ACTA BIOMATERIALIA 是 ELSEVIER 出版的月度同行评审科学期刊。它代表 ACTA MATERIALIA, INC. 出版，由 ASM INTERNATIONAL 和 THE MINERALS, METALS & MATERIALS SOCIETY 赞助。杂志创刊于2005年1月，主编为W.R. WAGNER（匹兹堡大学）。该杂志涵盖生物材料科学的研究，包括从宏观到纳米级的生物材料结构和功能的相互关系。专题报道包括生物医学和生物相容性材料。

Acta Biomaterialia is a monthly peer-reviewed scientific journal published by Elsevier. It is published on behalf of ACTA MATERIALIA, INC. and sponsored by ASM INTERNATIONAL and THE MINERALS, METALS & MATERIALS SOCIETY. The journal was established in January 2005, with W.R. WAGNER (University of Pittsburgh) as the editor-in-chief. It covers research in biomaterials science, focusing on the relationship between the structure and function of biomaterials at macro to nano scales. Topics include biomedical and biocompatible materials.

《Acta Biomaterialia》是由Elsevier出版的月度同行评审科学期刊。该期刊由ACTA MATERIALIA, INC.出版，并由ASM INTERNATIONAL和THE MINERALS, METALS & MATERIALS SOCIETY赞助。创刊于2005年1月，主编为W.R. WAGNER（匹兹堡大学）。期刊涵盖生物材料科学的研究，探讨生物材料的结构与功能之间的关系，范围从宏观到纳米级。专题报道包括生物医学和生物相容性材料。

Acta Biomaterialia

The success of cell therapy for tissue repair and regeneration demands efficient and reliable cell delivery methods. Here we established a novel microengineered cryogel (microcryogel) array chip containing microcryogels with predefined size and shape as injectable cell delivery vehicles. The microscale macroporous cryogels enabled automatic and homogeneous loading of tailored cellular niches (e.g. cells, matrices, bioactive factors) and could be easily harvested from the ready-to-use array chip. In contrast to microscale hydrogels, microcryogels exhibited excellent elasticity and could retain their shape and integrity after injection through the microsyringe routinely used for cell therapy. Human mesenchymal stromal cells loaded within microcryogels could be shielded from the mechanical insult and necrosis caused by during direct cell injection. After subcutaneous injection to the mice, cell-loaded microcryogels exhibited concentrated localization and enhanced retention at the injection site compared to dissociated cells. To demonstrate the potential therapeutic application for ischemic diseases, site-directed induction of angiogenesis was achieved subcutaneously in mice 2weeks after injection of NIH/3T3 fibroblast-loaded microcryogels, indicating long-term engraftment, accumulative paracrine stimulation and augmented host tissue integration. Our results convincingly showed the great promise of microcryogels as 3-D cellular microniches and injectable cell delivery vehicles to tackle major challenges faced by cell therapy-based regenerative medicine including shear-induced damages, uncontrolled localization, poor retention, limited cellular survival and functionalities in vivo.

Wei Liu

Yaqian Li

Yang Zeng

Xinyong Zhang

Jingyu Wang

Liping Xie

Xiaokang Li

Yanan Du

Acta biomaterialia

Acta Biomater

Microcryogels as injectable 3-D cellular microniches for site-directed and augmented cell delivery.

