Gerson Santos de Almeida, Matheus Luquirini Santos, Maria Gabriela Jacheto Carra, João de Freitas Gomes Neto, Luisa Camilo Suter, Yasmin Yokote Piconi, Pascale Chevallier, Eduardo Henrique Backes, Diego Mantovani, Willian Fernando Zambuzzi
{"title":"Bioactive Ion-Doped Monetite/Chitosan Thermosensitive Hydrogels with Dual Osteogenic and Pro-Angiogenic Stimuli for Bone Regeneration","authors":"Gerson Santos de Almeida, Matheus Luquirini Santos, Maria Gabriela Jacheto Carra, João de Freitas Gomes Neto, Luisa Camilo Suter, Yasmin Yokote Piconi, Pascale Chevallier, Eduardo Henrique Backes, Diego Mantovani, Willian Fernando Zambuzzi","doi":"10.1021/acsbiomaterials.6c00422","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c00422","url":null,"abstract":"<p>The development of multifunctional scaffolds capable of orchestrating the complex cascade of bone regeneration, cell recruitment, vascularization, and extracellular matrix deposition remains a significant challenge in regenerative medicine. This study introduces a dual-strategy biomaterial system. On one hand, pure monetite (CaP), cobalt-doped monetite (CoCaP), and magnesium-doped monetite (MgCaP) powders were synthesized via coprecipitation to deliver specific ionic cues. On the other hand, these bioactive powders were incorporated into a thermosensitive chitosan/β-glycerophosphate (β-GP) hydrogel to create an injectable, conformable composite. Then, comprehensive physicochemical characterization (X-ray diffraction, Raman, Fourier transform infrared (FTIR), and scanning electron microscopy/energy dispersive spectroscopy) confirmed phase-pure monetite with successful ionic incorporation. FTIR analysis of the hydrogels revealed characteristic bands for chitosan, with evidence of the establishment of electrostatic interactions between protonated amino groups and phosphate species. The composite hydrogels exhibited shear-thinning behavior, storage modulus (<em>G</em>′) exceeding loss modulus (<em>G</em>″), and tunable mechanical properties, with MgCaP composites displaying the highest stiffness. Indirect contact assays on CoCaP powders and hydrogels confirmed enhanced cell adhesion, migration, and expression of pro-angiogenic genes and matrix metalloproteinases. MgCaP formulations robustly upregulated osteogenic markers. Additionally, direct cell contact with composite hydrogels dramatically amplified transcriptional responses on adhesion, cell cycle, and osteogenic genes, particularly on MgCaP hydrogels. Altogether, this work demonstrates that ionic doping confers distinct and complementary bioactivities to monetite, pro-angiogenic/migratory Co<sup>2+</sup>, and osteogenic/matrix-synthetic Mg<sup>2+</sup>, and that chitosan hydrogels represent an injectable vehicle that amplifies bioactive signaling upon direct cell contact, thus offering a versatile and innovative platform for bone tissue engineering.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"4746–4764"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148950928","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}
Thien Ngoc Le, Manh Tuong Nguyen, Markos Negash Alemie, Giles Best, Neethu Ninan, Jordan Li, Vashe Chandrakanthan, Vi Khanh Truong, Richard Bright, Krasimir Vasilev
{"title":"Pathology-Adaptive Biomaterial Interfaces Selectively Modulate AGE-Modified Protein Corona To Restore Osteogenesis","authors":"Thien Ngoc Le, Manh Tuong Nguyen, Markos Negash Alemie, Giles Best, Neethu Ninan, Jordan Li, Vashe Chandrakanthan, Vi Khanh Truong, Richard Bright, Krasimir Vasilev","doi":"10.1021/acsbiomaterials.6c00431","DOIUrl":"10.1021/acsbiomaterials.6c00431","url":null,"abstract":"<p>Advanced glycation end products (AGEs) accumulate in the serum of people with diabetes, some chronic conditions, and aging and impair osseointegration by reshaping the protein corona and activating oxidative stress pathways at the biomaterial interface. Here, we introduce a pathology-adaptive surface engineering strategy in which plasma polymer coatings with defined functional chemistries are designed to selectively modulate AGE adsorption while preserving physiological protein interactions. Titanium was functionalized with carboxyl (–COOH), amine (–NH<sub>2</sub>), or hydrocarbon (–CH<sub>3</sub>) plasma polymers to precisely modulate interfacial chemistry. Carboxyl- and amine-functionalized surfaces significantly reduced AGE adsorption compared to hydrophobic controls while maintaining total serum protein adsorption, indicating selective exclusion of glycated species. This modulation of the AGE-modified protein corona attenuated the generation of reactive oxygen species, suppressed apoptosis, and restored osteogenic gene expression in bone marrow mesenchymal stem cells following exposure to AGEs. Functionalized coatings supported sustained proliferation and enhanced mineralization, demonstrating the recovery of regenerative capacity in a metabolically compromised environment. The AGE–RAGE axis was identified as a key driver of macrophage inflammatory activation. These findings establish pathology-adaptive surface chemistry as a materials strategy to selectively regulate disease-associated protein adsorption and restore regenerative performance under glycation stress.