Acta Biomaterialia最新文献

{"title":"Developing and characterising bovine decellularized extracellular matrix hydrogels to biofabricate female reproductive tissues","authors":"E. Ribes Martinez ,&nbsp;Y. Franko ,&nbsp;R. Franko ,&nbsp;G.A. Ferronato ,&nbsp;A.E.S. Viana ,&nbsp;E. Windenbach ,&nbsp;J.B. Stoeckl ,&nbsp;T. Fröhlich ,&nbsp;M.A.M.M. Ferraz","doi":"10.1016/j.actbio.2025.03.009","DOIUrl":"10.1016/j.actbio.2025.03.009","url":null,"abstract":"<div><div>This study investigated the development and characterization of decellularized extracellular matrix (dECM) hydrogels tailored for the biofabrication of female reproductive tissues, specifically targeting ovarian cortex, endometrium, ovarian medulla, and oviduct tissues. We aimed to evaluate the cytocompatibility, biomechanical properties, and overall efficacy of these dECMs in promoting cell viability, proliferation, and morphology using the bovine model. Bovine species provide a valuable model due to their accessibility from slaughterhouse tissues, offering a practical alternative to human samples, which are often limited in availability. Additionally, bovine tissue closely mirrors certain physiological and biological characteristics of humans, making it a relevant model for translational research. Our findings revealed that these dECMs exhibited high biocompatibility with embryo development and cell viability, supporting micro vascularization and cellular morphology without the need for external growth factors. It is important to note that the addition of alginate was crucial for maintaining the structural integrity of the hydrogel during long-term cultures. These hydrogels displayed biomechanical properties that closely mimicked native tissues, which was vital for maintaining their functional integrity and supporting cellular activities. The printability assessments showed that dECMs, particularly those from cortex tissues, achieved high precision in replicating the intended structures, though challenges such as low porosity remained. The bioprinted constructs demonstrated robust cell growth, with over 97% viability observed by day 7, indicating their suitability for cell culture. This work represented a significant advancement in reproductive tissue biofabrication, demonstrating the potential of dECM-based hydrogels in creating structurally and viable tissue constructs. By tailoring each dECM to match the unique biomechanical properties of different tissues, we paved the way for more effective and reliable applications in reproductive medicine and tissue engineering.</div></div><div><h3>Statement of Significance</h3><div>This research explores the use of decellularized extracellular matrix (dECM) hydrogels as bio-inks for creating reproductive tissues. Ovarian cortex and medulla, oviduct and endometrium dECMs demonstrated biomechanical properties that mimicked native tissues, which is essential for maintaining functional integrity and supporting cellular processes. Notably, these hydrogels exhibited high biocompatibility with embryo development and cell viability, promoting microvascularization and cell differentiation without the need for supplemental growth factors. The successful bioprinting of these bio-inks underscores their potential for creating more complex models. This work represents a significant advancement in tissue engineering, offering promising new avenues for reproductive medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 152-170"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical characterization of nonlinear elasticity of growing intestinal organoids with a microinjection method","authors":"Jidong Xiu ,&nbsp;Rui Xue ,&nbsp;Xiaocen Duan ,&nbsp;Fangyun Yao ,&nbsp;Xiaozhi Liu ,&nbsp;Fanlu Meng ,&nbsp;Chunyang Xiong ,&nbsp;Jianyong Huang","doi":"10.1016/j.actbio.2025.02.054","DOIUrl":"10.1016/j.actbio.2025.02.054","url":null,"abstract":"<div><div>Mechanical properties of intestinal organoids are crucial for intestinal development, homeostatic renewal, and pathogenesis. However, characterizing these properties remains challenging. Here, we developed a microinjection-based method to quantify the growth time-dependent nonlinear elasticity of intestinal organoids. With aid of the neo-Hookean hyperelastic constitutive model, we discovered that the global elastic modulus of intestinal organoids increased linearly during the early stages of culture, followed by a sharp rise, indicating a time-dependent nonlinear hardening behaviour