Acta Biomaterialia最新文献

{"title":"Oxygen-self-supplying biomimetic nanozymes synergize with methotrexate to reprogram macrophage polarization for rheumatoid arthritis therapy","authors":"Lingling Lv ,&nbsp;Xiaoling Qiu ,&nbsp;Weijie Chen ,&nbsp;Ziyu Lin ,&nbsp;Yating Guo ,&nbsp;Longhua Shen ,&nbsp;Yanping Deng ,&nbsp;Qing Hu","doi":"10.1016/j.actbio.2025.11.041","DOIUrl":"10.1016/j.actbio.2025.11.041","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) represents a long-term autoimmune condition that affects multiple systems in the body. The primary pathological feature stems from the imbalance in the polarization of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in the synovial membrane, triggering sequential release of inflammatory factors that drive gradual deterioration of articular structures. This study utilized a biomimetic albumin-inspired nanoreactor approach, where bovine serum albumin (BSA) acted as a dynamic template to guide the multi-stage cooperative self-assembly of cerium oxide and methotrexate (MTX). This process yielded MTX-Ce@BSA nanoparticles demonstrating antioxidant properties, enzyme-like catalytic activity, and the ability to modulate the immune system. Subsequent surface modification using macrophage-derived membranes (MMs) enabled the engineering of MTX-Ce@BSA@MMs (MCB@MMs), a bioinspired nano-carrier system designed for targeted therapeutic delivery. Following cellular uptake, the cerium-based nanozyme demonstrates sequential enzymatic activities mimicking catalase and superoxide dismutase, efficiently neutralizing oxidative stress mediators. Simultaneously, the cerium valence transition between +3 and +4 states promotes molecular oxygen generation, thereby downregulating hypoxia-inducible factor signaling pathways. The gradual liberation of MTX orchestrates anti-inflammatory responses through cytokine profile modification and promotes phenotypic transition of pro-inflammatory macrophages to regenerative subtypes. In a rat model with adjuvant-induced arthritis (AIA), this system significantly reduced joint inflammation and prevented bone erosion, with no signs of systemic toxicity observed. This multidimensional treatment paradigm integrates complementary biological mechanisms, offering a transformative approach to address persistent therapeutic limitations in autoimmune joint disorders.</div></div><div><h3>Statement of significance</h3><div>A biomimetic nanozyme platform (MCB@MMs) was developed to address the limitations associated with conventional disease-modifying antirheumatic drugs (DMARDs) and nano-antioxidants in RA treatment. This platform integrates three key mechanisms: (1) Tandem ROS-scavenging via cerium oxide nanozymes with dual SOD/CAT-mimetic activities, interrupting the ROS-HIF-1α-MAPK pathway; (2) Immunomodulatory synergy between MTX and nanozymes, promoting M1→M2 macrophage transition; (3) Active targeting of inflamed joints via macrophage membrane coating, significantly enhancing accumulation in the synovium. MCB@MMs showed superior efficacy in AIA rats by alleviating symptoms, suppressing bone erosion, and improving hypoxic microenvironments, while maintaining excellent biosafety. This study highlights the synergistic interplay between nanozymes and DMARDs, offering a promising and clinically relevant strategy for the treatment of inflammatory diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 566-582"},"PeriodicalIF":9.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145643730","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":"The application of 3D cell culture for melanoma in vitro models","authors":"Kailei Xu ,&nbsp;Jing Wu ,&nbsp;Zehuan Li ,&nbsp;Wenjie Chen ,&nbsp;Peng Wei ,&nbsp;Miaoben Wu","doi":"10.1016/j.actbio.2025.11.039","DOIUrl":"10.1016/j.actbio.2025.11.039","url":null,"abstract":"<div><div>Melanoma remains a formidable clinical challenge due to its high metastatic potential and resistance to conventional therapies, in part reflecting the failure of two-dimensional (2D) culture systems to recapitulate the complex tumor microenvironment (TME). Three-dimensional (3D) cell culture models have emerged as superior platforms over traditional 2D systems for recapitulating the complex TME of melanoma, including native extracellular matrix (ECM) architecture, cell-cell interactions, and biochemical gradients essential for accurate drug screening and mechanistic studies. In this review, we conducted a comprehensive literature survey to classify and critically evaluate melanoma 3D culture platforms into five categories, including melanoma spheroids, biomaterial-encapsulation cultures, melanoma skin equivalents, melanoma-on-chip, and bio-printed melanoma model, focusing on biomaterial composition, architectural