Acta Biomaterialia最新文献

{"title":"Phosphorous dendrimer-mediated biomineralization for synergistic blockade therapy and hypoxia-activated chemotherapy of tumors","authors":"Jiajia Liang ,&nbsp;Huxiao Sun ,&nbsp;Jingjing Li ,&nbsp;Yifan Huang ,&nbsp;Yu Zou ,&nbsp;Serge Mignani ,&nbsp;Jean-Pierre Majoral ,&nbsp;Xiangyang Shi ,&nbsp;Mingwu Shen","doi":"10.1016/j.actbio.2025.04.038","DOIUrl":"10.1016/j.actbio.2025.04.038","url":null,"abstract":"<div><div>Blockade therapy involving the artificial induction of biomineralization in tumor tissues has emerged as a promising strategy for treating malignant tumors. However, standalone blockade therapy which merely obstructs tumor growth rather than directly destroying the tumors is quite limited in therapeutic efficacy. Herein, we report the phosphite-terminated phosphorus dendrimers (AK176)/fibronectin (FN) nanocomplexes (NCs) with tumor-targeting and biomineralization-inducing properties to encapsulate a hypoxia-activated tirapazamine (TPZ) to achieve synergistic blockade therapy/chemotherapy of triple-negative breast cancer (TNBC). The constructed AK176@FN/TPZ (AFT) NCs exhibit a spherical shape with a size of 134.1 nm and good colloidal stability, can target tumor cells through specific recognition between the Arg-Gly-Asp sequence of FN and α_vβ₃ integrin receptors, and specifically induce mineral deposition on cancer cytomembranes by means of the inherent calcium ion adsorption property of dendrimers. Notably, the AFT-mediated biomineralization can generate tumor hypoxia and amplify the chemotherapeutic effect of TPZ, thereby effectively inhibiting tumor cell proliferation and lung metastasis through synergistic blockade therapy/chemotherapy in an orthotopic TNBC xenograft model. The developed AFT NCs with a simple composition represent an advanced nanomedicine formulation that can induce synergistic tumor-targeting blockade therapy and chemotherapy, which may be extended to tackle other cancer types.</div></div><div><h3>Statement of Significance</h3><div>Blockade therapy involving the artificial induction of biomineralization in tumor tissues has emerged as a promising strategy for treating malignant tumors. Herein, phosphite-terminated phosphorus dendrimers (AK176)/fibronectin (FN) nanocomplexes (NCs) with tumor-targeting and biomineralization-inducing properties are developed to encapsulate a hypoxia-activated drug tirapazamine (TPZ), resulting in synergistic blockade therapy/chemotherapy of triple-negative breast cancer in a mouse model. The developed AK176@FN/TPZ (AFT) NCs can target tumor cells through specific recognition between the Arg-Gly-Asp sequence of FN and α_vβ₃ integrin receptors, and specifically induce mineral deposition <em>via</em> the inherent calcium ion adsorption property of bisphosphonate groups of dendrimers, thereby triggering tumor biomineralization for blockade therapy. The AFT-mediated biomineralization on tumor cell membranes generates tumor hypoxia, which further amplifies the chemotherapeutic effect of TPZ.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 470-482"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032029","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":"IL-21R-Targeted Nano-immunosuppressant Prevents Acute Rejection in Allogeneic Transplantation by Blocking Maturation of T Follicular Helper Cells","authors":"Xiandong Zeng ,&nbsp;Yixiao Pan ,&nbsp;Jiangtao Lin ,&nbsp;Zhigang Zheng ,&nbsp;Huimin Wu ,&nbsp;Yining Wang ,&nbsp;You Wu ,&nbsp;Yufei Shen ,&nbsp;Yujia Chen ,&nbsp;Yifan Zhao ,&nbsp;Qiang Xia ,&nbsp;Yourong Duan ,&nbsp;Kang He","doi":"10.1016/j.actbio.2025.05.012","DOIUrl":"10.1016/j.actbio.2025.05.012","url":null,"abstract":"<div><div>During organ transplantation, immune rejection is a primary cause of graft failure. In the underlying pathophysiology of rejection, T follicular helper (Tfh) cells and interleukin-21 (IL-21) play pivotal roles. Tfh cells exacerbate the humoral immune response by promoting B cell differentiation and antibody production, which leads to damage of the transplanted tissue. IL-21, a key pro-inflammatory cytokine, binds to its receptor (IL-21R) to enhance both the growth and function of Tfh cells, while also further driving B cell activation and differentiation into plasma cells. Building on this knowledge, we have developed a tacrolimus-based nano-inhibitor designed to target Tfh cells. This nano-inhibitor is constructed using a mPEG-PLGA-PLL (PEAL) scaffold, with IL-21R monoclonal antibodies conjugated to its surface, and tacrolimus encapsulated within the structure. <em>In vitro</em> experiments demonstrated that this nano-inhibitor effectively targets Tfh cells, inhibiting the differentiation of naive CD4+ T cells into Tfh cells. In co-culture systems of T and B cells, it significantly suppresses the activation of both cell types, leading to a reduction in IgG antibody production. <em>In vivo</em>, the nano-inhibitor selectively targets secondary lymphoid organs, reduces systemic inflammation, minimizes lymphocyte infiltration into the graft, and induces immune tolerance toward the transplanted tissue. In addition, no significant toxicity was observed <em>in vitro</em> or <em>in vivo</em>. As a therapeutic agent that simultaneously modulates both T and B cell responses, we believe it holds significant promise for broader applications in transplantation immunotherapy.