Acta Biomaterialia最新文献

{"title":"Dual-responsive magnetic vortex nanorings co-deliver lenvatinib and localized heat for synergistic activation of antitumor immunity","authors":"Zirui Ye ,&nbsp;Bin Yan ,&nbsp;Hugang Li ,&nbsp;Qianqian Tang ,&nbsp;Kexin Yuan ,&nbsp;Jingjing Hou ,&nbsp;Lexuan Xu ,&nbsp;Jianlan Yuan ,&nbsp;Siyao Wang ,&nbsp;Wangbo Jiao ,&nbsp;Haiming Fan ,&nbsp;Yi Lyu ,&nbsp;Bo Wang ,&nbsp;Xiaoli Liu","doi":"10.1016/j.actbio.2025.04.014","DOIUrl":"10.1016/j.actbio.2025.04.014","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) presents significant treatment challenges, primarily due to its ability to suppress immune responses. Lenvatinib (LT), approved as a first-line therapy for HCC, modulates the immune microenvironment by reducing PD-L1 expression and decreasing the infiltration of regulatory T cells (T_regs) within the tumor. However, the low immunogenicity of HCC and high toxicity of LT often undermine its effectiveness. To address these challenges, polydopamine (PDA)-coated ferrimagnetic vortex-domain iron oxide nanorings (FVIO@PDA) were engineered to respond to both acidic conditions and magnetic fields, facilitating the simultaneous delivery of the drug (LT) and a physio-therapeutic heat modality. The dual-responsive nature of FVIO@PDA ensures a controlled and synergistic release of LT, activated by acidic tumor microenvironments and the heat produced by an alternating magnetic field (AMF). In a subcutaneous Hepa1–6 HCC model, LT-loaded FVIO@PDA-PEG (denoted as LT-loaded FPP)-mediated magnetic hyperthermia significantly increased the levels of cytotoxic T lymphocytes, showing an approximate 3.86-fold increase compared to the control groups. This combination of LT and magnetic hyperthermia also reduced Treg populations to 1.4 %, synergistically triggering a robust antitumor immune response. Additionally, it altered cytokine profiles, reducing the secretion of the immunosuppressive cytokine IL-10 to 0.41 times that of control levels, while increasing the secretion of pro-inflammatory cytokines IFN-γ and TNF-α by 3.25 and 4.34 times, respectively. Furthermore, LT-loaded FPP-mediated magnetic hyperthermia exhibits superior anti-tumor activity compared to either treatment alone. These results highlight the promise of combining LT with FPP-mediated immunogenic magnetic hyperthermia as a potent therapeutic strategy for HCC, offering a more effective approach to modulate the immune environment and enhance antitumor efficacy.</div></div><div><h3>Statement of significance</h3><div>Lenvatinib (LT) is a selective multi-targeted tyrosine kinase inhibitor used for patients with unresectable HCC who have not previously undergone systemic therapy. LT's immunomodulatory effects alone are often insufficient to induce an effective immune response, and treatment outcomes continue to be unsatisfactory. We developed FVIO@PDA for the delivery of LT and localized heat. FVIO@PDA allowed for controlled release of LT, triggered by the acidic tumor microenvironment and the heat generated under an AMF. LT combined with magnetic hyperthermia increased CTLs, reduced T_regs, decreased immunosuppressive cytokines, and elevated pro-inflammatory ones, collectively initiating a strong antitumor immune response. LT combined with magnetic hyperthermia showed superior antitumor effect compared to either treatment alone.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 389-400"},"PeriodicalIF":9.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917821","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":"Nanodrug-loaded microneedles promote scar-reduced repair after spinal cord injury by re-establishing microglial homeostasis","authors":"Wenbo He ,&nbsp;Li Zhang ,&nbsp;Datong Zheng ,&nbsp;Liansha Tang ,&nbsp;Yi Zhang ,&nbsp;Min Peng ,&nbsp;Zhigang Wang ,&nbsp;Chongxi Xu ,&nbsp;Zhouhaoran Chen ,&nbsp;Yi Liu ,&nbsp;Jianguo Xu ,&nbsp;Maling Gou ,&nbsp;Yu Hu","doi":"10.1016/j.actbio.2025.04.026","DOIUrl":"10.1016/j.actbio.2025.04.026","url":null,"abstract":"<div><div>The persistent activation of microglia is a key factor contributing to neuronal damage and inhibiting the repair of spinal cord injury (SCI). Re-establishing local microglial homeostasis during the early stages of injury presents a novel approach for scar-reduced repair after SCI. Nitroxoline (Nit) can reinstate microglial homeostasis after their activation in vitro. However, the poor water solubility and low blood-spinal cord barrier permeability limit the potential application of Nit in SCI. Here, a dual drug-delivering system (Nit-MNs) composed