Bioactive MaterialsPub Date : 2025-04-26DOI: 10.1016/j.bioactmat.2025.04.018
Wenshuai Li , Qichen Shen , Tong Tong , Hongsen Tian , Xiaowei Lian , Haoli Wang , Ke Yang , Zhanqiu Dai , Yijun Li , Xianhua Chen , Qingqing Wang , Dan Yang , Feng Wang , Feng Hao , Linfeng Wang
{"title":"Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration","authors":"Wenshuai Li , Qichen Shen , Tong Tong , Hongsen Tian , Xiaowei Lian , Haoli Wang , Ke Yang , Zhanqiu Dai , Yijun Li , Xianhua Chen , Qingqing Wang , Dan Yang , Feng Wang , Feng Hao , Linfeng Wang","doi":"10.1016/j.bioactmat.2025.04.018","DOIUrl":"10.1016/j.bioactmat.2025.04.018","url":null,"abstract":"<div><div>Bone regeneration is a complex and coordinated physiological process, and the different stages of this process have corresponding microenvironments to support cell development and physiological activities. However, biological scaffolds that provide different three-dimensional environments during different stages of bone regeneration are lacking. In this study, we report a novel composite scaffold (NPE@DCBM) inspired by the stages of bone regeneration; this scaffold was composed of a fibrin hydrogel loaded with nanoplatelet vesicles (NPVs), designated as NPE, and decellularized cancellous bone matrix (DCBM) microparticles. Initially, the NPE rapidly established a temporary microenvironment conducive to cell migration and angiogenesis. Subsequently, the DCBM simulated the molecular structure of bone and promoted new bone formation. <em>In vitro</em>, the NPVs regulated lipid metabolism in bone marrow mesenchymal stem cells (BMSCs), reprogramed the fate of BMSCs by activating the PI3K/AKT and MAPK/ERK positive feedback pathways, and increased BMSC functions, including proliferation, migration and proangiogenic potential. <em>In vivo</em>, NPV@DCBM accelerated bone tissue regeneration and repair. Initially, the NPE rapidly induced angiogenesis between DCBM microparticles, and subsequently, BMSCs differentiated into osteoblasts with DCBM microparticles at their core. In summary, the design of this composite scaffold that sequentially mimics different bone regeneration microenvironments may provide a promising strategy for bone regeneration, with clinical translational potential.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 475-493"},"PeriodicalIF":18.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-26DOI: 10.1016/j.bioactmat.2025.04.003
Lisa E. Tromp , Rik de Jong , Torben A.B. van der Boon , Alejandro Reina Mahecha , Ruud Bank , Jan de Boer , Patrick van Rijn
{"title":"Harnessing the power of physicochemical material property screening to direct breast epithelial and breast cancer cells","authors":"Lisa E. Tromp , Rik de Jong , Torben A.B. van der Boon , Alejandro Reina Mahecha , Ruud Bank , Jan de Boer , Patrick van Rijn","doi":"10.1016/j.bioactmat.2025.04.003","DOIUrl":"10.1016/j.bioactmat.2025.04.003","url":null,"abstract":"<div><div>Understanding cell-material interactions is crucial for advancing biomedical applications, influencing cellular behavior and medical device performance. Material properties can be manipulated to direct cell responses, benefiting applications from regenerative medicine to implantable devices such as silicone breast implants. Knowledge about the interaction differences between healthy and cancer cells with implants may guide implant design to more precisely influence cell adhesion and proliferation of healthy cells while inhibiting cancer cells, tailoring outcomes to specific cellular responses. To show-case this potential, breast epithelial cells and breast cancer cells were investigated regarding their interaction with a broad range of combined physicochemical properties. This study employed a silicone-based high-throughput screening method utilizing Double Orthogonal Gradients (DOGs) to investigate the influence of topography, stiffness, and wettability on breast epithelial cells (MCF10a) and breast cancer cells (MCF7). Results show distinct cellular responses, including decreased proliferation rates in both MCF10a and MCF7 cells with the introduction of surface topography and the dominant influence of wettability on cell adhesion, proliferation, and cluster formation. The screening identified specific regions of interest (ROIs) where MCF10a cell proliferation outperformed MCF7 cells and that topography inhibits cluster formation (tumorigenesis), offering potential prospects for the creation of novel implant surfaces.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 494-509"},"PeriodicalIF":18.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-25DOI: 10.1016/j.bioactmat.2025.04.027
