Biomaterials最新文献

{"title":"Biomimetic engineering peptidyl-based vehicles for efficient mRNA delivery","authors":"Yu Li ,&nbsp;Di Wang ,&nbsp;Jihong Li ,&nbsp;Xiaofan Zhao ,&nbsp;Mengran Yi ,&nbsp;Xiaodong Zai ,&nbsp;Jun Zhang ,&nbsp;Gong Cheng ,&nbsp;Yilong Yang ,&nbsp;Junjie Xu","doi":"10.1016/j.biomaterials.2025.123925","DOIUrl":"10.1016/j.biomaterials.2025.123925","url":null,"abstract":"<div><div>Antigen-encoding mRNA has emerged as a potent approach to prevent or treat various diseases, yet its clinical application necessitates consideration of reactogenicity and tolerability issues associated with existing delivery systems. The development of novel LNP-alternative delivery platforms represents a critical endeavor. Here, by screening and modifying functionalized motifs of an endogenous retrovirus-like protein, we developed a single-component engineered peptidyl-based vehicle, H3M1-5, which enables desirable biocompatibility, flexible modularity, and efficient mRNA delivery both <em>in vitro</em> and <em>in vivo</em>. H3M1-5 mediated potent delivery of linear mRNA, circular mRNA, and plasmid DNA, with an efficacy comparable to that of the leading commercial transfection reagent. The peptidyl-based mRNA vaccines efficiently facilitated germinal center responses and elicited robust immune responses. Notably, H3M1-5@M1R mRNA significantly protected mice in a lethal challenge model of orthopoxvirus, and H3M1-5@OVA mRNA delayed tumor growth in both prophylactic and therapeutic B16-OVA melanoma models. Importantly, in contrast to LNP formulations, the peptidyl-based mRNA vaccines didn't trigger a detectable pro-inflammatory response and had a restricted transgene expression in the injection site. This work demonstrates a promising biomimetic strategy for designing simple and efficient peptidyl-based vehicles for mRNA vaccines with favorable safety profiles.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123925"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838243","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}

{"title":"Harnessing the death switch: Empowering cancer therapy by modulating the apoptosis-pyroptosis transition","authors":"Yan Chen ,&nbsp;Jie Wang ,&nbsp;Quan Dai ,&nbsp;Peng Chen ,&nbsp;Haiqing Wang ,&nbsp;Ruolan Li ,&nbsp;Yanru Gu ,&nbsp;Han Liu ,&nbsp;Hongtao Xiao ,&nbsp;Shugang Qin ,&nbsp;Yuying Li ,&nbsp;Hongwei Zhang ,&nbsp;Qiuju Wang","doi":"10.1016/j.biomaterials.2025.123973","DOIUrl":"10.1016/j.biomaterials.2025.123973","url":null,"abstract":"<div><div>Overcoming therapeutic resistance mediated by apoptosis evasion represents a critical challenge in cancer treatment. Pyroptosis, an inflammatory form of regulated cell death, provides a promising alternative approach capable of stimulating robust anti-tumor immunity and converting immunologically inert (\"cold\") tumors into immunologically active (\"hot\") microenvironments. Importantly, these cell death pathways are not isolated but are interconnected through dynamic molecular switches that determine cellular fate. This review systematically examines the intricate molecular crosstalk between cell death modalities, with particular emphasis on the regulatory roles of the caspase-3/GSDME and caspase-8/GSDMD axes. Current evidence demonstrates that caspase family members, primarily associated with apoptosis, can selectively cleave gasdermin proteins, facilitating a transition from non-inflammatory apoptotic signaling to inflammatory pyroptotic events. We further analyze how inflammasomes, post-translational modifications, and the STING–NF–κB pathway precisely regulate this transition. Through integrated bioinformatic analysis, we identified novel hub genes (e.g., PRKAR1A, PPP2CA, FOSL2) and microRNA networks at the apoptosis-pyroptosis interface, providing novel insights and potential therapeutic targets. Exploiting this 'death switch' offers a novel therapeutic framework through three principal strategies: (1) inducing pyroptosis to eliminate apoptosis-resistant cells, (2) utilizing pyroptosis-induced inflammation to enhance immune checkpoint inhibitor efficacy, and (3) developing targeted therapeutics that directly modulate these switch molecules. Although controlling pyroptosis-associated inflammation remains challenging, understanding and manipulating the apoptosis-to-pyroptosis transition provides an innovative approach to overcome drug resistance and develop more effective cancer treatments.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123973"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905440","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}