of self-assembled nano-micelles and gelatin methacryloyl microneedles was further designed. The nano-micelles resolved the solubility issues of Nit while facilitating sustained release. The Nit-MNs enabled continuous drug delivery into the intrathecal space through the micro-perforations created in the dura mater. In the rat spinal cord contusion model, the implantation of Nit-MNs reduced scar formation, promoted neural regeneration, and subsequently restored neurological function. Further studies demonstrated that Nit-MNs promoted the re-establishment of microglial homeostasis, probably through inhibiting the expression of cathepsin B. Therefore, our functional Nit delivery system provides a promising drug-based delivery strategy for SCI treatment.</div></div><div><h3>Statement of significance</h3><div>Small molecule drugs have demonstrated therapeutic effects by targeting various pathological processes of SCI, but the efficacy and precise delivery often limit their broader application. In this study, we identified a small molecule drug (Nit) as a potential candidate for promoting SCI repair by facilitating the re-establishment of microglial homeostasis. Additionally, we developed a dual drug-delivering system comprising self-assembled nano-micelles and gelatin methacryloyl microneedles. This system achieved transdural delivery and dual sustained release of Nit at the precise injury site, effectively promoting the scar-reduced repair after SCI. Our research provides insights for the development of novel delivery systems that match the therapeutic characteristics of small molecule drugs for SCI.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 440-451"},"PeriodicalIF":9.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917734","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":"Engineered bioorthogonal cell delivery system for in situ antimicrobial peptide recruitment during systemic bacterial infection","authors":"Wenchang Peng ,&nbsp;Yun Fu ,&nbsp;Yajing Du ,&nbsp;Jingye Pan ,&nbsp;Bowen Li ,&nbsp;Yun Gu ,&nbsp;Yang Bai ,&nbsp;Bin Zheng ,&nbsp;Tao Wang","doi":"10.1016/j.actbio.2025.04.023","DOIUrl":"10.1016/j.actbio.2025.04.023","url":null,"abstract":"<div><div>Allogeneic cells represent promising intelligent delivery platforms owing to their intrinsic target homing ability, ready-to-use, scalability and broad applicability. However, implanted allogeneic cells are susceptible to rapid clearance by mononuclear phagocytic system (MPS), resulting in short half-life and compromised therapeutic efficacy. To overcome this limitation, we constructed genetically engineered allogeneic cells with surface-expressed CD24, a \"don't eat me\" signal protein, to evade phagocytosis by macrophages. Additionally, we modified the allogeneic cells with azide groups, creating a binding site for dibenzocyclooctyne (DBCO)-modified drugs through copper-free click chemistry. The results showed that mesenchymal stem cells (MSCs) have natural inflammation-targeting properties, and modification of allogeneic MSCs (M24N₃ cells) significantly prolonged their retention at the site of inflammation. Moreover, DBCO-modified antimicrobial peptides (DBCO-LL37) were more effectively recruited to inflammation sites via bioorthogonal reactions, resulting in sustained bacterial clearance. The M24N₃@DBCO-LL37 treatment cleared multiple sepsis mediators, extended circulation time, and increased tissue retention, ultimately protecting against organ damage and delaying sepsis-induced lethality, subsequently resulting in remarkable survival rate elevation. These findings underscore the potential of bioorthogonal system based on engineered allogeneic cells for the treatment of complex inflammatory diseases, highlighting their promising applications in evading rapid clearance systems <em>in vivo</em>.</div></div><div><h3>Statement of Significance</h3><div>In recent years, allogeneic cells have garnered significant research interest as emerging drug delivery carriers due to their off-the-shelf availability, scalable production, and broad therapeutic applicability. However, recognition and elimination mediated by the mononuclear phagocyte system (MPS) brings a substantial challenge to their clinical application. We developed an engineered bioorthogonal cell delivery system, M24N₃@DBCO-LL37, through genetic engineering and glucose metabolic engineering methods, which could avoid phagocytosis of allogeneic cells by macrophages, prolong the retention time of allogeneic cells at the site of inflammation, recruit more DBCO-modified antimicrobial peptides (DBCO-LL37), and significantly reduced the mortality rate and improved therapeutic efficiency in a mouse model of sepsis. This strategy can not only be used in the development of cell delivery systems, but also has the potential to be used in the design of more allogeneic cell therapy strategies, such as chimeric antigen receptor T-cell immunotherapy (CAR-T), haematopoietic stem cell transplantation and organ transplantation, to improve the therapeutic efficacy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 115-130"},"PeriodicalIF":9.