Alessandra Caliendo , Simona Camorani , Luis Exequiel Ibarra , Gabriella Pinto , Lisa Agnello , Sandra Albanese , Antonietta Caianiello , Anna Illiano , Rosaria Festa , Vincenzo Ambrosio , Giosuè Scognamiglio , Monica Cantile , Angela Amoresano , Monica Fedele , Antonella Zannetti , Laura Cerchia
{"title":"A novel CD44-targeting aptamer recognizes chemoresistant mesenchymal stem-like TNBC cells and inhibits tumor growth","authors":"Alessandra Caliendo , Simona Camorani , Luis Exequiel Ibarra , Gabriella Pinto , Lisa Agnello , Sandra Albanese , Antonietta Caianiello , Anna Illiano , Rosaria Festa , Vincenzo Ambrosio , Giosuè Scognamiglio , Monica Cantile , Angela Amoresano , Monica Fedele , Antonella Zannetti , Laura Cerchia","doi":"10.1016/j.bioactmat.2025.04.027","DOIUrl":"10.1016/j.bioactmat.2025.04.027","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) represents a significant therapeutic challenge owing to the scarcity of targeted medicines and elevated recurrence rates. We previously reported the development of the nuclease-resistant RNA sTN58 aptamer, which selectively targets TNBC cells. Here, sTN58 aptamer was employed to capture and purify its binding target from the membrane protein fraction of cisplatin-resistant mesenchymal stem-like TNBC cells. Mass spectrometry in conjunction with aptamer binding assays across various cancer cell lines identified CD44 as the cellular target of sTN58. By binding to CD44, sTN58 inhibits the invasive growth and hyaluronic acid-dependent tube formation in chemoresistant TNBC cells, where CD44 serves as a key driver of tumor cell aggressiveness and stem-like plasticity. Moreover, in vivo studies demonstrated the aptamer's high tumor targeting efficacy and its capacity to significantly inhibit tumor growth and lung metastases following intravenous administration in mice with orthotopic TNBC. Overall, our findings reveal the striking potential of sTN58 as a targeting reagent for the recognition and therapy of cancers overexpressing CD44.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 443-460"},"PeriodicalIF":18.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-24DOI: 10.1016/j.bioactmat.2025.04.004
Yufei Wang , Yiwen Sun , Tianyang Jie , Minqi Wang , Shutao Zhang , Hongtao Yang , Weiyan Jian , Dai Dai , Ruida Xu , Bing Yue , Xinhua Qu
{"title":"Association between serum Copper-Zinc-Selenium mixture and multiple health outcomes","authors":"Yufei Wang , Yiwen Sun , Tianyang Jie , Minqi Wang , Shutao Zhang , Hongtao Yang , Weiyan Jian , Dai Dai , Ruida Xu , Bing Yue , Xinhua Qu","doi":"10.1016/j.bioactmat.2025.04.004","DOIUrl":"10.1016/j.bioactmat.2025.04.004","url":null,"abstract":"<div><h3>Background</h3><div>Metallic biomaterials have transformed modern medicine, with copper (Cu), zinc (Zn), and selenium (Se) emerging as critical components in medical applications. The study of the single and synergistic effects of serum metal concentrations on human health can provide valuable insights for future clinical transformation of biodegradable alloys.</div></div><div><h3>Methods</h3><div>We evaluated 2381 NHANES 2011–2016 participants to study individual and combined effects of these metals on health outcomes. Multivariable logistic regression, restricted cubic splines, and piecewise linear regression were used to examine linear, nonlinear, and threshold relationships. Overall metal mixture effects were assessed using weighted quantile sum (WQS) and Bayesian kernel-machine regression (BKMR).</div></div><div><h3>Results</h3><div>Elevated serum Cu levels were significantly associated with an increased risk of osteoarthritis. When Serum Cu ≥ 99.48 μg/dL, each 1-unit increase in Ln Cu raised diabetes risk 4.55-fold. For Se ≥ 122.74 μg/L, each 1-unit increase in Ln Se led to a 29.96-fold rise in diabetes prevalence, for Se < 157.56 μg/L it increased heart attack risk 165.19-fold. Furthermore, mixtures of Cu, Se, and Zn were positively associated with diabetes, hypertension, and heart attack risks; each unit increase in the mixture corresponded to a 23 % rise in diabetes and a 15 % rise in hypertension prevalence.</div></div><div><h3>Conclusions</h3><div>Serum Cu levels ≥99.48 μg/dL are significantly linked to diabetes risk, while serum Se levels ≥122.74 μg/L are associated with diabetes risk and levels <157.56 μg/L with elevated heart attack risk. Serum metal mixtures containing Cu, Se and Zn were significantly and positively associated with risk of diabetes, hypertension and heart attack.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 432-442"},"PeriodicalIF":18.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-23DOI: 10.1016/j.bioactmat.2025.04.021
