Acta Biomaterialia最新文献

{"title":"A cross-linked coating loaded with antimicrobial peptides for corrosion control, early antibacterial, and sequential osteogenic promotion on a magnesium alloy as orthopedic implants","authors":"Hao Zhang ,&nbsp;Peng Zhang ,&nbsp;Xiaolong Shen ,&nbsp;Jiaping Han ,&nbsp;Haibo Wang ,&nbsp;Haotian Qin ,&nbsp;Binbin Wang ,&nbsp;Junyu Qian ,&nbsp;Anjaneyulu Udduttula ,&nbsp;Rifang Luo ,&nbsp;Kexin Zhao ,&nbsp;Yunbing Wang ,&nbsp;Yingqi Chen","doi":"10.1016/j.actbio.2024.12.046","DOIUrl":"10.1016/j.actbio.2024.12.046","url":null,"abstract":"<div><div>Magnesium (Mg)-based alloys have been recognized as desirable biodegradable materials for orthopedic implants. However, their clinical application has been limited by rapid degradation rates, insufficient antibacterial and osteogenic-promotion properties. Herein, a MgF₂ priming layer was first constructed on AZ31 surface. Then, dopamine and polyphenols (EGCG) were cross-linked onto this AZ31-F surface to promote osteogenesis and further enhance corrosion protection, followed by chemical grafting of antimicrobial peptides (AMPs) via Michael-addition and Schiff-base reaction to confer antibacterial properties. <em>In vitro</em> electrochemical corrosion tests showed that <em>i_corr</em> of AZ31-FE/AMPs (4.36×10⁻⁷ A/cm²) is two orders of magnitude lower than that of AZ31 (4.17×10⁻⁵ A/cm²). <em>In vitro</em> immersion degradation showed that AZ31-FE/AMPs exhibited the lowest hydrogen release (2.38 mL) after 400 h immersion with the lowest hydrogen evolution rate among them. Further, AZ31-FE/AMPs displayed inhibitory effects against <em>S. aureus</em> and <em>E. coil</em> in the initial stage and even after 7 days immersion in PBS (antibacterial rate &gt; 85 %). AZ31-FE/AMPs promoted ALP secretion and calcium nodule formation in MC3T3-E1 cells. Transcriptome sequencing results indicated that osteogenic promotion mechanism of AZ31-FE/AMPs in MC3T3-E1 may involve the PI3K-Akt signalling pathway. Further, AZ31-FE/AMPs enhanced new bone formation when implanted in a rat femoral bone defect model. This coating strategy addresses initial antibacterial and later osteogenesis needs based on the corrosion control, which is crucial for the surface design of Mg-based implants.</div></div><div><h3>Statement of significance</h3><div>It is critical for magnesium-based orthopedic implants to achieve sequential functions in the bone repair process while controlling an appropriate degradation rate. A MgF₂ priming layer/phenolic-amine grafted AMPs (antimicrobial peptides) duplex coating was constructed on AZ31 surface in this study. The MgF₂ layer provided a basic corrosion protection to magnesium substrate, and dopamine and polyphenols (EGCG) were then cross-linked to the MgF₂ pretreated AZ31 to promote osteogenesis and enhance corrosion resistance, followed by chemical grafting of AMPs to confer antibacterial property. This strategy effectively meets the initial need for infection resistance and later osteogenic promotion on the basis of controlling the substrate corrosion rate, thus holding significant implications for the surface design of magnesium-based implants.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 604-622"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883810","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":"Dually fluorinated unimolecular micelles for stable oxygen-carrying and enhanced photosensitive efficiency to boost photodynamic therapy against hypoxic tumors","authors":"Shunhu Zhang ,&nbsp;Nailin Yang ,&nbsp;Shumin Sun ,&nbsp;Haitao Zhao ,&nbsp;Wenxuan Wang ,&nbsp;Jihu Nie ,&nbsp;Zifan Pei ,&nbsp;Weiwei He ,&nbsp;Lifen Zhang ,&nbsp;Liang Cheng ,&nbsp;Zhenping Cheng","doi":"10.1016/j.actbio.2025.01.017","DOIUrl":"10.1016/j.actbio.2025.01.017","url":null,"abstract":"<div><div>Tumor hypoxia is one of key challenges in deep tumor photodynamic therapy (PDT), and how to fix this issue is attracting ongoing concerns worldwide. This work demonstrates dually fluorinated unimolecular micelles with desirable and stable oxygen-carrying capacity, high cellular penetration, and integrative type I &amp; II PDT for deep hypoxic tumors. Dually fluorinated star copolymers with fluorinated phthalocyanines as the core are prepared through photoinitiated electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization under irradiation with NIR LED light at room temperature, followed by assembly into unimolecular micelles. Perfluorocarbons (PFCs) are also introduced into the star polymers during the polymerization to further enhance and stabilize oxygen-carrying capacity, which is slightly affected by concentration-induced size transformation. PFCs assist unimolecular micelles with repelling mucin adsorption, which results in superior cellular uptake within 1 h and high effective accumulation rates in tumors of CT26 tumor-bearing mice within 24 h after systemic administration, and showing effective anti-tumor effects under the irradiation of NIR LED light. This work provides a new type of nano-photosensitizers for highly efficient hypoxic PDT.</div></div><div><h3>Statement of significance</h3><div>One of the major challenges in improving the efficiency of photodynamic therapy (PDT) for deep tumors is how to address tumor hypoxia, which is receiving continued attention worldwide. However, most of the reported oxygen carriers combine with photosensitizers by physical means and the carriers have the risk of dissociating easily, which is not conducive to long-term and efficient PDT, resulting in poor therapeutic effect. This work demonstrates dually fluorinated unimolecular micelles with desirable and stable oxygen-carrying capacity, high cellular penetration, and integrative type I &amp; II PDT for enhanced deep hypoxic tumors, overcoming the key challenges of tumor hypoxia and low photosensitizer efficiency.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 406-416"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973635","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 endothelial cells derived from transgene-free pig induced pluripotent stem cells for vascular tissue engineering","authors":"Luke Batty ,&nbsp;Jinkyu Park ,&nbsp;Lingfeng Qin ,&nbsp;Muhammad Riaz ,&nbsp;Yuyao Lin ,&nbsp;Zhen Xu ,&nbsp;Xuefei Gao ,&nbsp;Xin Li ,&nbsp;Colleen Lopez ,&nbsp;Wei Zhang ,&nbsp;Marie Hoareau ,&nbsp;Meghan E. Fallon ,&nbsp;Yan Huang ,&nbsp;Hangqi Luo ,&nbsp;Jiesi Luo ,&nbsp;Séverine Ménoret ,&nbsp;Peining Li ,&nbsp;Zhenting Jiang ,&nbsp;Peter Smith ,&nbsp;David H. Sachs ,&nbsp;Yibing Qyang","doi":"10.1016/j.actbio.2024.12.033","DOIUrl":"10.1016/j.actbio.2024.12.033","url":null,"abstract":"<div><div>Induced pluripotent stem cells (iPSCs) hold great promise for the treatment of cardiovascular diseases through cell-based therapies, but these therapies require extensive preclinical testing that is best done in species-in-species experiments. Pigs are a good large animal model for these tests due to the similarity of their cardiovascular system to humans. However, a lack of adequate pig iPSCs (piPSCs) that are analogous to human iPSCs has greatly limited the potential usefulness of this model system. Herein, transgene-free piPSCs with true pluripotency were generated by using reprogramming factors in an optimized pig pluripotency medium. Using an effective differentiation protocol, piPSCs were used to derive endothelial cells (ECs) which displayed EC markers and functionality comparable to native pig ECs. Further, piPSC-ECs demonstrated suitability for vascular tissue engineering, producing a tissue engineered vascular conduit (TEVC) that displayed the upregulation of flow responding markers. In an <em>in vivo</em> functional study, these piPSC-EC-TEVCs maintained the expression of endothelial markers and prevented thrombosis as interposition inferior vena cava grafts in immunodeficient rats. The piPSCs described in this study open up the possibility of unique preclinical species-in-species large animal modeling for the furtherance of modeling of cell-based cardiovascular tissue engineering therapies.</div></div><div><h3>Statement of Significance</h3><div>While there has been significant progress in the development of cellularized cardiovascular tissue engineered therapeutics using stem cells, few of them have moved into clinical trials. This is due to the lack of a robust preclinical large animal model to address the high safety and efficacy standards for transplanted therapeutics. In this study, pig stem cells that are analagous to human's were created to address this bottleneck. They demonstrated the ability to differentiate into functional endothelial cells and were able to create a tissue engineered therapeutic that is analogous to a human therapy. With these cells, future experiments testing the safety and efficacy of tissue engineered constructs are possible, bringing these crucial therapeutics closer to the patients that need them.