Seyfure Adıgüzel, Sevde Altuntaş, Şevval Çelikten, Mehmet Cem Gündüz, Merve Güdül Bacanlı
{"title":"A Multicellular 3D GelMA-Based Colorectal Cancer Model for Chemotherapeutic Responses.","authors":"Seyfure Adıgüzel, Sevde Altuntaş, Şevval Çelikten, Mehmet Cem Gündüz, Merve Güdül Bacanlı","doi":"10.1002/mabi.70190","DOIUrl":"https://doi.org/10.1002/mabi.70190","url":null,"abstract":"<p><p>Advanced biomaterials-based in vitro platforms are increasingly required to overcome the limited predictive power of conventional 2D cell cultures in colorectal cancer (CRC) drug screening. Herein, we report the development of a biomimetic, multicellular 3D CRC model based on gelatin methacrylate (GelMA) hydrogels, designed to recapitulate key structural and biological features of the tumor microenvironment. The platform integrates a vascularized hydrogel compartment with human endothelial cells, combined with cancer-associated fibroblasts and macrophages, enabling controlled tumor-stroma-vessel interactions within a physiologically relevant architecture. The GelMA hydrogels were comprehensively characterized, and their role in regulating endothelial viability, migration, and angiogenic marker expression was systematically evaluated. The drug screening capability of the platform was assessed using 5-fluorouracil (5-FU). Comparative analyses revealed that 3D cultures exhibited attenuated cytotoxicity, oxidative stress, and apoptotic responses relative to 2D monolayers, particularly at lower drug concentrations and prolonged exposure times. These findings demonstrate that GelMA-based microenvironment actively modulates cellular drug responses through multicellular interactions and diffusion-mediated effects, rather than acting as a passive scaffold. Overall, this study establishes a functional 3D in vitro platform that provides improved physiological relevance and predictive capability for preclinical CRC drug screening, while offering a human-relevant alternative aligned with the principles of the 3Rs.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 5","pages":"e70190"},"PeriodicalIF":4.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christoph Krauss, Maria Montero Mirabet, Blerta Sonja Thaqi, Sven Weber, Karsten Mäder
{"title":"Animal-Free Derived Collagen-Like Protein Based Electrospun Nanofibers for Biomedical Applications: Cell Interactions Studies","authors":"Christoph Krauss, Maria Montero Mirabet, Blerta Sonja Thaqi, Sven Weber, Karsten Mäder","doi":"10.1002/mabi.70180","DOIUrl":"10.1002/mabi.70180","url":null,"abstract":"<p>Biocompatibility of biomaterials is essential for their application in the biomedical field, particularly in tissue engineering and drug delivery systems. This study focuses on VECOLLAN, a recombinant, non-animal-derived collagen-like protein (CLP), which exhibits excellent biocompatibility while promoting in vitro cell proliferation and wound healing. We previously optimized electrospinning parameters and employed a coaxial crosslinking approach to produce VECOLLAN-based fibers with tunable dissolution, swelling behavior, and elasticity suitable for biomedical applications. The current study aims to assess the compatibility of these fibers with cells (NIH/3T3), investigate chemical leachables from three different formulations of DMTMM cross-linked VECOLLAN-fibers (according to ISO 10993-18), and conduct spectroscopic analysis to confirm crosslinking efficacy. Results indicate that most CLP-based nonwoven mats maintained cell viability above the 70% safety threshold as per ISO-10993-5. The sample with a CLP:DMTMM ratio of 1:0.1 demonstrated the most favorable cell compatibility and effective crosslinking. While the coaxial crosslinking method showed efficiency, residual crosslinker molecules and unexpected derivatives are identified. Spectroscopic investigations gave hints of successful crosslinking, although a direct correlation between crosslinker concentration and spectral band intensity is not established. Future research shall explore additional crosslinkers and cell types to further investigate the biocompatibility and potential applications of VECOLLAN-based nonwoven mats.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peyman Karami, Alexis Laurent, Virginie Philippe, Lee Ann Applegate, Dominique P. Pioletti, Robin Martin