Yanjiao Li , Bin Jiang , Zhen Wu , Zhaoxia Ma , Lihua Qiu , Wen Cui , Yunhui Zhao , Jinghe Yan , Daiping Ma , Xingfei Wu , Shu Liang , Sitao Wang , Yanqun Zhao , Mengting Wang , Min Hu
{"title":"Engineering fibroblast with reprogramming and spheronization for bone defect repair","authors":"Yanjiao Li , Bin Jiang , Zhen Wu , Zhaoxia Ma , Lihua Qiu , Wen Cui , Yunhui Zhao , Jinghe Yan , Daiping Ma , Xingfei Wu , Shu Liang , Sitao Wang , Yanqun Zhao , Mengting Wang , Min Hu","doi":"10.1016/j.bioactmat.2025.04.021","DOIUrl":"10.1016/j.bioactmat.2025.04.021","url":null,"abstract":"<div><div>Bone diseases profoundly affect patients, particularly the elderly, leading to severe health complications and disabilities. Osteoblasts play a crucial role in bone formation and are ideal candidates for treating bone diseases and engineering living materials. However, the stem and progenitor cells that give rise to osteoblasts, as well as osteoblasts themselves, exhibit dysfunction with aging. Although chemical reprogramming of fibroblasts into osteoblasts has been achieved, effective cell-based therapies or living materials have not been established in clinical practice. Here, we present a method to engineer fibroblasts through small molecule reprogramming and spheronization, achieving functional osteoblastic materials across all age groups. By primarily targeting the WNT signaling pathway and modularizing small molecules based on their effects on stage-specific genes, we optimized the temporal regulation of small molecules during reprogramming, acquiring a large number of healthy induced osteoblasts (iOBs). These iOBs with traits of functional native osteoblasts are ideal for forming transplantable tissue spheroids. As innovative living materials, the iOB spheroids (iOB-Sps) have demonstrated improved survival, significant self-bone formation, reduced ROS levels in the defect microenvironment, and accelerated endogenous osteogenesis and angiogenesis in vivo, promoting effective healing of bone defects. These material-free iOB-Sps function as self-scaffolding building blocks for biofunctional constructs, offering a promising avenue for clinical autologous bone defect repair, especially for the elderly.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 414-431"},"PeriodicalIF":18.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-22DOI: 10.1016/j.bioactmat.2025.04.011
Maoyu Cai , Haiping Zhong , Xindi Wang , Liangpin Li , Xueyan Zhou , Yan Wang , Xia Hua , Shutao Guo , Xiaoyong Yuan
{"title":"Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis","authors":"Maoyu Cai , Haiping Zhong , Xindi Wang , Liangpin Li , Xueyan Zhou , Yan Wang , Xia Hua , Shutao Guo , Xiaoyong Yuan","doi":"10.1016/j.bioactmat.2025.04.011","DOIUrl":"10.1016/j.bioactmat.2025.04.011","url":null,"abstract":"<div><div>Fungal keratitis (FK) is a challenging-to-manage blinding corneal infectious disease that often leads to severe sequelae, such as corneal leukoplakia regardless of curative care. Moreover, the unique anatomical structure and tear turnover of the eye significantly limit the bioavailability and therapeutic efficacy of traditional eye drops. Inspired by the unique pathological features of corneal ulcers, we report a thermosensitive multifunctional eye drop, designated PX-TA, based on a poloxamer (PX) and a collagen-adhesive tannic acid (TA), for prolonged and efficient treatment of FK. PX-TA transforms into a gel at body temperature and adheres to exposed collagen at the ulcer site; this significantly improves the corneal retention time and bioavailability. PX-TA maintains corneal retention for at least 90 min, substantially exceeding both the 15-min limit of commercial mucoadhesive eye drops and the 30-min threshold of conventional in situ gels. When loaded with amphotericin B (AmB), once-daily PX-TA-AmB administration effectively suppresses inflammation and corneal scarring, demonstrating superior efficacy over six-times-daily free AmB drops and a good safety profile. Mechanistic investigations reveal that PX-TA-AmB mediates its therapeutic effects through the MAPK6/PI3K/AKT signaling pathway. Moreover, the metal-chelating properties of TA inhibit the copper-dependent enzyme lysyl oxidase (LOX), resulting in reduced matrix fibrosis. Overall, the use of PX-TA-AmB drops represents a simplified yet effective strategy for the potential clinical management of FK, inspiring the design of eye drop formulations.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 396-413"},"PeriodicalIF":18.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-22DOI: 10.1016/j.bioactmat.2025.04.013