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 171-184"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840551","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":"Active and passive material response of urinary bladder smooth muscle tissue in uniaxial and biaxial tensile testing","authors":"Julian Geldner ,&nbsp;Stefan Papenkort ,&nbsp;Simon Kiem ,&nbsp;Markus Böl ,&nbsp;Tobias Siebert","doi":"10.1016/j.actbio.2024.12.045","DOIUrl":"10.1016/j.actbio.2024.12.045","url":null,"abstract":"<div><div>The urinary bladder is a hollow organ that undergoes significant deformation as it receives, stores, and releases urine. To understand the organ mechanics, it is necessary to obtain information about the material properties of the tissues involved. In displacement-controlled tensile tests, tissue samples are mounted on a device that applies stretches to the tissue in one or more directions, resulting in a specific stress response. For this study, we performed uniaxial and biaxial stretch experiments on tissue samples (<em>n</em> = 36) from the body region of the porcine urinary bladder. We analyzed the stress-relaxation, activation dynamics, and passive and active stretch-stress response. Main findings of our experiments are: (1) For uniaxial and biaxial stretching, the time constants for stress-relaxation depend on the stretch amplitude, (2) biaxially stretched samples experienced slower activation with <span><math><msub><mi>τ</mi><mrow><mi>a</mi><mi>c</mi><mi>t</mi></mrow></msub></math></span> increasing by +63% compared to uniaxial stretching, (3) biaxial tests are characterized by reduced optimum stretches <span><math><msub><mi>λ</mi><mrow><mi>o</mi><mi>p</mi><mi>t</mi></mrow></msub></math></span> by -18%, and (4) biaxial and uniaxial tests showed no significant difference in maximum active stresses <span><math><msub><mi>σ</mi><mi>opt</mi></msub></math></span>. To interpret the results, we present a continuum mechanical model based on a viscoelastic, isotropic solid extended by a set of active muscle fibers. Model predictions show that results (3) and (4) can be explained by a uniform distribution of fiber orientations and a specific shape of the active fiber stress-stretch relationship. This study highlights how deformation modes during tensile testing affects smooth muscle mechanics, proving insights for interpreting experimental data and improving organ modeling.</div></div><div><h3>Statement of Significance</h3><div>In this study, we examined the mechanical properties of porcine bladder smooth muscle using uniaxial and equibiaxial tensile tests. To our knowledge, this is the first instance where the active stress-stretch relationships of smooth muscle tissue have been analysed under equibiaxial stretch. The data collected offer a detailed understanding of the connection between deformation and active stress production, surpassing the insights provided by existing uniaxial tests in the literature. These findings are crucial for comprehending the physiology of smooth muscle tissue and for developing constitutive muscle models that can make more accurate predictions about the functionality of hollow organs in both health and disease. Additionally, our findings on smooth muscle active stress could aid in the creation of biomaterials that interact with or even replace natural muscle.