ACS Biomaterials Science & Engineering最新文献

{"title":"Nanostructuring and Antioxidant Activity of Nanotherapeutics Designed by Self-Assembly of Natural Lipids and Phytochemicals.","authors":"Thelma Akanchise, Borislav Angelov, Yuru Deng, Takehiko Fujino, Thomas Bizien, Angelina Angelova","doi":"10.1021/acsbiomaterials.5c00006","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00006","url":null,"abstract":"<p><p>Lyotropic liquid crystalline nanostructures formed by self-assembly in an aqueous medium are of fundamental interest and crucial for therapeutic applications, encapsulation of nutraceuticals, tissue engineering, and diagnostics. The biomimetic lipid bilayer building blocks impart biodegradable properties and low toxicity of the created nanoassemblies. The question of synergistic or quenching effects on the resulting bioactivity arises from the coencapsulation of multiple antioxidants (<i>e.g.,</i> vitamin E (VitE), curcumin (CU), or coenzyme Q₁₀) in nanocarriers of mixed nonlamellar-phase lipids (e.g., amphiphilic monoglycerides or plasmalogens with long polyunsaturated fatty acid (PUFA) chains). The response to this question should favor phytochemical-based therapies against oxidative stress and inflammatory disorders using sustainable nanomedicines. Herein, we investigate the nanodispersion of multicomponent antioxidant/lipid mixtures using the copolymer Pluronic F127 and three PEGylated amphiphiles (TPGS-PEG₁₀₀₀, MO-PEG_2000, and DSPE-PEG₂₀₀₀). The purpose is to establish possible relationships between the amphiphilic pharmaceutical compositions, structural stability, degradability in the biological cell culture medium, and the effects on antioxidant activity. The structures and the topologies of the phytochemical-loaded mesophases were revealed by synchrotron small-angle X-ray scattering and cryogenic transmission electron microscopy imaging. We found that encapsulated antioxidants (CU, Q_10, or VitE) fine-tune the lipid bilayer properties and the nanostructure of the self-assembled systems to form lamellar (L), inverted hexagonal (H_II), or cubic (<i>Im3m</i>) liquid crystalline phases. The results demonstrated that the composition of the nanoassemblies (lipids, dispersing agents, and antioxidants) governs the structural organization through changes in the interfacial curvature and miscibility effects. A minimal toxicity of the nanoassemblies was observed <i>in vitro</i> using the human neuroblastoma cell line (SH-SY5Y). The biodegradability/stability of the nanodispersions was linked with gradual dynamic changes in nanoparticle size distribution in the biological cell culture medium (DMEM). The established enhanced reactive oxygen species (ROS)-scavenging activity of the liquid crystalline nanoformulations is of interest for developing safe pharmaceutical nanosystems for multitargeted delivery of poorly soluble phytochemicals.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118354","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":"Fe-Doped Carbon Dots Alleviated Rheumatoid Arthritis by Inhibiting Neutrophil NETosis and Autophagy.","authors":"Hesong Wang, Aimin Yan, Congmin Xia, Yue Zhang, Yali Zhou, Huaijuan Huang, Xun Gong, Kai Yuan, Guangrui Huang","doi":"10.1021/acsbiomaterials.4c01880","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01880","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is an autoimmune disorder primarily affecting joints, characterized by high incidence rates and significantly impairing patients' quality of life. Neutrophils play a pivotal role in RA pathogenesis, making therapeutic interventions targeting neutrophil-mediated inflammatory cascades a promising strategy for RA treatment.</p><p><strong>Methods: </strong>Inspired by traditional Tibetan medicinal formulations, which typically combine metallic minerals and organic components, this study developed iron-doped carbon dots (MM-CDs) via a facile one-pot synthesis approach using magnetite (Cishi) and medicated leaven (Shenqu). The therapeutic efficacy of MM-CDs was subsequently evaluated in a mouse model of RA. The results indicated that MM-CDs effectively alleviated RA by disrupting neutrophil-induced inflammatory cascades. Specifically, MM-CDs inhibited NETosis, significantly downregulated myeloperoxidase (MPO), citrullinated histone H3 (Cit-H3), and peptidyl arginine deiminase 4 (PAD-4) in joint tissues (<i>P</i> < 0.05). Furthermore, MM-CDs modulated autophagy pathways, suppressing LC3B and Beclin-1 expression, thereby reducing neutrophil survival. Additionally, MM-CDs promoted apoptosis in neutrophils, evidenced by increased cleaved caspase-3/PARP expression and decreased Bcl-2 levels in LPS-stimulated neutrophils.</p><p><strong>Conclusion: </strong>This study demonstrates that MM-CDs represent a novel and effective therapeutic strategy for RA. Importantly, the treatment exhibited no liver or kidney toxicity in the RA mouse model, highlighting its potential for safe clinical translation.