Corneal neovascularization (CNV) is a sight-threatening pathological process that poses the challenge of controlling inflammation, preventing infection, and thereby inhibiting angiogenesis. To address this, we developed a novel pH-responsive smart micelle-integrated hydrogel, termed LEV@DG-HPMC. This system is composed of a three-dimensional network formed by dipotassium glycyrrhizinate (DG) and hydroxypropyl methylcellulose (HPMC) for the delivery of levofloxacin (LEV). The hydrogel network is formed by physical cross-linking. Within this system, LEV provides potent antibacterial activity, while DG contributes inherent anti-inflammatory properties. The LEV@DG-HPMC hydrogel demonstrated excellent biocompatibility and significantly prolonged ocular surface retention. Its unique pH-responsive drug release profile closely matched the temporal pH changes in the pathological microenvironment post-alkali injury. Crucially, the hydrogel exhibited synergistic therapeutic effects, combining potent antibacterial activity with the ability to significantly downregulate key inflammatory cytokines and suppress pro-angiogenic factors, such as such as interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, nuclear factor-κB, vascular endothelial growth factor A, matrix metalloproteinase-9. Consequently, it effectively inhibited CNV progression, reduced corneal opacity, and promoted corneal repair. This multifunctional smart hydrogel represents a highly promising strategy for the treatment of CNV.
{"title":"Micelle-integrated hydrogel combined with pH-response boosts eye burns therapy by inhibiting neovascularization, regulating inflammation and bacteriostasis.","authors":"Yahong Li, Xinyuan Wang, Meina Wu, Jieying Ren, Yanan Wang, Chaochao Wen, Xia Sen, Qingjun Tian, Yijie Wang, Yumeng Guo, Jian Xue, Yajian Duan, Tao Gong, Baofeng Yu","doi":"10.1016/j.bioadv.2026.214732","DOIUrl":"https://doi.org/10.1016/j.bioadv.2026.214732","url":null,"abstract":"<p><p>Corneal neovascularization (CNV) is a sight-threatening pathological process that poses the challenge of controlling inflammation, preventing infection, and thereby inhibiting angiogenesis. To address this, we developed a novel pH-responsive smart micelle-integrated hydrogel, termed LEV@DG-HPMC. This system is composed of a three-dimensional network formed by dipotassium glycyrrhizinate (DG) and hydroxypropyl methylcellulose (HPMC) for the delivery of levofloxacin (LEV). The hydrogel network is formed by physical cross-linking. Within this system, LEV provides potent antibacterial activity, while DG contributes inherent anti-inflammatory properties. The LEV@DG-HPMC hydrogel demonstrated excellent biocompatibility and significantly prolonged ocular surface retention. Its unique pH-responsive drug release profile closely matched the temporal pH changes in the pathological microenvironment post-alkali injury. Crucially, the hydrogel exhibited synergistic therapeutic effects, combining potent antibacterial activity with the ability to significantly downregulate key inflammatory cytokines and suppress pro-angiogenic factors, such as such as interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, nuclear factor-κB, vascular endothelial growth factor A, matrix metalloproteinase-9. Consequently, it effectively inhibited CNV progression, reduced corneal opacity, and promoted corneal repair. This multifunctional smart hydrogel represents a highly promising strategy for the treatment of CNV.</p>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"214732"},"PeriodicalIF":6.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127378","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}
Melanoma is an aggressive type of skin cancer due to its ability to rapidly spread to various organs. The oral drug administration is preferred for its convenience. However, the oral route faces challenges, including the first-pass metabolism and delayed onset of action. Therefore, the transdermal drug delivery system (TDDS) offers an alternative approach to overcome these limitations. This work developed an iontophoresis-based transdermal patch using LCB and XG hydrogel as the drug matrix. In addition, PAIn:PSS was synthesized and employed as the drug carrier, whereas Imatinib was used as the model drug. LCB:XG hydrogels were fabricated at the various weight ratios. The LCB:XG (60:40%w/w) hydrogel exhibited the largest pore size (261.3 ± 67.3 μm). In-vitro release and permeation studies demonstrated that a lower XG ratio resulted in increased Imatinib release. Additionally, incorporating PAIn:PSS further enhanced the release efficiency. Applying an electric field significantly improved drug permeation due to the electrorepulsion which promoted the transport of drug molecules across the skin. Additionally, the permeated release at the pH of 5.5 was slightly lower than that at the pH of 7.4; this can be attributed to the increased positive charge of Imatinib reducing skin permeation due to increased hydrophilicity. Cytotoxicity tests revealed that incorporating PAIn:PSS into the hydrogel patch maintained the high cell viability of 84%, confirming that the hydrogel patch was safe for human tissues. These findings highlight the potential of LCB:XG hydrogel-based transdermal patches combined with PAIn:PSS and iontophoresis for the controlled drug release and efficient Imatinib transdermal delivery.
