ACS Biomaterials Science & Engineering最新文献

{"title":"Detachable Microneedle Patch for Local Delivery of TGF-β Inhibitor to Suppress Scar Formation.","authors":"Yubeen Park, DoHun Kim, Suhyang Lee, Seung Jin Eo, Song Hee Kim, Ji Won Kim, Dong-Sung Won, Hyun-Do Jung, Dae-Kee Kim, KangJu Lee, Jung-Hoon Park","doi":"10.1021/acsbiomaterials.5c01389","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c01389","url":null,"abstract":"<p><p>Severe wounds often lead to delayed healing and fibrotic scar formation, primarily driven by dysregulated transforming growth factor beta (TGF-β) signaling, which causes excessive collagen accumulation. Current treatments face limitations, including poor drug delivery, systemic side effects, and patient compliance issues. To address these challenges, we developed a detachable microneedle (d-MN) patch made of biodegradable poly(lactic-<i>co</i>-glycolic acid) for the localized, sustained delivery of the selective TGF-β inhibitor EW-7197 directly into skin wounds. The patch features detachable drug-loaded tips that remain embedded in the tissue shortly after application, allowing for prolonged drug release without continuous attachment. Drug dosage was controlled by adjusting the tip size, and rapid detachment was confirmed within 1 min using ex vivo models. In vitro tests showed sustained EW-7197 release for up to 14 days. In vivo studies using a rat excisional wound model demonstrated that the d-MN patch reduced wound size by approximately 50% and suppressed fibrotic scar formation compared to the controls. This minimally invasive, patient-friendly approach effectively regulates TGF-β signaling to suppress fibrosis during the wound-healing process. Our findings indicate that EW-7197-loaded d-MN patches are a promising therapeutic strategy for improving healing outcomes and reducing fibrotic scar formation.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135965","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":"Simulated Coating Interface of (Au-<i>n</i>-HAP-TiO₂) Ti-Metal Bone Implants: Improved Coating Thickness and Long-Term Corrosion Resistance by the Electrophoretic Deposition Method.","authors":"R Vignesh, T S N Sankara Narayanan, Prasanth Babu Nandagopal, Venkatraman Manickam, T M Sridhar","doi":"10.1021/acsbiomaterials.5c01184","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c01184","url":null,"abstract":"<p><p>Recent investigations into novel biomaterials have revealed a necessary trade-off between mechanical and biological properties. This understanding has driven the exploration of various dopant elements to optimize the material performance for biomedical applications. The prime objective of this work is to develop gold-decorated nanohydroxyapatite coatings (Au-<i>n</i>-HAP) on titanium (Ti) via electrophoretic deposition (EPD) owing to their ability to enhance the corrosion resistance and biocompatibility of Ti. The crystalline nature of Au-<i>n</i>-HAP was evidenced by XRD, and the presence of phosphate groups was further confirmed by FTIR and Raman. The XPS survey spectrum confirms the presence of Au as distinct peaks at 83.7 and 87.5 eV with expected binding energy values. FE-SEM analysis indicates the formation of TiO₂-Au-<i>n</i>-HAP interfacial bonding at the titanium-coating interface. The corrosion resistance of <i>n</i>-HAP and Au-<i>n</i>-HAP composite coatings on titanium was assessed in Ringer's solution using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS). The sample coated at 80 V showed the best performance, with a maximum Vickers microhardness of 280 HV100 and excellent corrosion stability, as evidenced by a corrosion potential (<i>E</i>_corr) of -141.49 mV vs SCE and a low corrosion current density (<i>I</i>_corr) of 155.12 μA/cm². Furthermore, a COMSOL Multiphysics 6.1 model accurately predicted a coating thickness of 19 μm, which closely matched the experimental (20 μm) and FE-SEM cross-sectional (21 μm) measurements. Overall, the findings showed that the Au-<i>n</i>-HAP composite-coated Ti provided better corrosion resistance in Ringer's solution than both <i>n</i>-HAP-coated and bare Ti during both short- and long-term immersion (up to 28 days). The Au-<i>n</i>-HAP composite-coated Ti displayed enhanced in vitro cytocompatibility of MC3T3-E1 preosteoblastic cell lines up to 150 μg/mL and better antibacterial activity against <i>S. aureus</i> and <i>E. coli</i> besides being hemocompatible. In terms of its higher corrosion resistance, lower toxicity, and superior biocompatibility, the Au-<i>n</i>-HAP composite-coated Ti can be explored as an implant material for orthopedic applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129603","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":"Plastically Deformable, Mechanically Strong, and Degradable Polymeric Airway Stents from Sustainable Aliphatic Polyester Block Polymers.","authors":"Arpan Biswas, Daniel M Krajovic, Robroy Maclver, Marc A Hillmyer","doi":"10.1021/acsbiomaterials.5c01235","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c01235","url":null,"abstract":"<p><p>Airway stenting is an effective method for providing immediate relief from obstructions in tracheobronchial lumens. Standard airway stents made of silicone or metal have morbidities that motivate a transition to bioresorbable stents. Here, we reported a mechanically stiff and tough airway stent prepared from \"LML\" triblock copolymers featuring two polyesters, poly(l-lactide) (PLLA, \"L\") and