during growth. The global modulus of intestinal organoids was found to correlate with the cell phenotype ratio, revealing a significant relationship between mechanical properties and biological phenotypes. Furthermore, we developed a biomechanical model on the basis of the unsteady Bernoulli equation to quantitatively explore the global mechanical responses of intestinal organoids, which showed good agreement with the experimental data. The work not only elucidated the mechanical response and modulus characteristics of small intestinal organoids from a biomechanical perspective, but also presented a new microinjection-based methodology for quantifying the mechanical properties of organoids, offering significant potential for various organoid-related applications.</div></div><div><h3>Statement of significance</h3><div>Mechanical properties of intestinal organoids are essential for intestinal development, homeostatic renewal, and pathogenesis. However, how to quantitatively characterize their global mechanical properties remains challenging. Here, we developed a new microinjection-based experimental platform to quantify spatiotemporal dynamics of mechanical responses and global elasticity of intestinal organoids. Unlike traditional nanoindentation methods, the proposed characterization technique can quantitatively measure the global mechanical properties of organoids, which is crucial for detecting the inherent relationship between the global mechanical properties and the biological phenotypes of organoids. Likewise, it established a methodological foundation for revealing the mechanobiological characteristics associated with the growth and development of various organoids. This can enhance our understanding of mechanobiological mechanisms of organoids and is beneficial for various organoid-related applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 271-280"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544881","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":"Vascular grafts with a mimetic microenvironment extracted from extracellular matrix of adipocytes can promote endothelialization in vivo","authors":"Jian Wang ,&nbsp;Miaomiao Xu ,&nbsp;Hui Liu ,&nbsp;Danling Wang ,&nbsp;Hengyuan Zhang ,&nbsp;Zilong Xu ,&nbsp;Xiuyuan Shi ,&nbsp;Xiao Liu ,&nbsp;Zhikai Tan","doi":"10.1016/j.actbio.2025.03.050","DOIUrl":"10.1016/j.actbio.2025.03.050","url":null,"abstract":"<div><div>Synthetic vascular substitutes are widely studied for small-caliber arteries replacement but their efficacy requires further improvement. Vascular tissue engineering holds great promise for preparing small-caliber vascular grafts with therapeutic effects, and previous work has demonstrated that the cellular layer at the luminal surface of vascular grafts has the potential to provide high functionality to vascular tissue. Improved endothelialization has been proven to be a key strategy for promoting the efficacy of vascular regeneration. However, there still remains a challenge of finding proper endothelialization methods or cell types to guarantee vascular grafts the long-term patency and functions. Herein, a biomimetic bilayer vascular graft was developed by 3D printing and electrospinning techniques. The electrospun PCL nanofiber was fabricated as the outer supporting layer while a biomimetic inner layer structure composed of cell extracellular matrix microenvironment was prepared by a decellularization process. This inner layer was designed to favor endothelial cell (EC) adhesion and enhance endothelialization on the surfaces of vascular grafts. Fibronectin, derived from adipocytes, provided a naturally occurring substrate for EC adhesion. The findings showed that by binding fibronectin, integrin α5β1 mediates EC adherence to the designed vascular graft. The bilayer graft with a mimetic microenvironment extracted from extracellular matrix of adipocytes can promote endothelialization and sustain good patency <em>in vivo</em>, which may represent a promising biomaterial for clinical vascular transplantation.</div></div><div><h3>Statement of significance</h3><div>This study proposed a universal method for including any substrate type in vascular cell type-specific extracellular matrices (ECM) via regulating selective adhesion to promote vascular tissue regeneration.</div><div>The reconstructed 3D ECM recapitulating a vascular-like microenvironment promoted the orderly regeneration and functional recovery of vascular tissues <em>in vivo</em>.