Biomaterials Science最新文献

{"title":"Fibroblast proximity to a tumor impacts fibroblast extracellular vesicles produced by 3D bioprinted stromal models†","authors":"Jensen N. Amens, Jun Yang, Lauren Hawthorne and Pinar Zorlutuna","doi":"10.1039/D4BM01569J","DOIUrl":"10.1039/D4BM01569J","url":null,"abstract":"<p >Extracellular vesicles (EVs) are an important carrier of cellular communication that contain cargo such as cytokines, RNAs, or microRNAs (miRNA) and have been proven to play an important role in breast cancer tumorigenesis, progression, and metastasis. Although the role of cancer associated fibroblasts (CAFs), and EVs originated from them have been studied extensively, there is a lack in knowledge on the contribution of normal fibroblasts surrounding the tumor and their roles with respect to their proximity to the tumor. Here we investigate how the proximity of the tumor affects the EV production of the normal fibroblasts. We created stromal models by 3D bioprinting two different fibroblasts, normal human mammary fibroblasts (hMFs) and normal tumor adjacent fibroblasts (NTAF), within a collagen gel. We isolated EVs from both the effluent media and the 3D stromal model, which were then characterized and we found that EVs from each group were of consistent exosome size and displayed traditional exosome markers, however, the EVs from different groups also displayed different cytokine profiles of their cargo, with the NTAF media group showing an upregulation of cytokines associated with breast cancer progression. After this, we used the EVs to treat breast cancer cells to investigate the effects of the EV groups on the breast cancer cell behavior. The breast cancer cells treated with the NTAF groups had increased migration. Finally, we utilized a 3D breast tumor model to investigate the effects of the EVs on a tumor spheroid. Tumor spheroids treated with either NTAF EV groups showed increased proliferation, tumor diameter, and local invasion. This study is the first to investigate the effect of proximity to a breast tumor on EV production and the first to utilize 3D bioprinting of stromal models specifically to obtain EVs. Overall, our results show that EVs from normal fibroblasts closer to a tumor produce EVs that promote breast cancer progression, regardless of the secretion location of the EVs. These cells have a distinct EV secretome different from normal human mammary fibroblasts, showing that the proximity to a tumor influences the normal fibroblasts surrounding the tumor.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 14","pages":" 3814-3827"},"PeriodicalIF":5.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iohexol as a refractive index tuning agent for bioinks in high cell density bioprinting†","authors":"Yi Xiang, Yazhi Sun, Jiaao Guan, Tobias Meng-Saccoccio, Ting-Yu Lu, David Berry and Shaochen Chen","doi":"10.1039/D5BM00585J","DOIUrl":"10.1039/D5BM00585J","url":null,"abstract":"<p >Light-based 3D bioprinting has emerged as a transformative technology for fabrication of biomimetic tissues and artificial organs. High cell density (HCD) bioprinting aims to recapitulate the cellular density and interactions in native tissue, but faces significant challenges in achieving both high resolution and structural fidelity due to light scattering during the photopolymerization process. Refractive index (RI) tuning of the bioink mitigates light scattering to improve printing fidelity. In this study, we developed an iohexol (IHX)-based bioink for digital light processing (DLP) bioprinting. IHX effectively tuned the RI of the bioink to match cellular components to reduce light scattering while still maintaining printability. The bioink demonstrated excellent biocompatibility across multiple cell types, including epithelial, endothelial, parenchymal, and stem cells, while simultaneously supporting post-printing cellular viability, reorganization, and functionality. Using IHX-bioink, we fabricated tubular constructs with lumen diameters ranging from 400 μm to 1.1 mm and utilized strategies to minimize overpolymerization and ensure lumen fidelity. Our results underscore IHX-bioink as a promising biomaterial for scalable, RI-matching 3D bioprinting, enabling the creation of perfusable, HCD constructs for various applications in tissue engineering and regenerative medicine.