{"title":"In Vitro Evaluation of an Adhesive Hydrogel-Based Chondrocyte Carrier for Enhanced Therapeutic Delivery","authors":"Peyman Karami, Alexis Laurent, Virginie Philippe, Lee Ann Applegate, Dominique P. Pioletti, Robin Martin","doi":"10.1002/mabi.202500653","DOIUrl":"10.1002/mabi.202500653","url":null,"abstract":"<p>Large knee chondral defects remain a major challenge in orthopaedic surgery and may lead to osteoarthritis. Autologous chondrocyte implantation (ACI) is a widely used regenerative therapy; current techniques have inherent limitations related to cell delivery, retention, and integration. This study investigates a novel adhesive hydrogel as a cell carrier for enhanced therapeutic delivery in cartilage repair. This injectable hydrogel can lead to a paradigm shift in ACI through removing the need for membranes entirely and enabling direct in situ fixation of cell-laden constructs while preserving the chondrocytic phenotype. In this work, we report in vitro encapsulation of human autologous chondrocytes (HACs) using cells from five orthopedic patients within this hydrogel with subsequent in vitro evaluation of functional outcomes, including cell viability, glycosaminoglycan production, histological and immunohistological outcomes, and evolution of mechanical properties of the cell constructs. Moreover, by analyzing the hydrogel polymer content (PC), we identified an optimal formulation balancing biological activity and mechanical integrity.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrating Biological Architecture and Biomaterial Function: Exploring the Native Hydrogel Structure of Brown Seaweed","authors":"Linn Berglund, Richa Sharma","doi":"10.1002/mabi.202500622","DOIUrl":"10.1002/mabi.202500622","url":null,"abstract":"<p>Brown seaweed is a naturally occurring composite that integrates alginate and cellulose within a hierarchical, hydrated architecture analogous to engineered hydrogel systems. This study hypothesizes that leveraging the native structure–function relationships of brown seaweed enables the development of functional hydrogel biomaterials while minimizing synthetic and chemical processing. Strategies are investigated to exploit the intrinsic biological structure and composition of brown seaweed blades across multiple formats, including native and purified blade structures, as well as fibrillated blades reassembled into hydrogels and foam structures via 3D printing and freeze-drying. The resulting biomaterials are characterized in terms of structure, hydrogel stability, and liquid absorption capacity in different media. The effects of purification are compared with those of native materials. In addition, porosity, mechanical, rheological, and cytocompatibility properties of the fibrillated and reassembled structures are evaluated. By preserving the natural architecture and avoiding extensive fractionation, this approach demonstrates the potential to create resource-efficient biomaterials with high liquid absorption (∼3600%), high porosity (∼93%), and shape-memory behavior after compression. Cytocompatibility reaches ∼73% viability at 50% extract but decreases to ∼59% at full concentration, indicating a concentration-dependent biological response, underscoring the need to balance minimal processing with biological performance for biomedical applications.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13054773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differential Expression of LncRNA NEAT1 in 3D Tumoroids Compared to 2D Cultures Highlights Its Role in Glioblastoma Progression","authors":"Arpita Ghosh, Soundharya R, Mohit Kumar Jolly, Abhijit Majumder","doi":"10.1002/mabi.202500636","DOIUrl":"10.1002/mabi.202500636","url":null,"abstract":"<div>\u0000 \u0000 <p>NEAT1 (Nuclear-Enriched Abundant Transcript1) is a long non-coding RNA (lncRNA) that critically regulates tumorigenesis, with growing recognition of its potential as a therapeutic target. However, most functional in vitro studies of lncRNAs rely on 2D cell culture systems, which lack the architectural and physiological complexity of tumors. Here, we demonstrate that 3D tumor architecture reshapes lncRNA-driven oncogenic programs. In 3D tumoroids, microenvironmental features such as mechanical cues, cell-cell interactions, and metabolic gradients modulate NEAT1 expression, and function. Using GBM as a proof-of-concept, we show that these context-dependent changes influence stemness, invasion, and EMT pathways. NEAT1 expression was significantly elevated in 3D tumoroids and positively correlated with stemness, invasion, glucose transporter expression, and epithelial-mesenchymal transition (EMT), both at the mRNA and functional levels. siRNA-mediated NEAT1 downregulation in 3D tumoroids to levels comparable to 2D culture, reduced the expression of these cancer-associated markers and suppressed proliferation, migration, and invasion, establishing a causal relationship. To establish broader relevance, we further examined NEAT1 and another oncogenic lncRNA, MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript (1) expression levels across breast, cervical, GBM, liver, and lung cancer models observing consistent expression differences. Collectively, our findings highlight the importance of evaluating the role of lncRNAs in physiologically relevant 3D systems.