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17 pages, 1800 KiB  
Article
Healing Kinetics of Sinus Lift Augmentation Using Biphasic Calcium Phosphate Granules: A Case Series in Humans
by Michele Furlani, Valentina Notarstefano, Nicole Riberti, Emira D’Amico, Tania Vanessa Pierfelice, Carlo Mangano, Elisabetta Giorgini, Giovanna Iezzi and Alessandra Giuliani
Bioengineering 2025, 12(8), 848; https://doi.org/10.3390/bioengineering12080848 (registering DOI) - 6 Aug 2025
Abstract
Sinus augmentation provides a well-established model for investigating the three-dimensional morphometry and macromolecular dynamics of bone regeneration, particularly when using biphasic calcium phosphate (BCP) graft substitutes. This case series included six biopsies from patients who underwent maxillary sinus augmentation using BCP granules composed [...] Read more.
Sinus augmentation provides a well-established model for investigating the three-dimensional morphometry and macromolecular dynamics of bone regeneration, particularly when using biphasic calcium phosphate (BCP) graft substitutes. This case series included six biopsies from patients who underwent maxillary sinus augmentation using BCP granules composed of 30% hydroxyapatite (HA) and 70% β-tricalcium phosphate (β-TCP). Bone core biopsies were obtained at healing times of 6 months, 9 months, and 12 months. Histological evaluation yielded qualitative and quantitative insights into new bone distribution, while micro-computed tomography (micro-CT) and Raman microspectroscopy (RMS) were employed to assess the three-dimensional architecture and macromolecular composition of the regenerated bone. Micro-CT analysis revealed progressive maturation of the regenerated bone microstructure over time. At 6 months, the apical regenerated area exhibited a significantly higher mineralized volume fraction (58 ± 5%) compared to the basal native bone (44 ± 11%; p = 0.0170), as well as significantly reduced trabecular spacing (Tb.Sp: 187 ± 70 µm vs. 325 ± 96 µm; p = 0.0155) and degree of anisotropy (DA: 0.37 ± 0.05 vs. 0.73 ± 0.03; p < 0.0001). By 12 months, the mineralized volume fraction in the regenerated area (53 ± 5%) was statistically comparable to basal bone (44 ± 3%; p > 0.05), while Tb.Sp (211 ± 20 µm) and DA (0.23 ± 0.09) remained significantly lower (Tb.Sp: 395 ± 41 µm, p = 0.0041; DA: 0.46 ± 0.04, p = 0.0001), indicating continued structural remodelling and organization. Raman microspectroscopy further revealed dynamic macromolecular changes during healing. Characteristic β-TCP peaks (e.g., 1315, 1380, 1483 cm−1) progressively diminished over time and were completely absent in the regenerated tissue at 12 months, contrasting with their partial presence at 6 months. Simultaneously, increased intensity of collagen-specific bands (e.g., Amide I at 1661 cm−1, Amide III at 1250 cm−1) and carbonate peaks (1065 cm−1) reflected active matrix formation and mineralization. Overall, this case series provides qualitative and quantitative evidence that bone regeneration and integration of BCP granules in sinus augmentation continues beyond 6 months, with ongoing maturation observed up to 12 months post-grafting. Full article
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25 pages, 2042 KiB  
Article
Transcriptomic Profiling of Mouse Mesenchymal Stem Cells Exposed to Metal-Based Nanoparticles
by Michal Sima, Helena Libalova, Zuzana Simova, Barbora Echalar, Katerina Palacka, Tereza Cervena, Jiri Klema, Zdenek Krejcik, Vladimir Holan and Pavel Rossner
Int. J. Mol. Sci. 2025, 26(15), 7583; https://doi.org/10.3390/ijms26157583 - 5 Aug 2025
Abstract
Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of [...] Read more.
Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of Ag, CuO, and ZnO NPs after in vitro exposure of mouse MSCs at the transcriptional level in order to reveal the potential toxicity as well as modulation of other processes that may modify the activity of MSCs. mRNA–miRNA interactions were further investigated to explore the epigenetic regulation of gene expression. All the tested NPs mediated immunomodulatory effects on MSCs, generation of extracellular vesicles, inhibition of osteogenesis, and enhancement of adipogenesis. Ag NPs exhibited the most pronounced response; they impacted the expression of the highest number of mRNAs, including those encoding interferon-γ-stimulated genes and genes involved in drug metabolism/cytochrome P450 activity, suggesting a response to the potential toxicity of Ag NPs (oxidative stress). Highly interacting MiR-126 was upregulated by all NPs, while downregulation of MiR-92a was observed after the ZnO NP treatment only, and both effects might be associated with the improvement of MSCs’ healing potency. Overall, our results demonstrate positive effects of NPs on MSCs, although increased oxidative stress caused by Ag NPs may limit the therapeutical potential of the combined MSC+NP treatment. Full article
(This article belongs to the Section Molecular Nanoscience)
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19 pages, 3100 KiB  
Review
Casein-Based Biomaterials: Fabrication and Wound Healing Applications
by Nikolay Estiven Gomez Mesa, Krasimir Vasilev and Youhong Tang
Molecules 2025, 30(15), 3278; https://doi.org/10.3390/molecules30153278 - 5 Aug 2025
Abstract
Casein, the main phosphoprotein in milk, has a multifaceted molecular structure and unique physicochemical properties that make it a viable candidate for biomedical use, particularly in wound healing. This review presents a concise analysis of casein’s structural composition that comprises its hydrophobic and [...] Read more.
Casein, the main phosphoprotein in milk, has a multifaceted molecular structure and unique physicochemical properties that make it a viable candidate for biomedical use, particularly in wound healing. This review presents a concise analysis of casein’s structural composition that comprises its hydrophobic and hydrophilic nature, calcium phosphate nanocluster structure, and its response to different pH, temperature, and ionic conditions. These characteristics have direct implications for its colloidal stability, including features such as gelation, swelling capacity, and usability as a biomaterial in tissue engineering. This review also discusses industrial derivatives and recent advances in casein biomaterials based on different fabrication types such as hydrogels, electrospun fibres, films, and advanced systems. Furthermore, casein dressings’ functional and biological attributes have shown remarkable exudate absorption, retention of moisture, biocompatibility, and antimicrobial and anti-inflammatory activity in both in vivo and in vitro studies. The gathered evidence highlights casein’s versatile bioactivity and dynamic molecular properties, positioning it as a promising platform to address advanced wound dressing challenges. Full article
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42 pages, 7526 KiB  
Review
Novel Nanomaterials for Developing Bone Scaffolds and Tissue Regeneration
by Nazim Uddin Emon, Lu Zhang, Shelby Dawn Osborne, Mark Allen Lanoue, Yan Huang and Z. Ryan Tian
Nanomaterials 2025, 15(15), 1198; https://doi.org/10.3390/nano15151198 - 5 Aug 2025
Abstract
Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses [...] Read more.
Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses and prospects of current and next-generation nanomaterials in designing bioactive bone scaffolds, emphasizing hierarchical architecture, mechanical resilience, and regenerative precision. Mainly, this review elucidated the innovative findings, new capabilities, unmet challenges, and possible future opportunities associated with biocompatible inorganic ceramics (e.g., phosphates, metallic oxides) and the United States Food and Drug Administration (USFDA) approved synthetic polymers, including their nanoscale structures. Furthermore, this review demonstrates the newly available approaches for achieving customized standard porosity, mechanical strengths, and accelerated bioactivity to construct an optimized nanomaterial-oriented scaffold. Numerous strategies including three-dimensional bioprinting, electro-spinning techniques and meticulous nanomaterials (NMs) fabrication are well established to achieve radical scientific precision in BTR engineering. The contemporary research is unceasingly decoding the pathways for spatial and temporal release of osteoinductive agents to enhance targeted therapy and prompt healing processes. Additionally, successful material design and integration of an osteoinductive and osteoconductive agents with the blend of contemporary technologies will bring radical success in this field. Furthermore, machine learning (ML) and artificial intelligence (AI) can further decode the current complexities of material design for BTR, notwithstanding the fact that these methods call for an in-depth understanding of bone composition, relationships and impacts on biochemical processes, distribution of stem cells on the matrix, and functionalization strategies of NMs for better scaffold development. Overall, this review integrated important technological progress with ethical considerations, aiming for a future where nanotechnology-facilitated bone regeneration is boosted by enhanced functionality, safety, inclusivity, and long-term environmental responsibility. Therefore, the assimilation of a specialized research design, while upholding ethical standards, will elucidate the challenge and questions we are presently encountering. Full article
(This article belongs to the Special Issue Applications of Functional Nanomaterials in Biomedical Science)
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20 pages, 2267 KiB  
Article
Mechanical Properties of Collagen Implant Used in Neurosurgery Towards Industry 4.0/5.0 Reflected in ML Model
by Marek Andryszczyk, Izabela Rojek and Dariusz Mikołajewski
Appl. Sci. 2025, 15(15), 8630; https://doi.org/10.3390/app15158630 (registering DOI) - 4 Aug 2025
Abstract
Collagen implants in neurosurgery are widely used due to their biocompatibility, biodegradability, and ability to support tissue regeneration, but their mechanical properties, such as low tensile strength and susceptibility to enzymatic degradation, remain challenging. Current technologies are improving these implants through cross-linking, synthetic [...] Read more.