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 14","pages":" 3958-3971"},"PeriodicalIF":5.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese-chelated liposomes encapsulating antiepileptic drug molecules for epilepsy treatment†","authors":"Junchen Chen, Kaizhong Tao, Yuhao He and Sunfu Zhang","doi":"10.1039/D5BM00266D","DOIUrl":"10.1039/D5BM00266D","url":null,"abstract":"<p >Epilepsy is characterized by unpredictable and recurrent seizures, necessitating long-term prophylactic medication to maintain high drug concentrations at the site of onset. However, this approach, coupled with the blood–brain barrier (BBB)'s impediment, often leads to significant toxicity and drug resistance. We report a novel liposomal drug delivery system for epilepsy treatment: liposomes encapsulating two first-line clinical drugs chelated by metal ions. This liposomal formulation demonstrates high biosafety both <em>in vitro</em> and <em>in vivo</em>. Through <em>in vivo</em> fluorescence imaging and <em>T</em>1-weighted magnetic resonance imaging (MRI), we verified its efficient penetration into the blood–brain barrier and effective accumulation at epileptic foci. This targeted delivery prevented substantial brain tissue damage caused by epilepsy and maintained neurons in the normal physiological state. Our work presents a promising new therapeutic option for the clinical management of epilepsy.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 15","pages":" 4283-4292"},"PeriodicalIF":5.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designed gramicidin-inspired stabilized peptide-based therapeutics to potentiate immunotherapy against aggressive kidney cancer.","authors":"Argha Mario Mallick, Ananya Chatterjee, Arun Bahadur Gurung, Prithviraj Uttarasili, Archana Tripathi, Monjuri Hembram, Anand Srivastava, Rituparna Sinha Roy","doi":"10.1039/d5bm00109a","DOIUrl":"10.1039/d5bm00109a","url":null,"abstract":"<p><p>This study reports engineered protease-stable, gramicidin-inspired, peptide-based proton transporter LD8Δ, with alternating L- and D-amino acid residues, to treat the highly chemoresistant, radioresistant, immunosuppressive metastatic renal cell carcinoma (RCC) cell line SK-RC-45. Exploiting the potential of the LD8Δ proton transporter, this study proposes mechanistically rational combination therapy with high translational potential. Current treatment methods involve multi-targeted tyrosine kinase inhibitors, which are accompanied by serious side-effects and exhibit an alarmingly low median overall survival. Computational and experimental data suggested that LD8Δ induced considerable membrane deformation, which supported the destabilization of the intracellular pH regulating mechanism observed in LD8Δ-treated RCC. This mechanistically rational combination therapy using LD8Δ and HIF-2α silencing siRNA induced mitochondrial depolarization, cell cycle arrest, apoptosis, reduction in angiogenesis and disruption of the major oncogenic signalling pathways in SK-RC-45 cells. The designed therapy upregulated the VHL tumour suppressor protein and downregulated HIF-2α protein expression, thus decreasing the activity of the HIF transcriptional factor, which is the master regulator causing clear cell RCC. Additionally, it upregulated DAB2IP and facilitated radiosensitization in the radioresistant SK-RC-45 cells. To the best of our knowledge, this is the first study demonstrating that a designed biocompatible proton transporter can potentiate immunotherapy against RCC by inducing the downregulation of the dual checkpoint proteins CD47, PD-L1 and ganglioside GM2, resulting in enhanced phagocytosis and preventing T cell inactivation and T cell apoptosis.