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 255-266"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873574","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":"Osteosarcoma-targeting PtIV prodrug amphiphile for enhanced chemo-immunotherapy via Ca2+ trapping","authors":"Jianqin Yan,&nbsp;Dengshuai Wei,&nbsp;Zijian Zhao,&nbsp;Kaichuang Sun,&nbsp;Yong Sun","doi":"10.1016/j.actbio.2024.12.048","DOIUrl":"10.1016/j.actbio.2024.12.048","url":null,"abstract":"<div><div>Platinum (Pt^II)-based anticancer agents exhibit a lack of selectivity in the treatment of osteosarcoma, resulting in significant toxicity. Furthermore, immune surveillance withinthe tumor microenvironment impedes the uptake of platinum drugs by osteosarcoma cells. To overcome these challenges, an oxaliplatin-based Pt^IV prodrug amphiphile (Lipo-OXA-ALN) was designed and synthesized by incorporatingan osteosarcoma-targeting alendronate (ALN) alongside a lipid tail. The lipid nanoparticles (ALN-OXA), which self-assemble from Lipo-OXA-ALN, enhanced intracellular platinum uptake due to their superior Ca²⁺ trapping ability and significantly inhibit osteosarcoma cell activity. Moreover, ALN-OXA exhibited potent targeting capabilities, effectively suppressing osteosarcoma growth while preventing bone destruction. Importantly, ALN-OXA induces a series of immune responses characterized by the activation of immune cells, maturation of dendritic cells, and secretion of related cytokines, followed by the activation and infiltration of T lymphocytes and a significant increase in the ratio of cytotoxic T cells. Additionally, the ratio of M1/M2 macrophages increased markedly after ALN-OXA treatment, suggesting potential reprogramming of the tumor microenvironment by ALN-OXA. Overall, the improved therapeutic efficacy against osteosarcoma demonstrates that the Pt^IV prodrug amphiphile represents a promising strategy for combining targeted chemotherapy with strategies aimed at reversing immune suppression.</div></div><div><h3>Statement of significance</h3><div>Platinum (Pt^II)-based chemotherapy for osteosarcoma faces challenges due to poor tumor selectivity, leading to suboptimal efficacy and increased toxicity. Additionally, the osteosarcoma microenvironment impedes effective drug delivery. To overcome these limitations, we developed an oxaliplatin-based Pt^IV prodrug nanoparticle (ALN-OXA) for targeted chemo-immunotherapy. ALN-OXA showed significant <em>in vivo</em> efficacy, effectively preventing bone damage and enhancing the immune microenvironment to improve treatment outcomes. This innovative approach not only targets the tumor more efficiently but also boosts immune response, offering a promising strategy for tumor blockade, tumor starvation, and other therapeutic applications in osteosarcoma treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"193 ","pages":"Pages 474-483"},"PeriodicalIF":9.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886557","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":"Cell confinement by micropatterning induces phenotypic changes in cancer-associated fibroblasts","authors":"Aleksandr Mitriashkin ,&nbsp;Josephine Yu Yan Yap ,&nbsp;Elekuttige Anton Kanishka Fernando ,&nbsp;N. Gopalakrishna Iyer ,&nbsp;Gianluca Grenci ,&nbsp;Eliza Li Shan Fong","doi":"10.1016/j.actbio.2024.12.007","DOIUrl":"10.1016/j.actbio.2024.12.007","url":null,"abstract":"<div><div>Recent advances in single-cell studies have revealed the vast transcriptomic heterogeneity of cancer-associated fibroblasts (CAFs), with each subset likely having unique roles in the tumor microenvironment. However, it is still unclear how different CAF subsets should be cultured <em>in vitro</em> to recapitulate their <em>in vivo</em> phenotype. The inherent plasticity of CAFs, or their ability to dynamically change their phenotype in response to different environmental stimuli, makes it highly challenging to induce and maintain a specific CAF state <em>in vitro</em>. In this study, we investigated how cell shape and confinement on two-dimensional culture substrates with different stiffnesses influence CAF transcriptomic profile and phenotype. Using micropatterning of polyacrylamide hydrogels to induce shape- and confinement-dependent changes in cell morphology, we observed that micropatterned CAFs exhibited phenotypic shifts towards more desmoplastic and inflammatory CAF subsets. Additionally, micropatterning enabled control over a range of CAF-specific markers and pathways. Lastly, we report how micropatterned and non-micropatterned CAFs respond differently to anti-cancer drugs, highlighting the importance of phenotype-oriented therapy that considers for CAF plasticity and regulatory networks. Control over CAF morphology offers a unique opportunity to establish highly robust CAF phenotypes <em>in vitro</em>, facilitating deeper understanding of CAF plasticity, heterogeneity, and development of novel therapeutic targets.