. BTM was used in 32 patients. The indications varied including epidermolysis bullosa (n = 6), burns (n = 4), trauma (n = 7), infection (n = 4), ischemia or necrosis (n = 11). Results: The results were satisfying with acceptable aesthetic and functional outcomes. Complications included haematoma underneath the BTM leading to BTM removal and re-application (n = 1), BTM infection (n = 1) and split-thickness skin graft failure on top of BTM requiring re-grafting (n = 2). Conclusions: BTM can be a good alternative to large skin grafts, locoregional flaps or even free flaps. The big advantages over other dermal substitutes or skin grafts are that BTM is less prone to infection and offers excellent scarring by preserving the normal skin architecture. Specifically in children, BTM might not require grafting, resulting in spontaneous healing with good scarring. In critically ill patients, BTM reduces the operation time and there is no donor site morbidity. BTM should be considered in the reconstructive ladder when discussing defect coverage options in children and young people. Full article
(This article belongs to the Special Issue Trends in Plastic and Reconstructive Surgery)
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