L. Dupont , V.S. Tadimarri , R. Buret , S. Sankaran , L. Picton , A.M. Jonas , K. Glinel
{"title":"Influence of mechanical properties of agarose hydrogels on bacterial growth and secretory activity","authors":"L. Dupont , V.S. Tadimarri , R. Buret , S. Sankaran , L. Picton , A.M. Jonas , K. Glinel","doi":"10.1016/j.bioadv.2025.214653","DOIUrl":"10.1016/j.bioadv.2025.214653","url":null,"abstract":"<div><div>Engineered living materials (ELMs) rely on the ability to control cell behavior in material systems. ELMs containing bacteria secreting beneficial molecules are being developed for therapeutic purposes. Using commensal strains embedded in physically cross-linked agarose hydrogels, we systematically investigate how gel rigidity and initial bacterial density affect the morphology of bacterial colonies and their secretory function. Although often considered independently, these parameters jointly define the microscale environment experienced by embedded cells, influencing nutrient access, mechanical interactions, and potential cell-to-cell communication. We show that matrix rigidity effectively tunes aggregate morphology, modulating their shape and compactness, without compromising bacterial growth or secretion. In parallel, initial bacterial density determines the biomass accumulation dynamics and spatial distribution of aggregates, which in turn influence the onset and temporal profile of secretory activity, without altering its final magnitude. This decoupling between structural organization and secretory output opens new possibilities for engineering ELMs with tailored architectures and prolonged secretory and release activity.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214653"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727076","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}
Mohammad Sameer Khan , Taha Alqahtani , Humood Al Shmrany , Garima Gupta , Khang Wen Goh , Amirhossein Sahebkar , Prashant Kesharwani
{"title":"Enhanced permeability and retention (EPR) effect: Advances in nanomedicine for improved tumor targeting","authors":"Mohammad Sameer Khan , Taha Alqahtani , Humood Al Shmrany , Garima Gupta , Khang Wen Goh , Amirhossein Sahebkar , Prashant Kesharwani","doi":"10.1016/j.bioadv.2025.214636","DOIUrl":"10.1016/j.bioadv.2025.214636","url":null,"abstract":"<div><div>The enhanced permeability and retention (EPR) effect driven by abnormal tumor vasculature and impaired lymphatic drainage has long been considered a cornerstone of nanomedicine-based cancer therapy. While preclinical studies demonstrate substantial nanoparticle accumulation in solid tumors via passive targeting, clinical outcomes remain inconsistent due to the heterogeneous and dynamic nature of the EPR effect across tumor types and patients. Tumor vascular density, elevated interstitial fluid pressure, and stromal barriers frequently restrict drug penetration and retention, limiting therapeutic efficacy. This review provides a critical and translational perspective on strategies to amplify the EPR effect, including vascular normalization, transient modulation of blood flow, hypertension induction, and integration with active targeting ligands. We also highlight tumor microenvironment remodeling, image-guided delivery, and patient-specific predictive diagnostics as emerging avenues to enhance clinical predictability. By bridging mechanistic insights with therapeutic innovation, we propose a roadmap to reengineer EPR-based delivery systems for more consistent, potent, and personalized nanomedicine in solid tumor management.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214636"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715629","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}
Zhiping Fang , Yonghao Xiao , Jubo Li , Hailei Li , Xin Wu , Lin Ye , Zenggguo Feng