poly(γ-methyl-ε-caprolactone) (PγMCL, \"M\"). The LMLs could be thermally processed in the melt and transitioned from Newtonian to shear thinning viscosity behavior with increasing molar mass. By tuning molar mass, we optimized the viscosity profile for extrusion-based 3D printing, achieving high-resolution fabrication of solid and open-cell stents without significant sagging or delamination. We also report a new stent deployment strategy using radial dilation of LML stents to induce plastic deformation. Mechanical testing indicated that intermediate molar mass stents could plastically deform during balloon dilation, achieving robust postdeployment structural integrity. Prestretched tensile specimens, emulating balloon-dilated samples, exhibited enhanced tensile strength and toughness in poststretched samples, critical for maintaining stent shape under physiological conditions. <i>In situ</i> SAXS/WAXS revealed contributions from PγMCL domain deformation and PLLA crystal fragmentation to the shape retention and toughness of plastically deformed samples. We validated this new strategy <i>in vivo</i>, successfully deploying an LML stent in a human-mimetic porcine lumen. Finally, through an <i>in vitro</i> cytotoxicity assay with primary human airway epithelial cells, along with the degradation study in a buffer solution at 37 °C, we established the cytocompatibility and biodegradability of the LMLs over long time periods, making them promising candidates for future customizable 3D-printed airway stents with superior mechanical performance, printability, cytocompatibility, and biodegradability.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129637","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":"Cosmetic Potential of a Structural Protein Copolymer Based on Silk, Elastin, and Keratin.","authors":"Ana Mota, Marta Caçador, José Pedro Carvalho, Ana Tinoco, André da Costa, Artur Ribeiro, Filipa Gonçalves, Artur Cavaco-Paulo","doi":"10.1021/acsbiomaterials.5c01233","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c01233","url":null,"abstract":"<p><p>The hair cosmetic industry is constantly searching for new ingredients and innovative materials that can help enhance properties, such as softness, shine, shape, and color. However, conventional products contain harmful chemicals. In this study, we developed a biobased alternative using a recombinant protein composed of repetitions of consensus motifs from the structural proteins silk, elastin, and keratin, termed SELP::KP. This protein was expressed in <i>Escherichia coli</i> and purified by a nonchromatographic method to high purity. Fourier-transform infrared spectroscopy (FTIR) confirmed the β-sheet-rich structure, characteristic of silk and SELP-like proteins. Calorimetry studies confirmed the high thermal stability of SELP::KP. When applied to hair, SELP::KP colocalized at both the cuticle and cortex, indicating strong penetration capacity. Mechanical testing of treated virgin hair showed significant improvements: Young's modulus increased by 34.9%, and extensibility improved by 12.4% compared to untreated controls, indicating enhanced strength and elasticity. Additionally, the protein's potential as a safer perming agent was evaluated, maintaining a curling effect similar to the chemical treatment but with lower damaging effects. Furthermore, SELP::KP was shown to reduce by half the combing strength needed, acting as an effective conditioning agent. This research highlights SELP::KP as a promising biobased copolymer for hair cosmetics, offering both styling benefits and improved hair health, as a leave-in treatment or a hair mask that aids in combability and perming service.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129627","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":"Fabrication and Characterization of a Porous TiO₂-Modified PEEK Scaffold with Enhanced Flexural Compliance for Bone Tissue Engineering.","authors":"Martina Galea Mifsud, Andrew Sachan, Roger J Narayan, Lucy Di-Silvio, Trevor Coward","doi":"10.1021/acsbiomaterials.5c01032","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c01032","url":null,"abstract":"<p><p>Bone pathologies are becoming increasingly prevalent with an aging population, often necessitating bone grafting procedures. The current gold standard for grafting uses autologous tissue; however, this approach carries limitations such as donor site morbidity. Consequently, there is a growing interest in alternative biomaterials. Polyetheretherketone (PEEK), a thermoplastic with bone-like mechanical properties, has shown promise, although its limited bioactivity remains a critical constraint. Various functionalization strategies have been employed to enhance the biological performance of otherwise inert materials. This study aims to develop a functionalized porous PEEK scaffold to improve bioactivity of the material, thereby promoting human osteoblast (HOB) adhesion, proliferation, and differentiation. PEEK scaffolds were fabricated using fused deposition modeling (FDM) (Apium P155), with a rectilinear pattern alternating at +45° and -45° angles between layers. This configuration generated an interconnected pore network with sizes ranging from ∼100 to 400 μm. The scaffolds were further coated with titanium oxide as an additional intervention to enhance bioactivity. Mechanical properties of both porous and solid constructs were evaluated according to ISO 178, a