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916232","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":"Liposomic lubricants suppress acute inflammatory gene regulation in the joint in vivo","authors":"Linyi Zhu ,&nbsp;Weifeng Lin ,&nbsp;Monika Kluzek ,&nbsp;Jadwiga Miotla-Zarebska ,&nbsp;Vicky Batchelor ,&nbsp;Matthew Gardiner ,&nbsp;Chris Chan ,&nbsp;Peter Culmer ,&nbsp;Anastasios Chanalaris ,&nbsp;Ronit Goldberg ,&nbsp;Jacob Klein ,&nbsp;Tonia L. Vincent","doi":"10.1016/j.actbio.2025.04.022","DOIUrl":"10.1016/j.actbio.2025.04.022","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a widespread, debilitating joint disease associated with articular cartilage degradation. It is driven via mechano-inflammatory pathways, whereby catabolic genes in the cartilage-embedded chondrocytes are presumed up-regulated due to increased shear stress arising from friction at the cartilage surface as joints articulate. The enhanced expression of these cartilage-degrading and inflammatory genes leads to tissue degeneration. However, the nature of the stress, and how the cells within the joint respond to it, are poorly understood. Here we show, in a proof of concept study on a mouse model where surgical joint destabilisation has been carried out to induce OA, that the early up-regulation of the matrix metalloproteinase 3 (<em>Mmp3</em>) gene, a member of the matrix-degrading MMP family, and of the interleukin-1 beta (<em>Il1b</em>) gene, a key mediator of inflammatory response, are significantly suppressed when lipid-based lubricants are injected into the joints. We attribute this to the reduction in frictional stress on the chondrocytes due to the lubricant at the cartilage surface. At the same time, <em>Timp1</em>, a compression but not shear-stress sensitive gene, is unaffected by lubricant. Our results demonstrate that cartilage lubrication modulates catabolic gene regulation in OA, shed strong light on the nature of the chondrocytes’ response to shear stress, and have clear implications for novel OA treatments.</div></div><div><h3>Statement of Significance</h3><div>Osteoarthritis (OA) is a widespread, debilitating joint disease associated with degradation of the articular cartilage, the tissue that covers and protects the joint surfaces as they rotate. Such degradation is due to catabolic enzymes expressed by cartilage-embedded chondrocytes (the only cell type in cartilage) in response to mechanical stress. In this proof-of-concept study in a mouse OA model, we show that reduction of cartilage friction by liposome-based lubricants suppresses the production of the catabolic, OA-related genes in chondrocytes. Our findings provide direct evidence in an animal model that catabolic genes are induced in chondrocytes in a mechanosensitive manner, related to the friction at the cartilage surface, and identify putative novel OA treatments through efficient cartilage lubrication.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 366-376"},"PeriodicalIF":9.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917820","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":"3D-printed polycaprolactone scaffolds functionalized with poly(lactic-co-glycolic) acid microparticles enhance bone regeneration through tunable drug release","authors":"Juan Antonio Romero-Torrecilla ,&nbsp;Miguel Echanove-González de Anleo ,&nbsp;Cristina Martínez-Ohárriz ,&nbsp;Purificación Ripalda-Cemboráin ,&nbsp;Tania López-Martínez ,&nbsp;Gloria Abizanda ,&nbsp;José Valdés-Fernández ,&nbsp;Jakub Prandota ,&nbsp;Emma Muiños-López ,&nbsp;Elisa Garbayo ,&nbsp;Felipe Prósper ,&nbsp;María J. Blanco-Prieto ,&nbsp;Froilán Granero-Moltó","doi":"10.1016/j.actbio.2025.04.021","DOIUrl":"10.1016/j.actbio.2025.04.021","url":null,"abstract":"<div><div>Numerous tissue engineering strategies aim to enable the <em>in situ</em> and controlled release of both cells and biologically relevant factors, mimicking physiological regenerative processes. A notable example is the release of rhBMP-2 for