</p>\u0000 </div>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivo Anton Octave Beeren, Pieter Jelle Dijkstra, Ane Albillos Sanchez, Jopeth Ramis, Francesca Perin, Carlos Mota, Sandra Camarero-Espinosa, Lorenzo Moroni, Matthew Brandon Baker
{"title":"Sulfonated Hyaluronic Acid-Based Polymers and Hydrogels Using Thiol-Ene and Thiol-Michael Reactions","authors":"Ivo Anton Octave Beeren, Pieter Jelle Dijkstra, Ane Albillos Sanchez, Jopeth Ramis, Francesca Perin, Carlos Mota, Sandra Camarero-Espinosa, Lorenzo Moroni, Matthew Brandon Baker","doi":"10.1002/mabi.202500319","DOIUrl":"10.1002/mabi.202500319","url":null,"abstract":"<p>Non-sulfated polysaccharides like hyaluronic acid (HA) have been widely studied as scaffold material for tissue engineering applications. To mimic the function of sulfated glycosaminoglycan in the matrix, sulfate groups can be grafted. However, here, harsh reaction conditions are required which induce significant backbone degradation. As an alternative, sulfonates (R-SO<sub>3</sub><sup>−</sup>) have been shown to resemble the function of sulfates yet have not been introduced on polysaccharides. Using a two-step strategy, we introduced a tunable amount of sulfonate groups on HA, without requiring harsh reaction conditions and organic solvents. By varying the degree of carboxylic acid activation using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), norbornene (NB, 3–18%) or maleimide (MAL, 2–14%) groups were grafted. Subsequently, 3-mercapto-1-propanesulfonate was coupled in high efficiency on the addressable groups via orthogonal thiol-ene and thiol-Michael addition. Additionally, we demonstrated the formation of hydrogels using poly(ethylene glycol)-di-SH as a crosslinker. However, because of the low crosslinking kinetics, HA-MAL appeared not useful for application. Simultaneous addition of the crosslinker and MPS to norbornyl-conjugated HA's in various ratios enabled the formation of hydrogels with tunable stiffness and degree of sulfonate groups. The simple strategy is likely applicable to other commonly used polysaccharides and therefore interesting to the broader tissue engineering community.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimized Photo-Crosslinked Pectin Nanocomposite Hydrogel Incorporating Chitosan-Capped Silver Nanoparticles for Multifunctional Wound Healing","authors":"Peerapat Chidchai, Supusson Pengnam, Boonnada Pamornpathomkul, Thapakorn Charoenying, Praneet Opanasopit, Prin Chaksmithanont, Prasopchai Patrojanasophon, Chaiyakarn Pornpitchanarong","doi":"10.1002/mabi.202500580","DOIUrl":"10.1002/mabi.202500580","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to design and optimize a photo-crosslinked nanocomposite hydrogel for enhanced wound healing. The hydrogel was composed of pectin methacrylate (PAM) and polyethylene glycol diacrylate (PEGDA) and incorporates chitosan-capped silver nanoparticles (CS-AgNPs). PAM was synthesized by coupling pectin with 2-aminoethyl methacrylate (2-AM). Hydrogels were fabricated via photopolymerization, and their components were optimized using a Box–Behnken experimental design to achieve desirable gelling time, water absorption, content, and erosion. CS-AgNPs were synthesized via a microwave-assisted method and incorporated into the optimized hydrogel. Biocompatibility was evaluated using a fibroblast cell line, and antibacterial activity against <i>Staphylococcus aureus</i> and Escherichia coli was assessed. PAM was successfully synthesized with a 36.05% degree of substitution. The optimal formulation (PAM:PEGDA:LAP = 60:60:0.389) gelled within 2 min and demonstrated 85%–88% water content, high water absorption, with low erosion percentage. The synthesized CS-AgNPs imparted the hydrogel with potent antimicrobial activity against both <i>S. aureus</i> and <i>E. coli</i>. The hydrogel demonstrated excellent biocompatibility, significantly enhancing fibroblast proliferation and migration. This novel, systematically optimized nanocomposite hydrogel offered a promising multifunctional platform for combating bacterial infections and accelerating wound healing. Its balanced physical properties and potent biological activity present significant potential for clinical application in wound management.</p>\u0000 </div>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthias Vostatek, Elettra Verin, Marvin Tamm, Christoph Mehofer, Markus Wellenzohn, Karl H Schneider, Stefan Toegel, Francesco Moscato
