S A Lim, S Chen, I Suzuki, K Lambaren, A Soleimani, N Ho, M Mousavi, E J Chung
{"title":"Harnessing Microneedles for Delivery and Preservation of Natural Killer Cell-Derived Extracellular Vesicles.","authors":"S A Lim, S Chen, I Suzuki, K Lambaren, A Soleimani, N Ho, M Mousavi, E J Chung","doi":"10.1021/acsbiomaterials.5c00760","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00760","url":null,"abstract":"<p><p>Natural killer cell-derived extracellular vesicles (NK-EVs) have demonstrated anti-inflammatory properties similar to those of their parent cells. EVs have been commonly delivered via intravenous (IV) administration, which can be invasive and is not ideal for chronic treatment. Another limitation of nanotherapy is its storage requirements, as EVs are commonly stored at -80 °C to preserve EV cargo and stability. In order to address these limitations, we explored dissolvable microneedles (MNs) as a promising alternative method for the administration of EVs. MNs have been used to deliver drugs, vaccines, and biomolecules, offering a convenient, noninvasive route of administration while preserving the therapeutic efficacy of EVs for extended periods, even at room temperature. Thus, we hypothesize that MN has the potential to sustain NK-EV stability and successfully deliver NK-EVs with minimal invasion. To test our hypothesis, we first developed an optimal MN formulation composed of hyaluronic acid and trehalose, both protein-protective materials that are biocompatible and biodegradable. After preparing MNs, we evaluated their stiffness, EV release profile, and ability to puncture pig skin. Additionally, the long-term storage stability of the EVs in MNs in inflammatory models in vitro and in vivo was evaluated. The MN successfully maintained EV efficacy even after storage after six months at room temperature, reducing the pro-inflammatory cytokine IL-6 by about 70% in inflamed human fibroblast cells relative to nontreated groups. Furthermore, EV-loaded MN treatment reduced both pro-inflammatory cytokines (IL-6 and TNFα) and psoriasis markers (Ki67 and IL-17) expression in a psoriasis model of chronic inflammation by about 40% compared to nontreated groups. Herein, our MN demonstrates the potential for easy-to-administer NK-EV therapies with long-term storage capabilities that preserve the NK-EV's anti-inflammatory properties.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chao Liang, Kesheng Gan, Libin Guo, Zonghuang Ye, Biru Hu
{"title":"Design of a Thermoresponsive, Scalable, and Robust Recombinant Protein-Based Bioadhesive by Combining Elastin-like Polypeptide with Barnacle Cement Protein.","authors":"Chao Liang, Kesheng Gan, Libin Guo, Zonghuang Ye, Biru Hu","doi":"10.1021/acsbiomaterials.5c00880","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00880","url":null,"abstract":"<p><p>Protein-based adhesives hold great promise as biomedical adhesives (bioadhesives) due to their exceptional biocompatibility and biodegradability. However, their wet adhesion abilities remain a significant challenge. Marine adhesive proteins (MAPs), a class of proteins renowned for their superior underwater adhesion abilities, provide critical inspiration for the design of robust protein-based bioadhesives. Herein, inspired by the adhesion mechanisms of sandcastle worms and barnacles, a novel fusion protein termed E110B was genetically engineered by combining a phase-transition elastin-like polypeptide (ELP) with the self-assembling barnacle 19 kDa cement protein (cp19k), an adhesive protein capable of nonspecifically adhering to various substrates. It was demonstrated that E110B can undergo temperature-dependent reversible phase transition, enabling convenient and scalable purification of recombinant proteins through a nonchromatographic method. Moreover, E110B was able to self-assemble into ordered supramolecular nanofibers, probably facilitated by the β-sheet structure of the cp19k module. Both phase transition and self-assembly significantly enhanced the adhesive strength of E110B. As a result, the self-assembled and phase-transitioned E110B-based adhesive demonstrated robust adhesion, with a maximum adhesion strength surpassing 4.5 