</div><div>The findings represent a proof of principle for vascular cell selectivity in cell type-specific ECM microenvironments, and provide a valuable perspective for further investigations on the controlled regeneration of heterogeneous tissues.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 49-62"},"PeriodicalIF":9.4,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766150","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":"Nano-delivery of STING agonists: Unraveling the potential of immunotherapy","authors":"Meng Zhang ,&nbsp;Yating Ji ,&nbsp;Mingxia Liu ,&nbsp;Yixin Dai ,&nbsp;Hongxia Zhang ,&nbsp;Shiyu Tong ,&nbsp;Yuqing Cai ,&nbsp;Mengjiao Liu ,&nbsp;Na Qu","doi":"10.1016/j.actbio.2025.03.054","DOIUrl":"10.1016/j.actbio.2025.03.054","url":null,"abstract":"<div><div>The cyclic GMP-AMP synthetase-interferon gene stimulator (cGAS-STING) pathway possesses tremendous potential in immune responses, viral defense, and anti-tumor treatment. Currently, an increasing number of nanocarriers are being engineered to convey STING agonists, with the goal of booSTING the conveying capacity of cGAS-STING agonists and augment the therapeutic potency of STING agonists. In this review, we explore the mechanisms of cGAS-STING activators, the application of different nanocarriers in the STING pathway, and the application of nanocarriers in anti-tumor therapy, antiviral therapy and autoimmune diseases. Additionally, we also discuss the adverse effects of STING pathway activation and the challenges encountered in nano delivery, we hope that future research will delve into the development of new nanocarriers and the clinical translation of nanocarriers in STING-mediated immunotherapy.</div></div><div><h3>Statement of significance</h3><div>The cyclic GMP-AMP synthetase-interferon gene stimulator (cGAS-STING) pathway possesses tremendous potential in immune responses, viral defense, and anti-tumor treatment. In this review, we first explore the activation mechanism of cGAS-STING signal pathway and the diverse array of nanocarriers that have been employed in the context of the STING pathway, such as natural carrier, lipid nanoparticles, polymeric nanoparticles, and inorganic nanoparticles, highlighting their unique properties and the challenges they present in clinical applications. Furthermore, we discuss the research progress regarding nanocarriers in STING-mediated immunotherapy, such as the application of nanocarriers in anti-tumor therapy, antiviral therapy and autoimmune diseases therapy. Finally, the side effects of STING pathway activation and the issues encountered in nano delivery will be discussed, hoping that future research will delve into the development of new nanocarriers and the clinical translation of nanocarriers in STING-mediated immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 104-120"},"PeriodicalIF":9.4,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756434","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":"Tuning macrophage phenotype for enhancing patency rate and tissue regeneration of vascular grafts","authors":"Yifan Wu ,&nbsp;Xixi Wang ,&nbsp;Lili Song ,&nbsp;Zhe Zhao ,&nbsp;Ying Xia ,&nbsp;Kai Tang ,&nbsp;Huiquan Wang ,&nbsp;Jing Liu ,&nbsp;Zhihong Wang","doi":"10.1016/j.actbio.2025.03.053","DOIUrl":"10.1016/j.actbio.2025.03.053","url":null,"abstract":"<div><div>Macrophages are primary immune cells that play a crucial role in tissue regeneration during the early stages of biomaterial implantation. They create a microenvironment that facilitates cell infiltration, angiogenesis, and tissue remodeling. In the field of vascular tissue engineering, numerous studies have been conducted to modulate the macrophage phenotype by designing various biomaterials, which in turn enhances the regenerative capacity and long-term patency of vascular grafts. However, the mechanism underlying the different phenotypes of macrophages involved in the tissue regeneration of vascular grafts remains unclear. In this study, vascular grafts loaded with various macrophage phenotypes were developed, and their effects were evaluated both <em>in vivo</em> and <em>in vitro</em>. The RAW 264.7 macrophages (M0) were initially treated with LPS or IL-4/IL-10 and polarized into M1 and M2 phenotypes. Subsequently, M0, M1, and M2 macrophages were seeded onto electrospun PCL scaffolds to obtain macrophage-loaded vascular grafts (PCL-M0, PCL-M1, and PCL-M2). As prepared vascular grafts were implanted