Zhen Zhang , Ye Huang , Xu Hu , Yulei Mu , Huiqun Zhou , Liang Ma , Bangheng Liu , Hang Yao , Xieyuan Jiang , Dong-An Wang
{"title":"In situ implantation of type II collagen-based double-layer scaffolds for Articular Osteochondral Regeneration comprising hyaline cartilage and vascularized subchondral bones","authors":"Zhen Zhang , Ye Huang , Xu Hu , Yulei Mu , Huiqun Zhou , Liang Ma , Bangheng Liu , Hang Yao , Xieyuan Jiang , Dong-An Wang","doi":"10.1016/j.bioactmat.2025.04.013","DOIUrl":"10.1016/j.bioactmat.2025.04.013","url":null,"abstract":"<div><div>The articular osteochondral injury involves the repair of hyaline cartilage, subchondral bone plate, and cancellous bone. Due to the weak regeneration ability of chondrocytes and the complex structure of the bone-cartilage junction, there is currently no excellent repair method. The challenge of hyaline cartilage repair is to avoid fibrosis and hypertrophy, which has been solved to some extent after the advent of type II collagen scaffolds; the difficulty of the subchondral bone plate and cancellous bone repair lies in the repair of the complex transition structure of cartilage tidemark, calcified cartilage, subchondral bone plate, and cancellous bone. Inspired by developmental biology, the generation of this complex structure during development depends on endochondral ossification (ECO). ECO depends on some specific proteins, such as IHH, PTHrP, BMP, and WNT, and the receptors of these proteins. Studies have shown that polydopamine coating can promote the production of BMP and WNT proteins. We developed a type II collagen-based double-layer scaffold (Col II & Dopa-Col II) with type II collagen on the upper layer and polydopamine-coated type II collagen on the lower layer. Proteomics and RNA sequencing analysis have found that polydopamine coating can mobilize the proliferation and hypertrophy differentiation of chondrocytes, induce intra-chondral vascular nerve invasion, and promote ECO and bone remodeling by upregulating Parathyroid hormone signaling pathway, Hedgehog signaling pathway, VEGF signaling pathway, and Axon guidance. All the results indicate that Col II & Dopa-Col II can achieve hyaline cartilage and vascularized subchondral bone regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 364-381"},"PeriodicalIF":18.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-22DOI: 10.1016/j.bioactmat.2025.04.022
Bicong Gao , Haifeng Ni , Junhong Lai , Ning Gao , Xinxin Luo , Ying Wang , Yani Chen , Jiaying Zhao , Zhou Yu , Jing Zhang , Wenjin Cai , Guoli Yang
{"title":"Macrophage response to fibrin structure mediated by Tgm2-dependent mitochondrial mechanosensing","authors":"Bicong Gao , Haifeng Ni , Junhong Lai , Ning Gao , Xinxin Luo , Ying Wang , Yani Chen , Jiaying Zhao , Zhou Yu , Jing Zhang , Wenjin Cai , Guoli Yang","doi":"10.1016/j.bioactmat.2025.04.022","DOIUrl":"10.1016/j.bioactmat.2025.04.022","url":null,"abstract":"<div><div>Following an injury at the implantation position, blood-material interactions form a fibrin architecture, which serves as the initial activator of foreign body response (FBR). However, there is limited knowledge regarding how the topography of fibrin architectures regulates macrophage behavior in mitigating FBR. Mechanical cues of the microenvironment have been reported to shape immune cell functions. Here, we investigated macrophage mechanobiology at the organelle level by constructing heterogeneous fibrin networks. Based on findings <em>in vivo</em>, we demonstrated that adhesion-mediated differentiation of mitochondrial function modulated macrophage polarization. The finite activation of integrin signaling upregulated transglutaminase 2 (Tgm2) in a trans-manner, augments PGC1α-mediated mitochondrial biogenesis. Our study highlighted the previously overlooked spatial structures of host proteins adsorbed on material surfaces, advocating for a paradigm shift in material design strategies, from focusing solely on physical properties to considering the modification of host proteins.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 382-395"},"PeriodicalIF":18.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-18DOI: 10.1016/j.bioactmat.2025.04.009