</div></div><div><h3>Statement of Significance</h3><div>This study presents a groundbreaking nano-immunosuppressant designed to target both T and B cells, addressing the critical challenge of acute rejection in allogeneic transplantation. By combining tacrolimus nanoparticles with IL-21 receptor antibodies, this immunosuppressant effectively suppresses Tfh cell proliferation and B cell activation, significantly reducing IgG generation. The formulation enhances tacrolimus's bioavailability, minimizes off-target toxicity, and overcomes its narrow therapeutic window. In vitro and in vivo studies show reduced lymphocyte infiltration, lower inflammatory markers, and decreased nephrotoxicity compared to conventional tacrolimus.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 346-360"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037176","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":"Endogenous dysregulated energy and amino acid metabolism delay scaffold-guided large volume bone regeneration in a diabetic rat model with Leptin receptor deficiency","authors":"Daniela B. Dias ,&nbsp;WingLee Chan ,&nbsp;Agnes Ellinghaus ,&nbsp;Raphaela Fritsche-Guenther ,&nbsp;Janine Wiebach ,&nbsp;André Bembennek ,&nbsp;Tanja Laske ,&nbsp;Jan Baumbach ,&nbsp;Georg N. Duda ,&nbsp;Jennifer A. Kirwan ,&nbsp;Patrina S.P. Poh","doi":"10.1016/j.actbio.2025.05.007","DOIUrl":"10.1016/j.actbio.2025.05.007","url":null,"abstract":"<div><div>Scaffold-guided bone regeneration (SGBR) offers a promising solution for treating large-volume bone defects. However, its efficacy in compromised healing environments, such as those associated with metabolic conditions like Type 2 Diabetes (T2D), remains poorly understood. This study evaluates the potential of 3D-printed polycaprolactone (PCL) scaffolds for large-volume bone regeneration in preclinical models simulating T2D-induced metabolic challenges. Our results reveal that scaffolds alone are insufficient to overcome the metabolic barriers to effective bone regeneration. Metabolomic analysis of regenerating tissue identified significant disruptions in key metabolic pathways involved in energy production and amino acid synthesis in T2D rats compared to controls. Notably, aconitic acid, ornithine, and glycine levels were elevated in non-diabetic conditions, whereas phosphoenolpyruvate was markedly increased under T2D conditions. Secondary harmonic generation (SHG) imaging further demonstrated impaired collagen organization within T2D regenerating tissue, correlating with disrupted collagen synthesis critical for bone matrix formation. <em>In vitro</em>, the exogenous supplementation of alpha-ketoglutarate (α-KG)—a crucial citric acid cycle intermediate—enhanced mineralized tissue formation in human adipose-derived mesenchymal stem cells (hAdMSCs) from T2D donors, achieving levels superior to non-T2D cells. These findings underscore the metabolic underpinnings of impaired bone regeneration in T2D. Optimized 3D printed scaffolds alone do not counterbalance the impaired regeneration in T2D. Here we highlight a therapeutic potential of metabolic supplementation to optimize SGBR outcomes. This study provides a critical foundation for advancing translational research and developing regenerative therapies tailored to high-risk metabolic disease populations.</div></div><div><h3>Statement of significance</h3><div>SGBR holds great promise for addressing large bone defects, but its efficacy in metabolically challenged conditions like T2D remains limited. This study uses a metabolomics-driven approach to reveal how metabolic dysregulation in T2D, including disruptions in energy and amino acid pathways, impairs collagen organization and extracellular matrix (ECM) formation—critical for successful bone healing. By identifying α-KG as a potential supplement to restore metabolic balance, this work offers novel insights into enhancing scaffold performance under compromised conditions. These findings provide a foundation for integrating bioactive compounds into scaffold designs, advancing personalized strategies in regenerative medicine, and addressing a critical gap in bone defect treatment for diabetic patients.