Collagen implants in neurosurgery are widely used due to their biocompatibility, biodegradability, and ability to support tissue regeneration, but their mechanical properties, such as low tensile strength and susceptibility to enzymatic degradation, remain challenging. Current technologies are improving these implants through cross-linking, synthetic reinforcements, and advanced manufacturing techniques such as 3D bioprinting to improve durability and predictability. Industry 4.0 is contributing to this by automating production, using data analytics and machine learning to optimize implant properties and ensure quality control. In Industry 5.0, the focus is shifting to personalization, enabling the creation of patient-specific implants through human–machine collaboration and advanced biofabrication. eHealth integrates digital monitoring systems, enabling real-time tracking of implant healing and performance to inform personalized care. Despite progress, challenges such as cost, material property variability, and scalability for mass production remain. The future lies in smart biomaterials, AI-driven design, and precision biofabrication, which could mean the possibility of creating more effective, accessible, and patient-specific collagen implants. The aim of this article is to examine the current state and determine the prospects for the development of mechanical properties of collagen implant used in neurosurgery towards Industry 4.0/5.0, including ML model. Full article
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15 pages, 2179 KiB  
Review
From Nutrition to Innovation: Biomedical Applications of Egg Components
by Amin Mohseni Ghalehghazi and Wen Zhong
Molecules 2025, 30(15), 3260; https://doi.org/10.3390/molecules30153260 - 4 Aug 2025
Abstract
Valued for their nutritional content, eggs have recently gained attention as a versatile biomaterial owing to their biocompatibility, biodegradability, and unique structural and biochemical composition. This review highlights the biomedical potential of various egg components—eggshell, eggshell membrane, egg white, and egg yolk—and their [...] Read more.
Valued for their nutritional content, eggs have recently gained attention as a versatile biomaterial owing to their biocompatibility, biodegradability, and unique structural and biochemical composition. This review highlights the biomedical potential of various egg components—eggshell, eggshell membrane, egg white, and egg yolk—and their applications in bone grafting, tissue engineering, wound healing, drug delivery, and biosensors. Eggshells serve as a natural, calcium-rich source for bone tissue engineering and regenerative medicine. The eggshell membrane, with its antimicrobial and structural properties, offers promise as a wound healing scaffold. Egg white, known for its gelation and film-forming capabilities, is utilized in hydrogel-based systems for drug delivery and biosensing. Egg yolk, rich in lipids and immunoglobulin Y (IgY) antibodies, is being explored for diagnostic and therapeutic applications. This review critically examines the advantages and limitations of each egg-derived component and outlines current research gaps, offering insights into future directions for the development of egg-based biomaterials in biomedical engineering. Full article
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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 18
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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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 79
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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12 pages, 2807 KiB  
Article
Evaluation of Hydroxyapatite–β-Tricalcium Phosphate Collagen Composites for Socket Preservation in a Canine Model
by Dong Woo Kim, Donghyun Lee, Jaeyoung Ryu, Min-Suk Kook, Hong-Ju Park and Seunggon Jung
J. Funct. Biomater. 2025, 16(8), 286; https://doi.org/10.3390/jfb16080286 - 3 Aug 2025
Viewed by 218
Abstract
This study aimed to compare the performance of three hydroxyapatite–β-tricalcium phosphate (HA–β-TCP) collagen composite grafts in a canine model for extraction socket preservation. Eight mongrel dogs underwent atraumatic bilateral mandibular premolar extraction, and sockets were randomly grafted with HBC28 (20% high-crystalline HA, 80% [...] Read more.