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"4765–4777"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719423","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":"Photocurable Allyl-Succinylated Collagen Bioink for High-Resolution 3D Bioprinting and Regenerative Diabetic Wound Healing","authors":"Mingzhu Ye, Guoqi Cui, Ziheng Zhu, Weifeng Zheng, Huixia He, Jianxi Xiao","doi":"10.1021/acsbiomaterials.6c00462","DOIUrl":"10.1021/acsbiomaterials.6c00462","url":null,"abstract":"<p>Three-dimensional (3D) bioprinting of collagen-based hydrogels remains limited by poor solubility, weak mechanics, and slow photocrosslinking, which hinder print fidelity and restrict clinical translation. Here, we report a photocurable allyl-succinylated collagen (CAA) bioink that overcomes these long-standing challenges by integrating enhanced molecular solubility, rapid photocrosslinkability, and intrinsic bioactivity. The allyl-succinyl modification markedly improved collagen solubility and enabled efficient radical-mediated polymerization, yielding hydrogels with excellent structural integrity, tunable stiffness, and high-resolution DLP printing performance. In vitro, CAA demonstrates excellent cytocompatibility, promoting cell adhesion, proliferation, migration, and 3D encapsulation with high postprinting viability. In a full-thickness diabetic wound model, bioprinted CAA constructs, especially when combined with fibroblasts and keratinocytes, significantly accelerated wound closure, enhanced collagen I/III regeneration, restored elastic fiber integrity, stimulated angiogenesis, and reduced oxidative stress, collectively restoring ECM homeostasis and tissue architecture. Furthermore, the upregulation of regenerative markers, such as Ki67 and EGF, highlights the material’s ability to modulate the wound microenvironment and activate endogenous repair pathways. This work establishes CAA as a highly soluble, bioactive, and photoprintable collagen platform with strong potential for precision 3D bioprinting and regenerative therapy of chronic diabetic wounds.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"4934–4950"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756830","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":"Mechanical Response and Damage Evolution of PMMA-Based Bone Cement from Compressive Calibration to Shear Prediction","authors":"Huanli Qi, Yinwang Zhang, Zhen Xu, Jinyu Liu, Xu Hu, Yongmin Huang","doi":"10.1021/acsbiomaterials.6c00560","DOIUrl":"10.1021/acsbiomaterials.6c00560","url":null,"abstract":"<p>In this study, a three-dimensional viscoelastic lattice spring model (VLSM) is employed to evaluate the transferability of compression-calibrated material parameters to shear loading for poly(methyl methacrylate) (PMMA)-based bone cement (BC). The model is first calibrated using compressive stress–strain data and then applied to shear loading without further parameter re-identification. The model reproduces the main features of the compressive response, predicts the shear stress–strain response, and resolves the associated progression from homogeneous elastic deformation to diffuse microdamage and ultimately to localized failure. Moreover, analyses considering variations in shear location and shear-plane size further clarify the relationship between shear stress–strain response and damage patterns, revealing that more peripheral loading and smaller shear planes sustain higher load-carrying capacity due to differences in crack propagation pathways. Finally, parametric investigations demonstrate that loading rate, porosity, and BaSO<sub>4</sub> content exert systematic influences on the macroscopic stress–strain response and damage development. These findings suggest that the VLSM can transfer a compression-calibrated parameter set to shear loading, enabling analysis of the shear mechanical response and damage evolution of PMMA-based BC.