into the mouse carotid artery for up to one month. The results indicate that the loading of M2 macrophages effectively enhances the patency rate and neotissue formation of vascular grafts. This is achieved through the development of a well-defined endothelium and smooth muscle layer. RNA sequencing was used to investigate the mechanisms of action of different macrophages on tissue regeneration. The study found that M1 macrophages inhibited tissue regeneration by mediating angiogenesis and chronic inflammation through upregulation of VEGFa, IL-1β, and IL-6 expression. In contrast, M2 macrophages regulate the immune microenvironment by upregulating the expression of IL-4 and TGF-β, thereby promoting tissue regeneration. In conclusion, our study demonstrates how different macrophage phenotypes contribute to the initial inflammatory microenvironment surrounding vascular grafts, thereby modulating the biological process of vascular remodeling.</div></div><div><h3>Statement of significance</h3><div>Regulating the biophysical and biochemical characteristics of biomaterials can induce macrophage polarization and enhance vascular remodeling. In previous work, we fabricated a vascular graft with a macroporous structure that promoted macrophage infiltration and polarization into a pro-regenerative phenotype. To illustrate the mechanism, we established a new mouse model and evaluated the effects of different macrophages on vascular regeneration. The study revealed that tuning macrophage phenotype can impact the initial inflammatory microenvironment by secreting cytokines, which can increase the patency rate and regenerative capacity of vascular grafts. These findings provide essential theoretical support for the development of immunoregulatory scaffolds for vascular and other tissue regeneration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 245-256"},"PeriodicalIF":9.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756479","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":"Arg-Gly-Asp engineered mesenchymal stem cells as targeted nanotherapeutics against kidney fibrosis by modulating m6A","authors":"Xin Zhang ,&nbsp;Jiaqi Zhao ,&nbsp;Rui Ge ,&nbsp;Xiangyu Zhang ,&nbsp;Haihan Sun ,&nbsp;Yuhan Guo ,&nbsp;Yanping Wang ,&nbsp;Lu Chen ,&nbsp;Shulin Li ,&nbsp;Jing Yang ,&nbsp;Dong Sun","doi":"10.1016/j.actbio.2025.03.042","DOIUrl":"10.1016/j.actbio.2025.03.042","url":null,"abstract":"<div><div>Background The recent surge in research on extracellular vesicles has generated considerable interest in their clinical applications. Extracellular vesicles derived from mesenchymal stem cells (MSC-EV) have emerged as a promising cell-free therapy for chronic kidney disease (CKD), offering an alternative to traditional Mesenchymal stem/stromal cells (MSCs) in extracellular vesicle-based nanotherapeutics. However, challenges such as <em>in vivo</em> off-target effects and limited bioavailability have impeded the wider adoption of MSC-EV in clinical settings.</div><div>Methods Arginyl-glycyl-aspartic acid peptide-modified MSC-EV (RGD-MSC-EV) were developed using a donor cell-assisted membrane modification strategy. The targeting capability and therapeutic efficacy of RGD-MSC-EV were thoroughly evaluated both <em>in vitro</em> and <em>in vivo</em>. Additionally, the mechanisms of RNA N⁶-methyladenosine (m6A) methylation-mediated angiogenesis were extensively investigated to elucidate how RGD-MSC-EV mitigates renal fibrosis.</div><div>Results RGD-MSC-EV demonstrated exceptional targeted delivery efficiency, exhibiting optimal biodistribution and retention within the target tissue. This breakthrough positions them as significantly enhanced anti-fibrotic therapeutics. Notably, RGD-MSC-EV sustains the viability of renal peritubular capillary (PTCs) endothelial cells by transporting microRNA-126–5p (miR-126–5p) and modulating alkB homolog 5 (ALKBH5)-mediated m6A modification of SIRT1(Sirtuin 1), a crucial regulator in angiogenesis. By revitalizing endothelial cells and promoting microcirculation, this approach restored oxygen metabolism homeostasis, ultimately delaying fibrogenesis associated with CKD.</div><div>Conclusions RGD-MSC-EV offers a feasible and effective strategy to alleviate renal interstitial fibrosis by restoring m6A and mitigating the loss of renal PTCs.