{"title":"Semi-degradable biomimetic double-layer small diameter vascular graft for arteriovenous fistula in large animals","authors":"Zhiping Fang , Yonghao Xiao , Jubo Li , Hailei Li , Xin Wu , Lin Ye , Zenggguo Feng","doi":"10.1016/j.bioadv.2025.214655","DOIUrl":"10.1016/j.bioadv.2025.214655","url":null,"abstract":"<div><div>A double layer small diameter vascular graft (SDVG) was fabricated by sequential electrospinning. The inner layer was composed by three kinds of biodegradable poly (ε-caprolactone) (PCL) fibers with three different molecular weights to induce endothelial regeneration and the outer layer comprised non-degradable thermoplastic polyurethane (TPU) fibers and PCL fibers with the numerical molecular weight of 80,000 g/mol to provide long-term mechanical support. The SDVG was further heparinized through “erosion and graft” strategy. The surface heparin content, the clotting time and the mechanical properties were evaluated in vitro. Then, the double layer SDVG was implanted into the sheep for six months as the arteriovenous fistula connecting carotid artery and jugular vein. The Doppler ultrasonic measurement and angiography showed the patency of the transplanted SDVGs and the in situ puncture test exhibited the potential of the SDVG for hemodialysis. H&E and Masson staining characterized the remodeling of the inner layer, whereas Safranin O and von Kossa staining demonstrated the regeneration of extracellular matrix and the absence of the calcification in the implanted SDVG. More importantly, the perfect regeneration of endothelium on the lumen of the SDVG was proven by CD31 staining. Consequently, the as-prepared SDVG showed the potential to be the artificial arteriovenous fistula in the clinic.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214655"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776452","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}
G. Dei Rossi , F. Buccino , E. Longo , G. Tromba , L.M. Vergani
{"title":"Sustainable silk fibroin scaffolds for bone repair: assessing their osteogenic potential via AI-enhanced synchrotron imaging workflow","authors":"G. Dei Rossi , F. Buccino , E. Longo , G. Tromba , L.M. Vergani","doi":"10.1016/j.bioadv.2025.214658","DOIUrl":"10.1016/j.bioadv.2025.214658","url":null,"abstract":"<div><div>Effective bone regeneration requires scaffolds capable of guiding and supporting new mineralized matrix formation. In this study, silk fibroin constructs cultured with human mesenchymal stem cells (hBMSCs) in the presence of either Fetal Bovine Serum (FBS) or Human Platelet Lysate (hPL) are evaluated for their osteogenic potential. A distinctive aspect of this work is the combined use of synchrotron X-ray imaging and a convolutional neural network for high-resolution in situ three-dimensional scaffold osteogenic potential assessment. This approach enables precise evaluation of bone matrix arrangement within the scaffold architecture. Two-dimensional analysis reveals increased mineralization in pores with an average radius of ~115 μm, area of ~4.0 × 10<sup>4</sup> μm<sup>2</sup>, and eccentricity of ~0.7 in hPL construct. The subsequent three-dimensional analysis extends these findings by quantifying the spatial distribution and connectivity of the mineralized matrix across the scaffold volume. It identifies pores with an equivalent radius between 110 and 120 μm, high surface area, and moderate sphericity (0.65–0.75) as optimal not only for mineral deposition but also for uniform 3D matrix propagation. Moreover, unsupervised clustering analysis also identifies optimal geometric interdependencies between pore size, surface area, and sphericity, offering new insights for rational design of high-performance scaffolds. The study demonstrates both the efficacy of silk fibroin scaffolds cultured with hPL in promoting bone regeneration and the relevance of a combined synchrotron imaging-artificial intelligence approach in quantitatively correlating three-dimensional porous geometry with regenerative outcomes.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214658"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776442","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":"Nanomaterial-based strategies to modulate macrophage polarization in osteoarthritis: A systematic review","authors":"Giorgia Codispoti , Luca Cavazza , Melania Carniato , Gabriele Bilancia , Gianluca Giavaresi , Matilde Tschon","doi":"10.1016/j.bioadv.2025.214662","DOIUrl":"10.1016/j.bioadv.2025.214662","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a chronic degenerative joint disease characterised by progressive functional impairment due to erosion of the articular cartilage, remodelling of the subchondral bone and inflammation of the synovial tissue. In addition to mechanical and metabolic alterations, there is increasing evidence highlighting the pivotal role of macrophages in OA pathophysiology. The imbalance between pro-inflammatory M1 and anti-inflammatory M2 phenotypes drives