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"4709–4719"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785428","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":"Natural Bone Regeneration-Inspired Poly(Lipoic Acid)-Based Organic–Inorganic Bone Adhesive for Osteoporotic Bone Defect Repair","authors":"Linbo Wei, Ziyi Xu, Zihui Yu, Qingqian Zhao, Chuanchuan Fan, Yanhong Zhao, Chunyan Cui, Wenguang Liu","doi":"10.1021/acsbiomaterials.6c00916","DOIUrl":"10.1021/acsbiomaterials.6c00916","url":null,"abstract":"<p>Osteoporosis, featured by imbalanced bone remodeling, faces clinical challenges including microenvironment dysregulation, insufficient mineralization, and poor material fixation. Inspired by natural bone regeneration—where ossification centers and surrounding soft tissues orchestrate mineralization and tissue integration—we herein develop a biomimetic adhesive in which strontium titanate (SrTiO<sub>3</sub>) serves as the mineralization core to mimic ossification centers, boosting biomineralization and osteoblast differentiation. Meanwhile, poly(lipoic acid) (PolyLA), synthesized via one-step polymerization of lipoic acid (LA), replicates the role of soft tissues for structural support and biological regulation. Multiple coordination interactions between carboxyls and strontium ions substantially reinforce this organic–inorganic composite, resulting in a compressive strength, toughness, and tear resistance 11.65-fold, 9.1-fold, and 2.76-fold higher than those of pure PolyLA, respectively, thereby resisting anisotropic mechanical stresses at osteoporotic sites under physiological locomotion. Additionally, its hot-melt injectability enables robust interfacial fixation to osteoporotic bone, achieving an adhesion strength of up to 1.3 MPa, and facilitates sustained co-release of Sr<sup>2+</sup> and LA, conferring anti-inflammatory, antioxidant, and pro-angiogenic functions. In an osteoporotic rat femoral defect model, this adhesive outperforms commercial bone cement by accelerating bone regeneration, improving microarchitecture, and increasing bone density. Its biocompatibility, degradability, mineralization capacity, and stable fixation offer a biomimetic strategy for osteoporosis treatment.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"5005–5024"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862657","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":"Oral Milk-Derived Extracellular Vesicles: A Promising Drug Delivery System for Neuroinflammatory Diseases","authors":"Ming-Yue Bao, Yan-Hua Li, Zhe-An Zhou, Lin-Jie Zhang, Xin-Yan Han, Xin-Ya Guo, Xiao-Yan Guo, Meng-Yuan Tian, Dong-Xia Hao, Wei-Feng Zhang, Xiao-Li Ding, Yuan Zhang, Xing Li","doi":"10.1021/acsbiomaterials.6c00969","DOIUrl":"10.1021/acsbiomaterials.6c00969","url":null,"abstract":"<p>Oral drug delivery is the most patient-friendly and safest approach for disease treatment; however, the bioavailability of macromolecular drugs and poorly soluble small molecules is severely limited by gastrointestinal degradation and the blood−brain barrier (BBB). Here, we developed a cost-effective, chitosan-based isolation method to efficiently isolate milk-derived extracellular vesicles (mEVs), which exhibit good stability in the gastrointestinal tract and intrinsic BBB-penetrating capability. Biodistribution studies showed that mEVs were absorbed in both healthy and experimental autoimmune encephalomyelitis (EAE) mice, with increased CNS accumulation under neuroinflammation, especially in oligodendrocytes and neurons. To address the poor stability and bioavailability of ellagic acid (EA) and to explore the therapeutic potential of mEVs in neuroinflammation treatment, we encapsulated EA and interferon-β (IFN-β) into mEVs and evaluated their therapeutic effects in experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide-induced neuroinflammation models. The results showed that mEV@IFN-β and mEV@EA significantly relieved disease progression and improved neuroinflammation compared to free drugs, with enhanced stability and bioavailability. Overall, our study findings establish mEVs as an efficient oral delivery platform capable of overcoming biological barriers for treating neuroinflammatory diseases, with the chitosan-based isolation method offering a scalable production approach.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"4833–4847"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885780","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}
Bingwen Zhu, Zhuozhen Li, Tao Bi, Xuemei Yang, Shengdan Yao, Lei Chen, Qianqian Dong, Linguo Cao, Ting Wang, Yihuan Wang, Qin Sun, Zengjin Liu