MPa on glass and steel substrates under ambient conditions, outperforming all previously reported recombinant barnacle cement protein-based adhesives. Even in high-moisture environments (>90% relative humidity), the adhesive maintained a high adhesion strength of 0.31 ± 0.03 MPa. In addition to its robust adhesion, E110B achieved a comparable yield to other recombinant cp19k counterparts and exhibited good biocompatibility. These attributes make the E110B-based adhesive suitable for coating metallic and ceramic medical implants to improve their biocompatibility and biofunctionality. In summary, this study underscores the potential of combining ELPs with MAPs for designing scalable, thermoresponsive, and robust protein-based bioadhesives, opening a new avenue toward the development of advanced bioadhesives.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Zhang, Longhe Zhao, Rongzeng Hao, Yang Yang, Chaochao Shen, Zhengwang Shi, Yi Ru, Haixue Zheng
{"title":"Ferritin and Encapsulin Nanoparticles Enhance Immunogenicity of p30 Protein for ASFV Vaccine Development.","authors":"Yue Zhang, Longhe Zhao, Rongzeng Hao, Yang Yang, Chaochao Shen, Zhengwang Shi, Yi Ru, Haixue Zheng","doi":"10.1021/acsbiomaterials.5c00050","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00050","url":null,"abstract":"<p><p>African swine fever (ASF) represents a significant threat to the global swine industry due to the absence of a commercially available vaccine. The rational design of vaccine antigens is crucial for improving vaccine efficacy and guiding its development. The p30 protein of the African swine fever virus (ASFV) is an early membrane protein involved in the viral invasion of host cells. Antibodies against p30 effectively block viral internalization, highlighting its potential as a key vaccine antigen. In this study, ferritin and encapsulin nanoparticle platforms were utilized to display the p30 protein on their surfaces. The F/E-p30 nanoparticles significantly enhanced both the antigenicity and immunogenicity of the p30 protein. <i>In vivo</i> experiments revealed that the p30 protein, conjugated onto nanoparticles, accumulated in follicular dendritic cells (FDCs) within lymph nodes. This accumulation resulted in an increased number of T follicular helper (Tfh) and germinal center B (GCB) cells, thereby promoting the activation and maturation of both B and T cells. Compared to the p30 monomer, the p30 nanoparticles elicited stronger immune responses and facilitated the production of more potent, broad-spectrum antibodies that more effectively inhibit the internalization of genotype II and I/II recombinant ASFV strains. The p30-conjugated nanoparticles developed in this study present a competitive advantage as nanoparticle antigens, providing a robust foundation for ASFV vaccine development.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Poly(lactic-<i>co</i>-glycolic acid) Microspheres Encapsulating a Viral-Binding Protein, PmRab7, for Preventing White Spot Syndrome Virus in Shrimp.","authors":"Ruttanaporn Kriangsaksri, Suparat Taengchaiyaphum, Pattaree Payomhom, Dararat Thaiue, Ornchuma Itsathitphaisarn, Kallaya Sritunyalucksana, Kanlaya Prapainop Katewongsa","doi":"10.1021/acsbiomaterials.5c00928","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00928","url":null,"abstract":"<p><p>White spot syndrome virus (WSSV) is one of the most devastating pathogens affecting shrimp. Within a short time, it leads to a hundred percent mortality rate, which causes substantial economic losses. PmRab7 has been reported to bind to the envelope protein of WSSV, VP28, resulting in a reduction of viral replication. In order to apply PmRab7 in shrimp feed, the development of delivery systems is crucial. Poly(lactic-<i>co</i>-glycolic acid) (PLGA) is a biodegradable polymer extensively studied for drug delivery in the form of nanoparticles or microspheres (MSs). Despite its potential, PLGA has not been previously reported for antiviral use in shrimp. This study is the first to demonstrate the potential use of PLGA and chitosan-coated PLGA (PLGA/CS) MSs for the delivery of PmRab7 in shrimp. Both PLGA and PLGA/CS were optimized and characterized to allow for a sustained release of encapsulated PmRab7. Initial in vitro and in vivo evaluations demonstrated that both MSs are safe for use in shrimp, can sustain the release of PmRab7, and enhance its antiviral activity as shown by a decrease in the mortality rate in shrimp. The development of these MSs has the potential to significantly enhance disease control in shrimp aquaculture, leading to more effective and sustainable practices that will ultimately bolster the industry's growth and long-term stability.