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-atom silver-borophene hybrid hydrogels for electrically stimulated wound healing: a multifunctional antibacterial platform†","authors":"Davlatov Salim Sulaymonovich, Normurot Fayzullaev, Rakhnamokhon Nazirova, Alisher Ishankulov, Mohammad Omidi, Bareq N. Al-Nuaimi, Bobojonov Otabek Khakimboy ugli, Kamalova Dilnavoz Ikhtiyorovna, Mamatqul Mamatqulov and Monireh Faraji","doi":"10.1039/D5BM00609K","DOIUrl":"10.1039/D5BM00609K","url":null,"abstract":"<p >Chronic wound healing demands next-generation biomaterials that includes antibacterial properties, electrical responsiveness, and tissue-regenerative capabilities. This study presents a multifunctional hydrogel that incorporates single-atom silver (Ag-SA) and two-dimensional borophene nanosheets (BNSs) within a PVA/chitosan matrix (PCAB). The atomically dispersed Ag sites exhibit highly localized bactericidal activity at a silver amount 50 times lower than those in traditional AgNP systems, thus reducing cytotoxicity and hemolysis to less than 5%. Concurrently, borophene nanosheets provide elevated electrical conductivity (0.45 ± 0.02 S cm<small>⁻¹</small>), water retention, and matrix reinforcement, while facilitating real-time responsiveness under low-voltage stimulation (1 V). The PCAB-1 V hydrogel demonstrated robust antibacterial efficacy, eradicating more than 95% of <em>E. coli</em> and <em>S. aureus</em>, while markedly enhancing fibroblast proliferation (184.3 ± 3.6% viability). <em>In vivo</em> investigations utilizing a mouse full-thickness wound model demonstrated expedited wound closure (97.3%) and epithelium regeneration (124.5 μm) by Day 14. Statistical analysis validated substantial enhancements in all performance indicators (<em>p</em> &lt; 0.001). This study emphasizes the synergistic interaction between Ag-SA and borophene, providing a low-toxicity, electroactive hydrogel substrate for enhanced wound care.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 15","pages":" 4180-4198"},"PeriodicalIF":5.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper-doped PDA nanoparticles with self-enhanced ROS generation for boosting photothermal/chemodynamic combination therapy†","authors":"Xuan Wang, Ka Hong Wong, Yuying Yin, Zian Wang and Meiwan Chen","doi":"10.1039/D5BM00418G","DOIUrl":"10.1039/D5BM00418G","url":null,"abstract":"<p >Chemodynamic therapy (CDT) kills tumor cells by converting intracellular hydrogen peroxide (H<small>₂</small>O<small>₂</small>) into cytotoxic hydroxyl radicals (˙OH) using metal ion-based agents <em>via</em> Fenton/Fenton-like reactions, exhibiting cancer specificity, excellent safety, and minimal side effects. However, the therapeutic effect of CDT is largely limited by high levels of the antioxidant glutathione (GSH) in cancer cells and low catalytic reaction rates of Fenton/Fenton-like reactions. Herein, folic acid (FA)-modified copper-doped polydopamine (PDA) nanoparticles were constructed to load curcumin (FPCCD), achieving the generation of self-enhanced reactive oxygen species (ROS) by inhibiting antioxidants and promoting the Fenton-like reaction. Briefly, FPCCD exhibited the following anticancer advantages: (1) FPCCD targeted tumor cells <em>via</em> FA receptor-mediated endocytosis for increased cellular uptake; (2) PDA-based photothermal therapy (PTT) elevated the catalytic reaction rate and ˙OH generation efficiency of CDT through hyperthermia; (3) copper doping not only enhanced the photothermal effect of PDA but also facilitated CDT through the Fenton-like reaction to deplete GSH and catalyze intracellular H<small>₂</small>O<small>₂</small>; and (4) the delivery of curcumin further depleted GSH to increase cytotoxic ˙OH, which promoted the thermal sensitivity of tumor cells and led to cell apoptosis. FPCCD exhibited efficient anti-tumor efficacy in C6 tumor-bearing mice, representing a potential strategy for enhancing CDT/PTT through self-enhanced ROS generation.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 14","pages":" 3903-3914"},"PeriodicalIF":5.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An AAQPR peptide from Aspergillus oryzae-fermented wheat peptone promotes the regenerative potential of dermal and epidermal layers of the skin in in vitro assays and clinical trials†","authors":"Sae Woong Oh, Eunbi Yu, Kitae Kwon, Hye Ja Lee, Hyun Sook Yeom, Kyung Man Hahm, Jin Oh Park, Jae Youl Cho and Jongsung Lee","doi":"10.1039/D5BM00571J","DOIUrl":"10.1039/D5BM00571J","url":null,"abstract":"<p >Because of the activity and stability of existing traditional proteins, promoting the regenerative potential of skin defects caused by various environmental stresses is challenging. Small peptides with relatively high activity and stability show potential for skin tissue regeneration. We previously demonstrated that <em>Aspergillus oryzae</em>-fermented