{"title":"Integrated Microneedle Patches Combining PROTAC-Derived Phytochemicals, Ceria Nanozymes, and Puerarin Hydrogels for Targeted Treatment of Acetaminophen-Induced Acute Liver Injury","authors":"Bingwen Zhu, Zhuozhen Li, Tao Bi, Xuemei Yang, Shengdan Yao, Lei Chen, Qianqian Dong, Linguo Cao, Ting Wang, Yihuan Wang, Qin Sun, Zengjin Liu","doi":"10.1021/acsbiomaterials.6c00617","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c00617","url":null,"abstract":"<p>Acute liver failure (ALF) is a critical clinical condition associated with rapid deterioration and substantial mortality, in which dysregulated crosstalk between oxidative stress and inflammatory cascades plays a pivotal pathogenic role. However, current therapeutic strategies remain inadequate due to the pharmacokinetic barrier of achieving efficient hepatic drug accumulation. Herein, we report a multifunctional microneedle-based therapeutic platform (MN(PUE)−Hed#3/CeO<sub>2</sub>) for precise hepatic delivery and spatiotemporal modulation of the oxidative stress−inflammation axis in ALF management. Through rational PROTAC-mediated structural optimization of hederagenin, a novel proteolysis-targeting chimera (Hed#3) was developed, which retains the intrinsic antioxidant activity of the parent compound while exhibiting enhanced protein degradation efficiency, thereby amplifying cytoprotective effects. Integration with cerium oxide nanozymes yielded a Hed#3/CeO<sub>2</sub>@PLGA nanocomposite that synergistically couples molecular antioxidation with enzymatic reactive oxygen species (ROS) scavenging. Leveraging the thermoresponsive sol−gel transition and inherent anti-inflammatory activity of puerarin (PUE), this hybrid system was incorporated into a dissolvable microneedle array for localized and controlled hepatic drug release. Comprehensive pharmacodynamic studies demonstrated that MN(PUE)−Hed#3/CeO<sub>2</sub> markedly attenuated acetaminophen-induced hepatotoxicity via concurrent activation of the Nrf2/HO-1 antioxidant defense pathway and inhibition of NF-κB−mediated proinflammatory signaling. This work establishes a therapeutically viable and translatable strategy for ALF treatment and presents a conceptual paradigm for targeted intervention of oxidative stress−associated inflammatory diseases.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"5034–5050"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148950663","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}
Guohongfang Tan, Jialuo Chen, Teiling Xing, Subhas C. Kundu, Shenzhou Lu
{"title":"Structure-Regulated Silk Fibroin Microneedle Patches for Minimally Invasive Glucose-Responsive Colorimetric Sensing","authors":"Guohongfang Tan, Jialuo Chen, Teiling Xing, Subhas C. Kundu, Shenzhou Lu","doi":"10.1021/acsbiomaterials.6c00863","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c00863","url":null,"abstract":"<p>Minimally invasive microneedle devices have emerged as highly promising platforms for localized interstitial fluid (ISF) sensing and biomarker detection. In this study, we present a bilayer silk fibroin microneedle system that leverages material structure regulation to achieve optimal mechanical strength, controlled swelling, and limited dissolution. Our dual-layer architecture spatially separates skin penetration and local interstitial-fluid access from the sensing region, improving reagent retention and enabling clear, localized colorimetric readouts. Furthermore, the incorporation of 2-hydroxypropyl-β-cyclodextrin stabilizes chromogenic substrates within the hydrophilic silk matrix, delivering robust responses both in vitro and in vivo. The optimized microneedles exhibit uniform morphology and sufficient compressive strength for reliable transdermal insertion, successfully producing visually distinguishable outputs in animal models. Ultimately, this material-guided, device-integrated platform highlights the tremendous potential of combining biomaterial engineering with microscale design for next-generation minimally invasive biosensors.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"5063–5074"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148950862","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":"Bacteriophage-Grafted Implant Polymer Coating Prevents Biofilm Formation While Allowing Bone Cell Growth In Vitro","authors":"Yu-Sheng Chen, Min-Shin Ou, Hsin-Yi Lin","doi":"10.1021/acsbiomaterials.6c01225","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c01225","url":null,"abstract":"<p>Orthopedic implants often fail due to bacterial infections and biofilm formation caused by drug-resistant strains, particularly <em>Staphylococcus aureus</em>. Bacteriophages (phages) represent a promising strategy for controlling implant-associated infections. In this study, phages targeting <em>S. aureus</em> were purified from wastewater and chemically grafted onto a chitosan coating applied to a Ti-6Al-4V alloy. The phage-grafted coating was abraded against the spongy portion of a porcine femur bone, disinfected using ethanol and UV