{"title":"Enhancing Poly-ε-Caprolactone Implant Performance: Synergistic Surface Modifications With Osteon-Like Microstructure, Cold Atmospheric Plasma, and Extracellular Matrix Coating.","authors":"Matthias Vostatek, Elettra Verin, Marvin Tamm, Christoph Mehofer, Markus Wellenzohn, Karl H Schneider, Stefan Toegel, Francesco Moscato","doi":"10.1002/mabi.202500597","DOIUrl":"10.1002/mabi.202500597","url":null,"abstract":"<p><p>Surface modifications of polycaprolactone (PCL) implants influence osseointegration by altering cell adhesion, proliferation, and differentiation. Osteon-like microtopography has been shown to enhance these parameters compared to untreated PCL. Additional treatments, such as cold atmospheric plasma (CAP) and extracellular matrix (ECM) coatings, may further improve bioactivity. This study evaluates and compares the osteogenic potential of osteon-like microtopography, CAP treatment on non-microstructured PCL, ECM coating on non-microstructured PCL, and their combination. Modified PCL samples were analyzed for cell adhesion, proliferation, and differentiation using primary human mesenchymal stem cells. Compared to osteon-like microtopography, CAP-treated and ECM-coated surfaces the combination of all three increased cell adhesion by nearly two-fold. Cell proliferation followed a similar trend, with the combination treatment showing the greatest enhancement by day 10. Alkaline phosphatase activity peaked with osteon-like microtopography, while mineralization was maximized with the combination treatment. In summary, the integration of osteon-like microtopography with CAP treatment and ECM coating synergistically improves cell adhesion, proliferation, and differentiation, offering a promising strategy for optimizing PCL implants to improve osseointegration.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 4","pages":"e00597"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xianming Zhang, Tianyi Kang, Yuxin Shi, Yilian Liu, Xingyu Lyu, Songnan Qu, Kai Li
{"title":"Recent Progress on Carbon Dots for Tumor Photodynamic Therapy.","authors":"Xianming Zhang, Tianyi Kang, Yuxin Shi, Yilian Liu, Xingyu Lyu, Songnan Qu, Kai Li","doi":"10.1002/mabi.202500662","DOIUrl":"10.1002/mabi.202500662","url":null,"abstract":"<p><p>Carbon dots (CDs), as a burgeoning class of zero-dimensional carbon-based nanomaterials, have garnered significant attention in biomedicine due to their various advantages. While extensive studies have focused on their fluorescence and photothermal characteristics, their potential as advanced photosensitizers for photodynamic therapy (PDT) is increasingly recognized. This review provides a systematic and focused summary of recent advances in CD-based tumor PDT. Design strategies for CDs with photodynamic properties are comprehensively categorized, with the donor-acceptor strategy highlighted as the first-ever summary of this rational approach. By improving tumor targeting, alleviating hypoxia, and depleting overexpressed glutathione, the unfavorable tumor microenvironment for CD-based PDT can be effectively circumvented. To overcome the limitations of monotherapies, CD-based PDT is often integrated with photothermal therapy, chemotherapy, and immunotherapy, particularly in combination with immunogenic cell death and immune checkpoint blockade therapy. Such synergistic strategies enable effective eradication of primary tumors while simultaneously establishing long-term immune surveillance against circulating tumor cells. Furthermore, by integrating imaging guidance with therapeutic function, imaging-guided CD-based PDT offers a theranostic platform that paves the way for precise tumor therapy. Collectively, this review offers a comprehensive roadmap for the rational design and translational development of CD-based PDT.</p>","PeriodicalId":18103,"journal":{"name":"Macromolecular bioscience","volume":"26 4","pages":"e00662"},"PeriodicalIF":4.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}