Materials Today BioPub Date : 2026-07-01eCollection Date: 2026-08-01DOI: 10.1016/j.mtbio.2026.103410
Xianbo Liu, Xiaolin Li, Yang Yue, Ying Zheng, Wenkai Huang, Jiayue Niu, Haijiang Sun, Ming Xue, Qiang Ao, Yingxi Xu, Yang Yu, Qing Zhou, Tianhao Yu
{"title":"Selection of a novel MSC-targeted aptamer Pt-1 and its functionalized hydrogel for tissue regeneration.","authors":"Xianbo Liu, Xiaolin Li, Yang Yue, Ying Zheng, Wenkai Huang, Jiayue Niu, Haijiang Sun, Ming Xue, Qiang Ao, Yingxi Xu, Yang Yu, Qing Zhou, Tianhao Yu","doi":"10.1016/j.mtbio.2026.103410","DOIUrl":"10.1016/j.mtbio.2026.103410","url":null,"abstract":"<p><p>Mesenchymal stem cell (MSC)-based therapies present substantial opportunities for regenerative medicine, yet the absence of lineage-specific tools for precise cell recruitment constitutes a primary limitation. In this study, we developed a novel ssDNA aptamer, designated as Pt-1, specifically evolved against human dental pulp stem cells (hDPSCs) using Cell-SELEX technology. Pt-1 exhibited high target specificity, strong binding affinity, and favorable physiological stability. Notably, Pt-1 identified a distinct subpopulation within heterogeneous DPSCs; the Pt-1<sup>high</sup> subset displayed significantly enhanced proliferative capacity and osteo/odontogenic potential compared to the Pt-1<sup>Low</sup> group. Through proteomic analysis and molecular docking, we elucidated that Pt-1 recognizes Cav1-associated target as its membrane target. To translate this molecular recognition into a regenerative strategy, we engineered a Pt-1-functionalized ChSMA hydrogel. This bio-instructive scaffold demonstrated superior efficacy in orchestrating the homing of endogenous MSCs <i>in vitro</i> and <i>in vivo</i> compared to the established Apt19S aptamer. In rat models of dental pulp and femoral bone defects, the Pt-1-modified hydrogel significantly accelerated tissue restoration, promoting more mature trabecular bone formation and pulp tissue regeneration. In summary, we developed a novel ssDNA aptamer targeting MSCs and established an aptamer-based strategy for precise endogenous cell recruitment, opening new therapeutic avenues for regenerative medicine.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103410"},"PeriodicalIF":11.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604683","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}
Materials Today BioPub Date : 2026-06-29eCollection Date: 2026-08-01DOI: 10.1016/j.mtbio.2026.103414
Patrícia S Rodrigues, Margarida Henriques-Pereira, João F Mano, Vítor M Gaspar
{"title":"Advances in cell-derived extracellular matrix for 3D tumor modelling.","authors":"Patrícia S Rodrigues, Margarida Henriques-Pereira, João F Mano, Vítor M Gaspar","doi":"10.1016/j.mtbio.2026.103414","DOIUrl":"10.1016/j.mtbio.2026.103414","url":null,"abstract":"<p><p>Cell-derived decellularized extracellular matrix (cdECM) is being increasingly explored as a supportive biomaterial for bioengineering biomimetic 3D tumor models. The potential to represent the biomolecular diversity of the extracellular matrix in a tumor-specific mode and its production using human cell cultures renders <i>in vitro</i> produced matrix a particularly attractive alternative to non-human counterparts. In this review, we describe well-established and emerging strategies to modulate human ECM production <i>in vitro,</i> as well as showcase recent advances in decellularization and processing methodologies that have been explored across different scales and diverse biological complexities. The incorporation of cdECM into the design stages of bioengineered tumor models and its biological relevance are also discussed considering currently available alternatives to model tumor ECM. Finally, we look at the current challenges in using cdECM-based biomaterials to develop preclinically relevant models and discuss the need for innovative production approaches and methodological developments in downstream processing to widen the use of cell-derived biomaterials for tumor modelling and other applications in the tissue engineering field.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"39 ","pages":"103414"},"PeriodicalIF":11.0,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520455","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}
Materials Today BioPub Date : 2026-06-08eCollection Date: 2026-06-01DOI: 10.1016/j.mtbio.2026.103324
Xiaodong Hou, Yi Yang, Yilin Jiao, Wentao Deng, Jingjiang Duan, Ziran Zhou, Shaobin Ye, Chenyuan Guo, Biao Li, Dingyun You, Hongda Gong, Jia Yang, Bing Wang