fidelity, mechanical properties, and cellular integration, and systematically comparing their advantages and disadvantages. These models have advanced our understanding of melanoma progression, drug resistance mechanisms, cellular behavior, and they offer more reliable platforms for drug screening and development of personalized therapies. Although numerous challenges still need to be tackled, like the current biomaterials seldom replicate the distinct ECM of different skin layers and often neglect the incorporation of immune cells and adipocytes, emerging technologies hold promises for overcoming these challenges by enabling precise fabrication of tissue complexity, incorporation of vasculature, and integration of immune components. These innovations are poised to enhance the physiological relevance of melanoma models, ultimately facilitating the development of more effective treatments and improving patient outcomes.</div></div><div><h3>Statement of significance</h3><div>Melanoma remains a formidable clinical challenge due to its high metastatic potential and resistance to conventional therapies. 3D cell culture models have emerged as superior platforms over traditional 2D systems for recapitulating the complex TME of melanoma. In this review, we classified melanoma 3D cell culture models into five categories, including melanoma spheroids, biomaterial-encapsulation cultures, melanoma skin equivalents, melanoma-on-chip, and bio-printed melanoma model, focusing on biomaterial composition, architectural fidelity, mechanical properties, and cellular integration, and systematically comparing their benefits and costs. In addition, we also highlighted the challenges of the development on melanoma 3D culture platforms for drug screening and mechanistic studies and discussed the future perspective on the development on melanoma 3D culture platforms.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 148-166"},"PeriodicalIF":9.6,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145590172","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":"Fabrication and in vitro evaluation of a high-strength, flexible, and bioresorbable warp-knitted silk patch for tendon tissue repair","authors":"Linya Yan ,&nbsp;Qi Xu ,&nbsp;Jinfeng Wang ,&nbsp;Ying Mao ,&nbsp;Wenxing Chen ,&nbsp;Wangyang Lu","doi":"10.1016/j.actbio.2025.11.032","DOIUrl":"10.1016/j.actbio.2025.11.032","url":null,"abstract":"<div><div>The global incidence of rotator-cuff injuries demands mechanically robust and bioresorbable patches to address the high failure rates of surgical repair. Here, we present a digitally fabricated, warp-knitted silk patch designed to meet this need. Through systematic modulation of key parameters (guide-bar configuration, needle pitch, and gauge), we engineered 17 distinct scaffolds from extra-coarse, degummed silk. Among them, the 4 × 1 tricot-stitch architecture (sample #14) emerged as the optimal candidate, exhibiting an balanced combination of high porosity (70.2 ± 0.1 %), high strength (Longitudinal tensile strength: 274 ± 8 N; Transverse tensile strength: 634 ± 33 N; Longitudinal tear strength: 270 ± 52 N; Transverse tear strength: 125 ± 14 N; Burst strength: 1 554 ± 33 N; Suture-pullout strength: &gt; 46 N.), and controlled biodegradability (retaining 93 ± 3 % mass after 42 days). Critically, these properties not only exceed established mechanical benchmarks for tendon repair but are maintained under wet conditions simulating the in vivo environment. The patch further demonstrated good hemocompatibility (hemolysis rate 1.2 ± 0.1 %) and supported robust cell adhesion, spreading, and proliferation. Collectively, these data demonstrate that digital warp-knitting of coarse silk yarns enables single-step fabrication of lightweight, highly porous, and mechanically anisotropic patches that combine long-term strength retention with favorable biocompatibility—offering a promising off-the-shelf solution for tendon reconstruction.</div></div><div><h3>Statement of significance</h3><div>Recurrent tears after rotator cuff repair remain a significant clinical challenge, often due to inadequate mechanical strength and poor tissue integration of existing patches. We address this by digitally warp-knitting a bioresorbable silk patch that uniquely combines high tensile and burst strength, exceeding native tendon requirements, with a high-porosity architecture conducive to cell infiltration. This patch provides durable mechanical support in a wet physiological environment while degrading controllably. It represents a clinically promising, off-the-shelf solution to enhance repair outcomes, bridging the critical gap between robust mechanical performance and effective biological integration for tendon reconstruction.