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 108-119"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056029","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 dissolvable microneedle platform for the delivery of tumor-derived total RNA nanovaccines for enhanced tumor immunotherapy","authors":"Jiachen Wang ,&nbsp;Sicong Huang ,&nbsp;Huiye Wei ,&nbsp;Simin Liang ,&nbsp;Yuan Ding ,&nbsp;Zecong Xiao ,&nbsp;Xintao Shuai","doi":"10.1016/j.actbio.2025.04.039","DOIUrl":"10.1016/j.actbio.2025.04.039","url":null,"abstract":"<div><div>Tumor-derived total RNA (TdRNA) vaccines induce broad immune responses by either synthesizing tumor-specific antigens or activating pattern recognition receptors, making them a promising tool in cancer immunotherapy for the activation of cytotoxic T lymphocytes (CTLs). However, TdRNA vaccines face issues such as low stability and inadequate immune activation. To overcome these challenges, we have developed a dissolvable microneedle delivery platform, PTC NVs@MNs, designed for the simultaneous delivery of TdRNA and CpG oligodeoxynucleotides (CpG ODN). This platform stabilizes TdRNA, maintaining its activity for up to 30 days at room temperature and promotes dendritic cell maturation, and then activates T lymphocyte-mediated antitumor immunity through the targeted delivery of TdRNA and CpG. PTC NVs@MNs not only enhance dendritic cell maturation and increase CD8⁺ T cell infiltration into tumors, eliciting robust antitumor immune responses that inhibit tumor growth, but also induce antitumor immune memory to prevent tumor development. This innovative approach offers therapeutic and preventive benefits in tumor management.</div></div><div><h3>Statement of significance</h3><div>Tumor-derived total RNA (TdRNA) holds potential for eliciting a broad immune response; however, its therapeutic efficacy against triple-negative breast cancer (TNBC) is constrained by low stability and inadequate immune activation. To overcome these limitations, we engineered a dissolving microneedle patch for transdermal co-delivery of TdRNA and CpG oligodeoxynucleotides (CpG ODN). This system not only stabilizes TdRNA—maintaining its bioactivity for 30 days at room temperature—but also promotes dendritic cell maturation and activates T lymphocyte-mediated antitumor immunity . This study demonstrated that the well-designed microneedle patch effectively prevents RNA degradation without requiring stringent storage conditions, offering both therapeutic and preventive benefits in tumor management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 120-131"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061538","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":"Low-velocity impact resistance of bio-inspired interlayer hybrid composite laminates with a gradient waviness structure","authors":"Shicai Zhao ,&nbsp;Deyuan Zhang","doi":"10.1016/j.actbio.2025.04.046","DOIUrl":"10.1016/j.actbio.2025.04.046","url":null,"abstract":"<div><div>This study explores a bio-inspired design methodology for interlayer layups in hybrid carbon fiber reinforced polymer composites to enhance impact resistance. An impact-resistant and damage tolerance gradient waviness structure is discovered in the rapid mandible strike of trap-jaw ants. Inspired by this natural design, a gradient waviness structure was incorporated into fiber interlayer formation to improve impact resistance. Bio-inspired interlayer hybrid laminates, combining unidirectional fibers with multiple woven fabric arrangements, were fabricated using a mold press forming technique. The results demonstrate that the bio-inspired gradient waviness structure plays a crucial role in limiting crack propagation and generating large in elastic deformation. The 3K-PUP laminate exhibited a 10.2 % increase in peak contact force, an impressive 80.7 % reduction in damage area upon impact, and a 46.2 % increase in energy dissipation compared to traditional laminates. Additionally, the hybrid laminates displayed superior load-bearing capacity, with the 3K-PUP laminate achieving a 6.6 % increase in residual compressive strength. The bio-inspired laminates effectively provided crack tip shielding and enhanced fracture resistance mechanisms, significantly improving damage tolerance against through-the-thickness diffusion of impact damage.</div></div><div><h3>Statement of Significance</h3><div>An impact-resistant and damage tolerance gradient waviness structure is discovered in the rapid mandible strike of trap-jaw ants. Inspired by this natural design, a gradient waviness structure was incorporated into fiber interlayer formation to improve impact resistance. Bio-inspired interlayer hybrid laminates, combining unidirectional fibers with multiple woven fabric arrangements, were fabricated using a mold press forming technique. The results demonstrate that the bio-inspired gradient waviness structure plays a crucial role in limiting crack propagation and generating large in elastic deformation. The bio-inspired laminates effectively provided crack tip shielding and enhanced fracture resistance mechanisms, significantly improving damage tolerance against through-the-thickness diffusion of impact damage.