Bioactive MaterialsPub Date : 2026-06-01Epub Date: 2026-01-21DOI: 10.1016/j.bioactmat.2026.01.017
Leyan Xuan , Tingting Lu , Yingying Hou , Yuguang Zhu , Bingbing Zhan , Jialin Wu , Kaixiang Li , Jiachu Huang , Huaibin Wang , Ziyang Liu , Wenqi Xiao , Junjie Cai , Lijie Chen , Jie Wang , Jie Guo , Shufang Wang , Chenrui An , Xiyong Yu , Wei Fu , Guosheng Tang
{"title":"Bioenzymatic single-cell microencapsulation for enhanced stem Cell therapy","authors":"Leyan Xuan , Tingting Lu , Yingying Hou , Yuguang Zhu , Bingbing Zhan , Jialin Wu , Kaixiang Li , Jiachu Huang , Huaibin Wang , Ziyang Liu , Wenqi Xiao , Junjie Cai , Lijie Chen , Jie Wang , Jie Guo , Shufang Wang , Chenrui An , Xiyong Yu , Wei Fu , Guosheng Tang","doi":"10.1016/j.bioactmat.2026.01.017","DOIUrl":"10.1016/j.bioactmat.2026.01.017","url":null,"abstract":"<div><div>Cell therapy has achieved a critical breakthrough through single-cell microgel technology. This miniaturized encapsulation platform enables precise microenvironment recapitulation, efficient targeted delivery, and tunable pericellular matrix control. Nevertheless, prevailing microfluidic and surface chemical engineering methodologies confront fundamental challenges in preserving cell viability and functionality. Here, we establish a simple and bioenzymatic strategy for fabricating single-cell microgels, using microbial transglutaminase adsorption. This surfactant- and oil-free approach, without surface modification, permits universal, high-viability encapsulation of diverse cell types and biomaterials. We achieve 100 % encapsulation efficiency and robust mechanical protection. Therapeutic efficacy was assessed in myocardial infarction (MI) and pulmonary fibrosis (PF) models. In MI, microgel-encapsulated MSCs (MSC SCMs) significantly improved in vivo retention and survival, exhibiting superior tissue regeneration and cardiac function. In bleomycin-induced PF, TNF-α-loaded MSC SCMs potentiated MMP-13 secretion, achieving enhanced respiratory function and attenuated fibrotic lesions. This robust and universally applicable platform thus for advanced cell therapies, overcomes limitations in encapsulation while demonstrating potent therapeutic efficacy across disease models.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 95-112"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036674","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 : 2026-06-01Epub Date: 2026-01-30DOI: 10.1016/j.bioactmat.2026.01.024
Jie Ren , Junjin Li , Hongda Wang , Haiwen Feng , Huaying Hao , Junyu Chen , Yuanquan Li , Zhengyu Xu , Chuanhao Li , Wang Jiang , Yan Wang , Xiaoyang Zhang , Xiaomeng Song , Guangzhi Ning , Jun Liang , Shiqing Feng
{"title":"Integrated cryopreservation-thawing-transplantation platform for neural stem cell-based spinal cord injury repair","authors":"Jie Ren , Junjin Li , Hongda Wang , Haiwen Feng , Huaying Hao , Junyu Chen , Yuanquan Li , Zhengyu Xu , Chuanhao Li , Wang Jiang , Yan Wang , Xiaoyang Zhang , Xiaomeng Song , Guangzhi Ning , Jun Liang , Shiqing Feng","doi":"10.1016/j.bioactmat.2026.01.024","DOIUrl":"10.1016/j.bioactmat.2026.01.024","url":null,"abstract":"<div><div>Spinal cord injury (SCI) repair lacks clinically validated restorative therapies. Transplantation of exogenous neural stem cells (NSCs) offers significant potential for therapeutic applications; however, challenges remain, including substantial cell loss, uncontrolled differentiation, and limited tissue integration within inflammatory microenvironments. Furthermore, the workflow associated with traditional NSC transplantation—including cryopreservation, thawing, transportation, and injection—remains fragmented, resulting in systemic limitations. These issues manifest as reduced cell viability and stemness, an elevated risk of contamination, and dosing inaccuracies. All these significantly impede clinical translation. An integrated system for NSC preservation, transport, and transplantation is required to meet the following criteria: (i) maintenance of high cell viability and stemness post-cryopreservation and thawing; (ii) modulation of the acute-phase immune microenvironment; (iii) regulation of the differentiation fate of transplanted NSCs; (iv) injectable, standardized, and closed-system operation. To meet these