Regenerative Biomaterials最新文献

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Biocompatible exosomes derived from Pinctada martensii mucus for therapeutic melanin regulation via α-MSH/NF-κB/MITF pathway. 通过α-MSH/NF-κB/MITF途径从马氏平锥虫黏液中提取的生物相容性外泌体用于治疗性黑色素调节。
IF 8.1 1区 医学
Regenerative Biomaterials Pub Date : 2025-07-03 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf072
Dandan Mo, Weihao Zheng, Zixin Gao, Ke Ma, Ke Yang, Tao Zeng, Chaozheng Qin, Yan Luo, Li Zheng, Sheng Xu
{"title":"Biocompatible exosomes derived from <i>Pinctada martensii</i> mucus for therapeutic melanin regulation via α-MSH/NF-κB/MITF pathway.","authors":"Dandan Mo, Weihao Zheng, Zixin Gao, Ke Ma, Ke Yang, Tao Zeng, Chaozheng Qin, Yan Luo, Li Zheng, Sheng Xu","doi":"10.1093/rb/rbaf072","DOIUrl":"https://doi.org/10.1093/rb/rbaf072","url":null,"abstract":"<p><p>Abnormal melanin production can lead to various pigmentary disorders, which significantly affect patients' quality of life and overall health. However, current clinical melanogenesis inhibitors have adverse side effects such as skin dryness, itching, erythema, etc. In this study, we used naturally isolated exosomes derived from <i>Pinctada martensii</i> mucus (PMMEXOs) and investigated the effects on melanin synthesis based on B16-F10 melanoma cells and zebrafish. We demonstrated that PMMEXOs effectively inhibited melanin production while exhibiting excellent biocompatibility. To elucidate the underlying mechanisms, RNA sequencing and bioinformatics analysis were employed, identifying 556 differentially expressed genes associated with PMMEXOs treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the involvement of the NF-κB signaling pathway in the regulation of melanogenesis. Further mechanistic studies confirmed that PMMEXOs significantly reduced tyrosinase activity and melanin content, accompanied by the downregulation of critical melanogenesis-related genes and proteins, including MITF, TYR, TYRP-1 and TRP-2. Notably, the anti-melanogenic effects of PMMEXOs were mediated by activation of the NF-κB signaling pathway, underscoring their regulatory role in melanin biosynthesis. Additionally, microRNA (miRNA) sequencing of PMMEXOs identified specific miRNAs implicated in immune regulation and modulation of the NF-κB pathway, further supporting their mechanistic involvement in melanin inhibition. These findings collectively position PMMEXOs as a promising and innovative therapeutic strategy for the prevention and treatment of pigmentary disorders such as melasma, age spots and wrinkles.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf072"},"PeriodicalIF":8.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multifunctional dynamic cerium-polypeptide hydrogel with antibacterial antioxidative anti-inflammatory for multidrug-resistant bacterial infected wound healing. 具有抗菌、抗氧化、抗炎作用的多功能动态铈多肽水凝胶用于耐多药细菌感染创面愈合。
IF 8.1 1区 医学
Regenerative Biomaterials Pub Date : 2025-07-01 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf071
Meng Luo, Jing Tian, Chenxi Xie, Yanzi Zhao, Bo Lei
{"title":"Multifunctional dynamic cerium-polypeptide hydrogel with antibacterial antioxidative anti-inflammatory for multidrug-resistant bacterial infected wound healing.","authors":"Meng Luo, Jing Tian, Chenxi Xie, Yanzi Zhao, Bo Lei","doi":"10.1093/rb/rbaf071","DOIUrl":"https://doi.org/10.1093/rb/rbaf071","url":null,"abstract":"<p><p>Bacterial infection, especially multidrug-resistant (MDR) bacterial infection, is a great challenge in clinical wound repair, highlighting the urgent to develop antibacterial hydrogel dressing. In this work, a multifunctional cerium-polypeptide hydrogel (FEPC) with comprehensive antibacterial, antioxidant, anti-inflammatory and angiogenesis ability was developed for the treatment of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infected wounds. The FEPC hydrogel was constructed using Ce<sup>3+</sup> and antibacterial polypeptide co-crosslinked γ-polyglutamic acid (γ-PGA) through double dynamic electrostatic and coordination interaction. This unique dynamic architecture endowed FEPC with outstanding injectability and rapid self-healing capacity, ensuring conformal coverage of irregular wounds. <i>In vitro</i> experiments demonstrated that FEPC showed robust antibacterial activity, and could effectively eliminate reactive oxygen species (fixed terminology). Meanwhile, the FEPC hydrogel could downregulate the expression of pro-inflammatory cytokines and promote angiogenesis by