Materials Science & Engineering C-Materials for Biological Applications最新文献

{"title":"3D-bioprinted dual-crosslinked oxidized gellan gum-decellularized human amniotic membrane hydrogels reinforced with aminolyzed electrospun nanofibers for cartilage regeneration","authors":"Fariba Hashemi-Afzal ,&nbsp;Fatemeh Bagheri ,&nbsp;Ebrahim Vasheghani-Farahani ,&nbsp;Mahmoud Azami ,&nbsp;Lobat Tayebi ,&nbsp;Mohamadreza Baghaban Eslaminejad","doi":"10.1016/j.bioadv.2025.214654","DOIUrl":"10.1016/j.bioadv.2025.214654","url":null,"abstract":"<div><div>Articular cartilage has limited self-healing capacity, driving the need for biomaterial scaffolds that replicate its hierarchical architecture and mechanical resilience. In this study, we present a dual-crosslinked hydrogel system for 3D bioprinting, composed of gellan gum (GG), oxidized GG (OGG), decellularized human amniotic membrane (dHAM), and aminolyzed polycaprolactone nanofibers (A-PCL NFs). Schiff base linkages between OGG aldehydes and amine groups in dHAM/A-PCL NFs, combined with Ca²⁺-mediated ionic gelation, provided a reinforced hydrogel network with tunable physicochemical properties. The resulting scaffolds exhibited high structural fidelity, a compressive modulus of 232.6 kPa, controlled swelling, and sustained degradation (30 % mass loss over 21 days). The integration of A-PCL NFs significantly enhanced mechanical performance and stabilized the hydrogel matrix, while dHAM supplied native extracellular matrix (ECM) cues. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) encapsulated in the bioink showed &gt;85 % viability after 7 days and underwent robust chondrogenic differentiation, as confirmed by histology and increased glycosaminoglycan deposition. This biomimetic design—combining dynamic crosslinking, ECM-derived bioactivity, and NF reinforcement—demonstrates how structural and biochemical synergies can be harnessed to advance functional cartilage scaffolds. The platform shows strong potential for translational application in articular cartilage repair and may be extended to other load-bearing tissues requiring both mechanical integrity and biological functionality.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214654"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824271","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":"Lysophosphatidic acid-induced upregulation of exosomal miR-221-3p from corneal stromal cells promotes corneal endothelial healing","authors":"Hung-Chi Chen ,&nbsp;Yi-Jen Hsueh ,&nbsp;Yaa-Jyuhn James Meir ,&nbsp;Jui-Yang Lai ,&nbsp;Chieh-Cheng Huang ,&nbsp;Tsai-Te Lu ,&nbsp;Chao-Min Cheng ,&nbsp;Song-Shu Lin ,&nbsp;David Hui-Kang Ma ,&nbsp;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^Kip1. 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":"2026-05-01","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}

{"title":"Sustainable fabrication of biopolymer-based (starch/PVA) nanoscaffolds loaded with green-synthesized CuO nanoparticles from Sargassum wightii (marine macroalgae): Cytocompatibility and antioxidant activity","authors":"JinJin Pei ,&nbsp;Hanisha Govindaraj ,&nbsp;Sivaramakrishnan R ,&nbsp;Gopalakrishnan Velliyur Kanniappan ,&nbsp;Vijayalakshmi Pandurangan ,&nbsp;Selvaraj Jayaraman ,&nbsp;Vinoth Kumar Dhayalan ,&nbsp;Monica Mironescu ,&nbsp;Ion Dan Mironescu ,&nbsp;Chella Perumal Palanisamy","doi":"10.1016/j.bioadv.2025.214660","DOIUrl":"10.1016/j.bioadv.2025.214660","url":null,"abstract":"<div><div>This study presents an eco-friendly approach for synthesizing copper oxide nanoparticles (CuO NPs) using the aqueous extract of <em>Sargassum wightii</em>, a brown marine alga, and their integration into starch/polyvinyl alcohol (PVA)-based electrospun nanoscaffolds</div><div>. The biosynthesized CuO NPs were characterized by UV–Vis spectroscopy, FTIR, and XRD, confirming their formation, functional groups, and crystalline structure. Scanning electron microscopy revealed uniform distribution of CuO NPs within the nanofibrous matrix, while thermogravimetric analysis (TGA) confirmed enhanced thermal stability of the scaffolds. Dynamic light scattering (DLS) and zeta potential analyses indicated good colloidal stability and nanoscale size distribution. In vitro cytotoxicity studies demonstrated that all samples were non-cytotoxic to 3T3-L1 cells (<em>p</em> &gt; 0.05), supporting their basic biocompatibility. While the scaffolds showed apparent chemical radical-scavenging activity, no functional biological assays were performed; therefore, no claims regarding proliferation or wound-healing efficacy are made. The materials warrant further investigation in future biological models.