</div></div><div><h3>Statement of significance</h3><div>Chronic kidney disease (CKD) often leads to renal fibrosis, which worsens disease progression. This study introduces a novel strategy using engineered extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC-EV). By modifying these EVs with RGD peptides, we significantly enhance their targeting ability to hypoxic kidney tissues. The research reveals how these EVs deliver microRNA (miR-126–5p) to restore key molecular mechanisms, stabilizing SIRT1 expression through m6A RNA modifications. This approach promotes blood vessel health and delays fibrosis. Compared to current treatments, RGD-MSC-EV offers a safe, effective, and cell-free therapeutic alternative. These findings advance the understanding of EV-based therapies and their clinical potential, bridging basic research and real-world CKD treatment applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 85-101"},"PeriodicalIF":9.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756432","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":"Advancing atom probe tomography capabilities to understand bone microstructures at near-atomic scale","authors":"Tim M. Schwarz ,&nbsp;Maïtena Dumont ,&nbsp;Victoria Garcia-Giner ,&nbsp;Chanwon Jung ,&nbsp;Alexandra E. Porter ,&nbsp;Baptiste Gault","doi":"10.1016/j.actbio.2025.03.051","DOIUrl":"10.1016/j.actbio.2025.03.051","url":null,"abstract":"<div><div>Bone structure is generally hierarchically organized into organic (collagen, proteins, ...), inorganic (hydroxyapatite (HAP)) components. However, many fundamental mechanisms of the biomineralization processes such as HAP formation, the influence of trace elements, the mineral-collagen arrangement, etc., are not clearly understood. This is partly due to the analytical challenge of simultaneously characterizing the three-dimensional (3D) structure and chemical composition of biominerals in general at the nanometer scale, which can, in principle be achieved by atom probe tomography (APT). Yet, the hierarchical structures of bone represent a critical hurdle for APT analysis in terms of sample yield and analytical resolution, particularly for trace elements, and organic components from the collagen appear to systematically get lost from the analysis. Here, we applied in-situ metallic coating of APT specimens within the focused ion beam (FIB) used for preparing specimens, and demonstrate that the sample yield and chemical sensitivity are tremendously improved, allowing the analysis of individual collagen fibrils and trace elements such as Mg and Na. We explored a range of measurement parameters with and without coating, in terms of analytical resolution performance and determined the best practice parameters for analyzing bone samples in APT. To decipher the complex mass spectra of the bone specimens, reference spectra from pure HAP and collagen were acquired to unambiguously identify the signals, allowing us to analyze entire collagen fibrils and interfaces at the near-atomic scale. Our results open new possibilities for understanding the hierarchical structure and chemical heterogeneity of bone structures at the near-atomic level and demonstrate the potential of this new method to provide new, unexplored insights into biomineralization processes in the future.</div></div><div><h3>Statement of significance</h3><div>Atom probe tomography (APT) is a relatively new technique for the analysis of bones, teeth or biominerals in general. APT can characterize the microstructure of materials in 3D down to the near-atomic level, combined with a high elemental sensitivity, down to parts per million. APT application to study biomineralization phenomena is plagued by low sample yield and poorer analytical performance compared to metals. Here we have overcome these limitations by <em>in-situ</em> metal coating of APT specimens. This can unlock future APT analysis to gain insights into fundamental biomineralization processes, e.g. collagen/hydroxyapatite interaction, influence of trace elements and a better understanding of bone diseases or bone biomineralization in general.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 319-333"},"PeriodicalIF":9.