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianyi Feng, Liping Wei, Changhui Zhou, Shenning Li, Yingqi Li, Yali Fang, Wenteng Cui, Xiaohui Li, Lingzhi Bao, Lei Shen, Min Tang, Yan Chang
{"title":"Light-Based 3D Bioprinting of Testicular Organoid as an In Vitro Model for Reproductive Toxicity Assessment.","authors":"Tianyi Feng, Liping Wei, Changhui Zhou, Shenning Li, Yingqi Li, Yali Fang, Wenteng Cui, Xiaohui Li, Lingzhi Bao, Lei Shen, Min Tang, Yan Chang","doi":"10.1021/acsbiomaterials.5c00414","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00414","url":null,"abstract":"<p><p>Organoids can be used as an in vitro platform for studying tissue development and toxicology evaluation. While in vitro maturation of somatic and germ cells has been demonstrated in organoids, generating reproducible primary testicular cell-derived organoids for toxicity evaluation remains challenging. In this study, we developed testicular organoids using light-based 3D bioprinting of neonatal mouse primary testicular cells on transwell inserts. The bioprinting ink composition was specifically designed and optimized based on the extracellular matrix composition and mechanical properties of testicular tissue. The organoids were cultured for 21 days using an optimized medium to support testicular cell development and function. These bioprinted organoids recapitulated key features of the in vivo testicular architecture, forming tubule-like structures with cellular organization and gene expression profiles similar to native tissue. Following exposure to the known male reproductive toxic agent triptolide, testicular organoids showed loss of tight junction protein CLAUDIN-11 and altered transcript levels of somatic markers. Each bioprinted testicular organoid can be generated within 1 min, with toxicity evaluation results available within 1 month. This rapid turnaround makes it a promising high-throughput platform for toxicological studies, advancing our understanding of testicular development, function, and the impact of potential toxicants on male reproductive health.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigation and Characterization of Gold Nanoparticle-Loaded Poly(ε-caprolactone) Electrospun Nanofibrous Scaffolds with a Polydopamine Coating for Bone Regeneration.","authors":"Hongling Zhao, Guohou Miao, Sihan Zheng, Siying Lao, Hongru Chen, Wen Zhang, Qing Zhang, Zilin Li, Yin Xiao, Xuechao Yang","doi":"10.1021/acsbiomaterials.5c00682","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00682","url":null,"abstract":"<p><p>Electrospun nanofibrous scaffolds have attracted considerable attention in the field of bone tissue engineering, but most polymer-based scaffolds demonstrate restricted efficacy in promoting bone regeneration. In this study, a novel gold nanoparticles (AuNPs)-modified poly(ε-caprolactone) (PCL) electrospun nanofibrous scaffold (PCL/PDA@AuNPs) was developed via electrostatic interaction with a polydopamine (PDA) coating. The AuNPs, with an average diameter of 45 nm, exhibited excellent biocompatibility and enhanced alkaline phosphatase (ALP) activity in rat bone marrow mesenchymal stem cells (rBMSCs). The immobilization of AuNPs on the scaffold surface improved its hydrophilicity, mechanical properties, and biocompatibility. Furthermore, rBMSCs cultured on the PCL/PDA@AuNPs scaffolds showed enhanced osteogenic differentiation, as evidenced by a significant upregulation of ALP activity and osteogenic gene expression. <i>In vivo</i> experiments using a critical-sized rat calvarial defect model demonstrated that the implantation of PCL/PDA@AuNPs significantly promoted new bone formation and collagen deposition while