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214660"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885602","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":"Functional replacement of fetal bovine serum by extracts from Galdieria sulphuraria in muscle cell culture","authors":"Svenja Hütker ,&nbsp;Hanna Wellkamp ,&nbsp;Verena Tellstroem ,&nbsp;Imke Lang ,&nbsp;Felicitas Berger","doi":"10.1016/j.bioadv.2025.214701","DOIUrl":"10.1016/j.bioadv.2025.214701","url":null,"abstract":"<div><div>The development of serum-free culture systems is a major challenge in the large-scale production of cultured meat, where myoblasts must be expanded and differentiated without the use of fetal bovine serum (FBS). FBS remains the gold standard in myoblast culture, yet it poses ethical, economic, and environmental concerns. In this study, we tested the hypothesis, that protein-rich extracts derived from the red microalga <em>Galdieria sulphuraria</em> can functionally replace FBS during proliferation and differentiation of murine C2C12 skeletal muscle myoblasts. Native algal protein extracts were prepared, heat-treated, and fractionated by ammonium sulfate precipitation. The effects of these extracts on cell viability, metabolic activity, proliferation kinetics and terminal myogenic differentiation were systematically assessed under serum-reduced and serum-free conditions. Crude extracts exhibited cytotoxicity, whereas heat-treated and fractionated extracts enhanced cell viability and metabolic activity during short-term culture. During long-term cultivation, gradual replacement of FBS with heat-treated algal extracts supported sustained myoblast growth, albeit with reduced proliferation rates, and preserved the capacity for differentiation into multinucleated, myosin heavy chain-positive myotubes. Comparative proteomic analysis revealed distinct protein profiles between crude and heat-treated extracts, suggesting that thermal processing removes inhibitory components while enriching bioactive protein fractions. Collectively, these results demonstrate that <em>G. sulphuraria</em>-derived protein extracts can support long-term myoblast proliferation and differentiation following appropriate adaption, highlighting their potential as a sustainable and animal-free alternative to serum-derived supplements in muscle cell culture systems.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214701"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927248","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":"Prevention of brain scarring during cranial reconstruction through a bioactive polymer coating","authors":"Sara Shakibania ,&nbsp;Daria Niewolik ,&nbsp;Taral Patel ,&nbsp;Małgorzata Bogusz ,&nbsp;Roman Turczyn ,&nbsp;Marcin Basiaga ,&nbsp;Katarzyna Jaszcz ,&nbsp;Barbara Bednarczyk-Cwynar ,&nbsp;Magdalena Skonieczna ,&nbsp;Katarzyna Krukiewicz","doi":"10.1016/j.bioadv.2025.214696","DOIUrl":"10.1016/j.bioadv.2025.214696","url":null,"abstract":"<div><div>Although cranioplasty is a long-established surgical procedure used to repair or reshape skull defects, it is not devoid of side effects arising from the formation of a scar tissue between dura, implant, and subcutaneous tissue. To minimize these complications, we developed a bioactive coating comprising poly(vinyl alcohol) (PVA) electrospun fibers loaded with a polyanhydride based on betulin disuccinate and a tricarboxylic derivative of poly(ethylene glycol) (PEG-DBB), suitable for the modification of the surface of titanium alloys. Although cell viability assays proved biocompatibility of fibers, PVA/PEG-DBB was found to decrease the adhesion of neuroblastoma cells by 84 % and the adhesion of fibroblast cells by 11 %, while increasing the confluency of osteosarcoma cells by 40 %. To assess the potential of the PVA/PEG-DBB fibrous coating, it was deposited onto the surface of Ti-6Al-4V alloy