{"title":"Early-apoptotic membrane engineering of M2 macrophage-derived nanovesicles enables osteoimmunomodulatory bone repair.","authors":"Xiaodong Hou, Yi Yang, Yilin Jiao, Wentao Deng, Jingjiang Duan, Ziran Zhou, Shaobin Ye, Chenyuan Guo, Biao Li, Dingyun You, Hongda Gong, Jia Yang, Bing Wang","doi":"10.1016/j.mtbio.2026.103324","DOIUrl":"10.1016/j.mtbio.2026.103324","url":null,"abstract":"<p><p>Critical-sized bone defects remain difficult to repair because persistent inflammation, insufficient osteogenesis, and excessive osteoclast activity collectively compromise regenerative progression. Herein, an apoptotic reparative nanovesicle platform is developed by combining M2 macrophage polarization with early apoptotic membrane remodeling. Membrane-derived nanovesicles prepared from these donor cells (M2-Apo-NVs) retain the pro-repair imprint of M2 macrophages while displaying enhanced surface phosphatidylserine exposure. Relative to M2-derived nanovesicles, M2-Apo-NVs exhibit stronger cellular internalization, more effectively reprogram inflammatory macrophages toward a pro-resolution phenotype, promote osteogenic differentiation of bone marrow mesenchymal stem cells, and suppress RANKL-induced osteoclastogenesis through inhibition of the NF-κB/NFAT axis. For local delivery, M2-Apo-NVs are incorporated into a photocrosslinkable methacrylated hyaluronic acid hydrogel, enabling sustained presentation within a murine critical-sized calvarial defect. In vivo, the composite hydrogel markedly improves bone regeneration, accompanied by reduced inflammatory signaling, enhanced osteogenic activity, and restrained osteoclast-associated remodeling. These findings establish donor-membrane state engineering as an effective strategy for upgrading cell-derived nanovesicles and identify M2-Apo-NVs as a promising osteoimmunomodulatory therapeutic for bone defect repair.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"38 ","pages":"103324"},"PeriodicalIF":11.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252318","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}
{"title":"Engineered bone-targeting <i>Lycium barbarum L.</i>-derived extracellular vesicle-like nanoparticles deliver miR167a-5p to regulate mitochondrial dynamics and metabolic reprogramming in alleviating osteoporosis.","authors":"Shuai Chen, Miaochao Qin, Qilong Zhao, Ningsheng Tian, Lingling Yu, Liansheng Shao, Su Yan, Xinyu Ding, Pengfei Sun, Peng Ma, Junwu Wang, Penghua Fang, Wen Min","doi":"10.1016/j.mtbio.2026.103312","DOIUrl":"10.1016/j.mtbio.2026.103312","url":null,"abstract":"<p><p>With the exacerbation of global population aging, the development of novel therapeutic strategies for osteoporosis (OP) has emerged as a pressing worldwide challenge. As an emerging natural nanomedicine, medicinal plant-derived extracellular vesicle-like nanoparticles (EVLPs) have shown considerable potential in OP treatment due to their advantages, such as good bioavailability, high biosafety characteristics, and natural targeting. Herein, we isolated <i>Lycium barbarum L.</i>-derived EVLPs (LB-EVLPs) from fresh LB via ultracentrifugation combined with sucrose gradient centrifugation and further functionalized LB-EVLPs with the bone-targeting peptide SDSSD (BT-LB-EVLPs) to treat OP. This engineered LB-EVLPs exhibited selective targeting of bone tissue and were effectively internalized by bone marrow mesenchymal stem cells (BMSCs), with a distinct propensity for mitochondrial localization. In ovariectomized (OVX)-induced osteoporotic mice, BT-LB-EVLPs alleviated bone loss, improved bone microstructure, and enhanced bone strength. Proteomic profiling indicated that BT-LB-EVLPs reprogram mitochondrial metabolism by enhancing oxidative phosphorylation while suppressing excessive glycolytic flux, thereby exerting anti-osteoporotic effects. <i>In vitro</i> experiments demonstrated that BT-LB-EVLPs attenuated oxidative stress, promoted mitochondrial fusion, inhibited mitochondrial fission, and facilitated metabolic reprogramming in BMSCs, ultimately restoring mitochondrial function and enhancing osteogenic differentiation. Through lentiviral-mediated overexpression of <i>SLC25A26</i> combined with miR167a-5p mimic/inhibitor interventions, we verified that miR167a-5p derived from BT-LB-EVLPs directly targets the mitochondrial transporter gene <i>SLC25A26</i>, thereby regulating mitochondrial dynamics, sustaining energy metabolism balance, and promoting osteoblastogenesis. Additionally, <i>in vivo</i> knockdown of miR167a-5p exacerbated bone loss and bone microstructural damage, and abolished the anti-osteoporosis effect of BT-LB-EVLPs. Collectively, these findings emphasized this engineered LB-EVLPs as a promising targeted nanotherapeutic approach for OP treatment.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"38 ","pages":"103312"},"PeriodicalIF":11.0,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252312","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}