treating bone nonunion. By adopting a quasi-physiological approach, we can mitigate the side effects that have hindered its clinical application. Here, we present a customizable 3D-printed polycaprolactone (PCL) scaffold functionalized with poly(lactic-co-glycolic) acid (PLGA) microparticles through covalent binding, designed to mimic the periosteum structure. This scaffold was then functionalized with PLGA microparticles through covalent binding, enabling <em>in situ</em> delivery of rhBMP-2. This construct exhibits significant osteogenic and osteoinductive potential <em>in vitro</em>, promoting the differentiation of periosteum-derived mesenchymal progenitor cells into osteoblasts. Moreover, <em>in vivo</em> testing using a nonunion model (critical size defect) demonstrated therapeutic efficacy with a reduced net morphogen dose. Therefore, this customizable 3D scaffold represents a valuable approach for enhancing bone regeneration and holds significant potential for promoting healing in cases of nonunion fractures. This approach combines a customizable 3D scaffold with controlled rhBMP-2 release, offering a potentially more effective and safer solution for bone regeneration compared to current methods.</div></div><div><h3>Statement of Significance</h3><div>As the incidence of bone fractures continues to rise, nonunion remains a significant challenge in orthopedics, becoming a major clinical and economic burden. We present a tissue engineering strategy employing a customizable 3D-printed polycaprolactone scaffold functionalized with covalently bound poly(lactic-co-glycolic acid) microparticles for the localized release of rhBMP-2. By mimicking key features of the periosteum, this scaffold promotes bone regeneration while minimizing the risk of ectopic bone formation. <em>In vivo</em> tests conducted in a critical-size defect model demonstrated effective bone bridging, highlighting the therapeutic potential of the scaffold. The simple manufacturing process, potential for scale-up production, long-term storage capability, and options for customization, including combinations of different molecules or adjuvants, demonstrate that this approach possesses significant translational potential.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 219-233"},"PeriodicalIF":9.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916155","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":"Advanced manufacturing of coil-reinforced multilayer vascular grafts to optimize biomechanical performance","authors":"Andrew Robinson ,&nbsp;David Jiang ,&nbsp;Abbey Nkansah ,&nbsp;Juan S. Herrera Duran ,&nbsp;Jonathan Leung ,&nbsp;Madeline Laude ,&nbsp;John Craig ,&nbsp;Leopold Guo ,&nbsp;Lucas Timmins ,&nbsp;Elizabeth Cosgriff-Hernandez","doi":"10.1016/j.actbio.2025.04.020","DOIUrl":"10.1016/j.actbio.2025.04.020","url":null,"abstract":"<div><div>Small diameter vascular grafts require a complex balance of biomechanical properties to achieve target burst pressure, arterial compliance-matching, and kink resistance to prevent failure. Iterative design of our multilayer vascular grafts was previously used to achieve high compliance while retaining the requisite burst pressure and suture retention strength for clinical use. To impart kink resistance, a custom 3D solution printer was used to add a polymeric coil to the electrospun polyurethane graft to support the graft during bending. The addition of this reinforcing coil increased kink resistance but reduced compliance. A matrix of grafts were fabricated and tested to establish key structure-property relationships between coil parameters (spacing, diameter, modulus) and biomechanical properties (compliance, kink radius). A successful graft design was identified with a compliance similar to saphenous vein grafts (4.1 ± 0.4 %/mmHgx10⁻²) while maintaining a kink resistance comparable to clinically used synthetic grafts. To explore graft combinations that could increase graft compliance to match arterial values while retaining this kink resistance, finite element (FE) models of compliance and kink radius that simulated experiment testing were used. The FE-predicted graft compliance agreed well with experimental values. Although the kink model over-predicted the experimental kink radius values, key trends between graft parameters and kink resistance were reproduced. As an initial proof-of-concept, the validated models were then utilized to parse through a targeted graft design space. Although this initial parameter range tested did not yield a graft that improved upon the previous balance of graft properties<em>,</em> this combination of advanced manufacturing and computational framework paves the way for future model-driven design to further optimize graft performance.