discs <em>via</em> electrospinning. <em>In vitro</em> bioactivity of samples was assessed <em>via</em> immersion in a simulated body fluid for 21 days, revealing facilitated formation of hydroxyapatite layer (Ca/P ratio of 1.74) in the presence of PVA/PEG-DBB (54.0 ± 6.5 % surface coverage, 11.7 ± 1.3 μm thickness), as confirmed by scanning electron microscopy and Raman spectroscopy. Adhesion strength of the coating to the substrate (between 1.7 and 2.7 N) was quantified using scratch testing under progressive loading, with critical load values determined to evaluate interfacial bonding integrity. By integrating biocompatibility, modulated adhesiveness, and mechanical resilience, PVA/PEG-DBB coating presents a promising approach for enhancing cranioplasty outcomes and minimizing adhesion-related complications.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214696"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927396","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 novel ROS switcher potentiates the type-I photodynamic effect of sodium zinc chlorophyllin against Pseudomonas aeruginosa in diabetic wounds","authors":"Guodong Wang ,&nbsp;Hongjie Chen ,&nbsp;Lusheng Wu ,&nbsp;Cai Yuan ,&nbsp;Mingdong Huang","doi":"10.1016/j.bioadv.2026.214721","DOIUrl":"10.1016/j.bioadv.2026.214721","url":null,"abstract":"<div><div>Skin wound infections present a serious threat to human health, with bacterial infections in diabetic wounds being particularly challenging due to impaired healing. Gram-negative bacteria are common pathogens in diabetic wound infections and often exhibit high resistance to conventional treatments, necessitating prolonged and costly therapies. Photodynamic antibacterial therapy (PACT) is regarded as a non-invasive and effective approach, with minimal risk of inducing resistance. Sodium zinc chlorophyllin (ZnChl), a water-soluble metalloporphyrin photosensitizer, offers multiple advantages such as low cost, high safety, and the ability to promote wound healing. However, its bactericidal efficacy against Gram-negative bacteria is limited under the hypoxic conditions typically found in diabetic wounds. Herein, we report a strategy to develop an efficient chlorophyll-based photosensitizer operating via an oxygen-independent Type I mechanism by combining ZnChl with inorganic salts (NaI, KBr, or KI). This approach significantly improved antibacterial performance, particularly with NaI or KI. Upon 630 nm light irradiation, low concentrations of KI (5 mM) markedly enhanced the bactericidal effect of ZnChl (50 μM), reducing the survival of three Gram-negative bacterial strains by 3 logs (99.9%). Interestingly, we further discovered that KI acts as a “reactive oxygen species (ROS) converter,” shifting the photodynamic mechanism of ZnChl from a mixed Type I/Type II mode to a dominant Type I mechanism, generating highly reactive hydroxyl radicals (<img>OH). Moreover, the ZnChl-KI combination demonstrated significant therapeutic efficacy in treating <em>Pseudomonas aeruginosa</em>-infected diabetic wounds without inducing apparent toxicity in rats. This work provides a foundation for developing efficient and economical Type I photosensitizers for the treatment of bacterial infections in diabetic wounds.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214721"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038324","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 four-pronged approach to unleash the regenerative potential of extracellular vesicles for bone regeneration: A systematic review of in vitro and in vivo studies","authors":"Shayan Salehy ,&nbsp;Hanieh Nokhbatolfoghahaei ,&nbsp;Arash Khojasteh","doi":"10.1016/j.bioadv.2025.214661","DOIUrl":"10.1016/j.bioadv.2025.214661","url":null,"abstract":"<div><div>The clinical application of Extracellular vesicles for bone regeneration faces several key challenges, including low production yield and potency, a lack of standardized isolation and characterization methods, and an incomplete understanding of their regenerative mechanisms, which render their clinical use ineffective. This systematic review addresses these limitations by elucidating regenerative mechanisms and identifying strategies to improve EV potency through an assessment of existing