upregulating the VEGF expression. Importantly, <i>in vivo</i> assessments using MRSA-infected full-thickness wounds showed that FEPC hydrogel could rapidly repair the MRSA infected wounds (54% wound repair rate on Day 3 for FEPC <i>vs</i> reported hydrogel below 40% rate) and promote epithelialization and hair follicle regeneration within 14 days. Histological analysis confirmed that FEPC hydrogel could significantly inhibit infection and excessive inflammation, as well as accelerate angiogenesis. This work suggests that cerium-polypeptide hydrogel is a perfect partner for treating MDR bacterial infected wounds, providing a viable solution for synergistically combat infection, oxidative stress and other related-disease treatments.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf071"},"PeriodicalIF":8.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Recombinant collagen for the repair of skin wounds and photo-aging damage. 更正:重组胶原蛋白用于修复皮肤伤口和光老化损伤。
IF 5.6 1区 医学
Regenerative Biomaterials Pub Date : 2025-06-29 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf064
{"title":"Correction to: Recombinant collagen for the repair of skin wounds and photo-aging damage.","authors":"","doi":"10.1093/rb/rbaf064","DOIUrl":"https://doi.org/10.1093/rb/rbaf064","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/rb/rbae108.].</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf064"},"PeriodicalIF":5.6,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hypoxic niches established via endogenous oxygen production in scaffold under anoxia for enhanced bone regeneration. 在缺氧条件下,通过内源性产氧在支架中建立缺氧壁龛,以增强骨再生。
IF 8.1 1区 医学
Regenerative Biomaterials Pub Date : 2025-06-26 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf070
Kaifeng Gan, Leidong Lian, Zhe Luo, Yanxue Dong, Dingli Xu, Xufeng Li, Jie Li, Xuyang Zhang, Jian Chen, Liangjie Lu, Fengdong Zhao
{"title":"Hypoxic niches established via endogenous oxygen production in scaffold under anoxia for enhanced bone regeneration.","authors":"Kaifeng Gan, Leidong Lian, Zhe Luo, Yanxue Dong, Dingli Xu, Xufeng Li, Jie Li, Xuyang Zhang, Jian Chen, Liangjie Lu, Fengdong Zhao","doi":"10.1093/rb/rbaf070","DOIUrl":"10.1093/rb/rbaf070","url":null,"abstract":"<p><p>Anoxia remains a challenging problem to effective graft implantation in bone tissue engineering for managing large-size bone defects. One promising strategy is to provide immediate oxygen required for cell viability and graft maturation by introducing oxygen-generating biomaterials. In this study, we present a novel composite oxygen-generating scaffold by integrating oxygen-generating microspheres (OMs) comprised of emulsified calcium peroxides (CPOs) encapsulated in poly (lactic-co-glycolic acid; PLGA) into the gelatin methacryloyl (GelMA) hydrogel. The <i>in vitro</i> results reveal that the scaffold encapsulating 2% (w/v) OMs (OM@GelMA) mildly sustained oxygen production for approximately 16 days, and hence, established hypoxic niches with low oxygen tension (10-46 mmHg) under anoxic culture condition (0.2% oxygen) for the viability of bone marrow-derived mesenchymal stem cells (BMSCs) and their enhanced osteogenic differentiation, which may be induced by activation of HIF-1/β-catenin signaling pathway by the compatibly hypoxic level as one of the underlying molecular mechanisms verified via transcriptome sequencing, western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) tests on <i>in vitro</i> samples. Moreover, the oxygen-generating hydrogel could enhance angiogenesis of human umbilical vein endothelial cells (HUVECs) under anoxia by preserving cell viability, accelerating cell migration, promoting tube formation and activating angiogenic genes and proteins expression. <i>In vivo</i> studies using rat cranial critical-size defect models demonstrated that OM@GelMA significantly enhanced bone regeneration, effectively promoting bone defect repair. In summary, the OM@GelMA, as a novel endogenously oxygen-generating scaffold, holds great potential to facilitate bone tissue regeneration subject to oxygen-deprived scenarios. This study provides a new insight for future research and clinical applications in bone tissue engineering, particularly for large bone defect repair.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf070"},"PeriodicalIF":8.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144744487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Two-in-one: multifunctional poloxamer hydrogel accelerates endometrial regeneration and fertility restoration through synergistic regulation of KGF-2 and NO. 二合一:多功能波洛沙姆水凝胶通过协同调节KGF-2和NO加速子宫内膜再生和生育能力恢复。
