Yiting Yang , Hanwen Hu , Xinxin Zhang , Seiichi Tokula , Manting Zhao , Ling He , Hujing Zhang , Qiao Liu , Qiang Fu , Qin Song
{"title":"A novel polymeric hydrogel of Periplaneta americana polysaccharide loaded with kaempferol-chitosan microspheres, which possesses antibacterial, hemostatic, antioxidant and wound healing promoting activities","authors":"Yiting Yang , Hanwen Hu , Xinxin Zhang , Seiichi Tokula , Manting Zhao , Ling He , Hujing Zhang , Qiao Liu , Qiang Fu , Qin Song","doi":"10.1016/j.bioadv.2026.214722","DOIUrl":"10.1016/j.bioadv.2026.214722","url":null,"abstract":"<div><div><em>Periplaneta americana</em>, as a traditional Chinese medicine, is widely used in wound repair. We isolated and purified a heteropolysaccharide PAP55–1-2 (8.13 kDa) from <em>Periplaneta americana</em> medicinal materials, which is mainly composed of <em>N</em>-acetylgalactosamine, galactose, glucose and mannose, etc. Among them, the content of <em>N</em>-acetylgalactosamine is relatively high, with a large number of <em>N</em>-acetyl groups. Through the study of structure-activity relationship, it was found that the <em>N</em>-acetyl groups play an important role in the process of wound healing. Therefore, PAP55–1-2 was reacted with N, N′‑carbonyldiimidazole (CDI) in DMSO at 50 °C for 3 h, and then ethylenediamine was added and reacted for 48 h. By using this mild method, the amino-modified <em>Periplaneta americana</em> polysaccharide (PAP-AM) was prepared while retaining the <em>N</em>-acetyl groups and their activity, and then reacted with aldehyde-modified chondroitin sulfate (Chs-CHO) to prepare a hydrogel. The cross-linking mechanism is attributed to the Schiff base reaction between amino and aldehyde groups. Subsequently, we prepared kaempferol (Kae)-chitosan (CS) microspheres with a diameter of 89.01 μm by a modified emulsification method, and then embedded them into high-dose PAP-AM hydrogel (PH-C) to produce a composite scaffold. The composite hydrogel Kae-CS@PH-C has good biodegradability, injectability, adhesion, self-healing and mechanical properties. In addition, it can accelerate the wound healing process in mice through antibacterial, hemostatic, antioxidant and immunomodulatory activities. These experiments indicate that the composite hydrogel has potential for biological applications.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214722"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038323","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}
Wenbi Wu , Haofan Liu , Jiamei Zhang , Yinchu Dong , Min Peng , Qi Zhu , Yi Zhang , Wei Zhao , Li Zhang , Ya Ren , Jinlu Liu , Boya Li , Wentao Li , Yu Hu , Jingzhu Duan , Maling Gou
{"title":"3D printing of Y-27632 enhanced elastic hydrogel conduits for peripheral nerve repair","authors":"Wenbi Wu , Haofan Liu , Jiamei Zhang , Yinchu Dong , Min Peng , Qi Zhu , Yi Zhang , Wei Zhao , Li Zhang , Ya Ren , Jinlu Liu , Boya Li , Wentao Li , Yu Hu , Jingzhu Duan , Maling Gou","doi":"10.1016/j.bioadv.2025.214679","DOIUrl":"10.1016/j.bioadv.2025.214679","url":null,"abstract":"<div><div>Nerve guide conduits provide an advanced tool for peripheral nerve repair, but their efficacy remains limited due to suboptimal axon regeneration. Y-27632, a ROCK inhibitor, has the potential to promote axon regeneration and functional restoration. Here, we show a Y-27632 enhanced elastic hydrogel conduit for effective nerve repair. The conduit comprised of gelatin methacryloyl (GelMA)/silk fibroin methacryloyl (SF-MA) hydrogels with Y-27632 loaded poly(lactic-co-glycolic acid) (PLGA)/polyvinyl alcohol (PVA) nanoparticles, is rapidly fabricated by a continuous 3D printing process. The drug Y-27632 can be sustainedly released from the conduits to promote neurite elongation. Meanwhile, the bioactive gelatin/fibroin hydrogels can facilitate Schwann cell adhesion, proliferation, and migration. Moreover, the elastic hydrogel conduit can be surgically sutured with nerve stumps to bridge nerve defects. At 16 weeks post-surgery, this conduit efficiently promotes axon regeneration and remyelination, facilitates muscle re-innervation, and enhances functional recovery in a 12 mm nerve defect model. These findings implicate that elastic hydrogel conduits with Y-27632 release would provide a promising therapeutic strategy for long-gap peripheral nerve defects.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214679"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918999","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}
