Atsushi Mahara , Kaito Shimizu , Hue Thi Le , Raghav Soni , Yoshiaki Hirano , Tetsuji Yamaoka
{"title":"Cilostazol-loaded acellular vascular graft for suppressing intimal hyperplasia","authors":"Atsushi Mahara , Kaito Shimizu , Hue Thi Le , Raghav Soni , Yoshiaki Hirano , Tetsuji Yamaoka","doi":"10.1016/j.bioadv.2025.214433","DOIUrl":"10.1016/j.bioadv.2025.214433","url":null,"abstract":"<div><div>Local vascular injury caused by vascular transplantation and endarterectomy causes intimal hyperplasia accompanied by matrix degradation by the matrix metalloproteinase (MMP) and proliferation of acute smooth muscle cells (SMCs) during the wound healing. In small vessels, excessive intimal thickening easily induces graft occlusion, and regulation of these local events is critical for graft patency. Although cilostazol (CLZ) has been investigated in clinical trials as a stenosis-suppressing medicine, strategies targeting the suppression of anastomotic stenosis are insufficient. In this study, we developed CLZ-loaded acellular grafts that respond to MMP using a reprecipitation process. CLZ weighing 112 μg was loaded into an acellular graft (CLZ-Graft) weighing 10 mg via reprecipitation. The loaded CLZ was gradually released via matrix degradation but did not leak without degradation. The SMC phenotype changed to a contracted type and proliferation was suppressed when the SMCs were cultured with the CLZ-Graft lysate. The lysate did not inhibit endothelial cell migration or vasculogenesis. In a rat carotid artery ablation model, the graft diameter decreased to 48 % under control conditions. When the CLZ-Graft was placed around the injured carotid artery in rats, acute stenosis was suppressed to only 31 % and 18 % at two and four weeks, respectively. These results indicated that intimal hyperplasia was effectively suppressed by the local release of CLZ from CLZ-Graft in response to MMP. These findings demonstrate that drug-releasing from the decellularized tissue that responds to MMP is an effective strategy for inhibiting vascular stenosis.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214433"},"PeriodicalIF":6.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724626","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}
Jintao Wei , Jianshen Liu , Jianxing Wu , Yan Chen , Kunhua Wei , Jiao Guo , Zhengquan Su
{"title":"Preparation and osteogenic performance study of troxerutin-loaded carboxymethyl cellulose/Si-calcium phosphate cement composite bone cement","authors":"Jintao Wei , Jianshen Liu , Jianxing Wu , Yan Chen , Kunhua Wei , Jiao Guo , Zhengquan Su","doi":"10.1016/j.bioadv.2025.214434","DOIUrl":"10.1016/j.bioadv.2025.214434","url":null,"abstract":"<div><div>Bone defects from trauma, infection, and tumour resection are a growing clinical challenge due to global population aging. Current treatments like autologous and allogeneic bone grafting have limitations. This study focused on optimizing ion-doped α-tricalcium phosphate (α-TCP) preparation and developing calcium phosphate cement (CPC) with superior physicochemical and biological properties. Calcium pyrophosphate (CPP) and calcium carbonate (CaCO₃) showed the highest conversion efficiency during synthesis. Adding SiO₂ to this combination generated high-purity silicon-doped α-TCP (Si-α-TCP) powder at 1200 °C. To enhance CPC's performance, different amounts of sodium carboxymethyl cellulose (CMC) were added to the setting liquid. The CMC/Si-CPC with 1 %wt CMC demonstrated the best physicochemical properties, with improved setting time, compressive strength, injectability, and anti-dispersion. In drug-loading experiments, CMC promoted the release of Troxerutin (TRO), showing burst release within 6 h followed by sustained release. In vitro experiments with MC3T3-E1 cells confirmed good biocompatibility and osteogenic activity, further enhanced by Si-ion doping and 0.5 mg/mL TRO in the setting liquid. In vivo experiments, including rat subcutaneous and rabbit femoral defect implantation, confirmed effective osteoconductivity and osseointegration without inflammation or necrosis. In conclusion, this study successfully prepared high-purity Si-α-TCP powder by optimizing raw material combinations and Si-ion doping. CMC improved CPC's physicochemical properties, while Si-ion doping and TRO loading enhanced its biocompatibility and osteogenic activity. TRO/CMC/Si-CPC is promising for bone defect treatment and offers a new concept for bone tissue engineering materials.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214434"},"PeriodicalIF":6.