exposure, and evaluated <em>in vitro</em> for biofilm prevention and osteoblast mineralization. Following abrasion, part of the coating remained intact on the metal surface, and the grafted phages retained their lytic activity after disinfection. Abraded samples containing phages reduced bacterial growth by 90.5% compared with samples without phages (<em>p</em> < 0.01) and effectively prevented biofilm formation 16 h after bacterial inoculation. The 7F2 osteoblasts exhibited significantly higher proliferation on phage-grafted coatings (<em>p</em> < 0.05). Cells cultured on abraded samples showed increased maturation, indicated by alkaline phosphatase activity, and enhanced mineralization, measured by calcium deposition, relative to nonabraded samples (<em>p</em> < 0.01), likely due to increased surface roughness. However, the presence of phages on the coating was associated with reduced calcium deposition (<em>p</em> < 0.01). These results demonstrate that phage-grafted coatings can reduce bacterial growth and prevent biofilm formation without deactivation by biological residues, while maintaining compatibility with bone-forming cells <em>in vitro</em>. This approach may offer a feasible strategy for reducing implant-related infections while allowing bone cell growth.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"5025–5033"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148950900","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}
Tao Yang, Jiale He, Minghai Ma, Kaibo Mi, Yutong Chen, Min Wang, Hang Liu, Yanjia Liu, Nan Zhang, Dawei Luo, Mengzhao Zhang, Lei Wang, Jinhai Fan
{"title":"Mechanically Matched PGT Hydrogel Enables Functional Bladder Augmentation and Reconstruction without Fibrosis","authors":"Tao Yang, Jiale He, Minghai Ma, Kaibo Mi, Yutong Chen, Min Wang, Hang Liu, Yanjia Liu, Nan Zhang, Dawei Luo, Mengzhao Zhang, Lei Wang, Jinhai Fan","doi":"10.1021/acsbiomaterials.6c00179","DOIUrl":"10.1021/acsbiomaterials.6c00179","url":null,"abstract":"<p>Background: The clinical translation of engineered bladder scaffolds often faces challenges due to a mechanical mismatch with native tissue, which can lead to complications such as urine leakage, graft fibrosis, reduced compliance, and rupture. This study aims to overcome these limitations by developing a biomimetic hydrogel with viscoelastic properties that precisely match those of the natural bladder. Methods: A novel hydrogel (PGT) was synthesized by combining acrylated polycaprolactone/polyethylene glycol triblock polymer (PCECD) with gelatin methacryloyl (GelMA), followed by hydrogen-bond crosslinking using tannic acid (TA). Nine PGT formulations with varying concentrations and PCECD/GelMA ratios were fabricated. Their mechanical properties were systematically characterized. Biocompatibility was assessed in vitro using urothelial cells, and functional efficacy was evaluated in vivo using a rabbit model of augmentation cystoplasty. Methods: A novel hydrogel (PGT) was synthesized by combining acrylated polycaprolactone/polyethylene glycol triblock polymer (PCECD) with gelatin methacryloyl (GelMA), followed by hydrogen-bond crosslinking using tannic acid (TA). Nine PGT formulations with varying concentrations and PCECD/GelMA ratios were fabricated. Their mechanical properties were systematically characterized. Biocompatibility was assessed in vitro using urothelial cells, and functional efficacy was evaluated in vivo using a rabbit model of augmentation cystoplasty. Results: A specific formulation (10% concentration, PCECD:GelMA ratio of 1:1) demonstrated mechanical properties closely matched to the native bladder and exhibited excellent cytocompatibility in vitro. In the rabbit model, implantation of the optimized PGT hydrogel significantly improved bladder capacity and compliance compared to controls. Histological analysis revealed rapid epithelialization, with complete urothelial regeneration achieved within one month. Critically, the repaired tissue showed no evident fibrosis, indicating successful avoidance of this common pathological outcome. Conclusions: We successfully developed a mechanically biomimetic PGT hydrogel that supports functional bladder reconstruction. These findings underscore the pivotal role of precise mechanical compatibility in bladder tissue engineering, promoting regenerative healing while preventing fibrosis. This study provides a promising material strategy and a clear direction for future research toward effective clinical bladder augmentation.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 9","pages":"4866–4879"},"PeriodicalIF":6.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757060","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}