{"title":"Poly-5-aminoindole:Poly(4-styrenesulfonic acid) loaded locust bean gum/xanthan gum hydrogel for transdermal delivery of Imatinib via iontophoresis","authors":"Patamavadee Tapsarn , Phimchanok Sakunpongpitiporn , Nophawan Paradee , Katesara Phasuksom , Anuvat Sirivat","doi":"10.1016/j.bioadv.2026.214730","DOIUrl":"10.1016/j.bioadv.2026.214730","url":null,"abstract":"<div><div>Melanoma is an aggressive type of skin cancer due to its ability to rapidly spread to various organs. The oral drug administration is preferred for its convenience. However, the oral route faces challenges, including the first-pass metabolism and delayed onset of action. Therefore, the transdermal drug delivery system (TDDS) offers an alternative approach to overcome these limitations. This work developed an iontophoresis-based transdermal patch using LCB and XG hydrogel as the drug matrix. In addition, PAIn:PSS was synthesized and employed as the drug carrier, whereas Imatinib was used as the model drug. LCB:XG hydrogels were fabricated at the various weight ratios. The LCB:XG (60:40%w/w) hydrogel exhibited the largest pore size (261.3 ± 67.3 μm). In-vitro release and permeation studies demonstrated that a lower XG ratio resulted in increased Imatinib release. Additionally, incorporating PAIn:PSS further enhanced the release efficiency. Applying an electric field significantly improved drug permeation due to the electrorepulsion which promoted the transport of drug molecules across the skin. Additionally, the permeated release at the pH of 5.5 was slightly lower than that at the pH of 7.4; this can be attributed to the increased positive charge of Imatinib reducing skin permeation due to increased hydrophilicity. Cytotoxicity tests revealed that incorporating PAIn:PSS into the hydrogel patch maintained the high cell viability of 84%, confirming that the hydrogel patch was safe for human tissues. These findings highlight the potential of LCB:XG hydrogel-based transdermal patches combined with PAIn:PSS and iontophoresis for the controlled drug release and efficient Imatinib transdermal delivery.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"183 ","pages":"Article 214730"},"PeriodicalIF":6.0,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081885","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}
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 in vitro/ex vivo 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. In vitro 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. Ex vivo 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 in vivo studies and mechanistic investigations are required to define therapeutic efficacy, safety, and translational applicability.
{"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":"2026-01-23","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}
Pub Date : 2026-01-22DOI: 10.1016/j.bioadv.2026.214726
Ling Li , Anna Liu , Cai Wang , Ling Zhang , Houqiang Yu , Han Li , Hongfu Zhou
To achieve sustained release and prolonged tumor retention of oxaliplatin (OXA), a thermosensitive OXA-loaded poly(N-isopropyl acrylamide-co-acrylic acid) nanogel (PAAs) was developed via a synergistic mixing-stirring method. The formulation, consisting of 0.8 mg/mL OXA thoroughly dispersed in 8% poly(N-isopropyl acrylamide-co-acrylic acid) nanogel (PNAs), exhibited favorable radiofrequency responsiveness, thermosensitivity, and controlled-release properties, enabling continuous OXA release for up to five days. The sol–gel phase transition behavior of the thermosensitive PAAs nanogel was characterized using the vial-inversion method and rheological analysis. Platinum content analysis revealed enhanced tumor retention of the PAAs nanogel compared with free OXA, as evidenced by significantly higher platinum levels in tumors treated with the nanogel formulation. In vivo antitumor efficacy evaluation demonstrated that a single administration of the PAAs nanogel resulted in sustained tumor regression, reducing the relative tumor volume to 0.81 ± 0.06 times the initial volume within 14 days. In contrast, treatment with an equivalent dose of free OXA, PNAs alone, or normal saline led to rapid tumor progression, with tumor volumes increasing to 3.22 ± 0.65, 7.01 ± 0.47, and 10.07 ± 1.57 times the initial volume, respectively. Preliminary biocompatibility assessment indicated that the incorporation of OXA into PNAs within the nanogel significantly alleviated the toxic side effects associated with free OXA. These findings underscore the considerable potential of the PAAs nanogel as a versatile strategy to enhance the antitumor efficacy of platinum-based drugs while mitigating their systemic toxicity and size-related limitations. This system therefore represents a promising candidate for further development as a novel nanomedicine for localized chemotherapy.