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738819","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":"Scalable multi-layer collagen laminates for regenerative medicine","authors":"Tara Gaschik , Claudia Eßbach , Dirk Fischer , Daniela Nickel , Ulrike Ritz","doi":"10.1016/j.bioadv.2025.214422","DOIUrl":"10.1016/j.bioadv.2025.214422","url":null,"abstract":"<div><div>In regenerative medicine, the demand for biomaterials with customizable properties to address diverse clinical challenges is steadily increasing. Collagen-based scaffolds offer significant promise for tissue engineering applications. This study presents a novel 5-layer collagen laminate engineered to facilitate both infection control and bone and tissue regeneration in open bone fractures. The laminate employs a layering strategy with rose bengal and green light-induced crosslinking to facilitate assembly while enabling the controlled release of three bioactive molecules, vancomycin, Bone morphogenetic protein 2 (BMP-2) and Stromal cell-derived factor 1 (SDF-1<span><math><mi>α</mi></math></span>). Mechanical properties were evaluated using a high-capacity load cell, revealing that multi-layer configurations exhibited reduced stiffness and tensile strength compared to single-layer laminates. Notably, incubation with Normal Human Dermal Fibroblasts (NHDF) holds the potential to enhance interlayer cohesion and improve the mechanical integrity of 5-layer laminates. Furthermore, the composition of collagen within the laminate played a critical role in determining both mechanical behavior and release kinetics. Singular sheets of Endoform™ Natural (E) collagen displayed rapid release, while Geistlich Bio-Gide® (G) collagen sheets provided sustained release, reflecting their distinct structural characteristics. These findings underscore the potential of multi-layer collagen laminates as a versatile platform for tailored therapeutic applications in regenerative medicine.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214422"},"PeriodicalIF":6.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724629","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}
Camilo Mora-Navarro , Ethan Smith , Ziyu Wang , Maria del C. Ramos-Alamo , Leonard Collins , Nour Awad , Denzel Ryan D. Cruz , Tammy S. Tollison , Ian Huntress , Gary Gartling , Ryosuke Nakamura , Gregory R. Dion , Xinxia Peng , Ryan C. Branski , Donald O. Freytes
{"title":"Injection of vocal fold lamina propria-derived hydrogels modulates fibrosis in injured vocal folds","authors":"Camilo Mora-Navarro , Ethan Smith , Ziyu Wang , Maria del C. Ramos-Alamo , Leonard Collins , Nour Awad , Denzel Ryan D. Cruz , Tammy S. Tollison , Ian Huntress , Gary Gartling , Ryosuke Nakamura , Gregory R. Dion , Xinxia Peng , Ryan C. Branski , Donald O. Freytes","doi":"10.1016/j.bioadv.2025.214424","DOIUrl":"10.1016/j.bioadv.2025.214424","url":null,"abstract":"<div><div>Vocal fold (VF) fibrosis, often resulting from phonosurgery, radiation, or trauma, causes irreversible voice dysfunction due to excessive ECM deposition and increased tissue stiffness. No FDA-approved treatments for VF fibrosis exist, highlighting the need for novel antifibrotic therapies. TGF-β1 contributes to fibroblast-to-myofibroblast activation, leading to increased ACTA2 expression and collagen production via SMAD3, YAP1, and integrin signaling pathways. Leveraging the principle that local cells respond to tissue-specific signals, our ECM hydrogel, derived from decellularized vocal fold lamina propria (VFLP-ECM), reduced ACTA2 expression in TGF-β1-stimulated VF fibroblasts, showcasing antifibrotic potential. This study evaluates the therapeutic potential of VFLP-ECM hydrogel in a rabbit VF injury model. VFLP-ECM hydrogel or bovine type I collagen injections were administered 7 days post-injury and evaluated on day 28. We compared two VFLP-ECM formulations: a manual process (VFLP (man)) and an accelerated automated method (VFLP (au)). VFLP (man) modulated fibrosis-associated gene expressions more effectively than controls. Proteomics identified 229 proteins uniquely preserved in VFLP (man), including vitronectin, crucial in TGF-β1 signaling and ECM remodeling. Transcriptomic analysis suggests downregulation of fibrotic markers and inhibition of SMAD3, YAP1, and MRTFA, alongside upregulation of SMAD7, an inhibitor of TGF-β signaling. Notably, VFLP (man) treatment recovered stiffness comparable to uninjured controls (1.84 vs. 1.94 mN), whereas collagen-treated tissues remained stiff (2.7 mN), similar to the injury group (2.6 mN), indicating incomplete mechanical recovery. These in vivo data show that manually decellularized VFLP-ECM hydrogel attenuates fibrosis by disrupting key biochemical and mechanical cues driving myofibroblast activation.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"178 ","pages":"Article 214424"},"PeriodicalIF":6.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767042","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}