{"title":"Ischemic stroke nanomedicine","authors":"Lan Luo ,&nbsp;Meiqi Chang ,&nbsp;Ying Wang ,&nbsp;Yu Chen ,&nbsp;Bingcang Huang","doi":"10.1016/j.biomaterials.2025.123934","DOIUrl":"10.1016/j.biomaterials.2025.123934","url":null,"abstract":"<div><div>With the changes in lifestyle and the intensification of population aging, the incidence of stroke has been increasing annually, making it a global public health concern. Early diagnosis and precise treatment remain critical factors in improving patient outcomes. Despite advances in clinical management, current diagnostic and therapeutic approaches still face significant limitations. Nanomedicine, leveraging the unique physicochemical properties of nanomaterials, has emerged as a transformative strategy to overcome these challenges. Translating nanotechnology-based innovations into clinical practice for stroke management hinges on a clear understanding of recent advances, persistent challenges, and future research priorities. This review elucidates the pivotal role of nanomedicine in advancing the early diagnosis and treatment of ischemic stroke, focusing on its major pathogenic factors, the diverse compositional features of nanomaterials, and surface design strategies. The discussion encompasses nanoplatforms serving as contrast agents for various imaging modalities, nanocarriers for drug delivery, and multifunctional nanosystems for therapeutic applications. Furthermore, the review explores the current challenges and considerations in the clinical translation of nanomedicine for ischemic stroke management, while proposing future research directions to highlight the advantages of nanotechnology in stroke theranostics and facilitate its clinical adoption.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123934"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814884","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}

{"title":"Intelligent drug delivery-wound healing integrated hydrogel dressing for Type 2 Diabetes Mellitus wounds with wound microenvironment modulation","authors":"Lipeng Qiao ,&nbsp;Jueying Chen ,&nbsp;Yongping Liang ,&nbsp;Ying Huang ,&nbsp;Meng Li ,&nbsp;Yutong Yang ,&nbsp;Baolin Guo","doi":"10.1016/j.biomaterials.2026.123991","DOIUrl":"10.1016/j.biomaterials.2026.123991","url":null,"abstract":"<div><div>Diabetic wounds are a major complication for diabetic patients, with the high sugar and high ROS microenvironment leading to slow healing and a high risk of infection. To tackle these issues effectively, there is a critical need for advanced wound care solutions that can dynamically respond to the fluctuating conditions within the wound bed. In this study, we developed an intelligent, responsive hydrogel dressing designed to modulate the wound microenvironment to promote diabetic wound healing. This hydrogel is capable of responsively releasing the blood glucose-regulating drug (sitagliptin (Sit)) and, in accordance with the inflammatory condition, it dispenses the anti-inflammatory drug nimesulide (Nim) on demand. Consequently, it ameliorates the diabetic wound microenvironment, greatly accelerating wound healing. This hydrogel is composed of carboxymethyl chitosan (CMC), oxidized hyaluronic acid methacrylate (OHM), 1-butyl-3-vinylimidazolium bromide (IL), Sit, and methoxy poly(ethylene glycol)-thioketal-poly(ε-caprolactone)@Nim (GKL@Nim (GN)) micelles that release anti-inflammatory drugs in response to ROS, forming a Schiff base/double bond dual network intelligent hydrogel. The hydrogel demonstrates good performance in responsive drug release, <em>in vitro</em> inflammatory modulation, ionic conductivity, swelling, biodegradability, and self-healing capabilities. In the full-thickness skin defect wound healing assay using a Type 2 Diabetes Mellitus (T2DM) mouse model, the hydrogel group exhibited remarkable therapeutic effects, achieving an 80.2 % wound closure ratio on day 7, markedly superior to the Tegaderm™ film group (24.2 %). By day 14, wound closure in the hydrogel group reached 96.3 %. Histological assessments verified that hydrogel significantly enhanced angiogenesis and collagen deposition. Immunohistochemical analyses confirmed the hydrogel's efficacy in substantially decreasing IL-6 levels (25.7 %) and augmenting CD31 expression (315.3 %). Collectively, this intelligent hydrogel dressing holds immense promise for the treatment of diabetic wounds.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123991"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922187","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}