joint inflammation, extracellular matrix degradation, chondrocyte apoptosis and impaired tissue repair. Therefore, modulating macrophage polarization appears to be an attractive therapeutic target for preventing OA progression. In recent years, nanomaterials have emerged as an innovative approach to tackling this challenge. Their tunable size, morphology, and surface properties enable both direct immunomodulation and the delivery of therapeutic agents. This systematic review examined preclinical studies published between 2021 and 2025 that investigated the potential of various developed nanomaterials to polarize macrophages towards the M2 phenotype, thereby reducing joint inflammation and promoting cartilage protection and repair. Consistent results from both <em>in vitro</em> and <em>in vivo</em> included studies demonstrated their ability to reduce pro-inflammatory mediators related to M1-type macrophages while enhancing the expression of anti-inflammatory ones linked to M2-type macrophages, despite their differences in physicochemical properties. This suggested that nanomaterials could reprogram macrophages to suppress the inflammatory microenvironment of OA and slow down disease progression by lowering synovitis and cartilage damage. By influencing macrophage polarization and fostering a regenerative environment, nanotechnology may pave the way for more effective, targeted strategies in OA management.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214662"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783568","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}
Daniela León García , Karen Bolaños , Pamela Contreras , David Silva , Rodrigo Vásquez-Contreras , Eyleen Araya , Marcelo J. Kogan , Andrew F.G. Quest
{"title":"Exploiting mechanistic insights to improve the delivery of nanomaterials and extracellular vesicles to tumors","authors":"Daniela León García , Karen Bolaños , Pamela Contreras , David Silva , Rodrigo Vásquez-Contreras , Eyleen Araya , Marcelo J. Kogan , Andrew F.G. Quest","doi":"10.1016/j.bioadv.2025.214657","DOIUrl":"10.1016/j.bioadv.2025.214657","url":null,"abstract":"<div><div>The main current challenges in oncology therapy are (1) improving the targeting of chemotherapeutics to tumors and (2) developing alternative treatments for metastatic tumors. Nanomedicine can provide an answer to these problems; however, the delivery of sufficient therapeutic nanoparticles (NPs) to tumors remains a huge challenge in nanomaterial-based treatments. Extracellular vesicles (EVs) are key participants in intercellular communication processes that can be combined with nanomaterials to enhance their targeting. Available evidence indicates that Caveolin-1 (CAV1) when expressed in cancer cells modulates the protein cargos of EVs such as to enhance migration, invasion and metastasis of recipient cancer cells. Furthermore, these effects are favored by CAV1 phosphorylation at tyrosine 14. Considering this role of CAV1 and its phosphorylation on Y14 in the EV cargo sorting of certain cell adhesion proteins, such as β3 and β5 integrins important for EV tropism, we evaluated the biodistribution of EVs loaded with gold nanoparticles from B16F10 cells expressing wild-type (CAV1) phosphomimetic (CAV1/Y14E) and phospho-null (CAV1/Y14F) in a pre-clinical murine model of lung metastasis. The experiments revealed that EVs(CAV1)-AuNPs and EVs(CAV1/Y14E)-AuNPs reached more rapidly and accumulated to a greater extent in small metastatic lung tumors compared to control EVs or EVs(CAV1/Y14F). As expected, a higher accumulation of gold <em>in vitro</em> in B16F10 cells, as well as <em>in vivo</em> in small metastatic lung nodules was detected when EVs(CAV1) or EVs(CAV1/Y14E) were used as vehicles for the AuNPs. Thus, CAV1 expression enhances the accumulation and targeting of AuNP-loaded melanoma cell-derived EVs to small metastatic lung tumors formed by their parental B16F10 cells. Importantly, the enhanced targeting capacity of EVs(CAV1)-AuNPs was found to be dependent on CAV1 phosphorylation at tyrosine 14.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214657"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822157","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}
Olena Ivashchenko , Adriana Hvizdošová Annušová , Łukasz Popenda , Michal Šelc , Matej Jergel , Peter Nádaždy , Matej Mičušík , Emerson Coy