Narendra Pal Singh Chauhan , Behnaz Ashtari , Behnaz Sadat Eftekhari , Masoud Akhshik , Hanna J. Maria , Sadjad Khosravimelal , Nicholas Seifalian , Sabu Thomas , Mazaher Gholipourmalekabadi , Alexander M. Seifalian
{"title":"Functionalization of graphene oxide and its applications in tissue engineering and regenerative medicine","authors":"Narendra Pal Singh Chauhan , Behnaz Ashtari , Behnaz Sadat Eftekhari , Masoud Akhshik , Hanna J. Maria , Sadjad Khosravimelal , Nicholas Seifalian , Sabu Thomas , Mazaher Gholipourmalekabadi , Alexander M. Seifalian","doi":"10.1016/j.bioadv.2025.214421","DOIUrl":"10.1016/j.bioadv.2025.214421","url":null,"abstract":"<div><div>The unique physical and chemical characteristics of graphene oxide (GO) have recently attracted great attention, which highlighted its potential as a promising material for electronic, industrial, biomedical and others potential applications. GO has several functional groups of oxygen, which makes it easier to make GO dispersed in aqueous solution insulating in nature. The functionalization and surface modification of GO is one of the strategies that recently attracted much attention for various electrochemical and biological applications. In general overview, for the functionalization of GO surface, some methods have been proposed that make it possible for the GO-based materials and electrodes for various applications. This comprehensive review focuses on the promising characteristics and recent advances in the functionalization of GO, benefits and limitations, for regenerative medicine and tissue engineering applications.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"178 ","pages":"Article 214421"},"PeriodicalIF":6.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750373","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}
Ying Sun , Yining Cai , Shanshan Xu , Ningning Zhai , Zirui Wang , Zongpu Qiu , Shuying Han , Yuanqing Wei , Rui Liu , Hao Wu
{"title":"Cuttlebone inspired “S”-grooved topological structures facilitate osteogenic differentiation through the Rap1-ERK pathway","authors":"Ying Sun , Yining Cai , Shanshan Xu , Ningning Zhai , Zirui Wang , Zongpu Qiu , Shuying Han , Yuanqing Wei , Rui Liu , Hao Wu","doi":"10.1016/j.bioadv.2025.214431","DOIUrl":"10.1016/j.bioadv.2025.214431","url":null,"abstract":"<div><div>While the regulatory roles of biomaterial topology in bone regeneration are recognized, the specific osteogenic mechanisms driven by distinct morphological features, particularly without biochemical cues, remain poorly understood. This study aimed to independently elucidate the osteogenic potential and underlying mechanisms solely attributable to the distinctive “S”-grooved topology derived from cuttlebone. Inspired by cuttlebone, we successfully fabricated a biomimetic polycaprolactone (PCL) membranes sheet with “S”-grooved topology using liquid silicone mold replication combined with PCL recasting techniques. Comprehensive characterization (SEM, CLSM) confirmed precise replication of the native “S”-grooved morphology (width: 100 ± 30 μm, depth: 20 ± 6 μm). In vitro studies revealed that these grooves promoted directional adhesion and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) via contact guidance, as evidenced by cytoskeleton alignment. Furthermore, the “S”-grooved topology significantly enhanced osteogenic differentiation of mouse pre-osteoblasts (MC3T3-E1), demonstrated by increased alkaline phosphatase (ALP) activity and mineralized nodule formation. Mechanistic investigations using RT-qPCR, Western blot, and dimethyl labeling-based quantitative proteomics on rBMSCs identified key involvement of the Rap1-ERK signaling pathway. Specifically, the “S”-grooved topology upregulated Rap1 expression and enhanced ERK phosphorylation, leading to increased expression of osteogenic markers (e.g., Runx2, OPN). These findings demonstrate that the biomimetic “S”-grooved topology alone, through contact guidance and activation of the Rap1-ERK mechanotransduction pathway, significantly enhances osteogenic differentiation, providing a foundation for designing topologically optimized biomaterials for bone regeneration biomimetic PCL membranes sheet with the “S”-grooved topology.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214431"},"PeriodicalIF":5.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713308","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}