flexural testing standard for plastics. Results indicated that both porous scaffolds exhibited a 10-fold decrease in flexural modulus and were 10 times more flexible compared to the solid counterpart (<i>p</i> < 0.001). The mechanical properties of both porous scaffolds were consistent with values reported for trabecular bone, while the solid construct demonstrated a flexural modulus comparable to cortical bone. These findings suggest that the porous PEEK scaffold, both neat and titanium oxide-coated, possesses mechanical properties similar to bone <i>in vivo</i>, indicating its potential as a mechanically suitable biomaterial for bone grafting applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129632","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 Spider Silk in Core-Shell Multifunctional Fibrous Mat for Accelerated Chronic Diabetic Wound Healing via Macrophage Polarization.","authors":"Mercyjayapriya Jebakumar, Mohandass Pachaiyappan, Numbi Ramudu Kamini, Janani Radhakrishnan, Niraikulam Ayyadurai","doi":"10.1021/acsbiomaterials.5c00737","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00737","url":null,"abstract":"<p><p>Macrophage phenotypic switching from pro-inflammatory M1 to pro-regenerative M2 is impaired in chronic diabetic wounds, leading to excessive reactive oxygen species (ROS) production, poor angiogenesis, and decreased collagen deposition, thereby affecting the healing cascade. Development of multifunctional biomaterial with bioactive compounds to modulate the immune microenvironment and combat ROS, with the potential to facilitate angiogenesis and increase collagen deposition. Here, a novel combination therapy of silk DOPA-crisaborole conjugate (SDC, angiogenic and anti-inflammatory) and eugenol (Eu, antioxidant) has been devised to promote chronic wound healing. The core-shell electrospun fibrous mat has been fabricated with Eu in a polycaprolactone core (PCL-Eu) and SDC in a dextran shell (Dex-SDC), collectively termed Dex-SDC/PCL-Eu. In response to the acidic environment of chronic wounds, the dynamic benzoxaborole-catechol complex between crisaborole and silk DOPA cleaves, releasing crisaborole, while the matrix degradation of Dex-SDC/PCL-Eu over time enables the controlled release of Eu for 12 days. The initial release of crisaborole promotes polarization of M1 macrophages to M2 phenotype by significantly upregulating anti-inflammatory cytokine IL-10 and downregulating pro-inflammatory cytokine IL-6 gene expression in Dex-SDC/PCL-Eu-treated THP-1 cells compared to control. Subsequently, the sustained release of Eu mitigates oxidative damage. Dex-SDC/PCL-Eu fibers facilitate in vitro adhesion, migration, and proliferation of fibroblasts and endothelial cells as well as enhance endothelial tube formation. In the diabetic rat model, the Dex-SDC/PCL-Eu fibers reduce inflammatory granulation tissue and ulceration, while promoting neovascularization, complete re-epithelialization, and well-organized dermis and epidermis formation with uniform collagen deposition. Thus, the developed multifunctional Dex-SDC/PCL-Eu fibrous mat accelerates full-thickness skin wound healing and holds promise for the treatment of chronic diabetic wounds.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123832","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":"Bioengineering Approaches for the 3D Blood-Retinal Barrier: Disease Modeling and Drug Development.","authors":"Ruiyi Yan, Yusong Wang, Yinhan Wang, Mingchang Pang, Linfei Wei, Meijiao Zhu, Huayu Yang, Weihong Yu","doi":"10.1021/acsbiomaterials.5c00706","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00706","url":null,"abstract":"<p><p>The integrity and functionality of the blood-retina barrier (BRB) are essential for maintaining homeostasis of the retina. Disruption of the BRB is a key feature in different stages of retinal diseases including diabetic retinopathy, age-related macular degeneration (AMD), and inherited retinal diseases such as retinitis pigmentosa. In order to understand and recapitulate various retinal diseases, there has been significant interest in the progress of in vitro 3D-BRB models as they may address limitations associated with traditional 2D cultures and xenogeneic animal models. Therefore, it is crucial to explore 3D in vitro models for investigating mechanistic and therapeutic strategies in BRB-related diseases. In this review, we provide an overview of recent advances in BRB models, ranging from simple constructs to complex systems. In this review, commonly used techniques (extracellular matrix scaffolds, 3D bioprinting, and microfluidics), cell types utilized, and biomaterials employed are discussed. Additionally, we focus on new developments over the past three years, emphasizing applications of 3D-BRB models in disease evolution and drug screening. Overall, 3D modeling for the BRB holds promise for recapitulating the structural and functional characteristics of the in vivo BRB, which is a powerful armament for laboratory research and translational medicine for retinal diseases.