{"title":"Thermosensitive nanogel-based oxaliplatin delivery system for synergistic intratumoral radiofrequency chemotherapy","authors":"Ling Li , Anna Liu , Cai Wang , Ling Zhang , Houqiang Yu , Han Li , Hongfu Zhou","doi":"10.1016/j.bioadv.2026.214726","DOIUrl":"10.1016/j.bioadv.2026.214726","url":null,"abstract":"<div><div>To achieve sustained release and prolonged tumor retention of oxaliplatin (OXA), a thermosensitive OXA-loaded poly(N-isopropyl acrylamide-<em>co</em>-acrylic acid) nanogel (PAAs) was developed via a synergistic mixing-stirring method. The formulation, consisting of 0.8 mg/mL OXA thoroughly dispersed in 8% poly(N-isopropyl acrylamide-<em>co</em>-acrylic acid) nanogel (PNAs), exhibited favorable radiofrequency responsiveness, thermosensitivity, and controlled-release properties, enabling continuous OXA release for up to five days. The sol–gel phase transition behavior of the thermosensitive PAAs nanogel was characterized using the vial-inversion method and rheological analysis. Platinum content analysis revealed enhanced tumor retention of the PAAs nanogel compared with free OXA, as evidenced by significantly higher platinum levels in tumors treated with the nanogel formulation. In vivo antitumor efficacy evaluation demonstrated that a single administration of the PAAs nanogel resulted in sustained tumor regression, reducing the relative tumor volume to 0.81 ± 0.06 times the initial volume within 14 days. In contrast, treatment with an equivalent dose of free OXA, PNAs alone, or normal saline led to rapid tumor progression, with tumor volumes increasing to 3.22 ± 0.65, 7.01 ± 0.47, and 10.07 ± 1.57 times the initial volume, respectively. Preliminary biocompatibility assessment indicated that the incorporation of OXA into PNAs within the nanogel significantly alleviated the toxic side effects associated with free OXA. These findings underscore the considerable potential of the PAAs nanogel as a versatile strategy to enhance the antitumor efficacy of platinum-based drugs while mitigating their systemic toxicity and size-related limitations. This system therefore represents a promising candidate for further development as a novel nanomedicine for localized chemotherapy.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214726"},"PeriodicalIF":6.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037704","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}
Pub Date : 2026-01-22DOI: 10.1016/j.bioadv.2026.214719
Hung-Chi Chen , Yi-Jen Hsueh , Yaa-Jyuhn James Meir , Jui-Yang Lai , Chieh-Cheng Huang , Tsai-Te Lu , Chao-Min Cheng , Song-Shu Lin , David Hui-Kang Ma , Wei-Chi Wu
Corneal transparency maintenance relies on the water-pumping function of the corneal endothelium. Currently, corneal transplantation remains the only available treatment for corneal endothelial dysfunction, therefore, the development of alternative therapies is critical due to the global shortage of donor corneas. In our previous study, we confirmed that corneal stromal cells (CSCs) secretion can promote corneal endothelial cells (CEnCs) proliferation. This effect can be enhanced by treatment with lysophosphatidic acid (LPA), a bioactive phospholipid. Nevertheless, the components involved in CSC secretion remain to be elucidated. In this study, we investigated the therapeutic potential of CSC-derived exosomes and exosomal microRNAs (miRNAs) for enhancing CEnCs proliferation and corneal endothelial healing. CSC exosomes were characterized via nanoparticle tracking (NTA), transmission electron microscopy (TEM), and immunoassays. The miRNA expression profiles of CSC exosomes were identified via RNA sequencing, revealing a total of 767 distinct miRNAs. The proliferative effects of CSC exosomes and exosomal miR-221-3p were increased by LPA. Ectopic expression of miR-221-3p further increased CEnC proliferation and suppressed the expression of the CDK inhibitor p27Kip1. The therapeutic efficacy was evaluated using a transcorneal freezing rabbit model, where intrastromal injection of CSC exosomes or ectopic expression of miR-221-3p significantly ameliorated corneal endothelial damage, as supported by improved in vivo corneal recovery, including restoration of corneal thickness, and re-establishment of a hexagonal morphology in the corneal endothelium. Our findings suggest that CSC exosomes and miR-221-3p represent potentially promising cell-free therapies for treating corneal endothelial diseases, highlighting an innovative approach to improving corneal regeneration.