微低温凝胶作为可注射的三维细胞微环境用于定点增强细胞递送。

Tissue engineering using traditional size fixed scaffolds and injectable biomaterials are faced with many limitations due to the difficulties of producing macroscopic functional tissues. In this study, 3D functional tissue constructs were developed by inducing self-assembly of microniches, which were cell-laden gelatin microcryogels. During self-assembly, the accumulation of extracellular matrix (ECM) components was found to strengthen cell-cell and cell-ECM interactions, leading to the construction of a 'native' microenvironment that better preserved cell viability and functions. MSCs grown in self-assembled constructs showed increased maintenance of stemness, reduced senescence and improved paracrine activity compared with cells grown in individual microniches without self-assembly. As an example of applying the self-assembled constructs in tissue regeneration, the constructs were used to induce in vivo articular cartilage repair and successfully regenerated hyaline-like cartilage tissue in the absence of other extrinsic factors. This unique approach of developing self-assembled 3D functional constructs holds great promise for the generation of tissue engineered organoids and repair of challenging tissue defects. STATEMENT OF SIGNIFICANCE: We developed 3D functional tissue constructs using a unique gelatin-based microscopic hydrogel (microcryogels). Mesenchymal stem cells (MSCs) were loaded into gelatin microcryogels to form microscopic cell-laden units (microniches), which were induced to undergo self-assembly using a specially designed 3D printed frame. Extracellular matrix accumulation among the microniches resulted in self-assembled macroscopic constructs with superior ability to maintain the phenotypic characteristics and stemness of MSCs, together with the suppression of senescence and enhanced paracrine function. As an example of application in tissue regeneration, the self-assembled constructs were shown to successfully repair articular cartilage defects without any other supplements. This unique strategy for developing 3D functional tissue constructs allows the optimisation of stem cell functions and construction of biomimetic tissue organoids.

Dan Xing

Jiao Jiao Li

Longwei Liu

Anqi Guo

Bin Wang

Hongsheng Yu

Yu Zhao

Yuling Chen

Zhifeng You

Cheng Lyu

Wenjing Li

Aifeng Liu

Jianhao Lin

Engineering 3D functional tissue constructs using self-assembling cell-laden microniches.

Nanomedicines represent innovative and promising alternative technologies to improve the therapeutic effects of different drugs for cancer ablation. Targeting M2-like tumor-associated macrophages (TAMs) has emerged as a favorable therapeutic approach to fight against cancer through the modulation of the tumor microenvironment. However, the immunomodulatory molecules used for this purpose present side effects upon systemic administration, which limits their clinical translation. Here, the biocompatible lignin polymer is used to prepare lignin nanoparticles (LNPs) that carry a dual agonist of the toll-like receptors TLR7/8 (resiquimod, R848). These LNPs are targeted to the CD206-positive M2-like TAMs using the "mUNO" peptide, in order to revert their pro-tumor phenotype into anti-tumor M1-like macrophages in the tumor microenvironment of an aggressive triple-negative in vivo model of breast cancer. Overall, we show that targeting the resiquimod (R848)-loaded LNPs to the M2-like macrophages, using very low doses of R848, induces a profound shift in the immune cells in the tumor microenvironment towards an anti-tumor immune state, by increasing the representation of M1-like macrophages, cytotoxic T cells, and activated dendritic cells. This effect consequently enhances the anticancer effect of the vinblastine (Vin) when co-administered with R848-loaded LNPs. STATEMENT OF SIGNIFICANCE: Lignin-based nanoparticles (LNPs) were successfully developed to target a potent TLR7/8 agonist (R848) of the tumor microenvironment (TME). This was achieved by targeting the mannose receptor (CD206) on the tumor supportive (M2-like) macrophages with the "mUNO" peptide, to reprogram them into an anti-tumor (M1-like) phenotype for enhanced chemotherapy. LNPs modified the biodistribution of the R848, and enhanced its accumulation and efficacy in shifting the immunological profile of the cells in the TME, which was not achieved by systemic administration of free R848. Moreover, a reduction in the tumor volumes was observed at lower equivalent doses of R848 compared with other studies. Therefore, the co-administration of R848@LNPs is a promising chemotherapeutic application in aggressive tumors, such as the triple-negative breast cancer.

Patrícia Figueiredo

Anni Lepland

Pablo Scodeller

Flavia Fontana

Giulia Torrieri

Mattia Tiboni

Mohammad-Ali Shahbazi

Luca Casettari

Mauri A Kostiainen

Jouni Hirvonen

Tambet Teesalu

Hélder A Santos

Peptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapy.