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 178-192"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025116","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":"Platelet membrane-camouflaged bioactive glass nano-formulations for enhanced drug delivery in the treatment of acute arterial thrombosis","authors":"Minglin Ji ,&nbsp;Qinying Tang ,&nbsp;Olanrewaju Yaasir Olatunji ,&nbsp;Rufei Ge ,&nbsp;Yue Ying ,&nbsp;Jianwei Pan ,&nbsp;Khaydar E. Yunusov ,&nbsp;Guohua Jiang","doi":"10.1016/j.actbio.2025.04.036","DOIUrl":"10.1016/j.actbio.2025.04.036","url":null,"abstract":"<div><div>Thrombus treatment remains a significant challenge, primarily due to factors such as the short half-life of thrombolytic agents, suboptimal drug utilization, and limited therapeutic efficacy. In this study, we developed a platelet membrane-camouflaged bioactive glass nanoparticles (BGs) as drug carriers to load thrombolytic agent urokinase (UK) and anticoagulant drug tirofiban (TF). UK and TF were firstly incorporated onto BGs, and followed by a camouflage of polydopamine (PDA) and platelet membrane (PM) to form composite nano-formulation (TUBGs@PP). This composite nano-formulation leverages the PM camouflage to enhance its biocompatibility, prolong circulation time <em>in vivo</em>, and extend the half-life of drugs. Additionally, as-fabricated TUBGs@PP composite nano-formulation can circumvent immune system-mediated clearance, thereby facilitating targeted drug delivery to the thrombus sites and enhancing the thrombolytic efficacy. <em>In vivo</em> results demonstrated that the TUBGs@PP composite nano-formulations not only prolonged circulation time but also effectively unclogged blood vessels at the site of thrombosis, while reducing recurrence of thrombosis and drug side effects.</div></div><div><h3>Statement of significance</h3><div>The platelet membrane-camouflaged bioactive glass nanoparticles as drug carriers for the synergistic co-delivery of urokinase and tirofiban have been developed (TUBGs@PP) for the treatment of acute arterial thrombosis. This cutting-edge therapeutic strategy addresses several critical limitations inherent in current thrombolytic treatments, including the transient half-life of thrombolytic agents, suboptimal drug bioavailability, and limited therapeutic efficacy. <em>In vivo</em> studies demonstrate that TUBGs@PP not only achieves sustained circulation but also effectively restores vascular patency at thrombotic loci, concurrently reducing the risk of thrombotic recurrence and minimizing adverse drug effects. This study highlights the paradigm-shifting potential of TUBGs@PP in thrombolytic therapy, offering a transformative solution to existing challenges and promising to markedly improve clinical outcomes for patients.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 324-336"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037178","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":"Do human brain white matter and brain stem structures show direction-dependent mechanical behavior?","authors":"Nina Reiter ,&nbsp;Sophia Auer ,&nbsp;Lucas Hoffmann ,&nbsp;Lars Bräuer ,&nbsp;Friedrich Paulsen ,&nbsp;Silvia Budday","doi":"10.1016/j.actbio.2025.04.004","DOIUrl":"10.1016/j.actbio.2025.04.004","url":null,"abstract":"<div><div>Since the corpus callosum and the brain stem are both vulnerable to diffuse axonal injury during head impacts, there is a high interest in modeling the mechanical behavior of these brain structures. In recent years, different versions of fiber-reinforced material models have been proposed for the corpus callosum and other white matter regions, as well as for the brain stem, even though there is currently no consensus on whether those structures exhibit a significant direction-dependent behavior during mechanical loading. Here, we present the first large-strain, multimodal experimental study on human brain tissue that includes the corpus callosum and the lower brain stem (medulla oblongata) tested along two different directions. Additionally, we compare those two structures with other white matter (corona radiata, cerebellar white matter) and brain stem structures (pons, midbrain) to highlight differences in their material response. Cyclic compression–tension and shear tests reveal statistically significant direction-dependent material behavior in the corpus callosum. Directional differences in the brain stem are not statistically significant and do not indicate a clear directionality. Combined with histological findings, our results suggest that the mechanical behavior of white matter structures is influenced not only by axon caliber, orientation and density, but also by the architectural organization, i.e., clustering versus even distribution, of cells and tracts, and possibly vascular density. These findings highlight the need for micromechanical constitutive models for brain white matter that do not merely include axons embedded in a matrix.