Jing Peng , Weilai Zhu , Chi Zhang , Shuishui Yin , Jie Ye , Haijiao Mao , Mei Li , Jiyuan Zhao
{"title":"COL4A2 drives ECM remodeling and stiffness increasing to promote breast cancer metastasis via YAP signaling pathway in dECM induced models","authors":"Jing Peng , Weilai Zhu , Chi Zhang , Shuishui Yin , Jie Ye , Haijiao Mao , Mei Li , Jiyuan Zhao","doi":"10.1016/j.bioadv.2025.214430","DOIUrl":"10.1016/j.bioadv.2025.214430","url":null,"abstract":"<div><div>Mechanical stress significantly increases during tumor progression. Accumulated research focuses on mechanical transduction, due to the great therapeutic difficulties brought by the mechanical changes. Extracellular matrix (ECM) serves as the key tissue microenvironment providing mechanical cues for tumor cells. However, the mechanism of tumor ECM assembly, stiffness and the resulting cellular mechanical response were rarely reported. Here, decellularized ECM (dECM) models from low-metastatic and metastatic breast cancer tissues via in situ tumor implantation of mammary fat pad in immunodeficient mice were generated to simulate the tumor microenvironment. Wavy fiber structure, finer fibers, but higher stiffness were revealed in the metastatic dECM. Elevated expression of type IV collagen (COL IV) was correlated with the enhanced cell migration and the higher ECM stiffness due to the increased crosslinking of collagen fibers. Further analysis identified COL4A2 (a subunit of COLIV) as a key protein involved in this process. Virus infection of tumor cells led to a decrease in COL4A2 specificity in the dECM in situ, accompanied by the decreased ECM stiffness, the inhibition of cell migration in vitro, and the reduction of metastasis in vivo. Additionally, the increased ECM stiffness caused by the high content of COL4A2 in dECM scaffolds activated YAP1 expression, which might be a potential mechanism. Therefore, the promotion of the stiffness in the basement membrane by COL4A2 via collagen fiber cross-linking might be a key mechanical target for breast cancer metastasis. The targeting ECM mechanics could offer a new strategy to inhibit tumor progression.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214430"},"PeriodicalIF":5.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713309","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}
Nuraina Anisa Dahlan , Kim Lam R. Chiok , Xavier L. Tabil , Xiaoman Duan , Arinjay Banerjee , Neeraj Dhar , Xiongbiao Chen
{"title":"Development and characterization of a decellularized lung ECM-based bioink for bioprinting and fabricating a lung model","authors":"Nuraina Anisa Dahlan , Kim Lam R. Chiok , Xavier L. Tabil , Xiaoman Duan , Arinjay Banerjee , Neeraj Dhar , Xiongbiao Chen","doi":"10.1016/j.bioadv.2025.214428","DOIUrl":"10.1016/j.bioadv.2025.214428","url":null,"abstract":"<div><div>The construction of three-dimensional (3D) <em>in vitro</em> lung tissue models mimicking the physiological structure of the native lung poses a huge challenge in tissue engineering. While advances in bioprinting technology has made fabrication of 3D lung models feasible, the bioinks and printed constructs often fall short in achieving desired mechanical and biological properties. Toward this, we aimed to develop a novel bioink and use it to print and characterize <em>in vitro</em> 3D lung models with living cells. We generated porcine lung extracellular matrix (LdECM) which was then strategically combined with other hydrogels – alginate, carboxymethylcellulose (CMC), and collagen, to synthesize novel bioinks. The printability, mechanical and biological properties of the synthesized bioinks was characterized. We also characterized the rheological properties and identified the bioink composition – 3 % <em>w</em>/<em>v</em> alginate, 0.5 % w/v CMC, 0.5 mg/mL collagen Type 1 and 1 % <em>v</em>/v porcine LdECM was appropriate for bioprinting. To fabricate 3D lung models, we strategically designed and printed constructs featuring spatially organized patterns of MRC-5 human lung fibroblasts and A549-ACE2 human lung epithelial cells along with a cup-shaped structure to confine epithelial cells. Our results demonstrated that the bioinks with viscosities between 60 and 90 Pa.s were appropriate, which resulted in high printing resolution of cell-laden constructs and excellent cell viability. The bioprinted lung constructs also exhibited an elastic modulus of 2–4 kPa comparable to the stiffness of native lung tissues. Our findings establish a foundation for developing lung-specific 3D bioprinted models to address the growing global prevalence of respiratory diseases and for advancing preclinical therapeutic testing.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214428"},"PeriodicalIF":5.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702720","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}