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109031","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":"Changes in Generations of PAMAM Dendrimers and Compositions of Nucleic Acid Nanoparticles Govern Delivery and Immune Recognition.","authors":"Yelixza I Avila, Laura P Rebolledo, Nathalia Leal Santos, Brandon Rawlins, Yasmine Radwan, Melanie Andrade-Muñoz, Elizabeth Skelly, Morgan R Chandler, Luciana N S Andrade, Tae Jin Kim, Marina A Dobrovolskaia, Kirill A Afonin","doi":"10.1021/acsbiomaterials.5c00336","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00336","url":null,"abstract":"<p><p>Nucleic acid nanoparticles (NANPs) are promising immune modulators due to their well-established structural properties and distinct structure-activity relationship with the immune system. We previously identified that NANPs' size, shape, composition, and type of delivery vehicle define their uptake by immune cells and subsequently induced cytokine profile. In this work, we examined the delivery efficiencies and immunological impacts of two representative NANPs─DNA cubes and RNA cubes─complexed with a benchmark delivery vehicle, Lipofectamine 2000 vs. different generations of amine-terminated poly(amidoamine) dendrimers. Using molecular dynamics simulations, we modeled dendrimer interactions with nucleic acid cargos. Next, we used traditional 2D and more recently established 3D cell cultures to assess dendrimers' influence on NANPs uptake. Immune activation was evaluated in several cell lines engineered with reporter genes driven by key immune signaling pathways. Specifically, HEK-lucia reporter cells were used to evaluate RIG-I activation, while THP1-Dual cells provided quantitative readouts for both IRF and NF-κB transcription factor activity. Our findings demonstrate that both dendrimer generation and NANP composition influence cellular uptake and immune responses. This study underscores the importance of formulation in shaping NANPs' biological properties and further advances the understanding of their immunological properties critical for the development of NANPs-based adjuvants.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109026","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":"Improved Diabetic Wound Healing via Flower Extracellular Vesicles and Carbon-Dot-Infused Alginate-Polyethylenimine Antibacterial Hydrogel.","authors":"Safoora Zaffar, Sunita Saha, Tanya Agrawal, Sanjay Kumar Gupta, Parth Gulati, Debashish Paul, Anuj Verma, Suchetan Pal, Tatini Rakshit","doi":"10.1021/acsbiomaterials.5c00443","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00443","url":null,"abstract":"<p><p>Diabetic wounds lead to substantial challenges in healthcare systems due to prolonged healing and susceptibility to debilitating bacterial infections. Traditional wound dressings, designed to regenerate wound voids and aid healing, often lack antibacterial properties. In this study, we present a syringe-injectable hydrogel (HG) infused with rose-petal-derived extracellular vesicles (REVs) and fluorescent carbon dots (CDs), which exhibit intrinsic antibacterial activity. The HG matrix was created by combining oxidized sodium alginate (OA) with branched polyethylenimine (PEI). This formulation selectively targets Gram-negative bacteria through strong physical and mechanical interactions while preserving human erythrocytes, as confirmed by hemolytic assays. Using a Wistar rat type 1 diabetic model, we demonstrated that the HG effectively eradicates <i><i>E. coli</i></i> at the application site, ensuring slow release and retention of REVs and CDs at the wound site, causing minimal inflammation. REV-CD-HG represents a scalable, cost-efficient, and innovative wound dressing with promising clinical applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092012","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":"Self-Iron-Enriched Bacterial Membrane Nanovesicles for Cascade and Multi-Modal Antitumor Therapy.","authors":"Weizheng Li, Ruiqi Wang, Zhenzhen Su, Shang Li, Guoping Zhao, Qinghua Wang, Hongqian Cao, Lei Zhang","doi":"10.1021/acsbiomaterials.5c00217","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00217","url":null,"abstract":"<p><p>The integration of microbiology and nanotechnology offers a novel strategy for cancer treatment. In this study, we innovatively propose the use of <i>Pseudomonas aeruginosa</i> bacterial membranes as nanocarriers. These membranes possess a simple and unique self-enriching property for iron, which, in addition to the inherent immune effects of the membrane itself, can facilitate tumor chemodynamic therapy through Fenton reactions. The system encapsulates the anticancer drug β-Lapachone, which can generate a large amount of hydrogen peroxide within cells, further serving as a substrate for the Fenton reaction, leading to a cascade reaction that achieves a synergistic effect of three therapeutic modalities in tumor treatment. Moreover, the aptamer AS1411 is used to enhance tumor targeting and optimize drug delivery within the tumor microenvironment. This investigation presents a multimodal antitumor strategy that demonstrates enhanced antitumor effects both in vitro and in vivo, providing a new paradigm for the antitumor application of bacterial membrane nanocarriers.