</div><div><strong>Statement of significance</strong></div><div>Mechanical head injuries often result in insults like diffuse axonal injury in white matter regions of the human brain. Therefore, there is a high interest in understanding and predicting the mechanical properties of those regions in order to prevent injury and advance diagnosis and treatment strategies of neurological disorders. There has been a long controversy regarding the question whether human brain white matter regions show an anisotropic, direction-dependent mechanical response. With the goal of providing experimental evidence to conclusively answer this question, we here present large-strain, multimodal experimental data and representative histological analyses of different human brain white matter regions and brain stem structures, including directional investigations for both the corpus callosum and the medulla oblongata (lower brain stem).</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 230-251"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032006","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":"Microfluidic-assisted engineering of hydrogels with microscale complexity","authors":"Yuehong Li ,&nbsp;Danyang Huang ,&nbsp;Yuting Zhang ,&nbsp;Yun Xiao ,&nbsp;Xingdong Zhang","doi":"10.1016/j.actbio.2025.05.023","DOIUrl":"10.1016/j.actbio.2025.05.023","url":null,"abstract":"<div><div>Hydrogels have emerged as a promising 3D cell culture scaffold owing to their structural similarity to the extracellular matrix (ECM) and their tunable physicochemical properties. Recent advances in microfluidic technology have enabled the fabrication of hydrogels into precisely controlled microspheres and microfibers, which serve as modular units for scalable 3D tissue assembly. Furthermore, advances in 3D bioprinting have allowed facile and precise spatial engineering of these hydrogel-based structures into complex architectures. When integrated with microfluidics, these systems facilitate microscale heterogeneity, dynamic shear flow, and gradient generation—critical features for advancing organoids and organ-on-a-chip systems. In this review, we will discuss (1) microfluidic strategies for the preparation of hydrogel microspheres and microfibers, (2) the integration of microfluidics with 3D bioprinting technologies, and (3) their transformative applications in organoids and organ-on-a-chip systems.</div></div><div><h3>Statement of Significance</h3><div>Microfluidic-assisted preparation and assembly of hydrogel microspheres and microfibers have enabled unprecedented precision in size, morphology and compositional control. The diverse configurations of these hydrogel modules offer the opportunities to generate 3D constructs with microscale complexity—recapitulating critical features of native tissues such as compartmentalized microenvironments, cellular gradients, and vascular networks. In this review, we discuss the fundamental microfluidic principles governing the generation of hydrogel microspheres (0D) and microfibers (1D), their hierarchical assembly into 3D constructs, and their integration with 3D bioprinting platforms to generate and culture organoids and organ-on-a-chip systems. The synergistic integration of microfluidics and bioprinting overcomes longstanding limitations of conventional 3D culture, such as static microenvironments and poor spatial resolution. Advances in microfluidic design offer tunable hydrogel biophysical and biochemical properties that regulate cell behaviors dynamically. Looking forward, the growing mastery of these principles paves the way for next-generation organoids and organ-on-a-chip systems with improved cellular heterogeneity, integrated vasculature, and multicellular crosstalk, closing the gap between in vitro models and human pathophysiology.