{"title":"Lysophosphatidic acid-induced upregulation of exosomal miR-221-3p from corneal stromal cells promotes corneal endothelial healing","authors":"Hung-Chi Chen , Yi-Jen Hsueh , Yaa-Jyuhn James Meir , Jui-Yang Lai , Chieh-Cheng Huang , Tsai-Te Lu , Chao-Min Cheng , Song-Shu Lin , David Hui-Kang Ma , Wei-Chi Wu","doi":"10.1016/j.bioadv.2026.214719","DOIUrl":"10.1016/j.bioadv.2026.214719","url":null,"abstract":"<div><div>Corneal transparency maintenance relies on the water-pumping function of the corneal endothelium. Currently, corneal transplantation remains the only available treatment for corneal endothelial dysfunction, therefore, the development of alternative therapies is critical due to the global shortage of donor corneas. In our previous study, we confirmed that corneal stromal cells (CSCs) secretion can promote corneal endothelial cells (CEnCs) proliferation. This effect can be enhanced by treatment with lysophosphatidic acid (LPA), a bioactive phospholipid. Nevertheless, the components involved in CSC secretion remain to be elucidated. In this study, we investigated the therapeutic potential of CSC-derived exosomes and exosomal microRNAs (miRNAs) for enhancing CEnCs proliferation and corneal endothelial healing. CSC exosomes were characterized via nanoparticle tracking (NTA), transmission electron microscopy (TEM), and immunoassays. The miRNA expression profiles of CSC exosomes were identified via RNA sequencing, revealing a total of 767 distinct miRNAs. The proliferative effects of CSC exosomes and exosomal miR-221-3p were increased by LPA. Ectopic expression of miR-221-3p further increased CEnC proliferation and suppressed the expression of the CDK inhibitor p27<sup>Kip1</sup>. The therapeutic efficacy was evaluated using a transcorneal freezing rabbit model, where intrastromal injection of CSC exosomes or ectopic expression of miR-221-3p significantly ameliorated corneal endothelial damage, as supported by improved in vivo corneal recovery, including restoration of corneal thickness, and re-establishment of a hexagonal morphology in the corneal endothelium. Our findings suggest that CSC exosomes and miR-221-3p represent potentially promising cell-free therapies for treating corneal endothelial diseases, highlighting an innovative approach to improving corneal regeneration.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214719"},"PeriodicalIF":6.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146068438","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}
Pub Date : 2026-01-21DOI: 10.1016/j.bioadv.2026.214727
Fen Ao , Wen Shen , Xuemei Ge , Yan Zheng
Multilayer membranes that coordinate the release of different drugs to match the various stages of wound healing while managing excessive tissue exudate represent a promising therapeutic approach. However, achieving precise control over the dual-drug release and effective absorption of excess tissue exudate remains a significant clinical challenge. This study employed a “nano-in-nano” microsphere-embedded fiber strategy to construct a multilayered dual drug delivery system (ML-DDS) via sequential electrospinning. The system comprises three layers: an outer fiber layer loaded with the antibacterial drug amikacin (Am), an intermediate layer of microspheres loaded with the anti-inflammatory drug quercetin (Qu) embedded within the fibers and an inner hydrophobic ethyl cellulose layer. Structural characterization showed that the intermediate layer had a diameter of approximately 500 nm with embedded microspheres predominantly ranging from 2.5 to 3.5 μm, while the inner EC fibers measured about 150 nm in diameter. The system leverages interfacial capillary forces to transport exudate from the hydrophobic layer to the drug-carrying layer. The water contact angles of the innermost hydrophobic layer and the outermost hydrophilic layer decrease to 0° within 40 s and 60 s, respectively. Drug release channels were formed after the ethyl cellulose layer absorbs water and swells. The release time of Am extended from 120 min in the single layer to 24 h in the ML-DDS. Both Qu and Am were continuously released in an amorphous form within 24 h through matrix erosion. ML-DDS up-regulated the expression of antioxidant-related metabolites, maintained mitochondrial function and promoted wound healing with a higher healing rate at day 14 compared to the control, along with enhanced collagen deposition, up-regulated CD31 expression, and reduced COX-2 levels. This study demonstrates that ML-DDS effectively integrates multilayered exudate management with controlled dual-drug delivery, providing a novel treatment strategy for skin wounds with excessive tissue exudate.