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744600","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-powered casein hydrogel E-dressing with synergistic photothermal therapy, electrical stimulation, and antibacterial effects for chronic wound management","authors":"Yuhang Xu ,&nbsp;Xiaoyu Xu ,&nbsp;Yuan Zhao ,&nbsp;YaNing Tian ,&nbsp;Yubo Ma ,&nbsp;Xin Zhang ,&nbsp;Fanni Li ,&nbsp;Wei Zhao ,&nbsp;Jianzhong Ma ,&nbsp;Qunna Xu ,&nbsp;Qi Sun","doi":"10.1016/j.actbio.2025.03.047","DOIUrl":"10.1016/j.actbio.2025.03.047","url":null,"abstract":"<div><div>Triboelectric nanogenerators (TENGs) have recently demonstrated great application potential for accelerating wound healing in the field of medical research due to their unique electrical stimulation effect. Among the various types of TENGs, solid-liquid TENGs have attracted much attention due to their significant advantages, such as high contact-separation efficiency and a wide range of liquid motion. Therefore, this study innovatively proposed a solid-liquid biphasic TENG electronic dressing constructed from a casein hydrogel enhanced by the metal-organic framework Zeolitic Imidazolate Framework-8 (ZIF-8). This hydrogel dressing comprised sodium caseinate (SC)/multi-walled carbon nanotubes-polydopamine@polydopamine (MWCNT@PDA)/polyacrylamide (PAM)/ZIF-8. It ingeniously integrates multiple functions such as photothermal, photodynamic antibacterial, and electrical stimulation therapies, thereby establishing a new multimodal synergistic treatment paradigm. Notably, the addition of ZIF-8 not only controlled photothermal release of antibacterial agents but also facilitates the development of a distinctive solid-liquid biphasic operational modality in TENG system, achieving a 131 V peak output voltage through significant enhancement of electrical performance parameters. In addition, the TENG-based system adopts a non-contact electrical stimulation method for wound treatment, fundamentally reducing the risk of infection caused by direct contact. Experiments using mouse fibroblasts revealed that the simultaneous real-time use of near-infrared light and TENG can significantly improve the cell migration process. Empirical studies on animals demonstrated that it could accelerate tissue regeneration and wound healing by increasing collagen deposition and angiogenesis. Based on these results, this study provides new perspectives for the developing intelligent biomedical composites for future wound management.</div></div><div><h3>Statement of significance</h3><div>Chronic wounds have become a major threat to global medical and health fields due to pathogenic infections. Traditional wound dressings mostly focus on passive healing, which has limited effectiveness. To overcome these limitations, we developed an electronic dressing of a casein-based hydrogel TENG enhanced by a MOF. This electronic dressing combines photothermal, photodynamic antibacterial, and electrical stimulation functions and efficiently promotes wound healing through multifunctional synergy. This research provides a promising solution for diabetic wound care and a broader field of chronic wound treatment. It is a solid step in the scientific exploration of interdisciplinary integration, offering new ideas for making the wound treatment field more intelligent, efficient, and precise.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 63-84"},"PeriodicalIF":9.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744595","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 CXCR4-targeted immunomodulatory nanomedicine for photodynamic amplified immune checkpoint blockade therapy against breast cancer","authors":"Yibin Liu ,&nbsp;Xiayun Chen ,&nbsp;Wei Zhang ,&nbsp;Baixue Yu ,&nbsp;Yi Cen ,&nbsp;Qianqian Liu ,&nbsp;Youzhi Tang ,&nbsp;Shiying Li","doi":"10.1016/j.actbio.2025.03.049","DOIUrl":"10.1016/j.actbio.2025.03.049","url":null,"abstract":"<div><div>The therapeutic efficacy of immune checkpoint blockade (ICB) is critically compromised by inadequate T lymphocyte infiltration, low T cell-induced pro-inflammatory responses, and the accumulation of immunosuppressive cells within the tumor microenvironment (TME). In this work, a chimeric peptide-engineered immunomodulatory nanomedicine (designated as CXNP-CeBM) is developed for photodynamic amplified ICB therapy against breast cancer. CXNP-CeBM is composed of a CXCR4-targeting peptide ((C₁₆)₂-KLGASWHRPDK) loaded with the photosensitizer of Ce6 and the PD-1/PD-L1 inhibitor of BMS8. CXNP-CeBM specifically recognizes CXCR4 on breast cancer, thus suppressing CXCR4-mediated signaling pathways and enhancing the intracellular delivery of therapeutic agents. The photodynamic therapy (PDT) of CXNP-CeBM damages primary tumor cells to initiate immunogenic cell death (ICD), leading to the release of high mobility group box 1 (HMGB1) and the exposure of calreticulin (CRT). Simultaneously, the interruption of CXCR4 signaling reduces tumor fibrosis, promotes T-cell infiltration, and decreases the number of immunosuppressive cells, thereby enhancing the immunotherapeutic effect of ICB. Treatment with CXNP-CeBM would activate systemic anti-tumor immunity, leading to effective inhibition of both primary and lung metastatic tumors, while maintaining low systemic toxicity. This work provides a reliable strategy for the delivery of multi-synergistic agents, effectively activating breast cancer immunity through a multifaceted mechanism.