This study aimed to compare the performance of three hydroxyapatite–β-tricalcium phosphate (HA–β-TCP) collagen composite grafts in a canine model for extraction socket preservation. Eight mongrel dogs underwent atraumatic bilateral mandibular premolar extraction, and sockets were randomly grafted with HBC28 (20% high-crystalline HA, 80% β-TCP bovine collagen), HBC37 (30% HA, 70% β-TCP, bovine collagen), or HPC64 (60% HA, 40% β-TCP, porcine collagen). Grafts differed in their HA–β-TCP ratio and collagen origin and content. Animals were sacrificed at 4 and 12 weeks, and the healing sites were evaluated using micro-computed tomography (micro-CT) and histological analysis. At 12 weeks, all groups showed good socket maintenance with comparable new bone formation. However, histological analysis revealed that HBC28 had significantly higher residual graft volume, while HPC64 demonstrated more extensive graft resorption. Histomorphometric analysis confirmed these findings, with statistically significant differences in residual graft area and bone volume fraction. No inflammatory response or adverse tissue reactions were observed in any group. These results suggest that all three HA–β-TCP collagen composites are biocompatible and suitable for socket preservation, with varying resorption kinetics influenced by graft composition. Selection of graft material may thus be guided by the desired rate of replacement by new bone. Full article
(This article belongs to the Special Issue Biomechanical Studies and Biomaterials in Dentistry)
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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 242
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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29 pages, 1505 KiB  
Review
Biological Macromolecule-Based Dressings for Combat Wounds: From Collagen to Growth Factors—A Review
by Wojciech Kamysz and Patrycja Kleczkowska
Med. Sci. 2025, 13(3), 106; https://doi.org/10.3390/medsci13030106 - 1 Aug 2025
Viewed by 335
Abstract
Wound care in military and combat environments poses distinct challenges that set it apart from conventional medical practice in civilian settings. The nature of injuries sustained on the battlefield—often complex, contaminated, and involving extensive tissue damage—combined with limited access to immediate medical intervention, [...] Read more.
Wound care in military and combat environments poses distinct challenges that set it apart from conventional medical practice in civilian settings. The nature of injuries sustained on the battlefield—often complex, contaminated, and involving extensive tissue damage—combined with limited access to immediate medical intervention, significantly increases the risk of infection, delayed healing, and adverse outcomes. Traditional wound dressings frequently prove inadequate under such extreme conditions, as they have not been designed to address the specific physiological and logistical constraints present during armed conflicts. This review provides a comprehensive overview of recent progress in the development of advanced wound dressings tailored for use in military scenarios. Special attention has been given to multifunctional dressings that go beyond basic wound coverage by incorporating biologically active macromolecules such as collagen, chitosan, thrombin, alginate, therapeutic peptides, and growth factors. These compounds contribute to properties including moisture balance control, exudate absorption, microbial entrapment, and protection against secondary infection. This review highlights the critical role of advanced wound dressings in improving medical outcomes for injured military personnel. The potential of these technologies to reduce complications, enhance healing rates, and ultimately save lives underscores their growing importance in modern battlefield medicine. Full article
(This article belongs to the Collection Advances in Skin Wound Healing)
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13 pages, 4424 KiB  
Case Report
A Literature Review of Phantom Bladder Perforation: The Curious Case of Bladder Lipoma
by Surina Patel, Mehreet Kaur Chahal, Scott Durham, Haitham Elsamaloty and Puneet Sindhwani
Uro 2025, 5(3), 15; https://doi.org/10.3390/uro5030015 - 1 Aug 2025
Viewed by 97
Abstract
Introduction: Although lipomas are common benign tumors found in adults, lipomas of the bladder are extremely rare. Bladder lipomas are infrequently reported in the urologic literature, with only 19 cases published worldwide. These can present as a mass on cystoscopy and cause irritative [...] Read more.