María Carracedo-Pérez , Antonella Caterina Boccia , Inés Ardao , Cláudia P. Passos , Víctor Santos-Rosales , Beatriz Santos , Fabio Bernardo , María Blanco-Vales , Beatriz Magariños , Carlos A. García-González
{"title":"Engineering of green sterilization technology to obtain biocompatible aerogels: Supercritical CO2 versus ethylene oxide and gamma radiation","authors":"María Carracedo-Pérez , Antonella Caterina Boccia , Inés Ardao , Cláudia P. Passos , Víctor Santos-Rosales , Beatriz Santos , Fabio Bernardo , María Blanco-Vales , Beatriz Magariños , Carlos A. García-González","doi":"10.1016/j.bioadv.2025.214698","DOIUrl":"10.1016/j.bioadv.2025.214698","url":null,"abstract":"<div><div>The growing relevance of aerogels in biomedicine demands the choice of compatible sterilization techniques with these materials. Conventional methods, such as ethylene oxide (EO) and gamma radiation (γ-rays) sterilization, have significant drawbacks while facing important environmental restrictions. In this study, supercritical CO<sub>2</sub> (scCO<sub>2</sub>) sterilization is tested for polysaccharide (starch and alginate) aerogels as an eco-friendly alternative to conventional procedures. Three post-processing treatments under different CO<sub>2</sub> exposure regimes (static, dynamic and combined) and in the presence of H<sub>2</sub>O<sub>2</sub> as additive were developed and assessed to reach sterility assurance levels (SAL) below 10<sup>−6</sup>. After sterilization, a vacuum treatment was implemented to ensure a low residual presence of H<sub>2</sub>O<sub>2</sub> in the aerogels so that the material biocompatibility was not compromised according to <em>in vitro</em> cell tests with fibroblasts. The residual adsorbed H<sub>2</sub>O<sub>2</sub> was quantified for the first time in aerogels by nuclear magnetic resonance spectroscopy. The effects of the supercritical sterilization treatments on the textural and chemical properties of the aerogels were evaluated and compared to those treated with EO and γ-rays. Results highlight the unique efficiency of scCO<sub>2</sub> sterilization as a post-processing method that preserves the aerogel structure while offering an eco-sustainable potential for producing sterile and biocompatible materials.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214698"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927306","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":"Injectable silk fibroin hydrogel encapsulating pH-Responsive ZnS nanoparticles for synergistic redox modulation and diabetic wound healing","authors":"Xi Cheng , Yuchong Wang , Jiao Qian , Rong Bai","doi":"10.1016/j.bioadv.2025.214674","DOIUrl":"10.1016/j.bioadv.2025.214674","url":null,"abstract":"<div><div>Chronic diabetic wounds remain a major clinical challenge due to excessive reactive oxygen species (ROS), persistent inflammation, and impaired cellular function. Current wound dressings offer limited capacity to simultaneously regulate redox imbalance and support tissue regeneration, highlighting the necessity for adaptive, intelligent, and multifunctional platforms for regenerative therapy. Herein, we developed an injectable hydrogel system composed of methacrylated silk fibroin (SilMA) and aqueous-phase, pH-sensitive zinc sulfide nanoparticles (ZnS NPs). Spherical ZnS NPs were synthesized <em>via</em> a green aqueous-phase hydrothermal method, offering stable colloidal properties and controlled release of therapeutic H₂S and Zn<sup>2+</sup> under different pH conditions. Upon UV crosslinking, SilMA formed a porous, shear-thinning hydrogel (SF hydrogel) that facilitates <em>in situ</em> application and localized drug delivery. ZnS NPs were loaded into SF hydrogels and the resulting SF/ZnS hydrogel exhibited suitable mechanical strength, swelling and biodegradability for wound healing application. <em>In vitro</em> studies demonstrated the ZnS NPs' potent ROS-scavenging capacity and cytocompatibility, while the SF/ZnS hydrogel effectively restored fibroblasts and endothelial cells' function under oxidative stress and promoted macrophage polarization toward a reparative M2 phenotype. In a streptozotocin-induced diabetic mouse model, SF/ZnS hydrogel significantly accelerated wound closure, enhanced re-epithelialisation and collagen remodelling, and promoted neovascularization, while mitigating chronic inflammation. The SF/ZnS hydrogel developed in this study presents a promising therapeutic platform for chronic diabetic wounds, integrating redox regulation, immunomodulation, and regenerative enhancement within a single injectable system.