Materials Today BioPub Date : 2026-06-05eCollection Date: 2026-06-01DOI: 10.1016/j.mtbio.2026.103321
Shaowei Zhu, Jie Sun, Chenggang Yi, Jing Wang, Jun Yin
{"title":"Extracellular vesicles enriched with mitochondrial components from intermittently cold-exposed adipose tissue drive metabolically active adipose regeneration via miR-296-3p.","authors":"Shaowei Zhu, Jie Sun, Chenggang Yi, Jing Wang, Jun Yin","doi":"10.1016/j.mtbio.2026.103321","DOIUrl":"10.1016/j.mtbio.2026.103321","url":null,"abstract":"<p><p>Current acellular adipose tissue engineering focuses primarily on structural regeneration, whereas functional metabolic recovery remains a major challenge. Extracellular vesicles (EV) derived from adipose tissue (AT-EV) have recently emerged as potent mediators of tissue regeneration, and cold stimulation has been reported to enhance the metabolic reprogramming of AT-EV. We have previously reported that fat grafts from cold-stimulated mice exhibited enhanced survival and adipose regeneration. Yet whether cold-induced AT-EV contribute to in vivo metabolic adipose regeneration remains unclear. Moreover, the cold stimulation temperatures used in traditional mouse models are often intolerable for humans. To address this, we developed a short-term intermittent mild cold exposure (STIMCE) protocol to metabolically activate murine adipose tissue for EV isolation (STIMCE-EV). Following only 3 or 7 days of STIMCE treatment, adipose tissue exhibited increased EV secretion and enrichment of mitochondrial components. Moreover, STIMCE-EV were efficiently incorporated into human acellular adipose matrix (AAM) hydrogel and exhibited controlled release in vitro. Injectable AAM@STIMCE-EV hydrogel transplantation in nude mice showed improved adipogenesis and volume retention in situ after 2 months. Importantly, the AAM@STIMCE-EV grafts improved cold adaptation and enhanced the thermogenic function of the host mice. Mechanistically, mmu-miR-296-3p was identified as a key regulatory factor within STIMCE-EV. Exogenous mmu-miR-296-3p supplementation significantly improved the adipogenic regeneration of AAM. Overall, this study presents a metabolically activated, cell-free adipose regeneration strategy that combines STIMCE-EV with AAM scaffolds. This minimally invasive and injectable system enables functional adipose tissue regeneration with systemic thermogenic metabolic activity, providing a promising translational solution for soft tissue reconstruction.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"38 ","pages":"103321"},"PeriodicalIF":11.0,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252321","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}
{"title":"Advances and challenges of metal-organic frameworks in controlled drug delivery.","authors":"Xingqi Zhu, Menghui Liao, Hao Wei, Yue Jiang, Hong Cheng, Xin Xu, Shan Xu, Yangnan Hu, Renjie Chai, Xiaoyun Qian","doi":"10.1016/j.mtbio.2026.103318","DOIUrl":"10.1016/j.mtbio.2026.103318","url":null,"abstract":"<p><p>Metal-organic frameworks (MOFs) are a class of crystalline porous materials, which have become the main platform for drug delivery research because of their high specific surface area, adjustable pore size and high drug loading capacity. The selection of organic ligands, adjustment of metal nodes and post-synthetic modification enable precise control over drug loading, release kinetics and targeting specificity. These features overcome key limitations of traditional carriers, such as low loading capacity, easy inactivation and difficult biocompatibility. In addition, combining MOFs with stimulus-responsive polymers or photothermal agents has led to multifunctional systems that integrate therapeutic and diagnostic imaging, thereby enabling theranostic application. This review analyzes MOF surface engineering, stimulus response behavior, cytotoxicity and long-term biological interaction in detail. It also briefly describes the application of MOFs in various drug delivery modes, aiming to provide fundamental insights and guide the development of intelligent and adaptive drug delivery platforms for future biomedical applications.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"38 ","pages":"103318"},"PeriodicalIF":11.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252132","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}