Introduction: Although lipomas are common benign tumors found in adults, lipomas of the bladder are extremely rare. Bladder lipomas are infrequently reported in the urologic literature, with only 19 cases published worldwide. These can present as a mass on cystoscopy and cause irritative voiding symptoms, depending on their location. Upon transurethral resection, seeing fat can be concerning for a perforation, as lipoma can be mistaken for extravesical fat. Hence, familiarity with this rare entity is of paramount importance for urologists to prevent unnecessary investigations and interventions that are needed in case of a true bladder perforation. Case presentation: This study presents a case of bladder lipoma in a 73-year-old male with end-stage renal disease who presented for pretransplant urologic evaluation due to microscopic hematuria and irritative lower urinary tract symptoms (LUTS). During cystoscopy, a bladder mass was seen, and a transurethral resection of the bladder tumor (TURBT) revealed bright yellow adipose tissue immediately underneath the bladder mucosa. Concerns about perforation were obviated when seeing intact detrusor muscle underneath, visually confirming the integrity of the bladder wall. The resection was completed, and the CT scan was re-read with the radiologist, which confirmed the presence of a lipoma that was missed pre-operatively due to patient’s oliguria and collapsed bladder. No catheter drainage or cystogram was performed based on these findings. Outcome: The patient healed without any complications. Histopathology confirmed the diagnosis of a mature lipoma. The patient was cleared for transplant from a urologic standpoint and had a successful renal transplantation without delay. Discussion: This case documents the anomalous occurrence of a lipoma within the bladder and supports maintaining a broad differential, including liposarcoma, angiomyolipoma, and other non-malignant fatty tumors during the evaluation of a bladder mass. 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 159
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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16 pages, 2742 KiB  
Article
miRNA408 from Camellia japonica L. Mediates Cross-Kingdom Regulation in Human Skin Recovery
by Soll Jin, Jae-Goo Kim, Hye Jin Kim, Ji Young Kim, Sang Hoon Kim, Hee Cheol Kang and Mi Jung Kim
Biomolecules 2025, 15(8), 1108; https://doi.org/10.3390/biom15081108 - 1 Aug 2025
Viewed by 190
Abstract
Wound healing is a complex and dynamic process involving several stages of tissue repair. This study has shown that extracellular vesicles (EVs) derived from the callus of Camellia japonica L. and their associated microRNAs (miRNAs) possess significant wound healing activities. In human fibroblasts, [...] Read more.
Wound healing is a complex and dynamic process involving several stages of tissue repair. This study has shown that extracellular vesicles (EVs) derived from the callus of Camellia japonica L. and their associated microRNAs (miRNAs) possess significant wound healing activities. In human fibroblasts, EVs from C. japonica L. stimulated wound healing and upregulated collagen gene expression. The EVs also decreased inflammation levels in human keratinocytes, supporting wound healing. Among the miRNAs identified, miR408, one of the abundant miRNAs in the EVs, also showed similar wound healing efficacy. These findings suggest that both EVs and miR408 from the callus of C. japonica L. play a pivotal role in promoting wound healing. Additionally, this study shows that the regulation of miRNAs between different kingdoms can be achieved and suggests a new direction for the utilization of plant-derived components. Full article
(This article belongs to the Section Molecular Biophysics: Structure, Dynamics, and Function)
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22 pages, 11006 KiB  
Article
Supervised Machine-Based Learning and Computational Analysis to Reveal Unique Molecular Signatures Associated with Wound Healing and Fibrotic Outcomes to Lens Injury
by Catherine Lalman, Kylie R. Stabler, Yimin Yang and Janice L. Walker
Int. J. Mol. Sci. 2025, 26(15), 7422; https://doi.org/10.3390/ijms26157422 - 1 Aug 2025
Viewed by 134
Abstract
Posterior capsule opacification (PCO), a frequent complication of cataract surgery, arises from dysregulated wound healing and fibrotic transformation of residual lens epithelial cells. While transcriptomic and machine learning (ML) approaches have elucidated fibrosis-related pathways in other tissues, the molecular divergence between regenerative and [...] Read more.
Posterior capsule opacification (PCO), a frequent complication of cataract surgery, arises from dysregulated wound healing and fibrotic transformation of residual lens epithelial cells. While transcriptomic and machine learning (ML) approaches have elucidated fibrosis-related pathways in other tissues, the molecular divergence between regenerative and fibrotic outcomes in the lens remains unclear. Here, we used an ex vivo chick lens injury model to simulate post-surgical conditions, collecting RNA from lenses undergoing either regenerative wound healing or fibrosis between days 1–3 post-injury. Bulk RNA sequencing data were normalized, log-transformed, and subjected to univariate filtering prior to training LASSO, SVM, and RF ML models to identify discriminatory gene signatures. Each model was independently validated using a held-out test set. Distinct gene sets were identified, including fibrosis-associated genes (VGLL3, CEBPD, MXRA7, LMNA, gga-miR-143, RF00072) and wound-healing-associated genes (HS3ST2, ID1), with several achieving perfect classification. Gene Set Enrichment Analysis revealed divergent pathway activation, including extracellular matrix remodeling, DNA replication, and spliceosome associated with fibrosis. RT-PCR in independent explants confirmed key differential expression levels. These findings demonstrate the utility of supervised ML for discovering lens-specific fibrotic and regenerative gene features and nominate biomarkers for targeted intervention to mitigate PCO. Full article
(This article belongs to the Section Molecular Informatics)
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