{"title":"Multilayered electrospun membranes incorporating microspheres embedded nanofibers for enhanced wound healing","authors":"Fen Ao , Wen Shen , Xuemei Ge , Yan Zheng","doi":"10.1016/j.bioadv.2026.214727","DOIUrl":"10.1016/j.bioadv.2026.214727","url":null,"abstract":"<div><div>Multilayer membranes that coordinate the release of different drugs to match the various stages of wound healing while managing excessive tissue exudate represent a promising therapeutic approach. However, achieving precise control over the dual-drug release and effective absorption of excess tissue exudate remains a significant clinical challenge. This study employed a “nano-in-nano” microsphere-embedded fiber strategy to construct a multilayered dual drug delivery system (ML-DDS) via sequential electrospinning. The system comprises three layers: an outer fiber layer loaded with the antibacterial drug amikacin (Am), an intermediate layer of microspheres loaded with the anti-inflammatory drug quercetin (Qu) embedded within the fibers and an inner hydrophobic ethyl cellulose layer. Structural characterization showed that the intermediate layer had a diameter of approximately 500 nm with embedded microspheres predominantly ranging from 2.5 to 3.5 μm, while the inner EC fibers measured about 150 nm in diameter. The system leverages interfacial capillary forces to transport exudate from the hydrophobic layer to the drug-carrying layer. The water contact angles of the innermost hydrophobic layer and the outermost hydrophilic layer decrease to 0° within 40 s and 60 s, respectively. Drug release channels were formed after the ethyl cellulose layer absorbs water and swells. The release time of Am extended from 120 min in the single layer to 24 h in the ML-DDS. Both Qu and Am were continuously released in an amorphous form within 24 h through matrix erosion. ML-DDS up-regulated the expression of antioxidant-related metabolites, maintained mitochondrial function and promoted wound healing with a higher healing rate at day 14 compared to the control, along with enhanced collagen deposition, up-regulated CD31 expression, and reduced COX-2 levels. This study demonstrates that ML-DDS effectively integrates multilayered exudate management with controlled dual-drug delivery, providing a novel treatment strategy for skin wounds with excessive tissue exudate.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214727"},"PeriodicalIF":6.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037702","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}
Pub Date : 2026-01-21DOI: 10.1016/j.bioadv.2026.214718
Zijian Yang , Bowen Zhang , Yihao Liu , Kaiting Chen , Qing Zhang , Changning Sun , Ling Wang , Dichen Li , Qingchu Li , Huiyu Zhao
Polyetheretherketone (PEEK) is widely applied in orthopedic implants, yet its intrinsic surface bioinertness limits stable osseointegration. Although a nature solution is modifying its surface to enhance cellular adhesion, other pathways related to osseointegration also hold significant value. Here, we combined fused deposition modeling (FDM) 3D printing with a two-step poly (acrylic acid)–ethylenediamine (PAA–EDA) grafting method to engineer porous PEEK scaffolds with bioactive surface microstructures. Beyond improving hydrophilicity to optimize cellular adhesion, the modified surface activated the βPIX-mediated signaling cascade, which suppressed ITGB1–RAC1–NOX1 activity, potentially delaying bone mesenchymal stem cell (BMSC) senescence and promoting osteogenic differentiation. In vivo implantation further validated that the modified scaffolds promoted bone formation and integration. Together, this work highlights a new pathway on osseointegration for PEEK surface engineering, revealing the potential of βPIX-mediated regulation as a new direction for durable bone–implant integration.