</div></div><div><h3>Statement of Significance</h3><div>The development of a small-diameter vascular graft requires a balance of key biomechanical properties to prevent failure. To impart kink resistance, a polymeric coil was applied. A matrix of grafts was tested to establish structure-property relationships between coil parameters and biomechanical properties. A successful graft design was identified with a compliance similar to saphenous vein grafts and kink resistance within range of clinically grafts. Finite element models for compliance and kink resistance were developed to optimize graft performance. The validated models were utilized to parse a targeted design space. Although this initial range did not yield a graft that improved upon the previous graft properties<em>,</em> this combination of advanced manufacturing and computational framework paves the way for future model-driven design.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 281-290"},"PeriodicalIF":9.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917744","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":"Boosting the angiogenesis potential of self-assembled mesenchymal stem cell spheroids by size mediated physiological hypoxia for vascularized pulp regeneration","authors":"Xiaojing Yuan ,&nbsp;Shuyi Wang ,&nbsp;Zuoying Yuan ,&nbsp;Zhuo Wan ,&nbsp;Linxue Zhang ,&nbsp;Rui Song ,&nbsp;Lihong Ge ,&nbsp;Yuming Zhao","doi":"10.1016/j.actbio.2025.04.019","DOIUrl":"10.1016/j.actbio.2025.04.019","url":null,"abstract":"<div><div>Hypoxia is a pivotal factor in enhancing the vascularization potential of both two-dimensional (2D) cultured cells and three-dimensional (3D) cellular spheroids. Nevertheless, spheroids that closely mimic the in vivo microenvironment often experience excessive hypoxia, leading to the necrotic core and the release of toxic byproducts, ultimately impeding the regenerative process. To balance cell vitality and pro-angiogenic properties of cellular spheroids, this study investigates size-dependent hypoxia in stem cell spheroids utilizing an oxygen transfer finite element model. Subsequently, we develop 3D cultured stem cells from human exfoliated deciduous teeth (SHED) spheroids with regulated size-dependent hypoxia. Comprehensive assessments indicate that SHED spheroids, inoculated at a density of 50,000 cells, display moderate physiological hypoxia, which optimizes their pro-angiogenic potential, fusion capacity, and reattachment ability. Compared with SHED sheets, SHED spheroids enhance vascularized pulp regeneration more effectively with a tightly connected odontoblastic-like layer. Moreover, high-throughput transcriptome sequencing and RT-qPCR analysis further confirm the spheroids' ability to promote angiogenesis and odontogenic differentiation. This study not only introduces a practical and effective approach for regulating size-dependent hypoxia in cellular spheroids, and simultaneously enhancing cell vitality and angiogenic potential, but also paves the way for the clinical application of SHED spheroids in regenerative dental pulp therapies.</div></div><div><h3>Statement of significance</h3><div>The core of three-dimensionally cultured cellular spheroids often experiences hypoxia, and maintaining a balance between the activity and functionality of long-term cultured spheroids in the inevitably hypoxic microenvironment remains a significant challenge. This study introduces a method to optimize the hypoxic conditions of SHED spheroids by employing a reaction-diffusion model, which modulates internal hypoxia to balance cellular viability and angiogenic potential. Compared to two-dimensional cell sheets, the optimized SHED spheroids with high cell vitality, angiogenesis potential, tissue integration and reattatchment ability show superior efficacy in promoting the formation of vascularized pulp-like tissue. This work offers valuable insights into the role of hypoxia in stem cell spheroids functionality and provides a foundation for further research into the optimization of stem cell-based therapies for multiple clinical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 102-114"},"PeriodicalIF":9.