requirements, we established a comprehensive cryopreservation, thawing, and transplant (CTT) integrated platform. Utilizing the bioactive material PM-BMH@Exo, this platform enables seamless end-to-end workflow integration through a mechanism that preserves bioactivity. It not only ensures high viability retention and directed differentiation of NSCs but also effectively mitigates the rapid viability decline of cells observed after traditional cryopreservation. Furthermore, the system enables closed-loop operations spanning cryopreservation, thawing, and minimally invasive injection. It breaks through systemic bottlenecks from multi-step procedures, comprehensively enhancing the timeliness and standardization of therapeutic interventions. We systematically evaluated the system's feasibility and efficacy via in vitro and in vivo experiments. This study presents a technologically viable and clinically compatible pathway with potential applications for SCI repair.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 401-424"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075128","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 : 2026-06-01Epub Date: 2026-01-24DOI: 10.1016/j.bioactmat.2026.01.027
Tianqi Liu , Liang Chen , Xiaoyu Zhao , Min Xie , Ling Xie , Mi Wang , Zhenyuan Wang , Jiaheng Zhang
{"title":"An AI-assisted designed supramolecularly engineered nanoplatform reverses pigmentation by triggering an ineffective compensatory melanin production program","authors":"Tianqi Liu , Liang Chen , Xiaoyu Zhao , Min Xie , Ling Xie , Mi Wang , Zhenyuan Wang , Jiaheng Zhang","doi":"10.1016/j.bioactmat.2026.01.027","DOIUrl":"10.1016/j.bioactmat.2026.01.027","url":null,"abstract":"<div><div>The clinical applications of natural compounds are limited by their inherent physicochemical properties. This study reports a hierarchical supramolecular engineering strategy for constructing a dual-assembly nanosystem for the treatment of skin hyperpigmentation. Using an AI-assisted computational screening model, tranexamic acid was identified as a suitable molecular partner of the hydrophobic and active, baicalin. Subsequent dual assembly processes yielded a stable hybrid nanoplatform (DHBTC) that enhanced the solubility and delivery efficiency of baicalin. Single-cell transcriptomics revealed an unexpected mechanism of \"functional inhibition\"; despite the depigmenting efficacy of DHBTC, the melanogenesis-related gene network in melanocytes was upregulated. This was identified as compensatory transcriptional feedback triggered by drug-induced autophagy. DHBTC functionally inhibits pigment accumulation by accelerating melanosome degradation, which elicits ineffective transcriptional activation as the cell attempts to restore homeostasis. Furthermore, the platform remodeled the cutaneous immune microenvironment toward an anti-inflammatory state. This study presents a strategy for designing drug delivery systems, from computational prediction to supramolecular assembly, and describes a therapeutic mechanism based on the modulation of post-translational and organellar homeostasis.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 243-260"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036673","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 : 2026-06-01Epub Date: 2026-01-24DOI: 10.1016/j.bioactmat.2026.01.023
Zhuhao Wu , Jingjing Gan , Yuanjin Zhao
{"title":"Spatiotemporal acoustic meta-patches for multifactorial wound treatment","authors":"Zhuhao Wu , Jingjing Gan , Yuanjin Zhao","doi":"10.1016/j.bioactmat.2026.01.023","DOIUrl":"10.1016/j.bioactmat.2026.01.023","url":null,"abstract":"<div><div>Ultrasound patches have demonstrated values in non-invasive diagnostics through echo reception, while their therapeutic potentials are restricted by precisely controlling ultrasound energy and integrating multi-effects. Here, we introduce a spatiotemporal acoustic meta-patch (STAMP) that generates controllable heating, mechanical, and biological effects for synergistic multifactorial wound treatment. The STAMP utilizes acoustic metamaterial composites, including reconfigurable interdigital transducers (IDTs) and acoustic impedance matching layer, to focus and transport ultrasound energy with high spatial precision and efficiency. This patch exhibits multiple therapeutic effects, such as localized heating, ultrasound-enhanced bioactive agent delivery and cell migration. Based on these beneficial effects, we show that STAMP can precisely and spatiotemporally regulate wound microenvironments by modulating temperature, inflammation, and wound closure, providing a proof-of-concept for enhanced multifactorial wound healing. We believe that the reconfigurable and multifunctional acoustic metamaterials-based patch may open new possibilities for direct ultrasound-based therapeutics.