{"title":"Silver-doped MoOx NPs with phytochemicals for photodynamic therapy application: Playing with the sequence of surface modification steps","authors":"Olena Ivashchenko , Adriana Hvizdošová Annušová , Łukasz Popenda , Michal Šelc , Matej Jergel , Peter Nádaždy , Matej Mičušík , Emerson Coy","doi":"10.1016/j.bioadv.2025.214645","DOIUrl":"10.1016/j.bioadv.2025.214645","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) is a promising strategy for cancer treatment, employing photosensitizers activated by light to induce cytotoxicity. Hybrid organic–inorganic nanocomplexes, which integrate the unique properties of plasmonic metals and organic photosensitizers, are currently under intensive investigation. In this study, we propose the development of a novel photoactive nanoplatform for PDT based on a composite system comprising molybdenum oxide, silver, and phytochemicals from <em>Hypericum perforatum</em> and <em>Chelidonium majus</em>. To evaluate how the sequence of silver and phytochemicals deposition influences the optical characteristics and photodynamic performance of the resulting heterostructures, two modification strategies were employed, differing in the order of the applied synthesis steps. Primary attachment of phytomolecules led to lower silver content (8–13 wt%) and predominance of the metallic silver phase. In contrast, primary attachment of silver resulted in higher silver content (31 wt%) but predominance of the AgCl phase. Upon irradiation at 405 nm, the highest phototoxic response was observed for the sample modified first with <em>C. majus</em> phytochemicals and subsequently with silver. This nanocomplex exhibited a similarly strong photoresponse at both early and late irradiation stages, reducing lung cancer cell viability to ∼10 %. These findings highlight its potential for efficient and selective PDT-based cancer therapies.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214645"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716088","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}
Nicole Fratini , Carolina Castillo , Roberta Grillo , Stefania D'Amone , Luca Pacini , Maddalena Grieco , Maria Grazia Lolli , Sara Maria Giannitelli , Francesco Brasili , Ornella Ursini , Claudia Bearzi , Roberto Rizzi , Barbara Cortese
{"title":"The extracellular matrix HA promotes the YAP/hypoxia axis of glioblastoma cells on 3D agar/HA scaffolds","authors":"Nicole Fratini , Carolina Castillo , Roberta Grillo , Stefania D'Amone , Luca Pacini , Maddalena Grieco , Maria Grazia Lolli , Sara Maria Giannitelli , Francesco Brasili , Ornella Ursini , Claudia Bearzi , Roberto Rizzi , Barbara Cortese","doi":"10.1016/j.bioadv.2025.214664","DOIUrl":"10.1016/j.bioadv.2025.214664","url":null,"abstract":"<div><div>The tumour microenvironment of glioblastoma (GBM) as defined by mechanical heterogeneity, hypoxia, and hyaluronic acid (HA)–rich extracellular matrix (ECM), is a highly dynamic milieu which influences tumour progression and therapeutic resistance. Yet, how these cues converge to regulate mechanosensitive pathways in 3D remains poorly understood. Here, we engineered agar-based porous hydrogels functionalized with HA to independently tune stiffness and ECM composition, creating biomimetic 3D niches for GBM cells. The presence of HA coating showed to increase hydrogel stiffness, promote YAP/TAZ nuclear localisation, and elevate total LATS1/2 expression, consistent with Hippo pathway feedback regulation. Over time, however, hypoxic niches emerged that destabilised this feedback, enabling sustained YAP nuclear activity. HA also modulated OCT4 and Sox2 localisation and attenuated HIF-1α nuclear accumulation, indicating that HA also modulates the spatial distribution and nuclear accumulation of HIF-1α. Also, a cooperative regulation through the HA–CD44–CXCR4 axis, showed integrated biochemical and mechanical signals to reinforce YAP/HIF crosstalk. Together, these results reveal a dynamic interplay between ECM stiffness, HA signalling, and hypoxia in shaping YAP/HIF crosstalk and stem-like phenotypes in GBM and establish our hydrogel platform as a powerful tool to dissect and therapeutically exploit these interactions.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214664"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797472","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}
Amin Ebrahimi Sadrabadi , Seyed Shahriar Arab , Amir Kamali , Saghar Karimi , Mohamadreza Baghaban Eslaminejad , Samaneh Hosseini