Yu-Bao Liu , Xu Liu , Xiao-Fei Li , Liang Qiao , Hao-Liang Wang , Yue-Fu Dong , Feng Zhang , Yang Liu , Hao-Yang Liu , Ming-Liang Ji , Lan Li , Qing Jiang , Jun Lu
{"title":"Multifunctional piezoelectric hydrogels under ultrasound stimulation boost chondrogenesis by recruiting autologous stem cells and activating the Ca2+/CaM/CaN signaling pathway","authors":"Yu-Bao Liu , Xu Liu , Xiao-Fei Li , Liang Qiao , Hao-Liang Wang , Yue-Fu Dong , Feng Zhang , Yang Liu , Hao-Yang Liu , Ming-Liang Ji , Lan Li , Qing Jiang , Jun Lu","doi":"10.1016/j.bioactmat.2025.04.009","DOIUrl":"10.1016/j.bioactmat.2025.04.009","url":null,"abstract":"<div><div>Articular cartilage, owing to the lack of undifferentiated stem cells after injury, faces significant challenges in reconstruction and repair, making it a major clinical challenge. Therefore, there is an urgent need to design a multifunctional hydrogels capable of recruiting autologous stem cells to achieve <em>in situ</em> cartilage regeneration. Here, our study investigated the potential of a piezoelectric hydrogel (Hyd<sub>6</sub>) for enhancing cartilage regeneration through ultrasound (US) stimulation. Hyd<sub>6</sub> has multiple properties including injectability, self-healing capabilities, and piezoelectric characteristics. These properties synergistically promote stem cell chondrogenesis. The fabrication and characterization of Hyd<sub>6</sub> revealed its excellent biocompatibility, biodegradability, and electromechanical conversion capabilities. <em>In vitro</em> and <em>in vivo</em> experiments revealed that Hyd<sub>6</sub>, when combined with US stimulation, significantly promotes the recruitment of autologous stem cells and enhances chondrogenesis by generating electrical signals that promote the influx of Ca<sup>2+</sup>, activating downstream CaM/CaN signaling pathways and accelerating cartilage formation. An <em>in vivo</em> study in a rabbit model of chondral defects revealed that Hyd<sub>6</sub> combined with US treatment significantly improved cartilage regeneration, as evidenced by better integration of the regenerated tissue with the surrounding cartilage, greater collagen type II expression, and improved mechanical properties. The results highlight the potential of Hyd<sub>6</sub> as a novel therapeutic approach for treating cartilage injuries, offering a self-powered, noninvasive, and effective strategy for tissue engineering and regenerative medicine.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 344-363"},"PeriodicalIF":18.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-04-16DOI: 10.1016/j.bioactmat.2025.04.012
Li Yu , Hui Shi , Tingxin Gao , Wenrong Xu , Hui Qian , Jiajia Jiang , Xiao Yang , Xingdong Zhang
{"title":"Exomeres and supermeres: Current advances and perspectives","authors":"Li Yu , Hui Shi , Tingxin Gao , Wenrong Xu , Hui Qian , Jiajia Jiang , Xiao Yang , Xingdong Zhang","doi":"10.1016/j.bioactmat.2025.04.012","DOIUrl":"10.1016/j.bioactmat.2025.04.012","url":null,"abstract":"<div><div>Recent studies have revealed a great diversity and complexity in extracellular vesicles and particles (EVPs). The developments in techniques and the growing awareness of the particle heterogeneity have spurred active research on new particle subsets. Latest discoveries highlighted unique features and roles of non-vesicular extracellular nanoparticles (NVEPs) as promising biomarkers and targets for diseases. These nanoparticles are distinct from extracellular vesicles (EVs) in terms of their smaller particle sizes and lack of a bilayer membrane structure and they are enriched with diverse bioactive molecules particularly proteins and RNAs, which are widely reported to be delivered and packaged in exosomes. This review is focused on the two recently identified membraneless NVEPs, exomeres and supermeres, to provide an overview of their biogenesis and contents, particularly those bioactive substances linked to their bio-properties. This review also explains the concepts and characteristics of these nanoparticles, to compare them with other EVPs, especially EVs, as well as to discuss their isolation and identification methods, research interests, potential clinical applications and open questions.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"50 ","pages":"Pages 322-343"},"PeriodicalIF":18.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}