IF 8.1 1区 医学
Regenerative Biomaterials Pub Date : 2025-06-20 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf062
Yijia Zhang, Xinji Wang, Qin Gu, Cuitao Lu, Yingzheng Zhao, Xiaokun Li
{"title":"Two-in-one: multifunctional poloxamer hydrogel accelerates endometrial regeneration and fertility restoration through synergistic regulation of KGF-2 and NO.","authors":"Yijia Zhang, Xinji Wang, Qin Gu, Cuitao Lu, Yingzheng Zhao, Xiaokun Li","doi":"10.1093/rb/rbaf062","DOIUrl":"10.1093/rb/rbaf062","url":null,"abstract":"<p><p>A healthy endometrium is crucial for embryo implantation and pregnancy maintenance. Thin endometrium, reduced glands and fibrosis resulting from infection or mechanical injury, are the primary causes of long-term infertility and poor pregnancy outcomes. Unfortunately, these issues have not been resolved by conventional clinical methods. Keratinocyte growth factor-2 (KGF-2) is an epithelial mitogen that regulates proliferation and migration of epithelial cells. Nitric oxide (NO) is involved in maintaining vascular homeostasis and angiogenesis. Poloxamer-407 (P) hydrogel is a promising topical drug delivery system due to its excellent solution-gel transition properties in response to body temperature. In this study, therapeutic NO gas was first prepared into stabilized microbubbles (NO-MBs). Subsequently, KGF-2 and NO-MBs were encapsulated into micelles of P hydrogel to form a multifunctional temperature-sensitive (28.9-31.8°C) hydrogel (KGF-NO-MBs-P hydrogel). This hydrogel not only exhibited suitable apparent viscosity, bio-adhesive and mechanical properties for application <i>in situ</i> but also showed sustained release of KGF-2 and NO. <i>In vivo</i>, KGF-NO-MBs-P hydrogel effectively restored endometrial morphology, increased the number of glands and endometrial thickness, reversed endometrial fibrosis and improved pregnancy outcomes by synergistic regulation of KGF-2 and NO. Repair of endometrial injury was closely related to promoting neovascularization, inducing endometrial cell proliferation and epithelialization, inhibiting apoptosis and inflammation and balancing collagen subtypes. Therefore, KGF-NO-MBs-P hydrogel may be useful in promoting endometrial regeneration and fertility restoration through <i>in situ</i> microinjection. This study represented a convenient, safe and promising method for repair of endometrial injury.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf062"},"PeriodicalIF":8.1,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gelatin/hyaluronic acid-based in situ forming hydrogel promotes wound regeneration by the synergy of ROS-scavenging and pro-healing activity. 明胶/透明质酸原位形成的水凝胶通过活性氧清除和促愈合活性的协同作用促进伤口再生。
IF 5.6 1区 医学
Regenerative Biomaterials Pub Date : 2025-06-20 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf052
Xingchen Zhao, Wenling Dai, Chenxin Liu, Mei An, Shikui Li, Likun Guo, Yujiang Fan, Xingdong Zhang
{"title":"Gelatin/hyaluronic acid-based <i>in situ</i> forming hydrogel promotes wound regeneration by the synergy of ROS-scavenging and pro-healing activity.","authors":"Xingchen Zhao, Wenling Dai, Chenxin Liu, Mei An, Shikui Li, Likun Guo, Yujiang Fan, Xingdong Zhang","doi":"10.1093/rb/rbaf052","DOIUrl":"10.1093/rb/rbaf052","url":null,"abstract":"<p><p>The development of advanced hydrogel dressings that integrate biocompatibility, antioxidant activity and dynamic adaptability remains critical for addressing the complex demands of modern wound management. In this study, we designed a multinetwork hydrogel (GHrCT) through synergistic strategies: A robust covalent network is constructed through photocrosslinked gelatin methacryloyl, while a secondary dynamic network formed via hydrogen bonds and electrostatic interactions is established among dopamine-modified hyaluronic acid (HD), tannic acid (TA) and recombinant collagen type III (rhCol III). Through a series of experiments, we systematically characterized key properties of the hydrogel, including its microscopic morphology, swelling behavior, rheological characteristics and mechanical strength. Biocompatibility was assessed through <i>in vitro</i> assays, while the wound healing efficacy was validated <i>in vivo</i>. <i>In vitro</i> experiments demonstrated that GHrCT hydrogel has interconnected porosity, excellent hemocompatibility and good cytocompatibility. Its strong antioxidant capacity (DPPH scavenging rate of 88.63%) can cope with the excessive accumulation of ROS in the wound microenvironment and reduce the damage caused by oxidative stress. Further, <i>in vivo</i> experiments showed that it could improve wound healing therapy by accelerating epithelial re-formation, angiogenesis and collagen deposition at full-thickness skin defects in SD rats. This study presents a strategy for functionalizing natural polymer hydrogels to enhance wound repair through the synergistic effect of scavenging ROS and promoting repair.