wheat peptone enhanced the proliferation and hydration of human epidermal keratinocytes. In this study, the AAQPR peptide (INCI ID: 37800, PEP5) was selected from <em>Aspergillus oryzae</em>-fermented wheat peptone, and its regenerative potential was examined in both human primary dermal fibroblasts and epidermal keratinocytes. Moreover, the translational properties of PEP5 have been investigated in humans. Cell proliferation, collagen production, oxidative stress, and pro-inflammatory cytokines in fibroblasts and keratinocytes are important factors that affect skin regeneration. We observed that PEP5 induced collagen production through the Smad2/3 signaling pathway in human dermal fibroblasts. Autodock analysis showed the possibility that PEP5 physically interacts with the transforming growth factor-β receptor, leading to collagen production. PEP5 attenuated ultraviolet A (UVA)-induced dysregulation of metalloproteinase activity, collagen integrity, and inflammatory signaling in human fibroblasts. A comparable protective effect was observed in the human epidermal keratinocyte cell line, HaCaT cells, where PEP5 suppressed UVA-induced oxidative stress and cytokine production. Furthermore, PEP5 upregulated the expression of hydration-related genes in HaCaT cells, leading to skin hydration. In clinical studies, PEP5 treatment resulted in increased skin hydration and a reduction in fine wrinkles compared to the placebo group. These data suggest that PEP5 could be introduced as a potential therapeutic agent to help improve external stress on the skin.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 15","pages":" 4264-4282"},"PeriodicalIF":5.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoinductive IL-8/tDM/PLGA scaffolds based on autologous BMSC recruitment and endogenous growth factor regulation†","authors":"Zihao Zhao, Mengjie Xu, Zhou Zhang, Xing Yin, Ximing Pu, Juan Wang, Xiaoming Liao, Zhongbing Huang, Shunze Cao and Guangfu Yin","doi":"10.1039/D5BM00469A","DOIUrl":"10.1039/D5BM00469A","url":null,"abstract":"<p >The <em>in vitro</em> expanded seed cells and the supraphysiological doses of exogenous growth factors both pose huge safety risks in bone regeneration. In this study, a novel IL-8/tDM/PLGA composite scaffold was developed, where chemokine interleukin-8 (IL-8) and transferable decellularized matrix (tDM) were uniformly overlaid on exterior and interior surfaces of poly(lactic-<em>co</em>-glycolic acid) (PLGA) porous substrates. The <em>in vitro</em> experiments confirmed that the synergy of tDM and IL-8 achieved the obvious promotion of osteogenesis and angiogenesis <em>via</em> enhancing chemotaxis, adhesion, spreading, osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells (BMSCs). IL-8 mediated the <em>in situ</em> recruitment of BMSCs and macrophages <em>via</em> binding with C–X–C motif chemokine receptor 2 (CXCR2), while maintaining cellular viability without inducing macrophage polarization. Moreover, tDM improved BMSC adhesion and spreading <em>via</em> the recognition and binding of the affinitive ligand existing in tDM by the cell adhesion molecules (CAMs) on the BMSC cytomembrane. Furthermore, tDM promoted the osteogenic differentiation and mineralization of BMSCs, benefiting from the retained growth factors. In a rat femoral defect model, the IL-8/tDM/PLGA scaffold significantly accelerated new bone mineralization and maturation through synergistic regulations of cell recruitment, matrix adhesion, and osteogenic signaling pathways. After 8 weeks post-implantation of the IL-8/tDM/PLGA scaffolds, the bone volume fraction of the newly formed bone, trabecular number, and trabecular separation at the defect site were 47%, 1.21 mm<small>⁻²</small>, and 0.50 mm, respectively, which presented significantly better bone repair effects than those in other groups. These results demonstrated that the innovative bone regeneration strategy combining chemokine-driven recruitment and endogenous tDM regulation offered a potential solution for clinical repair of large-sized bone defects.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 14","pages":" 3972-3991"},"PeriodicalIF":5.