</div></div><div><h3>Statement of significance</h3><div>Cancer-associated fibroblasts (CAFs) are the dominant stromal cell type in many cancers, and recent studies have revealed that they are highly heterogeneous and comprise several subpopulations. It is still unclear how different subsets of CAFs should be cultured <em>in vitro</em> to recapitulate their <em>in vivo</em> phenotype. In this study, we investigated how cell shape and confinement affect CAF transcriptomic profile and phenotype. We report that micropatterned CAFs resemble desmoplastic and inflammatory CAF subsets observed <em>in vivo</em> and respond differently to anti-cancer drugs as compared to non-patterned CAFs. Control over CAF morphology enables the generation of highly robust CAF phenotypes <em>in vitro</em>, facilitating deeper understanding of CAF plasticity and heterogeneity.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 61-76"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786950","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":"Bio-functional niobium-based metallic biomaterials: Exploring their physicomechanical properties, biological significance, and implant applications","authors":"Ziyuan Liu ,&nbsp;Ming-Chun Zhao ,&nbsp;Dengfeng Yin ,&nbsp;Ying-Chao Zhao ,&nbsp;Andrej Atrens","doi":"10.1016/j.actbio.2024.12.036","DOIUrl":"10.1016/j.actbio.2024.12.036","url":null,"abstract":"<div><div>The significance of biomedical applications of bio-functional niobium (Nb)-based metallic biomaterials is underscored by their potential utilization in implant application. Nb-based metallic materials present reliable physicomechanical and biological properties, thus represent materials highly suitable for implant application. This review provides an overview on the advances of pure niobium and Nb-based metallic materials as implant materials over the past 20 years, and highlights the advantages of Nb-based metallic biomaterials for implant application in terms of their physicomechanical properties, corrosion resistance in biological media, magnetic resonance imaging (MRI) compatibility, cell compatibility, blood compatibility, osteogenesis, and bioactivity. An introduction is provided for the production and processing techniques for Nb-based metallic biomaterials, including traditional melting processes like vacuum arc remelting, additive manufacturing like selective laser melting (SLM), electron beam melting (EBM), spark plasma sintering (SPS), and severe plastic deformation like equal channel angular pressing (ECAP), multi-axial forging (MAF), high pressure torsion (HPT), as well as their physicomechanical properties and implant application. Also suggested are the critical issues, challenges, and prospects in the further development of Nb-based metallic biomaterials for implant applications.</div></div><div><h3>Statement of significance</h3><div>Nb-based biomaterials have gained significant interest for bioimplantable scaffolds because of their appropriate mechanical characteristics and biocompatibility. No prior work has been published specifically reviewing bio-functional Nb-based biomaterials for exploring their physicomechanical properties, biological significance, and implant applications. This review provides an overview on the advances of niobium and Nb-based materials as implant materials over the past 20 years, and highlights the advantages of Nb-based biomaterials for implant application. An introduction is provided for the production and processing techniques for Nb-based biomaterials, as well as their physicomechanical properties and implant application. Also suggested are the critical issues, challenges, and prospects in the further development of Nb-based biomaterials for implant applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 1-27"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840549","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":"Stimuli-responsive hydrogel microspheres encapsulated with tumor-cell-derived microparticles for malignant ascites treatment","authors":"Shishi Zhu ,&nbsp;Xin Shou ,&nbsp;Gaizhen Kuang ,&nbsp;Xiuyan Kong ,&nbsp;Weijian Sun ,&nbsp;Qingfei Zhang ,&nbsp;Jinglin