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf052"},"PeriodicalIF":5.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Injectable exosome-reinforced konjac glucomannan composite hydrogel for repairing cartilage defect: activation of endogenous antioxidant pathways. 注射外泌体增强魔芋葡甘露聚糖复合水凝胶修复软骨缺损:内源性抗氧化途径的激活。
IF 8.1 1区 医学
Regenerative Biomaterials Pub Date : 2025-06-17 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf060
Cong Ye, Jiabao Xu, Youjian Wang, Minrui Ji, Ran Tao, Fei Han, Peng Zhou
{"title":"Injectable exosome-reinforced konjac glucomannan composite hydrogel for repairing cartilage defect: activation of endogenous antioxidant pathways.","authors":"Cong Ye, Jiabao Xu, Youjian Wang, Minrui Ji, Ran Tao, Fei Han, Peng Zhou","doi":"10.1093/rb/rbaf060","DOIUrl":"https://doi.org/10.1093/rb/rbaf060","url":null,"abstract":"<p><p>Enhancing the regeneration of cartilage defects remains a formidable challenge, as the dysregulated microenvironment and its crosstalk with chondrocytes play pivotal roles in impairing regeneration. In this study, we proposed a natural plant polysaccharides-derived injectable hydrogel (Exos@EKM) for adapting to irregular cartilage defects. By encapsulating stem cell-derived exosomes (Exos) into polyphenol modified methacryloylated konjac glucomannan (EKM), this hydrogel exerting a potent biological synergistic effect. First, the hydrogel demonstrates favorable biocompatibility and has the capability to modulate cellular behavior through the delivery of Exos. Additionally, it demonstrates significant chondroprotective effects and reprograms macrophages to the pro-healing state. Furthermore, konjac glucomannan and polyphenols in hydrogel synergistically activate the endogenous antioxidant capacity of chondrocytes through nuclear factor erythroid 2-related factor 2 (NRF2)-dependent pathway, thereby optimizing the biological function of Exos in regulating chondrocyte behavior and maintaining normal cartilage metabolism. In a full-thickness cartilage defect model, in vivo implantation of Exos@EKM hydrogel successfully improved cartilage regeneration and ultimately restoring knee joint functionalities. Overall, this combination of natural konjac glucomannan, polyphenols and Exos has resulted in the promotion the harmony between the microenvironment, chondrocyte and ECM. This study offers a novel approach for designing biomaterials for cartilage tissue engineering.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf060"},"PeriodicalIF":8.1,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Degradation behavior of porous magnesium alloy scaffold under the low-intensity pulsed ultrasound intervention and their effect on bone defects repair. 修正:低强度脉冲超声介入下多孔镁合金支架的降解行为及其对骨缺损修复的影响。
IF 5.6 1区 医学
Regenerative Biomaterials Pub Date : 2025-06-17 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf055
{"title":"Correction to: Degradation behavior of porous magnesium alloy scaffold under the low-intensity pulsed ultrasound intervention and their effect on bone defects repair.","authors":"","doi":"10.1093/rb/rbaf055","DOIUrl":"https://doi.org/10.1093/rb/rbaf055","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/rb/rbaf011.].</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf055"},"PeriodicalIF":5.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Matrix stiffness boosts PDAC chemoresistance via SCD1-dependent lipid metabolic reprogramming. 基质硬度通过scd1依赖性脂质代谢重编程增强PDAC化疗耐药。
IF 8.1 1区 医学
Regenerative Biomaterials Pub Date : 2025-06-16 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf056
Xue Zhang, Biwen Zhu, Jiashuai Yan, Xi Chen, Di Wu, Zhen Wang, Xiaoqi Guan, Yan Huang, Yahong Zhao, Yumin Yang, Yibing Guo