{"title":"Extracellular vesicles secreted by LRP1+ ligament-derived stem cells promote tendon-bone healing after ACL reconstruction via miR-708-5p/Bambi axis","authors":"Pengling Yao ,&nbsp;Yuying Yang ,&nbsp;Feifei Yuan ,&nbsp;Ziyang Lin ,&nbsp;Yiming Qin ,&nbsp;Shen Liu ,&nbsp;Yiyang Mao ,&nbsp;Linfeng Wang ,&nbsp;Ruixue Du ,&nbsp;Yiting Xu ,&nbsp;Chengjun Li ,&nbsp;Hongbin Lu ,&nbsp;Tao Zhang","doi":"10.1016/j.biomaterials.2026.123977","DOIUrl":"10.1016/j.biomaterials.2026.123977","url":null,"abstract":"<div><div>Anterior cruciate ligament (ACL) rupture often requires reconstruction surgery, with a key postoperative challenge being robust integration between the graft and bone tunnel. Studies have shown that extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) can enhance tendon-bone healing strength. As tissue-resident stem cells in the ACL, ligament-derived stem cells (LDSCs) are among the first activated after injury, migrating to the damaged site to participate in regenerative repair. In this study, single-cell RNA sequencing (scRNA-seq) of human ACL remnant samples revealed that LRP1-positive LDSCs (LRP1⁺LDSCs) have significantly stronger stemness and chondrogenic differentiation potential than LRP1-negative ones. Based on this, EVs from LRP1⁺LDSCs (LRP1⁺LDSCs-EVs) were isolated and delivered into bone tunnels of a rat ACL reconstruction (ACLR) model using gelatin methacryloyl (GelMA) hydrogel as a carrier. Results showed that LRP1⁺LDSCs-EVs effectively promoted cartilage regeneration at the tendon-bone interface (TBI) post-ACLR and significantly improved biomechanical function recovery. MiRNA sequencing characterized the miRNA cargo in LRP1⁺LDSCs-EVs, identifying highly enriched miR-708-5p as a key mediator. This miRNA directly binds to and suppresses Bambi mRNA expression, reducing Bambi protein's competitive inhibition of BMP signaling (Bambi acts as a decoy receptor for the TGF-β pathway). This mechanism activates chondrogenic differentiation and promotes TBI regenerative healing. Overall, EVs from the LRP1-positive LDSCs subpopulation significantly enhance graft-bone tunnel integration efficiency after ACLR, providing a novel targeted and efficient cell-free therapeutic strategy for enhancing tendon-bone integration in orthopedic surgery.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123977"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922315","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}

{"title":"Engineering a Wnt-activated osteomimetic microenvironment with iPSC-derived MSCs for synergistic bone regeneration, angiogenesis, and neurogenesis","authors":"Qiqi Bu ,&nbsp;Hao Bai ,&nbsp;Minjie Ruan ,&nbsp;Lu Gao ,&nbsp;Liuqing Wang ,&nbsp;Mao Nie ,&nbsp;Mingming Zhao ,&nbsp;Xiaolin Tu ,&nbsp;Chengzhu Zhao","doi":"10.1016/j.biomaterials.2026.123978","DOIUrl":"10.1016/j.biomaterials.2026.123978","url":null,"abstract":"<div><div>To advance the bioactivity of artificial bone grafts, human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal seed cells. However, the instability in iMSC generation and their limited osteogenic capacity challenge their clinical application. In this study, we applied a novel strategy that combines a stable iMSC induction method that mimics the developmental process with an osteocytic Wnt-based osteogenic microenvironment, with the aim of creating a scalable, mechanistically defined platform to enhance bone regenerative efficiency. The small-molecule Wnt activator SKL2001-treated osteocyte osteogenic microenvironment (SOOME) substantially enhanced the osteogenic differentiation of iMSCs and promoted iMSCs-mediated bone defect repair in a rat femoral condyle defect model. Moreover, the SOOME-iMSC composite demonstrated its ability to promote angiogenesis and neurogenesis both <em>in vitro</em> and <em>in vivo</em>, and also enhanced osteoclast activity at the regeneration site. These findings suggest that the SOOME-treated iMSCs create a native-like osteomimetic microenvironment, which improves implant integration and bone tissue regeneration. This approach introduces a novel strategy for the standardized fabrication of seed cells with enhanced osteogenic potential, offering a promising solution for the fabrication and clinical application of bioactive bone graft materials.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123978"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916250","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}