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 260-278"},"PeriodicalIF":9.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582632","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":"The human osteocyte lacunocanalicular network structure in osteons of the iliac crest of elderly women depends on mineral content but not individual age","authors":"Chloe E. Jones ,&nbsp;Stéphane Blouin ,&nbsp;Emeline Raguin ,&nbsp;Richard Weinkamer ,&nbsp;Andrea Berzlanovich ,&nbsp;Peter Fratzl ,&nbsp;Markus A. Hartmann","doi":"10.1016/j.actbio.2025.11.036","DOIUrl":"10.1016/j.actbio.2025.11.036","url":null,"abstract":"<div><div>Osteocytes provide essential functions for the maintenance of healthy bone tissue. They are embedded in lacunar pores within the mineralised bone matrix and communicate through interconnected dendritic cell processes that are housed in canalicular channels constituting the osteocyte lacunocanalicular network (LCN). Ageing is associated with increased fracture risk and bone fragility, particularly in elderly women. Despite the LCN playing a critical role in bone remodelling, characteristics of the network in bone tissue of different individual age and mineral content is thus far largely unexplored. Confocal laser scanning microscopy was used to image the fluorescent-stained LCN of cortical osteons in iliac crest bone specimens from female donors with mean age 60 years (<em>n</em> = 6) and 94 years (<em>n</em> = 6) in 3D. Quantitative backscattered electron imaging was also used to assess osteonal mineral content to compare LCN structure in highly and lowly mineralised osteons. Network defects were identified in one-third of osteons, which were further investigated using focussed ion beam scanning electron microscopy. Assessment of the LCN revealed no influence of individual age on the canalicular density, the volume of the lacunae or the degree of the lacunae, whereas canalicular density is inversely correlated with osteonal mineral content. An increase in the volume of non-mineralised matrix is demonstrated in defective regions that are prevalent in all individuals. While relative osteon age, as characterised by mineral content, influences the density of the canaliculi in the LCN, there is no influence of the age of the individual women over 60 years.</div></div><div><h3>Statement of significance</h3><div>Osteocytes play a central and ongoing role in bone health throughout the lifespan: they orchestrate bone remodelling by regulating osteoclastic bone resorption and osteoblastic bone deposition, as well as controlling subsequent bone mineralisation. Deterioration of the osteocyte lacunocanalicular network may contribute to the decline in bone quality observed with age. Consequently, we studied this communication system in 3D in bone from middle-aged to elderly donors. Unexpectedly, individual age had no influence on network characteristics, but the density of the network was decreased in older osteons. Furthermore, we observed network defects that are surprisingly common at all ages investigated. The size of these defects increases with age, suggesting a possible link to the concurrent reduction in bone quality.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 493-503"},"PeriodicalIF":9.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582768","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":"Elastic and viscoelastic properties of human cortical organoids","authors":"Yasaman Samei ,&nbsp;Ingrid Cheung ,&nbsp;Paraskevi Papavasileiou ,&nbsp;Colin K. Franz ,&nbsp;John D. Finan","doi":"10.1016/j.actbio.2025.11.034","DOIUrl":"10.1016/j.actbio.2025.11.034","url":null,"abstract":"<div><div>Human cortical organoids are becoming increasingly popular as models of disease and development in the human brain and as tools for energy-efficient computing. However, their mechanical properties, which are critical to understanding how they self-organize and how they interact with synthetic devices, remain poorly understood. In this study, we used microindentation to quantify the size, elastic properties, and viscoelastic properties of cortical organoids derived from three human induced pluripotent stem cell (hiPSC) lines. The organoids exhibited low stiffness (mean effective Young’s modulus: 285 ± 148 Pa) and were highly viscoelastic, with significant reductions in effective shear modulus between 0.5 and 180 s. Mechanical properties varied by cell line and batch, underscoring the need to consider biological variability in experimental and computational studies. Organoids were significantly more compliant than the synthetic materials commonly used in organoid-on-chip systems, resembling hydrogels like Matrigel in stiffness. These findings will increase the accuracy of computational models of cortical organoids and support the rational design of microphysiological systems, electrode interfaces, and injury models involving these tissues.