{"title":"Matrix stiffness boosts PDAC chemoresistance via SCD1-dependent lipid metabolic reprogramming.","authors":"Xue Zhang, Biwen Zhu, Jiashuai Yan, Xi Chen, Di Wu, Zhen Wang, Xiaoqi Guan, Yan Huang, Yahong Zhao, Yumin Yang, Yibing Guo","doi":"10.1093/rb/rbaf056","DOIUrl":"10.1093/rb/rbaf056","url":null,"abstract":"<p><p>PDAC cells perceive and respond to mechanical stimuli in their extracellular microenvironments (ECMs), playing a crucial role in chemoresistance, while the underlying mechanisms are not fully understood. The progression of various solid tumors is accompanied by metabolic reprogramming. RNA-seq and untargeted metabolomics analysis indicated that stiff substrate may regulate lipid metabolism. The expression of lipogenesis-related genes, including fatty acid synthase (FASN), ATP citrate lyase (ACLY) and acetyl-CoA carboxylase (ACC) was elevated, also the sum of lipid droplets and the triglyceride content. Herein, whether lipid metabolism is involved in matrix stiffness-mediated PDAC chemoresistance and the in-depth mechanism were further explored. Rescue with C75 (FASN inhibitor) validated that fatty acid synthesis participated in matrix stiffness-regulated chemoresistance. Simultaneously, the SCD1 expression was reinforced, consistent with PDAC tissues. The concurrent restraint SCD1 (with inhibitor CAY10566 or shSCD1) and addition of oleic acid confirmed that SCD1 is involved in matrix stiffness-mediated chemoresistance through fatty acid synthesis. In addition, Piezo1 regulated SCD1 expression through the augmentation of Ca<sup>2+</sup> influx, and the PI3K/Akt pathway participated in this process. Taken together, our research sheds light on lipid metabolism exerts an essential role during matrix stiffness-mediated chemoresistance through Piezo1-elicited elevation of SCD1. Our findings delivered a supplement PDAC chemoresistance mechanism mediated by matrix stiffness from the perspective of lipid metabolic reprogramming, and provided a novel strategy for improving clinical therapies.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf056"},"PeriodicalIF":8.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineering of tissue in microphysiological systems demonstrated by modelling skeletal muscle. 骨骼肌模型证明了微生理系统中的组织工程。
IF 8.1 1区 医学
Regenerative Biomaterials Pub Date : 2025-06-16 eCollection Date: 2025-01-01 DOI: 10.1093/rb/rbaf059
Yuan Gao, Zilin Zhang, Yu Yao, Jing Zhang, Xiaoran Li, Keyu Yang, Nuo Si, Zaozao Chen, Zhongze Gu, Ningbei Yin
{"title":"Engineering of tissue in microphysiological systems demonstrated by modelling skeletal muscle.","authors":"Yuan Gao, Zilin Zhang, Yu Yao, Jing Zhang, Xiaoran Li, Keyu Yang, Nuo Si, Zaozao Chen, Zhongze Gu, Ningbei Yin","doi":"10.1093/rb/rbaf059","DOIUrl":"10.1093/rb/rbaf059","url":null,"abstract":"<p><p>Research on myogenesis and myogenic pathologies has garnered significant attention in recent years. However, traditional <i>in vitro</i> modeling approaches have struggled to fully replicate the complex functions of skeletal muscle. This limitation is primarily due to the insufficient reconstruction of the muscle tissue microenvironment and the role of physical cues in regulating muscle cell activity. Recent studies have highlighted the importance of the microenvironment, which includes cells, extracellular matrix (ECM) and cytokines, in influencing myogenesis, regeneration and inflammation. This review focuses on advances in skeletal muscle construction toward a complete microphysiological system, such as organoids and muscle-on-a-chip technology, as well as innovative interventions like bioprinting and electrical stimulation. These advancements have enabled researchers to restore functional skeletal muscle tissue, bringing us closer to achieving a fully functional microphysiological system. Compared to traditional models, these systems allow for the collection of more comprehensive data, providing insights across multiple scales. Researchers can now study skeletal muscle and disease models <i>in vitro</i> with increased precision, enabling more advanced research into the physiological and biochemical cues affecting skeletal muscle activity. With these advancements, new applications are emerging, including drug screening, disease modeling and the development of artificial tissues. Progression in this field holds great promise for advancing our understanding of skeletal muscle function and its associated pathologies, offering potential therapeutic solutions for a variety of muscle-related diseases.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbaf059"},"PeriodicalIF":8.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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