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214674"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842855","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":"Theranostic platforms for skin tissue engineering: Bridging healing and real-time monitoring","authors":"Lidia Maeso , Mohammadsadegh Nadimifar , Saptarshi Biswas , Shounak Roy , Akhilesh K. Gaharwar , Alireza Dolatshahi-Pirouz , Gorka Orive","doi":"10.1016/j.bioadv.2026.214724","DOIUrl":"10.1016/j.bioadv.2026.214724","url":null,"abstract":"<div><div>Chronic wounds are a major healthcare challenge, contributing to significant morbidity and reduced quality of life while imposing a substantial economic burden on healthcare systems. Traditional wound care approaches often fail to provide real-time feedback on treatment efficacy, limiting the ability to adapt therapeutic strategies dynamically. Theranostic platforms, which can integrate both diagnostic and therapeutic functionalities, have emerged as a promising solution to bridge this gap. These advanced systems enable continuous monitoring of key wound parameters, such as temperature, pH, oxygen levels, glucose, and reactive oxygen species (ROS), while simultaneously delivering targeted therapies, including drug release, gene and cell therapies, immunomodulation, and photothermal or photodynamic treatments. By incorporating both healing and monitoring capabilities into acellular scaffolds, hydrogel-based matrices, self-healing hydrogels, and 3D-bioprinted skin substitutes, researchers aim to optimize therapeutic efficacy and improve clinical outcomes. This review explores the different platforms available for skin tissue engineering that serve as the foundation for theranostic systems, alongside the most relevant diagnostic and therapeutic strategies for enhanced wound healing, and discusses future directions and challenges in this evolving field.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214724"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038321","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}
Ignacio Sallent , Lefki Chaniotaki , Dimitrios I. Zeugolis
{"title":"Freeze-dried and imprinted collagen scaffolds in tendon engineering","authors":"Ignacio Sallent , Lefki Chaniotaki , Dimitrios I. Zeugolis","doi":"10.1016/j.bioadv.2025.214681","DOIUrl":"10.1016/j.bioadv.2025.214681","url":null,"abstract":"<div><div>Collagen type I, as the main component of tendons, is an attractive biomaterial for the development of scaffolds for tendon repair and regeneration. Herein, we review advancements in freeze-drying and soft lithography scaffold fabrication procedures that permit the manufacturing of collagen scaffolds with precise architectural features. We also provide an overview of collagen crosslinking strategies that allow for the development of scaffolds with appropriate stiffness and cytocompatibility. In addition, we appraise the contribution of freeze-dried and imprinted collagen scaffolds in tendon engineering.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214681"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865935","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}
Jing Yang , Jie Wang , Chao Tao , Xiaowei Tang , Liuxuan Yang , Ke Wang , Weiyi Chen , Zhirong Zhong , Siqiong Wu , Meiling Zhou