{"title":"Surface microstructure of PEEK scaffolds regulates osteogenic differentiation via the βPIX–RAC1–NOX1 pathway","authors":"Zijian Yang , Bowen Zhang , Yihao Liu , Kaiting Chen , Qing Zhang , Changning Sun , Ling Wang , Dichen Li , Qingchu Li , Huiyu Zhao","doi":"10.1016/j.bioadv.2026.214718","DOIUrl":"10.1016/j.bioadv.2026.214718","url":null,"abstract":"<div><div>Polyetheretherketone (PEEK) is widely applied in orthopedic implants, yet its intrinsic surface bioinertness limits stable osseointegration. Although a nature solution is modifying its surface to enhance cellular adhesion, other pathways related to osseointegration also hold significant value. Here, we combined fused deposition modeling (FDM) 3D printing with a two-step poly (acrylic acid)–ethylenediamine (PAA–EDA) grafting method to engineer porous PEEK scaffolds with bioactive surface microstructures. Beyond improving hydrophilicity to optimize cellular adhesion, the modified surface activated the βPIX-mediated signaling cascade, which suppressed ITGB1–RAC1–NOX1 activity, potentially delaying bone mesenchymal stem cell (BMSC) senescence and promoting osteogenic differentiation. In vivo implantation further validated that the modified scaffolds promoted bone formation and integration. Together, this work highlights a new pathway on osseointegration for PEEK surface engineering, revealing the potential of βPIX-mediated regulation as a new direction for durable bone–implant integration.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214718"},"PeriodicalIF":6.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038325","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}
Pub Date : 2026-01-21DOI: 10.1016/j.bioadv.2026.214728
Yujiao Yan , Yutong Chen , Fengmei Yang , Ruixin Zhao , Die Tian , Liran Deng , Meng Xie
To address the complex pathology of Alzheimer’s disease (AD), including abnormal amyloid-β (Aβ) aggregation, metal ion homeostasis disruption and oxidative stress, we developed an integrated multifunctional nanoplatform. This platform leveraged a covalent organic framework (TD-COF) with intrinsic capabilities for Cu2+ chelation and Aβ inhibition as the carrier. Through in-situ engineering, ultrafine palladium nanoparticles (PdNPs) were anchored to construct a stable, functionally integrated core (Pd-COF). However, due to limitations of nanomaterials such as short half-life and poor brain targeting, we further employed red blood cell (RBC) membrane for biomimetic modification, yielding the final platform Pd-COF-RBC. In vitro experiments demonstrated that Pd-COF-RBC concurrently achieved Cu2+ chelation, Aβ fibrillation inhibition and reactive oxygen species (ROS) scavenging. Notably, the design of Pd-COF also regulated the size and dispersibility of PdNPs, enhancing catalase-like (CAT) activity by 34.7%. In Aβ-induced cellular models, the material effectively alleviated oxidative stress and mitochondrial dysfunction, increasing cell survival by over 78.4%. Further experiments confirmed that Pd-COF-RBC modified with RBC membrane possessed good biocompatibility, long circulation property and brain accumulation capacity. Based on these findings, we evaluated its therapeutic potential in the transgenic AD C. elegans model. The results demonstrated the motor and cognitive functions of the worms were markedly restored, with the average paralysis time prolonged by approximately 37.3% and the chemotactic index recovering to near wild-type levels. Thus, the study has promise for providing experimental evidence for multi-target intervention against the complex pathological network of AD via an integrated strategy of in situ engineering and biomimetic modification.