Materials Today BioPub Date : 2026-06-04eCollection Date: 2026-06-01DOI: 10.1016/j.mtbio.2026.103317
Wen Li, Yuan-Yuan Xin, Ming-Zhu Jin, Wei-Lin Jin
{"title":"The mechano-immunological landscape in the tumor microenvironment: From mechanical sensing to a new therapeutic paradigm.","authors":"Wen Li, Yuan-Yuan Xin, Ming-Zhu Jin, Wei-Lin Jin","doi":"10.1016/j.mtbio.2026.103317","DOIUrl":"10.1016/j.mtbio.2026.103317","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a complex ecosystem where mechanical forces are now recognized not as passive byproducts but as active drivers critically shaping anti-tumor immunity. This review introduces the integrative concept of the \"Mechano-immunological Landscape\" (MIL) to delineate the dynamic and spatially heterogeneous network of interactions between mechanical cues and immune cells within tumors. We systematically elaborate on its three core pillars: Mechano-immunological Checkpoints, Mechano-immune Memory, and Landscape Plasticity. Building upon this framework, we propose a novel therapeutic paradigm termed \"Mechano-immunological Landscape Remodeling Therapy\" (MILRT). This paradigm discusses potential strategies to reverse immune suppression and enhance anti-tumor efficacy by modulating the mechanical TME, including matrix de-stiffening, mechanical empowerment of immune cells, and targeting mechano-immunological checkpoints. Finally, we outline future research trajectories, pivotal challenges, and clinical translation prospects in this burgeoning field. We position MILRT as a multi-pronged and synergistic framework that leverages advanced biomaterials and biophysical tools to overcome current limitations in drug delivery and immunotherapy resistance, thereby paving the way for next-generation, mechano-aware immunotherapies and redefining the future of solid tumor treatment.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"38 ","pages":"103317"},"PeriodicalIF":11.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252299","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}
{"title":"Dual-tunable liquid crystal-forming system enables sustained ropivacaine delivery for prolonged local analgesia.","authors":"Chuansheng Fu, Donghong Chen, Sihan Yu, Jiao Zhang, Qi Xie, Bingzheng Shen, Conglian Yang, Li Kong, Zhiping Zhang","doi":"10.1016/j.mtbio.2026.103319","DOIUrl":"10.1016/j.mtbio.2026.103319","url":null,"abstract":"<p><p>Postoperative pain management remains a challenge in clinical practice. Traditional local anesthetics often require repeated administration due to their short duration of action, which increases the risk of systemic toxicity and nerve damage. Herein, we developed an injectable, dual-tunable, low-ethanol lyotropic liquid crystal-forming system (LCFS) for sustained local ropivacaine (Rop) release, achieving long-lasting analgesia. Upon injection, the precursor solution transformed into a gel <i>in situ</i>, forming a drug reservoir for sustained release of Rop. The system was optimized by adjusting the ratio of phosphatidylcholine to glyceryl monooleate and the content of corn oil, enabling dual modulation of drug release kinetics. The optimized Rop@LCFS formulation demonstrated sustained release for up to 7 days, with an initial burst followed by controlled release. Compared with commercial bupivacaine liposome injection, Rop@LCFS exhibited 8-fold prolongation of effective sensory blockade duration in the rat sciatic nerve block model, while maintaining over 12 h of sustained analgesia in the subcutaneous infiltration anesthesia model. The formulation also displayed favorable biodegradability and biocompatibility both <i>in vitro</i> and <i>in vivo</i>. The Rop@LCFS features easy preparation, sustained release, and biocompatibility, offering potential for clinical translation and long-acting local anesthetics development.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"38 ","pages":"103319"},"PeriodicalIF":11.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252252","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}