{"title":"Biphasic bone-mimicking constructs containing silk fibroin peptide enhanced bone regeneration in segmental defects in rats","authors":"Amin Ebrahimi Sadrabadi , Seyed Shahriar Arab , Amir Kamali , Saghar Karimi , Mohamadreza Baghaban Eslaminejad , Samaneh Hosseini","doi":"10.1016/j.bioadv.2025.214650","DOIUrl":"10.1016/j.bioadv.2025.214650","url":null,"abstract":"<div><div>To advance bone tissue engineering, it is essential to design and integrate biomaterials that can closely mimic the microarchitecture of native tissue and enhance biological functionality. This study presents a biphasic bone-mimicking construct that integrates decellularized extracellular matrix (dECM), calcium phosphate cement (CPC), and tailored silk fibroin (SFp) peptides to synergize with biological and mechanical cues for enhanced regeneration. The dECM/CPC hydrogel (dECM/CPC-Hy) layer provides robust structural support, whereas the inner SFp-functionalized dECM hydrogel drives cellular activity. Dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy measurements confirmed distinct secondary structures and zeta potentials ranging from −8.8 ± 0.13 mV to −1.3 ± 0.09 mV for SFp1 and SFp2, respectively. MTT assays demonstrated nontoxicity for all peptides over a concentration range from 10 μg/ml to 200 μg/ml. SFp1 upregulated the expression of the Col1, Opn, Ocn and CD31 genes after 21 days in the dECM/SFp/CPC construct. In a rat radius defect model, the dECM/SFp/CPC construct resulted in significant bone regeneration after 12 weeks, as evidenced by micro-CT and X-ray imaging. In conclusion, the dECM/SFp/CPC construct shows great potential as an advanced biomaterial for bone tissue engineering, combining the biological cues of dECM and SFp with the mechanical properties of CPC to enhance bone regeneration.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214650"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797473","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}
M. McGrath , J.C. Palomeque-Chávez , C. O’Connor , J. Maughan , A. Dervan , S. Browne , F.J. O’Brien
{"title":"Laminin 1 enhances the angiogenic and neurogenic potential of collagen-based scaffolds for complex wound healing applications","authors":"M. McGrath , J.C. Palomeque-Chávez , C. O’Connor , J. Maughan , A. Dervan , S. Browne , F.J. O’Brien","doi":"10.1016/j.bioadv.2025.214633","DOIUrl":"10.1016/j.bioadv.2025.214633","url":null,"abstract":"<div><div>Chronic wounds fail to progress through the normal stages of healing, with insufficient vascularisation and dysfunctional neural regrowth playing a key role in their inability to heal. Collagen-glycosaminoglycan scaffolds have shown promise for wound healing as they provide a platform for infiltrating cells to support wound repair, but may require further functionalisation to drive wound closure in chronic wounds. To improve wound healing potential, we sought to enhance the collagen-glycosaminoglycan scaffold's pro-angiogenic and pro-neurogenic capacity through addition of fibronectin, collagen IV, or laminin 1 to the scaffold, key extracellular matrix components known to support angiogenic and neurogenic processes. Laminin 1 functionalised scaffolds showed enhanced angiogenic properties, with human dermal fibroblasts producing significantly more vascular endothelial growth factor (VEGF). Endothelial cell coverage on laminin 1 functionalised scaffolds was also significantly enhanced, with cells forming distinct vascular structures. The individual addition of fibronectin, collagen IV, and laminin 1 also increased the neurogenic potential of the collagen-glycosaminoglycan scaffolds, enhancing neurite outgrowth from neurons, as well as supporting axon outgrowth in <em>ex vivo</em> injured tissue explants. Fibronectin, collagen IV, and laminin 1 were then added in combination to the scaffold, but no additional benefit to angiogenic or neurogenic potential was seen. Taken together, laminin 1 functionalisation of a collagen-glycosaminoglycan scaffold provides a multifaceted enhancement of wound healing potential, supporting both angiogenesis and axon regrowth, two processes essential for healing complex wounds.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214633"},"PeriodicalIF":6.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145694369","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}