{"title":"An antioxidant, injectable hydrogel with mitochondrial fusion effect promotes inflamed dental pulp repair via immunomodulation and reactive oxygen species scavenging","authors":"Dan Wang ,&nbsp;Yongle Lv ,&nbsp;Fei Xie ,&nbsp;Yanqiang Zhao ,&nbsp;Bowen Ren ,&nbsp;Shanshan Jin ,&nbsp;Ningxin Zhu ,&nbsp;Man Qin ,&nbsp;Zhiqiang Lin ,&nbsp;Lei Wang ,&nbsp;Yuanyuan Wang","doi":"10.1016/j.biomaterials.2026.123985","DOIUrl":"10.1016/j.biomaterials.2026.123985","url":null,"abstract":"<div><div>Vital dental pulp is crucial for the self-repair and long-term retention of teeth with pulpitis; pulp capping materials used for vital pulp therapy must involve controlling inflammatory cascade and regulating inflammatory microenvironment at the same time. Here, we designed a dual-effect hydrogel with immunoregulatory and antioxidant properties to achieve inflamed pulp tissue repair. MASM7, a “mitochondrial glue” promoting mitochondrial fusion, could modulate THP-1-derived macrophages (THP-1-M) polarization to the M2 type under LPS-stimulated inflammatory conditions. Seahorse assay and metabolic-flux analysis (MFA) revealed that mitochondrial fusion modulated metabolic reprogramming of THP-1-M under inflammation from glycolysis to OXPHOS. Moreover, MASM7-treated THP-1-M cells enhanced the repair ability of DPSCs under inflammatory conditions. To realize the application of MASM7 and antioxidant property, chitosan (CS) and methacrylic anhydride (MA) were used to synthesize a methacrylated CS (CSMA) hydrogel, which was then modified with gallic acid (GA) to form a CSMAGA hydrogel. We next confirmed the biocompatibility of this hydrogel. The CSMAGA hydrogel also demonstrated antioxidant properties by scavenging reactive oxygen species. We then confirmed the dual effects of MASM7@CSMAGA hydrogel in rats with LPS-stimulated pulpitis. In conclusion, MASM7@CSMAGA hydrogel can promote pulp tissue repair under inflammatory conditions by modulating macrophage polarization and oxidative stress.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123985"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916334","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}

{"title":"Engineering vascularized inner ear organoids: Challenges and advances in recapitulating the cochlear microenvironment","authors":"Hao Rong ,&nbsp;Qian Zhu ,&nbsp;Zhonghong Zhang ,&nbsp;Xinyi Pang ,&nbsp;Jiyang Zuo ,&nbsp;Yusong Wang ,&nbsp;Pan Feng ,&nbsp;Xu Zhang ,&nbsp;Liuying Gao ,&nbsp;Lei Tian ,&nbsp;Yangnan Hu ,&nbsp;Zhisen Shen ,&nbsp;Renjie Chai","doi":"10.1016/j.biomaterials.2025.123909","DOIUrl":"10.1016/j.biomaterials.2025.123909","url":null,"abstract":"<div><div>The inner ear is a highly specialized structure responsible for auditory and vestibular functions; however, research progress has been limited by its deep anatomical location and the difficulty of obtaining human tissue samples. Recent advances in inner ear organoids (IEOs) and organoid-on-a-chip technologies offer powerful platforms for studying hearing loss mechanisms and testing therapies. This review outlines progress in generating IEOs from human pluripotent stem cells, including differentiation into hair cells and spiral ganglion neuron-like cells, and improvements in 3D culture, co-culture, and microfluidics. Special attention is given to the reconstruction of the blood-labyrinth barrier (BLB) within organoids, focusing on vascular formation, barrier integrity, and drug delivery limitations. Drawing from advances in brain and kidney organoid models, we explore strategies to improve vascularization using microfluidic technologies. Ultimately, building vascularized IEOs that recapitulate the cochlear microenvironment offers significant potential for drug screening, disease modeling, and regenerative therapies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123909"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792783","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}