Justin J.Y. Tan , Win Lwin Thuya , Hongyu Zhu , Jessie G. Kristo , John E. Common , Chunyong Wu , Paul C.L. Ho , Lifeng Kang
{"title":"Comparative analysis of 3D and 2D cell-culturing methods in hair follicle spheroid morphogenesis and drug responsiveness","authors":"Justin J.Y. Tan , Win Lwin Thuya , Hongyu Zhu , Jessie G. Kristo , John E. Common , Chunyong Wu , Paul C.L. Ho , Lifeng Kang","doi":"10.1016/j.bioadv.2025.214423","DOIUrl":"10.1016/j.bioadv.2025.214423","url":null,"abstract":"<div><div>Three-dimensional (3D) cell-culturing methods have usually been considered superior to two-dimensional (2D) culturing for in-vitro tissue formation intended for tissue engineering and drug research applications, including hair follicle (HF) development. However, cellular interactions within 3D cultures are generally more complex and therefore, may require further investigation. Apart from grafting in-vitro cultured (2D and 3D) dermal papilla cells directly onto the skin of animals to study the impact of 3D culturing on hair inductivity, molecular studies remain lacking in the understanding of how 2D and 3D culturing methods influence the morphogenesis of early stage HF models. The proposition that 3D cultures is always superior to 2D cultures for mimicking HF at its early developmental stage remains unknown. Therefore, this study aimed to investigate the influence of 3D and 2D culturing methods on the morphogenesis of HFs. 3D-cultured spheroids were assumed to exhibit greater expressions of HF-associated proteins and more expected drug-induced expression responses than 2D cultures. Dermal papilla cells and keratinocytes were cultured together in 2D and 3D cultures, where polyethylene glycol diacrylate microwell arrays were designed to provide the 3D culturing environment. Both 2D and 3D cultures were treated with either minoxidil or dihydrotestosterone (DHT) and the expressions of four hair proteins were analyzed.</div><div>The results showed that 3D cultures responded in more expected ways than 2D cultures when exposed to minoxidil, demonstrating a significant increase in trichohyalin (AE15, one of the 4 proteins) as expected, while 2D cultures exhibited a significant down-regulation. On the other hand, surprisingly, DHT treatment significantly reduced all protein expressions in 2D culture as expected, but did not significantly alter protein expression in 3D culture, suggesting that 2D cultures could respond better than 3D cultures in DHT treatment.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214423"},"PeriodicalIF":5.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713763","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}
Yi Yang , Bei Qian , Dingjie Zhou , Feixiang Zhu , Dong Lei , Shixing Huang , Xinyi Wang , Xiaofeng Ye , Kai Huang , Qi Yang , Qiang Zhao
{"title":"External stent ameliorates vein graft remodeling through Ajuba-mediated suppression of Hippo signaling pathway","authors":"Yi Yang , Bei Qian , Dingjie Zhou , Feixiang Zhu , Dong Lei , Shixing Huang , Xinyi Wang , Xiaofeng Ye , Kai Huang , Qi Yang , Qiang Zhao","doi":"10.1016/j.bioadv.2025.214427","DOIUrl":"10.1016/j.bioadv.2025.214427","url":null,"abstract":"<div><div>Saphenous vein grafts (SVGs), commonly used in coronary artery bypass graft procedures, are prone to failure due to intimal hyperplasia. Although the external stents have been applied to reduce mechanical stress and ameliorated vein graft remodeling, the biological mechanisms linked to mechanical stress remains incomplete. In this study, we identify biological significance of Ajuba, a LIM-domain protein, and defined its mechanism for stress-regulation of Hippo signaling pathway in SVGs. The in vivo application of external stents decreases the mechanical stress, downregulates Ajuba and maintains Hippo signaling pathway. Additionally, we developed an in vitro model to examine how mechanical stress influences Ajuba expression and its impact on the regulation of the Hippo signaling pathway, stimulating cell proliferation, invasion and cell cycle progression. Overall, our research unveils the mechanisms behind external stents and highlights Ajuba as a promising therapeutic target for preventing SVG failure.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214427"},"PeriodicalIF":6.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724628","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}