{"title":"In-situ engineering of a covalent organic framework-based biomimetic nanoplatform for multi-target therapy of Alzheimer’s disease","authors":"Yujiao Yan , Yutong Chen , Fengmei Yang , Ruixin Zhao , Die Tian , Liran Deng , Meng Xie","doi":"10.1016/j.bioadv.2026.214728","DOIUrl":"10.1016/j.bioadv.2026.214728","url":null,"abstract":"<div><div>To address the complex pathology of Alzheimer’s disease (AD), including abnormal amyloid-β (Aβ) aggregation, metal ion homeostasis disruption and oxidative stress, we developed an integrated multifunctional nanoplatform. This platform leveraged a covalent organic framework (TD-COF) with intrinsic capabilities for Cu<sup>2+</sup> chelation and Aβ inhibition as the carrier. Through <em>in</em>-<em>situ</em> engineering, ultrafine palladium nanoparticles (PdNPs) were anchored to construct a stable, functionally integrated core (Pd-COF). However, due to limitations of nanomaterials such as short half-life and poor brain targeting, we further employed red blood cell (RBC) membrane for biomimetic modification, yielding the final platform Pd-COF-RBC. <em>In vitro</em> experiments demonstrated that Pd-COF-RBC concurrently achieved Cu<sup>2+</sup> chelation, Aβ fibrillation inhibition and reactive oxygen species (ROS) scavenging. Notably, the design of Pd-COF also regulated the size and dispersibility of PdNPs, enhancing catalase-like (CAT) activity by 34.7%. In Aβ-induced cellular models, the material effectively alleviated oxidative stress and mitochondrial dysfunction, increasing cell survival by over 78.4%. Further experiments confirmed that Pd-COF-RBC modified with RBC membrane possessed good biocompatibility, long circulation property and brain accumulation capacity. Based on these findings, we evaluated its therapeutic potential in the transgenic AD <em>C. elegans</em> model. The results demonstrated the motor and cognitive functions of the worms were markedly restored, with the average paralysis time prolonged by approximately 37.3% and the chemotactic index recovering to near wild-type levels. Thus, the study has promise for providing experimental evidence for multi-target intervention against the complex pathological network of AD <em>via</em> an integrated strategy of <em>in situ</em> engineering and biomimetic modification.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214728"},"PeriodicalIF":6.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078207","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}
Pub Date : 2026-01-20DOI: 10.1016/j.bioadv.2026.214716
Weibin Wang , Yufeng Huang , Xuehui Chen , Yuxiang Lei , Yunquan Zheng , Xianai Shi , Jianmin Yang
Diabetic wound healing is severely hampered by persistent inflammation, vascular dysfunction, infection risk, and oxidative stress. To overcome these challenges, we developed a multifunctional conductive hydrogel platform (Gel@Exo-ES). This system integrates exosomes derived from adipose-derived mesenchymal stem cells into a dynamic hydrogel network formed by cross-linking quaternized chitosan-polyaniline (QCS-PANI) with oxidized dextran (ODex). The resulting hydrogel exhibits good injectability, pH-responsive degradability, high antibacterial activity and conductivity. When combined with electrical stimulation, the Gel@Exo-ES significantly enhanced the proliferation, migration, and differentiation of fibroblasts (NIH-3T3), endothelial cells (HUVECs), and macrophages (Raw 264.7) in vitro. This synergy is attributed to the biocompatible hydrogel matrix, electrical stimulation-activated pro-healing signaling, and exosome-mediated bioactive cue delivery. In a diabetic rat model, the Gel@Exo-ES markedly accelerated wound closure by recruiting macrophages, upregulating IL-10 to drive M2 polarization, and thereby alleviating inflammation. The treatment concurrently enhanced re-epithelialization, collagen deposition, and angiogenesis. These findings demonstrate that the combined strategy of exosome-loaded conductive hydrogel and electrical stimulation presents a highly promising therapeutic platform for diabetic wound repair.