</div></div><div><h3>Statement of significance</h3><div>This study provides the first measurements of the viscoelastic properties of human cortical organoids. The findings reveal that organoids are highly compliant and time-dependent in their mechanical behavior, with variability across cell lines and batches within each cell line. These data are critical to understanding how organoids assume their form and how they interact with human-made devices in biomedical and energy-efficient computing applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 481-492"},"PeriodicalIF":9.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575032","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":"A self-supplying nitric oxide coating on Mg alloy for vascular stents promotes re-endothelialization","authors":"Zhaoqi Zhang ,&nbsp;Hongfei Zhang ,&nbsp;Rui Li ,&nbsp;Haoran Wu ,&nbsp;Shuguang Cao ,&nbsp;Liujie Qi ,&nbsp;Jingan Li ,&nbsp;Shaokang Guan","doi":"10.1016/j.actbio.2025.11.033","DOIUrl":"10.1016/j.actbio.2025.11.033","url":null,"abstract":"<div><div>Mimicking the function of healthy endothelial cells (ECs) to catalyze NO release from endogenous donors represents an effective strategy for repairing the inevitable endothelial injury following stent implantation. However, insufficient levels of endogenous NO donors often limit catalytic NO generation, challenging the maintenance of cardiovascular homeostasis. To address this, a poly(thioctic acid)-arginine (TA-Arg) coating on a fluorinated magnesium (Mg) alloy for in-situ NO supply to address delayed endothelialization. The coating adhered firmly to the MgF₂ surface via hydrogen bonding, with TA and Arg connected through salt-bridge hydrogen bond interactions. The immobilized Arg acted as a precursor for NO synthesis, which was catalytically generated in situ by ECs via endothelial nitric oxide synthase (eNOS). Meanwhile, TA served as an eNOS enhancer, boosting intracellular eNOS activity and facilitating the conversion of Arg to NO, enabling sustained and stable localized NO release. In vitro tests showed that the coating significantly decelerated Mg alloy degradation and exhibited high hemocompatibility with pronounced pro-endothelial potential. RNA-seq analyses further revealed that the coating promoted activation of NO-associated PI3K-Akt and MAPK pathways and activated the core antioxidant transcription factor Nrf2 (evidenced by the coordinated upregulation of HMOX1 and NQO1), while concurrently suppressing ferroptosis through genes such as SLC7A11 and FTH1. In vivo implantation confirmed reduced inflammation, enhanced endothelial repair, and inhibited hyperplasia, highlighting the dual role of NO release and antioxidative activity in promoting rapid endothelialization with good biosafety.</div></div><div><h3>Statement of significance</h3><div>Magnesium (Mg) alloys hold significant promise as next-generation materials for cardiovascular stents owing to their complete biodegradability and excellent biocompatibility. However, their rapid degradation rate and delayed endothelialization remain major obstacles to clinical applications. To address these challenges, this study developed a nitric oxide (NO)-self-supplying poly(thioctic acid)-arginine (TA-Arg) coating on a fluorinated Mg alloy substrate. Both in vitro and in vivo results demonstrated that the TA-Arg sample not only markedly decelerated the degradation of the Mg alloy but also regulated vascular cell behavior, showing considerable potential to promote rapid endothelialization. Overall, this endogenous NO‑supplying strategy is highly straightforward, cost-effective, and scalable, offering a versatile and practical approach for surface modification to facilitate real-world applications of Mg-based stents.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 624-636"},"PeriodicalIF":9.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574979","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":"Collagen nanofiber alignment attenuates leader-follower energetic and metabolic differences during collective migration in pancreatic cancer","authors":"Madison R. Pickett ,&nbsp;Mohini Kamra ,&nbsp;David A. Castilla-Casadiego ,&nbsp;Sepehr Noori ,&nbsp;William Matsui ,&nbsp;Adrianne M. Rosales ,&nbsp;Janet Zoldan ,&nbsp;Sapun H. Parekh","doi":"10.1016/j.actbio.2025.11.031","DOIUrl":"10.1016/j.actbio.2025.11.031","url":null,"abstract":"<div><div>The extracellular matrix (ECM) is a dynamic microenvironment that influences cell behavior and fate, with changes in its architecture linked to processes such as differentiation and disease progression in cancer. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer associated with a dense ECM composed of collagen I fibers. While considerable research on PDAC metastasis has focused on single-cell migration, recent studies suggest PDAC cells undergo a process called “collective migration” as groups. This study investigates PDAC migration and metabolism on electrospun collagen I nanofiber meshes. A 3D-printed, removable insert is used to create a gap–like a scratch–that allows for analysis of cell migration on intact fibers. By tuning nanofiber orientation, this study replicates the PDAC ECM during stromal remodeling to assess cellular metabolism and the energetic state of leader and follower cells during migration. Interestingly, the data suggests that nanofiber architecture strongly modulates differences between PDAC leader and follower cells during collective migration. While leader cells require more ATP and rely more on oxidative phosphorylation in both conditions, this reliance is particularly pronounced in the random condition. These findings underscore the interplay between collective migration, ECM architecture, and metabolism in PDAC migration.</div></div><div><h3>Statement of significance</h3><div>The role of the stromal extracellular matrix (ECM) in metastasis and migration is well studied, yet its impact on metabolic processes underlying metastasis, especially in pancreatic ductal adenocarcinoma (PDAC), remains unclear. PDAC is marked by high metastasis rates and a densely fibrotic ECM, with increased collagen alignment correlating to poor prognosis. In this study, we explore how ECM architecture, represented by near-native electrospun collagen nanofibers, influences collective migration and metabolism in PDAC. Our findings show that increased collagen alignment reduces metabolic differences, including ATP/ADP ratio, gene expression, and mitochondrial membrane potential, between leader and follower cells during migration. This is the first study to investigate leader-follower dynamics in PDAC collective migration using tunable, stromal-mimicking, fibrous substrates.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 183-193"},"PeriodicalIF":9.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575093","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":"Recipients of the 2024 Acta Materialia, Inc. student awards","authors":"","doi":"10.1016/j.actbio.2025.11.009","DOIUrl":"10.1016/j.actbio.2025.11.009","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"208 ","pages":"Page 589"},"PeriodicalIF":9.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145584411","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":"Presentation of hemagglutinin on adjuvant-bearing self-assembling peptide nanofibers increases heterologous responses against influenza","authors":"Emily F Roe ,&nbsp;Nicole L Votaw ,&nbsp;Kat M Lazar ,&nbsp;Kaitlyn N Burke ,&nbsp;Hector A Miranda ,&nbsp;Chelsea N Fries ,&nbsp;Michelle L Rock ,&nbsp;Andrew N Macintyre ,&nbsp;Erica L Stover ,&nbsp;Jessica B Huskey ,&nbsp;Summer J Harris ,&nbsp;Chelsea D Landon ,&nbsp;Katayoun Mansouri ,&nbsp;Robert J Edwards ,&nbsp;Nicholas S Heaton ,&nbsp;Joel H Collier","doi":"10.1016/j.actbio.2025.11.025","DOIUrl":"10.1016/j.actbio.2025.11.025","url":null,"abstract":"<div><div>Influenza presents a global threat representing hundreds of thousands of deaths each year worldwide, yet influenza vaccines currently do not offer full protection against infection and must be updated each year to account for antigenic drift. Subunit vaccines using hemagglutinin (HA) are a promising approach to decrease reactogenicity while still providing protection, but these vaccines require large antigen doses or inclusion of reactogenic adjuvants. Here, we use multivalent presentation of HA on the self-assembling nanofiber platform Q11 coupled with a nanoscale adjuvant to augment responses to HA vaccines. We leverage polypeptides containing random combinations of lysine, glutamic acid, tyrosine, and alanine (KEYA) as a nanoscale, non-reactogenic adjuvant and demonstrate two methods of bioconjugation of HA to Q11 nanofibers, namely β-tail co-assembly and SortaseA (SrtA)-mediated ligation. Both conjugation methods demonstrated effective conjugation to Q11, with minimal perturbation of HA antigenicity with the inclusion of low concentrations of KEYA. β-tail co-assembly offered increased humoral responses, and the inclusion of KEYA-Q11 enabled modest increases in breadth of antibody binding and survival against influenza challenge. SrtA-mediated conjugation additionally augmented humoral immune responses and also elicited a significant increase in breadth of antibody binding, achieving significant binding to HA trimers with up to 30 years of antigenic drift from the immunized antigen, increased hemagglutinin inhibition to homologous and heterologous viruses, and survival in a lethal disease challenge. Together, these results demonstrate the utility of peptide nanofiber bioconjugation strategies to augment subunit vaccines, particularly in the context of influenza.