literature. A comprehensive search on MEDLINE, Scopus, and Web of Science yielded 133 articles, 72 (68 in vitro, 27 in vivo) of which met the inclusion criteria based on studies investigating methods to enhance EV bone regenerative potential. Data regarding EV source, affected cells and signaling pathways, study design, animal model, bone defect, administration route, and outcomes (bone formation and vascularization) were extracted and synthesized. Four distinct approaches were identified to improve EV bone regenerative potential at the cell source level: Targeted gene modification, chemical manipulation, Physical stimulation, and Culture-Based Optimization. While all included in vivo studies reported a significant increase in bone formation, none of the studies specified a method to eliminate bias (specifically selection bias, reporting bias, attrition bias, performance bias, and detection bias) in their studies; thus, any interpretations should be made with caution. Future studies should prioritize rigorous methodology centered around EV optimization, including targeted mechanisms for enhanced bone formation, and explore ways to improve clinical translatability. This systematic review was registered with <em>PROSPERO</em> (CDR42024511757).</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214661"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864804","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":"Regulation of osteogenic differentiation of boronized Ti6Al4V/HA composite involving TRIP13-PI3K/Akt signaling pathway","authors":"Yihong Chen ,&nbsp;Xiaojie Chen ,&nbsp;Boyu Liu ,&nbsp;Hengrong Xiong ,&nbsp;Zhiwei Peng ,&nbsp;Qian Peng","doi":"10.1016/j.bioadv.2026.214720","DOIUrl":"10.1016/j.bioadv.2026.214720","url":null,"abstract":"<div><div>Titanium and its alloys are widely used in dental implants owing to their excellent biocompatibility and corrosion resistance, despite their elastic moduli mismatch with bone and insufficient interfacial bioactivity which often restrict their osseointegration performance, particularly in the early stage after implantation. To address these limitations, a boronized Ti6Al4V/hydroxyapatite (HA) composite with improved structural and biological performance was developed. Scanning electron microscopy and atomic force microscopy confirmed a micro/nanostructured surface with increased roughness. RNA sequencing of osteoblasts cultured on the composite identified 683 upregulated and 838 downregulated genes relative to Ti6Al4V. Gene ontology enrichment revealed biological processes related to cell adhesion, extracellular matrix remodeling, and integrin-mediated signaling, whereas KEGG pathway analysis indicated activation of cell cycle, PI3K/Akt, and calcium signaling pathways. Gene set variation analysis further highlighted eight key upregulated genes-CYP1A1, CRLF2, HBEGF, IRAK2, DLL1, CYP1B1, BLOC1S5-TXNDC5, and TRIP13. Functional validation demonstrated that the TRIP13 expression correlated positively with osteogenic differentiation, in conjunction with activation of the PI3K/Akt signaling pathway. Collectively, these findings proved a TRIP13-associated transcriptional response linked to osteogenic regulation on the boronized Ti6Al4V/HA composite surface, offering a mechanistic insight into the design of bioactive titanium-based implants with improved osseointegration.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214720"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037703","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":"Combining cartilaginous microtissues primed under altered oxygen environments with melt electrowritten meshes to engineer scaled-up grafts","authors":"Nadia Rodriguez ,&nbsp;Inês F. Gonçalves ,&nbsp;Tom Hodgkinson ,&nbsp;Fergal J. O'Brien ,&nbsp;Daniel J. Kelly","doi":"10.1016/j.bioadv.2025.214680","DOIUrl":"10.1016/j.bioadv.2025.214680","url":null,"abstract":"<div><div>Current articular cartilage tissue engineering strategies fail to produce grafts that recapitulate the complex zonal composition and organisation of the native tissue. Developmental engineering strategies might overcome such limitations, leading to the generation of more biomimetic grafts by mimicking key steps of normal tissue development. One such approach