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092067","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":"Advances in the Fabrication of Polycaprolactone-Based Composite Scaffolds for Bone Tissue Engineering: From Chemical Composition to Scaffold Architecture.","authors":"Daniil O Golubchikov, Alexander K Petrov, Vasily A Popkov, Pavel V Evdokimov, Valery I Putlayev","doi":"10.1021/acsbiomaterials.5c00205","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00205","url":null,"abstract":"<p><p>Thermoplastic polymer-based materials, which feature essential biological properties and opportunities to implement the cutting-edge additive manufacturing technologies aimed at obtaining high-precision 3D models, have attracted intense interest for porous and bioresorbable bone tissue implants development. Among the wide range of materials, polycaprolactone was found to provide a balance between the biodegradation rate and biocompatibility with various tissues. Recent advances in the fabrication of polymer-polymer and polymer-inorganic composites have opened new ways to improve biological and mechanical outcomes and expanded the range of applications for bone and cartilage restoration, including the development of conductive composites for electrostimulation. While the chemical composition of the manufactured scaffolds played a vital role in their general biological performance and biocompatibility with bone tissue, the micropattern and roughness of the surface were shown to be additional stimuli for stem cell differentiation. More challenges came from the fabrication technique suitable for the proposed scaffold design. Here we summarize the key challenges and advances in fabrication and approaches to the optimization of certain chemical, morphological, or geometrical parameters of polycaprolactone-based scaffolds for bone tissue engineering applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091980","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":"Hybrid Biological Hydrogel Provides Favorable Bioenergetic, Adhesive, and Antioxidative Effects on Wound Healing.","authors":"Xinyi Zhang, Zhijuan Hu, Ralf Pörtner, An-Ping Zeng","doi":"10.1021/acsbiomaterials.5c00072","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00072","url":null,"abstract":"<p><p>Wound healing is a dynamic and complex process that demands substantial energy expenditure and a biomimetic microenvironment. Developing a simple and effective biological hydrogel to enhance mitochondrial energy metabolism could effectively promote wound healing. To this end, we developed a hybrid biological hydrogel based on <i>Escherichia coli</i> lipoate protein ligase A (LplA), which combines its catalytic and self-assembling properties to promote wound healing. In murine fibroblast L929 cell models, LplA significantly enhances cellular activity and intracellular metabolism, promoting cell proliferation and energy supply. However, cells aggregated into spherical clusters on the pure LplA hydrogel. To address this issue, we integrated glutaraldehyde (GA) as a cross-linker into the LplA hydrogel. The GA-LplA hydrogel enhances cell adhesion and proliferation and, unexpectedly, exhibits higher catalytic activity compared with the pure LplA hydrogel. Furthermore, LplA was observed to decompose H₂O₂, and the GA-LplA hybrid hydrogel significantly reduced reactive oxygen species (ROS) production. The promise of this hybrid hydrogel is successfully demonstrated in a male mice full-thickness skin defect model with accelerated re-epithelialization and cell proliferation while reducing inflammation.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091996","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":"Engineered PLGA Nanoparticles for Brain-Targeted Codelivery of Cannabidiol and pApoE2 through the Intranasal Route for the Treatment of Alzheimer's Disease.","authors":"Arun Kumar Mahanta, Bivek Chaulagain, Avinash Gothwal, Jagdish Singh","doi":"10.1021/acsbiomaterials.5c00465","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00465","url":null,"abstract":"<p><p>Neuroinflammation induced by the accumulation of amyloid beta plaques expedites the progression of Alzheimer's disease (AD). Reducing Aβ plaques and associated neuroinflammation could potentially help to delay the progression of AD. Cannabidiol (CBD) is well-known for its antioxidant, anti-inflammatory, and neuroprotective nature, and the ApoE2 is effective in binding and clearing Aβ plaques in the brain. Therefore, codelivery of CBD and pApoE2 to the brain would be a promising therapeutic approach in developing effective therapeutics against AD. This research aims to design a nonviral delivery agent that delivers both drugs and genes to the brain through a noninvasive intranasal route. We have developed mPEG-PLGA nanoparticles coated with mannose, a brain-targeting ligand, to deliver CBD and pApoE2. The designed CBD-loaded coated nanoparticles showed an average diameter of 179.3 ± 4.57 nm and a zeta potential of 30.3 ± 6.45 mV. The coated nanoparticles prolonged the CBD release and showed a 93% release of its payload in 30 days. CBD-loaded nanoparticles, as compared to the free CBD, significantly reduced lipopolysaccharide and amyloid beta-induced inflammation in immortalized microglia cells. Cytotoxicity of the designed nanoparticles was assessed against brain endothelial cells (bEND.3) and found to be nontoxic in nature. The mannose-conjugated chitosan-coated nanoparticles were cationic and able to bind with the pApoE2, protecting the encapsulated pApoE2 from enzymatic degradation. Quantitative in vitro transfection efficiency study in primary astrocytes and primary neurons revealed that the ApoE2 expression level is significantly (<i>P</i> < 0.0001) higher for mPLGA-CBD-MC/pApoE2 than the control. The ApoE2 expression level in the brain of C57BL6/J mice was significantly (<i>P</i> < 0.0001) increased after intranasal administration of mPLGA-CBD-MC/pApoE2. Henceforth, the mannose-conjugated chitosan-coated mPLGA nanoparticles could serve as a nonviral delivery system to deliver both drugs and genes to the brain through the intranasal route for the management of AD.