Xia","doi":"10.1016/j.actbio.2024.11.034","DOIUrl":"10.1016/j.actbio.2024.11.034","url":null,"abstract":"<div><div>Tumor-cell-derived microparticles (TMPs) have been recognized as chemotherapeutic drug carriers and immunomodulators for anti-tumor therapy. Research in the clinical application of TMPs has been devoted to developing an effective delivery formulation that could enhance their therapeutic effects. Here, we propose thermal-responsive agarose hydrogel microspheres (MTX-TMPs@MSs) with encapsulation of Methotrexate (MTX)-packaging TMPs (MTX-TMPs) and black phosphorus quantum dots (BPQDs) by microfluidic technology for synergistic treatment of malignant ascites. The laden MTX-TMPs, separated from apoptotic tumor cells, could target tumor cells for the delivery of chemotherapy drugs and modulate the tumor immune microenvironment. Under near-infrared (NIR) induced thermal stimulation, MTX-TMPs could be controllably released from the low-melting-point agarose matrix hydrogel microspheres for chemotherapy (CHT) and immunotherapy (IMT). In addition, benefiting from photothermal therapy (PTT)-induced tumor immunogenic death, the anti-tumor immune response triggered by MTX-TMPs was further enhanced. Based on these features, the MTX-TMPs@MSs could remarkably eliminate tumor cells <em>in vitro</em> and obviously suppress tumor growth <em>in vivo</em> through synergistic PTT, CHT, and IMT. Therefore, it is envisaged that this TMPs-integrated microcarrier will have promising applications in clinical tumor therapy.</div></div><div><h3>Statement of Significance</h3><div>Primary liver cancer ranks third among the causes of cancer deaths globally, with hepatocellular carcinoma (HCC) being the most common type. In particular, patients with advanced HCC accompanied by malignant ascites, a common complication, indicate tumor metastasis and a poor prognosis. In this paper, we developed stimuli-responsive hydrogel microspheres from microfluidics for the delivery of methotrexate (MTX)-loaded tumor-cell-derived microparticles (MTX-TMPs) for synergistic chemotherapy, photothermal therapy, and immunotherapy. The release of MTX-TMPs from hydrogel microspheres could be on-demand controlled through BPQDs-mediated photothermal stimulus. On the other hand, BPQDs-mediated mild hyperthermia cooperatesss with MTX-TMPs-induced chemotherapy could participate in remodeling the tumor immunosuppressive microenvironment. Thus, the prepared microcarrier system holds great promise for tumor therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 328-339"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717809","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":"Black phosphorus nanoplatform coated with platelet membrane improves inhibition of atherosclerosis progression through macrophage targeting and efferocytosis","authors":"Jiahui Zhang ,&nbsp;Zhiwen Wang ,&nbsp;Yuhan Liao ,&nbsp;Junran Tong ,&nbsp;Ran Gao ,&nbsp;Zhuanglin Zeng ,&nbsp;Yu Bai ,&nbsp;Yumiao Wei ,&nbsp;Xiaopeng Guo","doi":"10.1016/j.actbio.2024.11.041","DOIUrl":"10.1016/j.actbio.2024.11.041","url":null,"abstract":"<div><div>Plaque rupture in atherosclerosis (AS) is a major cause of acute cardiovascular events. Macrophage-induced inflammatory responses and accumulation of excess reactive oxygen species (ROS) primarily induce unstable plaques. Therefore, targeting ROS clearance and functional modulation of macrophages are clinically crucial for improving plaque stability and inhibiting AS progression. Here, we constructed a bionic nano-delivery platform, PBP@siR@PM, using platelet membranes (PM) coated with black phosphorus nanosheets (BPNSs) to target macrophages in atherosclerotic plaques. Meanwhile, PM-coated BPNSs (PBP@siR@PM) were used to deliver small interfering RNA silencing Ca²⁺/calmodulin-dependent protein kinase γ (CaMKIIγ) into macrophages. Furthermore, macrophage efferocytosis was restored by inhibiting CaMKIIγ and increasing the expression of MerTK, a cytosolic receptor, thus promoting the clearance of apoptotic cells from plaques. This study demonstrated that intraplaque macrophage-targeted therapy using the bionic nano-delivery platform PBP@siR@PM effectively removed excess ROS from macrophages, promoted efferocytosis, cleared apoptotic cells in plaques, improved plaque stability, and largely inhibited AS progression in ApoE^–/– mice after high fat diet. In summary, this study proposes a therapeutic strategy for AS and highlights the outstanding therapeutic potential of biomimetic nanomaterials in this type of chronic inflammatory disease.