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive DNA hydrogel interfacing with living cells and extracellular vesicles","authors":"Rui Zhang, Mingxing Liu, Hongjin Li, Yan Huang, Coo Yee Nah, Chi Yao and Dayong Yang","doi":"10.1039/D5BM00690B","DOIUrl":"10.1039/D5BM00690B","url":null,"abstract":"<p >Biological vesicles, such as living cells and extracellular vesicles (EVs) in biological systems, are important agents and regulators of life functions and play an irreplaceable role in physiological processes and disease progression. The maintenance of high bioactivity and structural integrity as well as selective isolation of target biological vesicles from complex biological systems are of great significance for downstream applications, such as early diagnosis, treatment and prognostic monitoring of major diseases. Bioactive hydrogel is a material made of hydrogel containing bioactive molecules that simulate living systems <em>in vitro</em>. By exploiting the unique molecular recognition and sequence programmability of deoxyribonucleic acid (DNA), DNA containing multifunctional modules serves as the material chemistry basis. Through molecular design and functional unit incorporation, these strategies enable the construction of DNA hydrogels capable of targeted vesicle recognition. This review discusses interactions between DNA hydrogels and biological vesicles, focuses on controllable release mechanisms of vesicles, and highlights recent advances in biomedical applications boosted by bioactive DNA hydrogels, including cell and EV isolation, cell engineering and three-dimensional (3D) culture, disease detection, and disease treatments. First, the interaction and controllable release mechanisms of bioactive DNA hydrogels are summarized, and relevant research based on these mechanisms is reviewed. Second, pioneering work in biomaterial applications is summarized. Finally, it is concluded with the challenges faced by DNA hydrogels and the future prospects of bioactive DNA hydrogels.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 14","pages":" 3772-3788"},"PeriodicalIF":5.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing hand hygiene compliance through the long-lasting antimicrobial effects of nitric oxide-releasing hand sanitizer gel†","authors":"Manjyot Kaur Chug, Gabrielle Aluisio, Cole Bousquet, Mark Garren, Yun Qian, Joseph H. Campbell and Elizabeth J. Brisbois","doi":"10.1039/D5BM00359H","DOIUrl":"10.1039/D5BM00359H","url":null,"abstract":"<p >Effective hand hygiene is crucial for reducing the transmission of disease-causing pathogens. While alcohol-based hand sanitizers have become popular, their increased usage during the COVID-19 pandemic raised concerns about their short-lived activity and potential side effects. The increased application of hand sanitizers and harmful side effects has necessitated an effective alternative with prolonged and enhanced antimicrobial properties which could result in a reduced number of sanitizer applications. To address these issues and improve antimicrobial efficacy, this study developed a nitric oxide (NO)-releasing hand sanitizer (NORel) gel enriched with other antimicrobial and moisturizing ingredients like ethanol, tea tree oil, and glycerin. The NORel gel underwent comprehensive analysis, including assessments of pH for 60 d, rheology, NO release, cytocompatibility, and <em>in vitro</em> and <em>ex vivo</em> antimicrobial effectiveness on rabbit skin proving its ability to eliminate over 97% of bacteria and fungi, including antibiotic-resistant strains. One NORel gel formulation, NORel2, demonstrated antimicrobial activity comparable to a commercial alcohol-based gel containing 62% ethyl alcohol, achieving a reduction of more than 5 logs in <em>S. aureus</em> bacteria on a rabbit skin model. Additionally, the NORel gel significantly outperformed the commercial alcohol gel by maintaining its antimicrobial efficacy on infected rabbit skin, showing a persistent activity with a 1.6-log reduction in viable <em>S. aureus</em> 2 h after application. This research introduces a biocompatible NO-releasing gel with superior antimicrobial properties compared to common alcohol-based sanitizers, making it an effective hand hygiene solution to reduce infections, especially in high-risk environments.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 14","pages":" 3915-3928"},"PeriodicalIF":5.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}