{"title":"ROS-amplifying HKUST-1 nanozyme for enhanced colon cancer therapy","authors":"Jing Yang , Jie Wang , Chao Tao , Xiaowei Tang , Liuxuan Yang , Ke Wang , Weiyi Chen , Zhirong Zhong , Siqiong Wu , Meiling Zhou","doi":"10.1016/j.bioadv.2025.214671","DOIUrl":"10.1016/j.bioadv.2025.214671","url":null,"abstract":"<div><div>The development of effective strategies to amplify reactive oxygen species (ROS) within tumors has great potential to improve colon cancer therapy. In this study, we developed a multifunctional nanozyme platform (HHOC) based on the copper metal-organic framework HKUST-1, co-loading the photosensitizer chlorin e6 (Ce6) and the chemotherapeutic agent oxaliplatin (OXA), with surface modification by hyaluronic acid (HA). Benefiting from HA-mediated CD44 targeting, HHOC preferentially accumulated in colon cancer cells, resulting in enhanced cellular uptake. Upon laser irradiation, Ce6 generated abundant singlet oxygen to induce photodynamic therapy. Meanwhile, the HKUST-1 nanozyme exhibited peroxidase-like activity, with its Cu<sup>2+</sup> sites readily reduced by the elevated intracellular glutathione to Cu<sup>+</sup>, which depleted this key antioxidant and impaired cellular redox homeostasis. The generated Cu<sup>+</sup> further catalyzed endogenous hydrogen peroxide through Fenton-like reactions to produce highly cytotoxic hydroxyl radicals, thereby amplifying ROS-mediated oxidative stress. Moreover, HKUST-1 converted light energy into heat, producing a photothermal effect that promoted tumor cell damage and accelerated drug release. Released OXA exerted chemotherapeutic cytotoxicity, synergizing with ROS-mediated therapies. <em>In vivo</em> studies using CT26 tumor-bearing mice demonstrated that HHOC achieved a tumor growth inhibition rate of 94.51 %, confirming the efficacy of this ROS-amplifying nanozyme platform. This work presents HKUST-1-based nanozyme as an effective approach for multimodal colon cancer therapy through enhanced ROS generation and combinational treatment modalities.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214671"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865886","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":"Cerium-based nanoplatforms inhibiting goblet cell–associated antigen passages to stabilize barrier function in ulcerative colitis","authors":"Mao Tang , Laixian Zhou , Haitao Ran","doi":"10.1016/j.bioadv.2026.214706","DOIUrl":"10.1016/j.bioadv.2026.214706","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by recurrent mucosal inflammation and ulceration. Since managing UC remains challenging due to frequent therapeutic resistance and relapse, there is a pressing need for new strategies that target the underlying disease mechanisms to achieve long-term remission. Recent studies have highlighted the functional heterogeneity of intestinal goblet cells (GCs) beyond their classical role in mucus secretion. The goblet cell–associated passages (GAPs) have been identified as a luminal antigen delivery to lamina propria immune cells. Excessive GAP opening contributes to barrier dysfunction and mucosal inflammation, suggesting that GAPs are a promising therapeutic target. In this study, we designed a chondroitin sulfate–coated cerium nanoplatform (CS/CeO₂) loaded with the BAPTA-AM (BA) to stabilize the barrier function in colon. Briefly, BA was used to suppress excessive GAPs opening during the early stage of colitis, thereby alleviating abnormal immune activation. At the same time, CeO₂ served as a carrier to restrict the free diffusion of BA. Meanwhile, CS enabled efficient targeting of ulcerative lesions, allowing CeO₂ to fully exert its reactive oxygen species (ROS)–scavenging and CT imaging capabilities. Upon oral administration, BA-CS/CeO₂ successfully inhibited aberrant GAPs opening in DSS-induced colitis mice and enhanced intestinal barrier integrity, with restoration of mucus layer thickness and epithelial tight junctions, alongside reduced immune cell infiltration. Overall, this work leverages GC heterogeneity to re-establish intestinal barrier homeostasis, offering a promising nanotherapeutic strategy for UC through GAPs regulation, ROS scavenging, and CT monitoring.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214706"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927302","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}
Yi-Kai Chen , Ketav Kulkarni , Marie-Isabel Aguilar , Brad R.S. Broughton , Mark P. Del Borgo