</div></div><div><h3>Statement of significance</h3><div>Rupture of atherosclerotic unstable plaques is a major cause of acute cardiovascular events. Macrophage-induced chronic inflammation and oxidative stress due to overloaded ROS are major contributors to plaque rupture. In this study, we focused on the improvement of macrophage efferocytosis within the plaque for the effective treatment of atherosclerosis. A bionic nano-delivery platform was constructed using platelet membranes (PM) coated black phosphorus nanosheets (BPNSs) to target macrophages in atherosclerotic plaques. In conclusion, intraplaque macrophage-targeted therapy based on the bionic nano-delivery platform PBP@siR@PM effectively scavenges overloaded ROS in macrophages, promotes efferocytosis, removes apoptotic cells from plaques, and improves plaque stability, which significantly inhibits the progression of atherosclerosis in ApoE^–/– mice after a high-fat diet.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 377-393"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752579","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":"3D printing of stiff, tough, and ROS-scavenging nanocomposite hydrogel scaffold for in situ corneal repair","authors":"Tan Li ,&nbsp;Xiaoyu Zhang ,&nbsp;Li Ma ,&nbsp;Xia Qi ,&nbsp;Hongwei Wang ,&nbsp;Qingjun Zhou ,&nbsp;Xiuli Sun ,&nbsp;Fuyan Wang ,&nbsp;Long Zhao ,&nbsp;Weiyun Shi","doi":"10.1016/j.actbio.2024.12.005","DOIUrl":"10.1016/j.actbio.2024.12.005","url":null,"abstract":"<div><div>Despite significant advancements in hydrogels in recent years, their application in corneal repair remains limited by several challenges, including unfitted curvatures, inferior mechanical properties, and insufficient reactive oxygen species (ROS)-scavenging activities. To address these issues, this study introduces a 3D-printed corneal scaffold with nanocomposite hydrogel consisting of gelatin methacrylate (GelMA), poly (ethylene glycol) diacrylate (PEGDA), Laponite, and dopamine. GelMA and PEGDA act as matrix materials with photo-crosslinking abilities. As a two-dimensional nanoclay, Laponite enhances the rheological properties of the hydrogel, making it suitable for 3D printing. Dopamine self-polymerizes into polydopamine (PDA), providing the hydrogel with ROS-scavenging activity. The incorporation of Laponite and the synergistic effect of PDA endow the hydrogel with good mechanical properties. In vitro investigations demonstrated the cytocompatibility of GelMA-PEGDA-Laponite-dopamine (GPLD) hydrogel and its ROS-scavenging activity. Furthermore, in vivo experiments using a rabbit model of lamellar keratoplasty showed accelerated corneal re-epithelialization and complete stromal repair after the implantation of the 3D-printed scaffold. Overall, due to its high bioactivity and simple preparation, the 3D-printed scaffold using GPLD hydrogel offers an alternative for corneal repair with potential for clinical translation.</div></div><div><h3>Statement of Significance</h3><div>The clinical application of hydrogel corneal scaffolds has been constrained by their inadequate mechanical properties and the complex microenvironment created by elevated levels of ROS post-transplantation. In this study, we developed a kind of nanocomposite hydrogel by integrating Laponite and dopamine into GelMA and PEGDA. This advanced hydrogel was utilized to 3D print a corneal scaffold with high mechanical strength and ROS-scavenging abilities. When applied to a rabbit model of lamellar keratoplasty, the 3D-printed scaffold enabled complete re-epithelialization of the cornea within one week. Three months after surgery, the corneal stroma was fully repaired, and regeneration of corneal nerve fibers was also observed. This 3D-printed scaffold demonstrated exceptional efficacy in repairing corneal defects with potential for clinical translation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 189-205"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792945","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}