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085540","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":"Rheological Characterization and 3D Fabrication of Artificial Bacterial Biofilms.","authors":"Annie Scutte, Kiram Harrison, Tyler Gregory, David Quashie, Subramanian Ramakrishnan, Jamel Ali","doi":"10.1021/acsbiomaterials.5c00223","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00223","url":null,"abstract":"<p><p>Biofilms are significantly involved in the progression of many diseases, such as cancer and upper respiratory infections, due to their ability to adhere to soft tissues. Factors influencing biofilm development have been extensively studied on planar substrates; however, there is limited understanding regarding biofilm growth and interactions within 3D matrices. Developing biofilm models that closely mimic natural bacterial communities' chemical and mechanical properties in soft tissues is essential for developing next-generation antibacterial compounds and therapeutics, as 3D biofilms are more complex and less susceptible to treatment than their 2D counterparts. Here, to understand environmental viscoelastic effects on biofilms within 3D matrix environments, two types of alginate-based hydrogels are formulated and used to encapsulatevarying concentrations of <i>Salmonella</i> Typhimurium. We explore the effects of increasing <i>S</i>. Typhimurium concentrations on hydrogel rheological properties and assess the impact of printing parameters on bacterial viability. Results show that hydrogels exhibit shear thinning behavior and that increasing the bacterial concentration up to 1 × 10⁷ CFU mL^-1 has no significant effect on the hydrogel precursor moduli and low shear viscosity. However, increasing the bacterial concentration to 1 × 10¹⁰ CFU mL^-1 significantly decreases the hydrogel shear viscosity and modulus. Utilizing extrusion-based bioprinting, the optimal printing parameters (Pr > 0.8) have minimal effects on bacterial viability (>80%) over a 4 day incubation period. Additionally, we find that lower concentrations of bacteria form larger aggregates over time than hydrogels with higher cell concentrations. We show that biofilm growth in 3D depends on both initial bacterial density and matrix rigidity. Further development of physicochemically tuned bioprinted bacterial communities will aid our understanding of bacterial interactions within their 3D environments and enable the use of <i>in vitro</i> tissue models that incorporate biofilms for high-throughput therapeutic screening.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074877","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":"Structural and Mechanical Characterization of Collagen-Hyaluronan Hydrogels Used to Study Cancer Cell Invasion through the Bladder Wall.","authors":"Sara Metwally, Justyna Śmiałek-Bartyzel, Joanna Pabijan, Małgorzata Lekka","doi":"10.1021/acsbiomaterials.5c00136","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00136","url":null,"abstract":"<p><p>Collagen-hyaluronic acid (Col-HA) hydrogels are widely studied as biomimetic materials that recapitulate the environmental physical and mechanical properties crucial for understanding the cell behavior during cancer invasion and progression. Our research focused on Col-HA hydrogels as an environment to study the invasion of bladder cancer cells through the bladder wall. The bladder is a heterogeneous structure composed of three main layers: urothelium (the softest), lamina propria (the stiffest), and the muscle outer layer, with elastic properties lying between the two. Thus, the bladder cancer cells migrate through the mechanically distinct environments. We investigated the impact of Col-HA hydrogel microstructure and rheology on migrating bladder cancer T24 cells from the cancer spheroid surface to the surrounding environment formed from various collagen I and HA concentrations and chemical structures. The designed hydrogels showed variability in network density and rheological properties. The migration of bladder cancer cells was inhibited inside hydrogels of ∼1 kPa storage modulus. The correlation analysis showed that collagen concentration primarily defined the rheological properties of Col-HA hydrogels, but hydrogels can soften or stiffen depending on the type of HA used. Within soft Col-HA hydrogels, cells freely invade the surrounding environment, while its stiffening impedes cell movement and almost inhibits cell migration. Only individual, probably leading, cells are observed at the spheroid edges initiating the invasion. Our findings showed that the rheological properties of the hydrogels dominate in regulating cancer cell migration, providing a platform to study how bladder cancer cells migrate through the heterogeneous structure of the bladder wall.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074878","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}