{"title":"An antagomiR-loaded β-peptide hydrogel promotes functional recovery in mice post-ischaemic stroke","authors":"Yi-Kai Chen , Ketav Kulkarni , Marie-Isabel Aguilar , Brad R.S. Broughton , Mark P. Del Borgo","doi":"10.1016/j.bioadv.2026.214712","DOIUrl":"10.1016/j.bioadv.2026.214712","url":null,"abstract":"<div><div>Ischaemic stroke is a leading cause of mortality and disability, arising from interrupted cerebral blood flow and subsequent neuronal death. MicroRNAs, particularly miR-181a, have emerged as promising therapeutic targets due to their roles in regulating apoptosis and oxidative stress. While miR-181a inhibition using antagomirs can improve neuronal survival, translation to clinical practice is hampered by inefficient delivery across the blood–brain barrier and poor pharmacokinetics. Here, we developed a series of novel β-peptide hydrogels as injectable delivery systems to encapsulate and release a miR-181a antagomir in a controlled manner within the infarct region. β-peptides were synthesised with varied incorporation of β-homolysine residues to modulate electrostatic interactions with nucleic acids. The resulting hydrogels demonstrated shear-thinning and self-healing properties, stiffness values within the physiological range of brain tissue and tunable nucleic acid release profiles extending over 3 weeks. Following photothrombotic stroke in mice, intracerebral injection of antagomir-loaded hydrogel achieved precise infarct delivery and sustained presence for at least 7 days. Although infarct size reduction was modest, functional recovery, measured by improved motor coordination in the hanging wire test, was significantly enhanced in the hydrogel-antagomir group compared with controls. These findings highlight β-peptide hydrogels as promising platforms for localised, sustained delivery of nucleic acid therapeutics. This work establishes proof-of-concept for hydrogel-mediated miRNA delivery in stroke and provides a foundation for further optimisation in clinically relevant models.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214712"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967639","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":"In vitro and ex vivo evaluation of a papain-loaded mucoadhesive buccal patch with potential antifibrotic and anticancer activity","authors":"Nandita Parida , Rekha Rani Kokkanti , Soumyajit Biswas , Abikshyeet Panda , Srinivas Patnaik , Atul Anand Bajoria","doi":"10.1016/j.bioadv.2026.214731","DOIUrl":"10.1016/j.bioadv.2026.214731","url":null,"abstract":"<div><div>Oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC) are characterized by aberrant extracellular matrix remodeling, chronic inflammation, and limited responsiveness to current local treatment modalities. In this study, we report the design and <em>in vitro</em>/<em>ex vivo</em> evaluation of a papain-loaded bilayer mucoadhesive buccal patch as a proof-of-concept platform for localized enzyme delivery. Papain, a plant-derived cysteine protease with collagenolytic activity, was incorporated into a biocompatible polymeric matrix to enable controlled, site-specific release within the buccal environment. The optimized formulation exhibited acceptable physicochemical properties, including uniform thickness, flexibility, near-neutral surface pH, sustained hydration, and controlled papain release within a clinically relevant residence window. <em>In vitro</em> biological evaluation demonstrated differential responses in HGF and CAL-27 cells, with reduced cytotoxicity toward normal fibroblasts and decreased viability, clonogenicity, migration, invasion, and three-dimensional spheroid outgrowth in carcinoma cells under experimental conditions. <em>Ex vivo</em> collagen degradation studies using rat tail tissue further supported the ability of the formulation to interact with collagen-rich matrices. Hemocompatibility testing indicated minimal hemolysis, suggesting preliminary blood compatibility. Collectively, these findings establish the formulation feasibility and biological plausibility of a papain-loaded mucoadhesive buccal patch (P-MABP) as a localized enzyme delivery system. While the results support its potential relevance for fibrotic and neoplastic oral conditions, further <em>in vivo</em> studies and mechanistic investigations are required to define therapeutic efficacy, safety, and translational applicability.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214731"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078208","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}