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 191-202"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036678","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 : 2026-06-01Epub Date: 2026-01-25DOI: 10.1016/j.bioactmat.2026.01.029
Jiayin Fu , Meng Zhao , Jing Zhao , Shaofei Wu , Jiahui Wu , Xulin Hong , He Huang , Guosheng Fu , Shengjie Xu
{"title":"Apolipoprotein E knockout attenuates vascular graft fibrosis by reducing profibrotic macrophage formation through low-density lipoprotein receptor related protein 1","authors":"Jiayin Fu , Meng Zhao , Jing Zhao , Shaofei Wu , Jiahui Wu , Xulin Hong , He Huang , Guosheng Fu , Shengjie Xu","doi":"10.1016/j.bioactmat.2026.01.029","DOIUrl":"10.1016/j.bioactmat.2026.01.029","url":null,"abstract":"<div><div>Vascular graft fibrosis can cause a decrease in cellular infiltration and capillary ingrowth in vascular walls. It can also lead to vascular stiffening. As such, there are still no vascular grafts that can be used in blood vessels where their diameters are less than 6 mm in patients. Although various approaches have been evaluated to mitigate implant-associated fibrosis, effective treatments remain quite limited. In this study, we demonstrated that Apolipoprotein E (APOE) significantly increased during vascular regeneration after graft implantation <em>in vivo</em>. APOE knockout (KO) increased compliance of the regenerated aortas, reduced extracellular matrix (ECM) deposition, and increased capillary ingrowth in adventitia of the regenerated aortas. Using single cell RNA sequencing (scRNA-seq), a subset of profibrotic macrophages was found to be involved in graft fibrosis. APOE KO reduced the formation of profibrotic macrophages during vascular regeneration. The interaction between APOE and low-density lipoprotein receptor related protein 1 (LRP1) partially mediated the profibrotic macrophage formation. The profibrotic macrophages promoted graft fibrosis mainly through secretion of insulin-like growth factor-1 (IGF-1) that could support fibroblast proliferation. Finally, we showed that APOE knockdown <em>in vivo</em> using adeno-associated virus (AAV) improved the compliance of the regenerated aortas, reduced extracellular matrix (ECM) deposition and increased capillary ingrowth in the adventitial areas of the regenerated aortas by reducing the formation of profibrotic macrophages and their secreted IGF-1. Collectively, these data indicate that APOE can promote profibrotic macrophage formation partially through LRP1, and the profibrotic macrophages mediate graft fibrosis by increasing fibroblast proliferation via IGF-1. Inhibition of APOE generation in regenerated aortas can alleviate graft fibrosis that occurs during vascular regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 261-279"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074956","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 : 2026-06-01Epub Date: 2026-01-19DOI: 10.1016/j.bioactmat.2025.11.047
Wenan Peng , Ziming Wang , Zenan Zhuang , Simin Zeng , Yu Xia , Qiwen Chen , Xuan Bai , Ying Tang , Cui Huang , Xianzheng Zhang