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916231","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 general method to improve imprinting efficiency in surface protein imprinting by enhanced pre-assembly","authors":"Yafei Wang ,&nbsp;Shun Liu ,&nbsp;Yibo Zhao ,&nbsp;Zhuo Zhao ,&nbsp;Yi Liu ,&nbsp;Jianchen Zhang ,&nbsp;Jia Yao ,&nbsp;Lei Zou ,&nbsp;Yan Zhang ,&nbsp;Ying Guan ,&nbsp;Yongjun Zhang","doi":"10.1016/j.actbio.2025.04.017","DOIUrl":"10.1016/j.actbio.2025.04.017","url":null,"abstract":"<div><div>Surface protein-imprinted nanoparticles may replace the expensive and unstable antibodies in biomedical applications but still suffers from a low imprinting efficiency. A main reason may be the insufficient pre-assembly between monomers and template protein in surface imprinting using the conventional surface graft polymerization method. Increasing monomer concentrations enhances pre-assembly, but leads to agglomeration of the particles. To solve the dilemma, here an initiating system consisting of surface-immobilized glucose oxidase and horseradish peroxidase, glucose and acetylacetone was used to synthesize the imprinted coatings. No agglomeration occurs even at high monomer concentrations because of the localized polymerization. When surface imprinting of lysozyme over silica nanoparticles, both adsorption capacity and imprinting factor increase with increasing monomer concentration, because of the enhanced pre-assembly. This strategy was further combined with the “shape-memorable imprint cavity” strategy in which the conventional crosslinker is replaced with a peptide crosslinker capable of undergoing pH-induced helix-coil transition. The resulting surface lysozyme-imprinted silica nanoparticles exhibit high adsorption capacity, high imprinting factor, high selectivity, good reusability, easy and complete template removal under mild conditions, and fast rebinding kinetics. Surface imprinting of other proteins with high imprinting efficiency were also successfully carried out, demonstrating the generality of the strategy.</div></div><div><h3>Statement of significance</h3><div>Surface protein-imprinted nanoparticles have emerged as promising artificial antibodies, but still suffering from low imprinting efficiency, primarily due to insufficient pre-assembly between functional monomers and template proteins. Increasing monomer concentrations enhances pre-assembly but causes particle agglomeration. Here the dilemma was solved by using an initiating system consisting of surface-immobilized glucose oxidase/horseradish peroxidase, glucose, and acetylacetone to achieve localized polymerization. Imprinting efficiency was significantly improved because of enhanced pre-assembly. This strategy was further combined with the “shape-memorable imprint cavity” strategy. Lysozyme-imprinted nanoparticles with high capacity (146.4 mg g⁻¹), high imprinting factor (13.94), reusability, and fast rebinding kinetics was synthesized. Surface imprinting of other proteins with high imprinting efficiency were also successfully carried out, demonstrating the generality of the strategy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 428-439"},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917733","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":"Drug-loaded microneedle patches containing regulatory T cell-derived exosomes for psoriasis treatment","authors":"Meitong Ou ,&nbsp;Jiahui Cao ,&nbsp;Ran Luo,&nbsp;Baisong Zhu,&nbsp;Rourou Miao,&nbsp;Liu Yu,&nbsp;Xinyi Wang,&nbsp;Wen Li,&nbsp;Yiqiu Fu,&nbsp;Jinxie Zhang,&nbsp;Fan Zhang,&nbsp;Qiangsong Wang,&nbsp;Lin Mei","doi":"10.1016/j.actbio.2025.04.015","DOIUrl":"10.1016/j.actbio.2025.04.015","url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia, skin inflammation, and immune dysregulation. These factors contribute to the persistent progression of the disease. While addressing excessive keratinocyte proliferation or inhibiting inflammation may provide temporary therapeutic relief, unresolved immune dysregulation often exacerbates the condition. Therefore, comprehensive treatments that alleviate skin symptoms and regulate immune tolerance are urgently required. An ideal treatment would target multiple factors, including keratinocyte proliferation, inflammation, and immune tolerance, while minimizing systemic side effects. In this study, we developed a dissolvable hyaluronic acid microneedle patch containing regulatory T cell (Treg) exosomes loaded with dimethyl fumarate (DMF) (rExo@DMF MNs). DMF acts as an inhibitor of keratinocyte proliferation and an anti-inflammatory agent through NF-κB suppression and Nrf2 activation, inhibiting the production of pro-inflammatory cytokines and the activation of inflammatory cells. Delivering DMF via Treg exosomes