{"title":"ROS-triggered transformation of microgels to bioadhesive patch for orally administrated treatment of inflammatory bowel disease","authors":"Yi-jing Yin ,&nbsp;Kuo-ran Xing ,&nbsp;Yu-tong Li ,&nbsp;Fan Jia ,&nbsp;Ting Ding ,&nbsp;Min-jie Chen ,&nbsp;Tian-tian Zhang ,&nbsp;Jian Ji ,&nbsp;Ke-feng Ren ,&nbsp;Cheng-fu Xu ,&nbsp;Jie Zhang","doi":"10.1016/j.biomaterials.2025.123937","DOIUrl":"10.1016/j.biomaterials.2025.123937","url":null,"abstract":"<div><div>Inflammatory bowel diseases (IBD) are driven by excessive reactive oxygen species (ROS) and progressive disruption of the intestinal mucus barrier, yet sustained mucosal protection remains insufficiently addressed by current therapies. Here, we develop an orally administered, inflammation-activated microgel system (<em>iPatch</em>) that undergoes a ROS-triggered microgel-to-patch transformation specifically at inflamed intestinal sites. Unlike pre-formed hydrogels or enema-based formulations, this <em>in situ</em> transformation enables prolonged mucosal retention, adaptive barrier reconstruction, and sequential dual-drug release after oral dosing. In colitis mouse models, <em>iPatch</em> restores epithelial integrity, suppresses inflammation, and significantly improves clinical outcomes. This self-transforming oral patch system offers a patient-friendly and mechanistically distinct strategy for IBD treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123937"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881561","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}

{"title":"Ultrabirght organic nanocrystals by amphiphile-templated crystallization for high-contrast NIR-II bioimaging","authors":"Peng Zhao ,&nbsp;Minghui Cao ,&nbsp;Hao Wang ,&nbsp;Bohan Li ,&nbsp;Yicheng Liu ,&nbsp;Yan Lu ,&nbsp;Linjie Xu ,&nbsp;Qingyu Fu ,&nbsp;Yanxin Chen ,&nbsp;Pengxin Liu ,&nbsp;Xingjun Zhu ,&nbsp;Yijun Zheng","doi":"10.1016/j.biomaterials.2025.123949","DOIUrl":"10.1016/j.biomaterials.2025.123949","url":null,"abstract":"<div><div>Fluorescence imaging in the second near-infrared window (NIR-II) has emerged as a powerful, radiation-free diagnostic tool with high temporal and spatial resolution. However, the low brightness of organic fluorophores remains a major challenge for precise clinical diagnosis. To tackle this, here, we present ultrabright NIR-II nanocrystals via an amphiphile-templated crystallization strategy. Amphiphilic dispersants bearing fluorophore-mimetic hydrophobic domains provides a template for the ordered assembly of NIR-II AIEgens through specific molecular recognition, yielding well-defined crystalline architectures. This approach promotes dense molecular packing of AIEgens, effectively constraining intramolecular rotations while forming robust water-resistant interfaces that prevent dark-state formation. As a result, the nanocrystals exhibit a sevenfold improvement over amorphous systems. The ultrabright organic nanocrystals enabled high-resolution imaging for abdominal vasculature (110 μm <em>vs.</em> &gt;200 μm for amorphous counterparts), and supported the first NIR-II luciferase reporter gene assay for <em>in vivo</em> visualization of endogenous gene expression and cellular viability. This work provides an advanced platform for designing ultrabright NIR-II nanomaterials by crystallization, with significant implications for enhanced diagnostic precision and therapeutic efficacy in image-guided biomedical applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123949"},"PeriodicalIF":12.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909387","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}