{"title":"Synergistic targeting of senolytic and senomorphic action with dual-engineered biomimetic macrophage nanovesicles for mitigating osteoarthritis","authors":"Wenan Peng , Ziming Wang , Zenan Zhuang , Simin Zeng , Yu Xia , Qiwen Chen , Xuan Bai , Ying Tang , Cui Huang , Xianzheng Zhang","doi":"10.1016/j.bioactmat.2025.11.047","DOIUrl":"10.1016/j.bioactmat.2025.11.047","url":null,"abstract":"<div><div>Osteoarthritis (OA), a leading cause of chronic disability worldwide, is increasingly recognized to be driven by the accumulation of senescent chondrocytes (sCDs) and their deleterious pro-inflammatory senescence-associated secretory phenotype (SASP). Existing therapies, including senolytics and senomorphics, lack cell-specific targeting and fail to neutralize the heterogeneous components of SASP. Here, we develop a dual-engineered macrophage membrane camouflaged, self-assembled nanoplatform (BS@MD) that combines senolytic and senomorphic functions synergistically. Within the OA microenvironment, BS@MD acts as a “nanosponge” to broadly neutralize SASP through overexpressed cytokine receptors derived from LPS-primed macrophage membranes. This process alleviates chondrocyte senescence and facilitates the phenotypic shift of pro-inflammatory M1 macrophages toward an anti-inflammatory M2 state. Additionally, surface conjugation with an anti-DPP4 antibody enables BS@MD to selectively target sCDs and disassemble in the acidic lysosomal environment, releasing bortezomib (BTZ) and sabutoclax (Sab). These agents act synergistically to inhibit the NF-κB and BCL-2 pathways, thereby inducing sCDs apoptosis and suppressing SASP production, effectively disrupting the senescence-inflammation feedback loop. In the anterior cruciate ligament transection (ACLT)-induced OA mouse model and naturally aged OA mouse model, BS@MD enhances joint retention, reduces cartilage degradation and inflammation, and promotes cartilage homeostasis. Overall, this work pioneers a dual-pronged senotherapeutic strategy for non-surgical OA management.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 20-39"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036609","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 : 2026-06-01Epub Date: 2026-01-21DOI: 10.1016/j.bioactmat.2026.01.009
Yun Dou , Fangxue Zhang , Zhiruo Jiang , Junqiang Mao , Haoling Guo , Yubin Li , Wujia Wang , Xiangyu Meng , Qingrui Fan , Jianjun Wang , Dong Jiang
{"title":"Precisely regulated physically-crosslinked carriers enable synergetic release of bioactive factors for MSC-mediated cartilage regeneration","authors":"Yun Dou , Fangxue Zhang , Zhiruo Jiang , Junqiang Mao , Haoling Guo , Yubin Li , Wujia Wang , Xiangyu Meng , Qingrui Fan , Jianjun Wang , Dong Jiang","doi":"10.1016/j.bioactmat.2026.01.009","DOIUrl":"10.1016/j.bioactmat.2026.01.009","url":null,"abstract":"<div><div>Articular cartilage has limited capacity for self-repair due to its avascular nature. Successful cartilage repair requires the harmonious integration of sufficient stem cell recruitment, an optimal local microenvironment and a sustained repair timeframe. Here, we present a biocompatible, physically crosslinked silk fibroin platform with tunable β-sheet content (5–50 %) via freeze-assembly. This platform enables flexible and precise tuning of drug release kinetics without chemical cross-linkers. This system allows controlled drug release durations ranging from 1 to 35 days, suitable for both hydrophilic (MSC affinity peptide, MAP, serving a pro-recruiting role) and hydrophobic (kartogenin, KGN, pro-differentiating role) drugs. In a rat cartilage defect model, a sustained 21-day MAP release profile was identified as optimal, achieving an unprecedented high density of MSC recruitment (∼2.34 × 10<sup>4</sup> cells/mm<sup>3</sup>) within a differentiating-friendly timeframe. Synchronized with KGN delivery, the co-delivery system further promoted robust hyaline cartilage regeneration. This outcome may be attributed to the effect of <em>Cdh2</em> genes involved in cell adhesion and p38 MAPK pathways. This work provides a structurally programmable, scalable strategy to achieve coordinated, high-density MSC recruitment and timed differentiation, advancing the paradigm of precise biomaterial design for tissue repair.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 113-127"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036675","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 : 2026-06-01Epub Date: 2026-01-22DOI: 10.1016/j.bioactmat.2025.11.039
Shuang Zhang , Shunshu Deng , Kai Dai , Yang Liu , Jing Wang , Changsheng Liu