enhances its retention at the lesion site. This system inhibits keratinocyte proliferation and migration, reduces pro-inflammatory cytokine release, and alleviates epidermal hyperplasia and inflammation in an imiquimod-induced psoriasis mouse model. Additionally, Treg exosomes modulate immune responses to promote tolerance. rExo@DMF MNs demonstrate immunomodulatory effects by inhibiting T helper 17 (Th17) cells and inducing regulatory immune cells such as Tregs and tolerogenic dendritic cells (tDCs) differentiation. rExo@DMF MNs alleviate skin symptoms and regulate immune cells in the skin, spleen, and lymph nodes, demonstrating both local and systemic immunoregulation with promising therapeutic potential for psoriasis.</div></div><div><h3>Statement of significance</h3><div>Novel therapies are urgently needed to alleviate skin symptoms and regulate immunity, as current psoriasis treatments focus on symptom relief while neglecting the underlying immune dysfunction, resulting in limited efficacy. Moreover, systemic immunosuppression often leads to severe side effects. This study introduces a hybrid microneedle system (rExo@DMF MNs) that alleviates psoriasis symptoms and modulates immune responses locally and systemically. In addition, rExo@DMF MNs penetrate hyperkeratotic skin, ensuring targeted rExo@DMF release while minimizing systemic exposure and side effects. All components of the system, including hyaluronic acid (a key component of the skin matrix), regulatory T cell-derived exosomes, and DMF (a clinically validated drug), exhibit biocompatibility. This comprehensive approach addresses multiple pathogenic factors, promising an effective and safe psoriasis treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 452-466"},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917735","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":"Engineered probiotics remodel the intestinal epithelial barrier and enhance bacteriotherapy for inflammatory bowel diseases","authors":"Yu Chen ,&nbsp;Shijie Bi ,&nbsp;Xiaoli Zhang ,&nbsp;Junjie Chen ,&nbsp;Jianfeng Xin ,&nbsp;Zhaonan Liu ,&nbsp;Qing Guan ,&nbsp;Peiju Qiu ,&nbsp;Peng Wang ,&nbsp;Jun Liu","doi":"10.1016/j.actbio.2025.04.016","DOIUrl":"10.1016/j.actbio.2025.04.016","url":null,"abstract":"<div><div>Inflammatory bowel diseases (IBDs) are often associated with compromised epithelial barriers and dysregulated gut microbiota. In this study, we revealed the synergistic effect that zinc and indole-3-carbinol (I3C) have in restoring the epithelial barrier, and co-localized them on a ZI platform, which was further conjugated to the surface of <em>Escherichia coli</em> Nissle 1917 (EcN). The ZI@EcN formulation effectively delivered ZI to colon tissues and extended its retention in the intestines due to the colonic colonization effect of EcN, thereby promoting the sustained release of zinc and I3C for optimal synergistic effects on epithelial barrier remodeling. The restored epithelium acts as a protective barrier, preventing the infiltration of toxins and pathogens, which significantly reduces inflammation in colonic tissues. Additionally, EcN enriched the gut microbiome, increasing the abundance of beneficial bacteria while reducing that of pathogens, demonstrating its significant efficacy in gut microbiome regulation. In dextran sulfate sodium-induced mouse colitis models, ZI@EcN exhibited substantially improved prophylactic and therapeutic efficacy with favorable safety profiles, highlighting its potential for clinical applications.</div></div><div><h3>Statement of significance</h3><div>This study highlighted the synergistic effects that zinc and indole-3-carbinol, both derived from dietary sources, have on restoring integrity of the intestinal epithelial barrier. A platform (ZI@EcN) was also developed for the targeted delivery and sustained release of zinc and indole-3-carbinol, specifically in colonic tissues, for colitis treatment. This platform not only restores the compromised intestinal epithelial barrier but also regulates the dysbiotic gut microbiota, promoting the recovery of a healthy intestinal microenvironment and showing promise in alleviating complex symptoms in a single formulation. Furthermore, the formulation demonstrated potent prophylactic and therapeutic efficacy against colitis, with favorable safety profiles, and a strong potential for clinical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 467-481"},"PeriodicalIF":9.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917736","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}