concurrently mitigating inflammatory responses. Overall, these findings suggest that the AuNP-loaded nanofibrous scaffolds are highly promising for bone tissue engineering applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sphingosine-1-Phosphate (S1P) in Whole Liver Recellularization Improves Endothelization of Acellular Liver Scaffold.","authors":"Usha Yadav, Chandra J Yadav, Sadia Afrin, Jun-Yeong Lee, Jihad Kamel, Kyung-Mee Park","doi":"10.1021/acsbiomaterials.5c00411","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00411","url":null,"abstract":"<p><p>Endothelialization is crucial for tissue bioengineering, particularly in developing functional blood vessel linings to ensure proper vascularization. Effective re-endothelialization of the vasculature in bioengineered organs is challenging, often leading to blood coagulation and hindering successful engraftment. Endothelial cell proliferation, migration, and angiogenesis are essential processes for constructing functional and vascularized bioengineered organs. Sphingosine-1-phosphate (S1P), a low-molecular-weight phospholipid mediator, regulates various biological activities in endothelial cells including survival, proliferation, and cell barrier integrity. In this study, we present a novel approach to enhance the re-endothelialization of decellularized rat liver scaffolds by seeding human umbilical vein endothelial cells (HUVECs) in the presence of S1P, aiming to bioengineer a fully endothelialized liver. Initially, we validated the effects of S1P on HUVECs in a 2D cell culture system, confirming that S1P significantly promotes endothelial functions. Following this validation, we seeded HUVECs in the presence of S1P into decellularized rat liver scaffolds via the portal vein. The seeded liver was maintained in the bioreactor and perfused with medium supplemented with S1P for 7 days. The efficacy of S1P on liver scaffolds was evaluated through the longitudinal monitoring of cell proliferation using the resazurin reduction assay, indicating higher cell proliferation in the constructs. Further characterization through histological and molecular analyses demonstrated efficient coverage of vessels of re-endothelialized scaffolds maintaining their function. The antithrombotic effect of the fully endothelialized scaffold was assessed via ex vivo whole-blood perfusion. Our results indicate that S1P is a key regulator of endothelialization processes, promoting HUVECs proliferation and survival and facilitating the formation of a functional endothelial layer on the vascular structure of re-endothelialized liver scaffold.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Longzhen Chen, Zhuofeng Li, Ziyi Su, Yuqi Luo, Xunwu Hu, Ye Zhang
{"title":"Engineering Heparan Sulfate-Guided Peptide Self-Assembly to Restore Endothelial Angiogenesis under Hyperglycemia.","authors":"Longzhen Chen, Zhuofeng Li, Ziyi Su, Yuqi Luo, Xunwu Hu, Ye Zhang","doi":"10.1021/acsbiomaterials.5c00802","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00802","url":null,"abstract":"<p><p>Hyperglycemia-induced endothelial dysfunction impairs cytoskeletal plasticity, cell migration, and angiogenesis, contributing to the pathogenesis of diabetic vascular complications. To address this, we engineered a heparan sulfate (HS)-targeting peptide that couples a glycan-binding motif with a self-assembling domain, enabling localized formation of supramolecular nanostructures at the endothelial surface. These assemblies attenuate actomyosin contractility by remodeling cell-matrix interactions, thereby restoring contractile homeostasis, the dynamic equilibrium of intracellular tension and cytoskeletal adaptability, without compromising global cytoskeletal integrity. In vitro, the peptide reverses hyperglycemia-induced cytoskeletal stiffening, enhances endothelial motility, and rescues network formation in Matrigel tube formation assays, without inducing cytotoxicity. Through plasma membrane surface-selective self-assembly, this HS-guided platform offers a localized, biomimetic strategy for correcting mechanical dysfunction in diabetic endothelium and holds translational potential for vascular repair in metabolic diseases.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Markos Negash Alemie, Richard Bright, Neethu Ninan, Thien Ngoc Le, Ngoc Huu Nguyen, Vi Khanh Truong, Giles Best, Jitraporn Vongsvivut, Dennis Palms, John D Hayball, Krasimir Vasilev