{"title":"Sulfated polysaccharide prevents senescent adipocyte-driven osteonecrosis by stem cell fate reprogramming","authors":"Shuang Zhang , Shunshu Deng , Kai Dai , Yang Liu , Jing Wang , Changsheng Liu","doi":"10.1016/j.bioactmat.2025.11.039","DOIUrl":"10.1016/j.bioactmat.2025.11.039","url":null,"abstract":"<div><div>Excessive glucocorticoid (GC) administration is a major contributor to bone marrow senescence, which subsequently contributes to the development of osteonecrosis. Conventional therapeutic approaches have shown limited efficacy, largely because current interventions are typically initiated only after a definitive diagnosis of bone deterioration—by which time the disease has often progressed to an intermediate or advanced stage, thereby missing the optimal therapeutic window for effective intervention. Here, we report that a semi-synthetic sulfated chitosan (SCS) can effectively prevent the onset of GC-induced osteonecrosis by suppressing complete senescence of the bone marrow and maintaining coupling between arterial vascularization and osteogenesis. SCS attenuates the spread of GC-induced primary adipocyte senescence into secondary senescence, effectively limiting the progressive amplification of the senescence cascade. Rather than directly intervening in the prostaglandin/PPARγ/INK positive feedback loop within the senescent adipocyte lineage, SCS functions as an extracellular matrix component that activates the IGF-1/PI3K/Akt/mTOR signaling cascade. This activation reprograms the GC-induced lineage commitment bias of bone marrow leptin receptor<sup>+</sup> (LepR<sup>+</sup>) mesenchymal stem cells (MSCs), leading to the downregulation of adipogenic differentiation and lipid biosynthesis pathways. By attenuating upstream senescence-driving cues at the source, SCS effectively suppresses the initiation and propagation of bone marrow adipocyte senescence. Thus, this highly bioactive polysaccharide halts the onset of senescence-driven osteonecrosis at an early stage, offering a promising avenue toward upstream, preventive interventions for skeletal aging and degeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 163-190"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036677","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 : 2026-06-01Epub Date: 2026-01-29DOI: 10.1016/j.bioactmat.2025.12.034
Alvile Kasarinaite , Junhan Ou , Kailin Chen , Dayang Peng , Wendi Jia , Chenyang Ding , Wenwen Huang , David C. Hay , Yishan Chen
{"title":"Glycosaminoglycans in tissue regeneration: Insights into glycobiology and their biomedical application","authors":"Alvile Kasarinaite , Junhan Ou , Kailin Chen , Dayang Peng , Wendi Jia , Chenyang Ding , Wenwen Huang , David C. Hay , Yishan Chen","doi":"10.1016/j.bioactmat.2025.12.034","DOIUrl":"10.1016/j.bioactmat.2025.12.034","url":null,"abstract":"<div><div>Tissue regeneration is orchestrated by both intracellular signaling programs and extracellular matrix remodeling. Glycosaminoglycans (GAGs) are essential sugar chains ubiquitously expressed throughout the body. Their spatiotemporal turnover is an important part of normal organ biology and essential to tissue repair following injury. Glycoscience is a hot topic and is its role in organ physiology is being increasingly unraveled due to both scientific and technological advances. The mechanistic understanding of GAG regulation and manipulation is multidisciplinary effort, spanning biology, chemistry, materials science and translational medicine. This review broadly examines how GAG biology is naturally regulated and precisely controlled in health and disease, including data analysis from a stem cell-based model of liver disease. Despite being limited in types, GAGs successfully regulate complex cell and tissue level biology. We also discuss preclinical and clinical applications of GAGs, with a focus on biomaterials for tissue engineering and precision drug delivery, stressing their importance in biomedical engineering and clinical therapy. In addition, we outline state-of-art detection techniques and molecular modeling tools for analyzing GAG quantity, structure and interactions with other molecules. This review provides a timely and comprehensive overview of GAG biology highlighting their role in tissue repair and engineering, and outlines future directions for their design and next-generation therapies.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"60 ","pages":"Pages 320-337"},"PeriodicalIF":18.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074957","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}