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 1-17"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038189","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":"Endogenous nanoplatforms for tumor photoimmunotherapy: Hypoxia modulation and STING pathway activation","authors":"Yongqing Yang ,&nbsp;Ni Shao ,&nbsp;Qiao Luo ,&nbsp;Nianlan Cheng ,&nbsp;Jifeng Chen ,&nbsp;Yanyu Huang ,&nbsp;Cuiqing Huang ,&nbsp;Jiang Ouyang ,&nbsp;Liangping Luo ,&nbsp;Zeyu Xiao","doi":"10.1016/j.actbio.2025.04.030","DOIUrl":"10.1016/j.actbio.2025.04.030","url":null,"abstract":"<div><div>Photoimmunotherapy (PIT) holds significant promise for cancer treatment due to its spatial precision and sustained therapeutic effects. However, overcoming the immunosuppression and hypoxia of the tumor microenvironment (TME) remains a major challenge. To solve this problem, we developed a multifunctional PIT nanoplatform (BYMnNps). Its composition plays different roles: i) Biliverdin can induce mild photothermal and photodynamic therapy, enhance the penetration of nanoplatforms into tumors, and induce immunogenic cell death; ii) the immunotherapy peptide tyroserleutide induces tumor cell apoptosis and enhances tumor-specific immune responses; iii) Mn²⁺ can catalyze the generation of oxygen from hydrogen peroxide, reducing tumor hypoxia, while activating the cGAS-STING pathway, further boosting cancer immunotherapy. The nanoplatforms significantly inhibit tumor growth and increase tumor sensitivity to α-PD 1 therapy. Notably, BYMnNps also exhibit photoacoustic and magnetic resonance imaging capabilities. Overall, BYMnNps effectively counteract tumor immune suppression and alleviates TME hypoxia, demonstrating good biocompatibility and antitumor efficacy, with broad potential for precision cancer treatment guided by multimodal imaging.</div></div><div><h3>Statement of significance</h3><div>Photoimmunotherapy holds great promise for cancer treatment due to its spatial precision and sustained therapeutic effects. However, phototherapy-induced tumor hypoxia leads to resistance, posing a significant challenge. This study utilizes endogenous photosensitizer biliverdin, immunotherapy peptide tyroserleutide, and Mn²⁺ to self-assemble into a multifunctional nanoparticle, aimed at simultaneously reversing the immunosuppression of the tumor microenvironment and alleviating hypoxia. It demonstrates good biosafety and antitumor efficacy, enhancing tumor sensitivity to α-PD1 therapy. Additionally, it exhibits photoacoustic and magnetic resonance imaging capabilities, showing broad potential for precision cancer treatment guided by multimodal imaging. It has the potential to overcome the current limitations of photoimmunotherapy, offering a new avenue for cancer treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 398-411"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051883","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":"Self-polymerized metal-phenolic ionogel with multifunctional properties towards theranostic wearable electronics","authors":"Lanbo Shen ,&nbsp;Tingting Kong ,&nbsp;Jiahao Yu ,&nbsp;Fuchun Nan ,&nbsp;Zilong Wu ,&nbsp;Bin Li ,&nbsp;Jianhua Li ,&nbsp;William W. Yu","doi":"10.1016/j.actbio.2025.04.053","DOIUrl":"10.1016/j.actbio.2025.04.053","url":null,"abstract":"<div><div>With the rapid development of wearable technology toward integrated diagnostics and therapy, wearable electronic materials are required to possess a range of properties, such as stretchable, compressible, conductive, anti-freezing, biocompatible, and antimicrobial properties. Metal-phenolic dual-network ionogel (MP-DN ionogel) was thus prepared by using Fe^III-tannic acid and H₂O₂ as dual self-catalysis system to trigger the polymerization of hydrophilic ionic liquid monomer and hydrophobic acrylamide glycidyl ester monomer. The prepared ionogel showed well-rounded properties including high conductivity, good self-healing, anti-freezing (remains ice-free at -20 °C), anti-swelling, effective antibacterial property (anti-bacterial ratio &gt; 99.9 %), and good cell and tissue biocompatibility. The ionogel exhibited the capability of recording electrocardiogram (ECG), electromyography (EMG), monitoring motion of finger bending and promoting wound healing. The present work provides a simple one-pot strategy to prepare multifunctional ionogels, to meet various application conditions for the next-generation theranostics wearable electronic devices.</div></div><div><h3>Statement of significance</h3><div>1. A dual-network ionogel with tuned mechanical properties was prepared using a simple one-pot method. 2. The ionogel exhibited superior conductivity, antifreeze, anti-swelling, good adhesion and antibacterial properties. 3. The prepared ionogel demonstrated good performance in rat ECG and EMG signal and high sensitivity to finger bending motions. 4. The ionogel could promote the healing of infected wounds. 5. Offer valuable guidance for the theranostic wearable electronics.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"199 ","pages":"Pages 154-165"},"PeriodicalIF":9.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063355","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}