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111464","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":"Interconnected Porous Hydroxyapatite Scaffolds Functionalized by the Peptide DP7-C Incorporating miR-26a with Enhanced Osteogenic Activity for Critical Bone Defect Regeneration.","authors":"Xinlun Li, Lun Yuan, Shasha Lei, Pairan Peng, Yushu Zhu, Xun Xiao, Yandong Mu","doi":"10.1021/acsbiomaterials.5c00595","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00595","url":null,"abstract":"<p><p>The reconstruction of large critical bone defects remains a major challenge in clinical practice. The multifunctional scaffolds modified by miRNA with osteogenic induction have become an effective strategy for bone regeneration. Herein, an interconnected porous hydroxyapatite (HA) scaffold was prepared for bone regeneration. First, the porous PLGA microspheres were obtained by the double emulsification solvent evaporation method and loaded with the DP7-C/miR-26a complex. Then, the functionalized scaffold was prepared by a template-leaching technique and modified with the above microspheres. The scaffold possessed interconnected porous microstructures with a high porosity of 64%, efficient compressive strength of 10.54 kPa, and controlled release ability of 21 days. In vitro experiments suggested that the prepared scaffold showed good cytocompatibility and the potential to promote osteogenic differentiation of rat BMSCs. Moreover, in the cranial critical bone defect model, the scaffold was demonstrated to possess good in vivo biocompatibility and osteogenic efficacy. Overall, the functionalized scaffold prepared in this study will provide a potential therapeutic strategy for the treatment of critical bone defects.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111486","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":"Incremental Stretch Increases Strength and Toughness while Growing Engineered Trileaflet Heart Valves.","authors":"Benjamin J Albert, John T Toftegaard, Gaetano Scuderi, Brianna Hou, Kathleen M Clifford, Ludia Cho, Coral Wang, Daniel Cheung, Jonathan T Butcher","doi":"10.1021/acsbiomaterials.5c01169","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c01169","url":null,"abstract":"<p><p>Tissue engineered heart valves (TEHVs) represent a promising method for fulfilling the needs of young, growing individuals with an insufficient valve function. Many current approaches that use natural biomaterials rely on either very long culture times or a secondary polymer network to create viable mechanical properties. While these materials can create correct sizes or mechanical properties, issues such as dilation of grafts still occur when strengthening does not correlate with a stretch in size. Utilizing an adaptable, mechanical anchorage-based culture system, we inquired how fibrin with encapsulated stem cells could be stimulated to both grow and strengthen under an incrementally increasing stretch (iStretch). We modified our culture system to assess how the timing and magnitude of stretch affect both linear and planar tissues, additionally creating leaflet-shaped tissues. In this study, we show that iStretch stimulates cell alignment and increases tissue modulus, failure stress, and toughness while achieving a 100% increase in tissue length. The timing of iStretch increments also drives cell differentiation, with almost doubling of a remodeling mesenchymal phenotype achieved with early increments. Planar leaflet tissues stretched to 50% greater diameter over 14 days increased in cell density and vimentin expression. When placed in a pulse duplicator system, engineered trileaflet valves opened completely to a maximal effective orifice area and coapted with systolic ventricular pressures up to 80 mmHg. These results demonstrate the potential of iStretch for generating both rapid growth and the strengthening of engineered tissues.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090733","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":"Sustained and Localized Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles by an In Situ Forming Click PEG Hydrogel for Diabetic Nephropathy Therapy.","authors":"Mohsen Bakhtiari, Mohammad Hossein Ghanian, Reza Moghadasali","doi":"10.1021/acsbiomaterials.5c00798","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00798","url":null,"abstract":"<p><p>Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) hold great promise as a cell-free therapy for diabetic nephropathy (DN), but their therapeutic efficacy is limited by rapid clearance from the target site after bolus injection. Herein, an in situ-forming biodegradable hydrogel has been developed for sustained and localized release of EVs into the renal subcapsular space. The MSC-EVs were encapsulated within a synthetic hydrogel based on poly(ethylene glycol) (PEG) during a click reaction between thiol and vinyl sulfone end groups of four-arm PEG macromers at the site of injection in the kidney capsule of DN-modeled mice. The MSC-EV-laden PEG hydrogel gradually swelled and released EVs in a sustained manner over one month. The DN mice treated with the EV-delivering hydrogel exhibited further improved renal function with attenuated histopathological damage, reduced proinflammatory cytokine levels, and lower tubular cell apoptosis compared with the DN mice treated with free EVs. Specifically, the hydrogel-mediated delivery of MSC-EVs could significantly enhance antifibrotic effects of MSC-EVs and even prevent and reverse the progression of renal fibrosis in a DN mouse model, an event that was not observed by the free EV treatment. Collectively, this prolonged delivery system may open a new paradigm for improved EV therapies for various chronic diseases.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079157","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}