</div></div><div><h3>Statement of significance</h3><div>Although immune checkpoint blockade (ICB) has shown great potential for malignant tumor therapy, its efficacy is compromised by immunosuppressive microenvironments. Herein, a CXCR4-targeted immunomodulatory nanomedicine (CXNP-CeBM) was constructed for photodynamic amplified ICB therapy of breast cancer. CXNP-CeBM could selectively deliver photosensitizers and PD-1/PD-L1 inhibitors to breast cancer cells that overexpressed the chemokine receptor CXCR4, while interrupting CXCR4 signaling to reduce tumor fibrosis, promote T-cell infiltration, and decrease the number of immunosuppressive cells. Moreover, CXNP-CeBM induced photodynamic therapy to trigger immunogenic cell death while downregulating the PD-L1 level to destroy immune evasion mechanisms, thus activating immunological cascades to treat both primary and lung metastatic tumors. This study provided a multi-synergistic strategy for breast cancer immunotherapy through a multifaceted mechanism.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 400-415"},"PeriodicalIF":9.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744593","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-luminous nanoengineered bacteria with the sustained release of interleukin 2 as an in situ vaccine for enhanced cancer immunotherapy","authors":"Guannan Liu ,&nbsp;Huiqin Wang ,&nbsp;Zhengyue Fei ,&nbsp;Xinyue Tao ,&nbsp;Jiamin Zheng ,&nbsp;Guohao Cai ,&nbsp;Xueming Li ,&nbsp;Junlong Zhuang ,&nbsp;Hao Ren","doi":"10.1016/j.actbio.2025.03.046","DOIUrl":"10.1016/j.actbio.2025.03.046","url":null,"abstract":"<div><div>Bacteria-based <em>in situ</em> vaccination (ISV) has emerged as an effective therapeutic approach by activating anti-tumor immunity. However, inducing immunogenic cell death (ICD) and promoting effector T cell activation remain critical challenges in clinical applications of bacteria-based ISV. Here, we have developed a tumor microenvironment-activated nano-hybrid engineered bacterium as ISV. It was engineered with a blue-light response module (EL222) and self-luminous luminal hyaluronic acid (LHA) nanoparticles. Our study demonstrates that LHA generates local blue light stimulated by hydrogen peroxide, non-invasively activating the engineered <em>Escherichia coli</em> to produce IL-2. The engineered bacteria serve as an immunological adjuvant, promoting dendritic cell maturation, synergistically promoting T cell infiltration, and ultimately triggering a comprehensive activation of the immune system. Furthermore, when combined with the immune checkpoint inhibitor anti-PD-L1, this approach further effectively enhances cancer immunotherapy. Our results provide new strategies and promising prospects for the development of bacteria-based ISV immunotherapy.</div></div><div><h3>Statement of significance</h3><div>This study developed a tumor microenvironment-activated nano-hybrid engineered bacteria (Ec-mIL2@LHA) as <em>in situ</em> vaccine for enhanced cancer immunotherapy. The LHA in bacterial vaccine non-invasively generated blue light upon stimulation by hydrogen peroxide of TME, leading to the sustained release of low-dose IL2 by engineered bacteria. <em>In vitro</em> and <em>in vivo</em> studies have demonstrated the bacterial <em>in situ</em> vaccine induced the immunogenic cell death and promote maturation of dendritic cells, ultimately triggering a comprehensive activation of anti-tumor immunity. After combination with anti-PD-L1, the bacterial <em>in situ</em> vaccine further effectively enhance cancer immunotherapy and inhibit metastasis. We provide a promising strategy to amplify antitumor immune effects by an engineered bacterial vaccine, showing potential clinical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"197 ","pages":"Pages 386-399"},"PeriodicalIF":9.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744606","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}