</div></div><div><h3>Statement of significance</h3><div>Influenza causes hundreds of thousands of deaths each year worldwide, yet current influenza vaccines do not offer full protection and must be updated each year. In this report, we describe self-assembled peptide nanofiber subunit vaccines comprised of the Q11 nanofiber platform, hemagglutinin antigens, and a nanoscale adjuvant consisting of randomized lysine, glutamic acid, tyrosine, and alanine (KEYA). Optimized formulations augmented humoral immune responses and elicited a significant increase in the breadth of antibody binding, achieving significant binding to HA trimers with up to 30 years of antigenic drift from the original antigen. These findings illustrate the utility of peptide nanofibers as platforms for subunit vaccines</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 211-224"},"PeriodicalIF":9.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566742","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":"Hydrogels with hierarchical hydrogen bonds enable tunable stress relaxation to direct macrophage-driven immunoregulation","authors":"Xiaoman Han ,&nbsp;Xueying Yang ,&nbsp;Ruifeng Zhang ,&nbsp;Kaiwen Chen ,&nbsp;Chuanfeng An ,&nbsp;Dawei Li ,&nbsp;Shuang Guo ,&nbsp;Fei Shao ,&nbsp;Chengze Li ,&nbsp;Yi Shen ,&nbsp;Yue Zhang ,&nbsp;Qiwei Ying ,&nbsp;Huanan Wang","doi":"10.1016/j.actbio.2025.11.024","DOIUrl":"10.1016/j.actbio.2025.11.024","url":null,"abstract":"<div><div>Matrix viscoelasticity as the typical mechanical feature of the extracellular matrix (ECM) of living tissues has been recently identified to impose profound impact on cellular behavior and functionalities. However, their effect on macrophages and the related inflammatory responses have been rarely explored, in which a major hurdle is the lack of candidate ECM-mimicking biomaterials with independently fine-tunable viscoelasticity. Herein, we developed a class of photopolymerizable hydrogels based on hierarchical hydrogen bond (H-bond) design to enable controllable stress relaxation behavior. Specifically, acrylamide (AM) and N-acryloyl glycinamide (NAGA) monomers were polymerized to form hydrogel networks consisting of varying ratio of single H-bond by AM and dual H-bond by NAGA, thus hydrogels with tunable stress relaxation rate but constant matrix elasticity can be developed via mediating monomer mixing ratios and polymerization degree. We further revealed that slower stress relaxation induced macrophage towards pro-inflammatory M1 polarization, while faster stress relaxation stimulated macrophage to polarize towards anti-inflammatory M2 phenotype. In vivo subcutaneous implantation of different hydrogel matrices using a mice model showed similar impact on host immune responses, as evidenced by severer inflammation characterized by thicker fibrosis encapsulation for matrix with slower stress relaxation than the faster ones. In general, we demonstrate that matrix viscoelasticity can significantly affect macrophage-mediated inflammatory responses, which provides new insights for the design and applications of implantable biomaterials.</div></div><div><h3>Statement of significance</h3><div>This work revealed how extracellular matrix viscoelasticity characterized by stress relaxation rate can significantly impact macrophage polarization and inflammatory responses, which has rarely been explored previously. We proposed an innovative and ease-of-preparation class of copolymer hydrogels based on tailoring the mixing ratio of acrylamide (AM) and N-acryloyl glycinamide (NAGA) monomers, wherein matrix with fine-tunable stress relaxation rates can be achieved via controlling the combination of singular or dual hydrogen bonds. We further demonstrated that slower stress relaxation induced macrophage towards pro-inflammatory M1 polarization, while faster stress relaxation stimulated macrophage to polarize towards anti-inflammatory M2 phenotype. Our study suggests matrix viscoelasticity can significantly affect macrophage-mediated inflammatory responses, and provides new insights for the design and applications of implantable biomaterials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"209 ","pages":"Pages 391-407"},"PeriodicalIF":9.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566727","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}