leverages the capacity of stem/progenitor cells to self-organise into microtissues or organoids, which can be used as the building blocks of larger grafts. In this study, adult human bone marrow-derived mesenchymal stem/stromal cells (hMSCs) were used to engineer phenotypically distinct hyaline cartilage microtissues for the modular assembly of zonally defined grafts. Altered oxygen (O₂) levels, within the physiological range, were first explored to modulate the microtissue phenotype. Melt electrowritten (MEW) meshes were then used to guide the fusion of such microtissues into scaled-up grafts. Priming hMSC-derived microtissues at oxygen levels representative of different regions of the native tissue supported the development of distinct cartilaginous phenotypes. In addition, short-term exposure to 2 % O₂ significantly enhanced the deposition of glycosaminoglycans compared to exposure to 5 % O₂. Combining such microtissues with a supporting MEW mesh enabled the development of a larger graft with controlled geometry. In conclusion, this study highlights the potential of hMSC-derived cartilage microtissues, primed under altered oxygen environments, as building blocks for the biofabrication of articular cartilage grafts when combined with supporting MEW meshes.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214680"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919006","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":"Targeted nanotheranostics mitigates radiation-induced fibrosis to promote immune infiltration and enhance radio-chemotherapy in pancreatic ductal adenocarcinoma","authors":"Arjun Sabu ,&nbsp;Ying-Chieh Yang ,&nbsp;Ritwick Ranjan Sarma ,&nbsp;Lakshminarayan Ramesan ,&nbsp;Yi-Hsuan Lin ,&nbsp;Hsin-Cheng Chiu","doi":"10.1016/j.bioadv.2025.214677","DOIUrl":"10.1016/j.bioadv.2025.214677","url":null,"abstract":"<div><div>Radiotherapy and chemotherapy exhibit limited clinical efficacy in pancreatic ductal adenocarcinoma (PDAC) due to its dense stromal desmoplasia, acting as a physical barrier that hinders drug penetration and immune cell infiltration while also promoting the formation of intratumoral radiation-induced fibrosis (RIF). In the present study, topoisomerase I inhibitor SN-38-loaded mesoporous silica-coated Bi₂O₃ nanoparticles (S-MBO NPs) were prepared and camouflaged with PDAC/red blood cell hybrid membranes loaded with the stromal reprogramming drug all-trans retinoic acid. The nanotherapeutics referred to as (S-MBO@A-RPCM NPs) were found capable of effectively overcoming the stromal barrier, mitigating RIF, and enhancing the radio/chemotherapeutic efficacy against PDAC. Both the <em>in vitro</em> and <em>in vivo</em> studies strongly confirmed the homotypic uptake and homologous targeting ability of S-MBO@A-RPCM NPs. The combined radiosensitizing effects of Bi₂O₃ and SN-38 resulted in enhanced DNA damage in UN-KC-6141 cells, decreased colony formation, and induction of immunogenic cell death by combined chemo/radiotherapy. Biodistribution data of S-MBO@A-RPCM NPs showed enhanced homologous targeting property toward PDAC, attributed to the hybrid membrane coating extracted from erythrocytes and UN-KC-6141 cancer cells on NPs. Importantly, S-MBO@A-RPCM NP treatment was found capable of deactivating the activated pancreatic stellate cells induced by radiation and TGF-β-thereby directly mitigating the fibrogenic activity characteristic of RIF <em>in vitro</em> and <em>in vivo</em>. Significantly reduced expression of α-SMA, collagen I, and fibronectin was observed after the treatment, accounting largely for the disruption of the stroma barrier, chronic inflammation signaling and tumor-stroma crosstalk, resulting in enhanced sensitization of UN-KC-6141 cells to SN-38 and radiation alongside improved immune infiltration. The <em>in vivo</em> data strongly signify that combining radiotherapy with the treatment of S-MBO@A-RPCM NPs exhibits superior tumor microenvironment reprogramming, attenuation of RIF and effective tumor growth inhibition in UN-KC-6141 tumor-bearing mice with minimal side effects.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214677"},"PeriodicalIF":6.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824127","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}