{"title":"Multifunctional conductive hydrogel integrating exosome delivery and electrical stimulation for enhanced diabetic wound healing","authors":"Weibin Wang , Yufeng Huang , Xuehui Chen , Yuxiang Lei , Yunquan Zheng , Xianai Shi , Jianmin Yang","doi":"10.1016/j.bioadv.2026.214716","DOIUrl":"10.1016/j.bioadv.2026.214716","url":null,"abstract":"<div><div>Diabetic wound healing is severely hampered by persistent inflammation, vascular dysfunction, infection risk, and oxidative stress. To overcome these challenges, we developed a multifunctional conductive hydrogel platform (Gel@Exo-ES). This system integrates exosomes derived from adipose-derived mesenchymal stem cells into a dynamic hydrogel network formed by cross-linking quaternized chitosan-polyaniline (QCS-PANI) with oxidized dextran (ODex). The resulting hydrogel exhibits good injectability, pH-responsive degradability, high antibacterial activity and conductivity. When combined with electrical stimulation, the Gel@Exo-ES significantly enhanced the proliferation, migration, and differentiation of fibroblasts (NIH-3T3), endothelial cells (HUVECs), and macrophages (Raw 264.7) <em>in vitro</em>. This synergy is attributed to the biocompatible hydrogel matrix, electrical stimulation-activated pro-healing signaling, and exosome-mediated bioactive cue delivery. In a diabetic rat model, the Gel@Exo-ES markedly accelerated wound closure by recruiting macrophages, upregulating IL-10 to drive M2 polarization, and thereby alleviating inflammation. The treatment concurrently enhanced re-epithelialization, collagen deposition, and angiogenesis. These findings demonstrate that the combined strategy of exosome-loaded conductive hydrogel and electrical stimulation presents a highly promising therapeutic platform for diabetic wound repair.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214716"},"PeriodicalIF":6.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038326","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}
Pub Date : 2026-01-19DOI: 10.1016/j.bioadv.2026.214725
Tao Wang , Yuxuan Chen , Xuyang Zhang , Yuejie Dou , Ying Chen , Maobin Xie , Antonella Motta , Zhaozhu Zheng , Xiaoqin Wang , Xiaying Kuang , Zhifen Han , Gang Li
Breast cancer (BC) remains a global health challenge, with treatment limitations from systemic toxicity, poor drug bioavailability, and multidrug resistance (MDR). Recent advancements in nanotechnology have revolutionized drug delivery systems (DDS), offering targeted, controlled, and synergistic therapeutic strategies. This review explores cutting-edge micro- and nanocarriers, including liposomes (Lips), nanoparticles (NPs), metal-organic frameworks (MOFs), exosomes and nanofibers (NFs)-designed to optimize the delivery of chemotherapeutic agents. Key design parameters are critically analyzed for their roles in optimizing drug encapsulation, tumor specificity, and biocompatibility. We highlight innovations in carrier engineering that enable biological modulation. Furthermore, co-delivery systems combining chemotherapy drugs with siRNA, P-glycoprotein inhibitors, or photothermal agents demonstrate remarkable success in reversing MDR in vitro and in vivo. Despite progress, challenges such as tumor heterogeneity, long-term carrier safety, and cost-effectiveness require further investigation. This review underscores the transformative potential of nanotechnology-driven DDS in precision oncology, paving the way for next-generation therapies to combat breast BC.
{"title":"Nanotechnology-driven drug delivery systems for breast cancer: A review","authors":"Tao Wang , Yuxuan Chen , Xuyang Zhang , Yuejie Dou , Ying Chen , Maobin Xie , Antonella Motta , Zhaozhu Zheng , Xiaoqin Wang , Xiaying Kuang , Zhifen Han , Gang Li","doi":"10.1016/j.bioadv.2026.214725","DOIUrl":"10.1016/j.bioadv.2026.214725","url":null,"abstract":"<div><div>Breast cancer (BC) remains a global health challenge, with treatment limitations from systemic toxicity, poor drug bioavailability, and multidrug resistance (MDR). Recent advancements in nanotechnology have revolutionized drug delivery systems (DDS), offering targeted, controlled, and synergistic therapeutic strategies. This review explores cutting-edge micro- and nanocarriers, including liposomes (Lips), nanoparticles (NPs), metal-organic frameworks (MOFs), exosomes and nanofibers (NFs)-designed to optimize the delivery of chemotherapeutic agents. Key design parameters are critically analyzed for their roles in optimizing drug encapsulation, tumor specificity, and biocompatibility. We highlight innovations in carrier engineering that enable biological modulation. Furthermore, co-delivery systems combining chemotherapy drugs with siRNA, P-glycoprotein inhibitors, or photothermal agents demonstrate remarkable success in reversing MDR <em>in vitro</em> and <em>in vivo</em>. Despite progress, challenges such as tumor heterogeneity, long-term carrier safety, and cost-effectiveness require further investigation. This review underscores the transformative potential of nanotechnology-driven DDS in precision oncology, paving the way for next-generation therapies to combat breast BC.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214725"},"PeriodicalIF":6.0,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038322","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}
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