{"title":"Deciphering the Role of Biomaterial Surface Chemistry in Toll-Like Receptor-Mediated Immune Modulation.","authors":"Markos Negash Alemie, Richard Bright, Neethu Ninan, Thien Ngoc Le, Ngoc Huu Nguyen, Vi Khanh Truong, Giles Best, Jitraporn Vongsvivut, Dennis Palms, John D Hayball, Krasimir Vasilev","doi":"10.1021/acsbiomaterials.5c00489","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00489","url":null,"abstract":"<p><p>The inflammatory response to biomaterials plays a critical role in determining the implant performance and longevity. As key early responders, macrophages detect the implant surface and orchestrate immune reactions. Biomaterial surface properties are a key modifiable factor that significantly influences macrophage activation and local immune response. Because macrophages depend on Toll-like receptor (TLR) signaling to identify and respond to foreign materials, understanding how biomaterials influence this pathway is crucial. In this study, we aim to investigate the role of surface chemistry in TLR signaling. To achieve this, we utilized plasma polymerization to engineer biomaterial surfaces with four distinct surface chemistries. Synchrotron ATR-FTIR microspectroscopy revealed shifts in the infrared spectra, indicating changes in macromolecules in macrophages upon interaction with various surface coatings. Gene expression analysis showed that macrophages cultured on hydrocarbon-rich surfaces exhibited increased TLR2 expression and upregulated proinflammatory genes, including TNF-α, IL-1β, IL-6, and iNOS. In contrast, surfaces rich in carboxylic acid, amine, and oxazoline functionalities heightened TLR4 expression and upregulated anti-inflammatory genes, such as IL-1RA, arginase, and IL-10. These findings highlight the impact of biomaterial surface chemistry on immune signaling pathways, demonstrating that surface modifications can actively influence the polarization of macrophages. By leveraging these insights, we can refine biomaterial design to create immune-modulatory surfaces that optimize healing, reduce inflammation, and enhance success with implantable medical devices.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Lithium-Containing Hydrogel for Topical Prevention of Radiation-Induced Oral Mucositis and Dysgeusia.","authors":"Shuhao Zheng, Zixia Li, Yu Luo, Zihan Ding, Wenhui Liang, Hang Zhao, Liwei Zheng, Xin Xu","doi":"10.1021/acsbiomaterials.5c00703","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00703","url":null,"abstract":"<p><p>Radiation-induced oral mucositis (RIOM) and taste dysfunction (dysgeusia) are common complications of radiotherapy in cancer patients. Current clinical interventions for RIOM mainly focus on symptom alleviation but with limited efficacy and nonevidenced taste protection. Our previous study showed that systemic administration of lithium (a Wnt agonist) ameliorated radiation-induced oral mucositis and dysgeusia by promoting basal cell proliferation and taste bud renewal. However, the potential cytotoxicity of systemic administration of lithium necessitates topical application. In this study, a poly(vinyl alcohol)-lithium citrate (PVA-LC) hydrogel was developed, which promoted the substantivity of lithium in the moist and dynamic oral cavity with a good biocompatibility. The hydrogel significantly alleviated RIOM, as shown by the decrease in the proportion of ulcer area from 37.09% (±5.58%) to 0.54% (±0.40%), and protected taste perception in mice. Mechanistically, lithium citrate (Li<sub>3</sub>C<sub>6</sub>H<sub>5</sub>O<sub>7</sub>) effectively blocked X-ray-induced apoptosis and promoted cell proliferation and migration, which were crucial for the reconstitution of oral mucosa. In summary, the current study developed a lithium-containing mucoadhesive hydrogel, showing good clinical translational potential in the management of radiotherapy-associated oral complications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}