Regeneration of the gradient structure of the tendon-to-bone interface (TBI) is a crucial goal after rotator cuff repair. The purpose of this study was to investigate the efficacy of a biomimetic hydroxyapatite-gradient scaffold (HA-G scaffold) isolated from adipose tissue (AD) with umbilical cord derived mesenchymal stem cells (UC MSCs) on the regeneration of the structure of the TBI by analyzing the histological and biomechanical changes in a rat repair model. As a result, the HA-G scaffold had progressively increased numbers of hydroxyapatite (HA) particles from the tendon to the bone phase. After seeding UC MSCs to the scaffold, specific matrices, such as collagen, glycoaminoglycan, and calcium, were synthesized with respect to the HA density. In a rat repair model, compared to the repair group, the UC MSCs seeded HA-G scaffold group had improved collagen organization and cartilage formation by 52% at 8 weeks and 262.96% at 4 weeks respectively. Moreover, ultimate failure load also increased by 30.71% at 4 weeks in the UC MSCs seeded HA-G scaffold group compared to the repair group. Especially, the improved values were comparable to values in normal tissue. This study demonstrated that HA-G scaffold isolated from AD induced UC MSCs to form tendon, cartilage and bone matrices similar to the TBI structure according to the HA density. Furthermore, UC MSC-seeded HA-G scaffold regenerated the TBI of the rotator cuff in a rat repair model in terms of histological and biomechanical properties similar to the normal TBI. Statement of Significance We found specific extracellular matrix (ECM) formation in the biomimetic-hydroxyapatite-gradient-scaffold (HA-G-scaffold) in vitro as well as improved histological and biomechanical results of repaired rotator cuff after the scaffold implantation in a rat model. This study has four strengths; An ECM scaffold derived from human adipose tissue; only one-layer used for a gradient scaffold not a multilayer used to mimic the unique structure of the gradient tendon-to-bone-interface (TBI) of the rotator cuff; UC-MSCs as a new cell source for TBI regeneration; and the UC-MSCs synthesized specific matrices with respect to the HA density without any other stimuli. This study suggested that the UC-MSC seeded HA-G-scaffold could be used as a promising strategy for the regeneration of rotator cuff tears.

Ji-Hye Yea

Tae Soo Bae

Byoung Jae Kim

Yong Woo Cho

Chris Hyunchul Jo

Regeneration of the rotator cuff tendon-to-bone interface using umbilical cord-derived mesenchymal stem cells and gradient extracellular matrix scaffolds from adipose tissue in a rat model.

利用脐带来源间充质干细胞和脂肪组织梯度细胞外基质支架在大鼠模型中再生肩袖肌腱-骨界面。

Substantial challenges remain in constructing the native tendon-to-bone interface for rotator cuff healing owing to the enthesis tissues' highly organized structural and compositional gradients. Herein, we propose to bioprint living tissue constructs with layer-specific growth factors (GFs) to promote enthesis regeneration by guiding the zonal differentiation of the loaded stem cells in situ. The sustained release of tenogenic, chondrogenic, and osteogenic GFs was achieved via microsphere-based delivery carriers embedded in the bioprinted constructs. Compared to the basal construct without GFs, the layer-specific tissue analogs realized region-specific differentiation of stem cells in vitro. More importantly, bioprinted living tissue constructs with layer-specific GFs rapidly enhanced the enthesis regeneration in a rabbit rotator cuff tear model in terms of biomechanical restoration, collagen deposition, and alignment, showing gradient interface of fibrocartilage structures with aligned collagen fibrils and an ultimate load failure of 154.3 ± 9.5 N resembling those of native enthesis tissues in 12 weeks. This exploration provides a feasible strategy to engineer living tissue constructions with region-specific differentiation potentials for the functional repair of gradient enthesis tissues. STATEMENT OF SIGNIFICANCE: Previous studies that employed acellular layer-specific scaffolds or stem cells for the reconstruction of the rotator cuff faced challenges due to their insufficient capability to rebuild the anisotropic compositional and structural gradients of native enthesis tissues. This manuscript proposed a living tissue construct with layer-specific, GFs-loaded µS, which can direct in situ and region-specific differentiation of the embedded stem cells to tenogenic, chondrogenic, and osteogenic lineages for functional regeneration of the enthesis tissues. This bioprinted living tissue construct with the unique capability to reduce fibrovascular scar tissue formation and simultaneously facilitate enthesis tissue remodeling might provide a promising strategy to repair complex and gradient tissues in the future.

Lang Bai

Qian Han

Zijie Meng

Baojun Chen

Xiaoli Qu

Meiguang Xu

Yanwen Su

Zhennan Qiu

Yuan Xue

Jiankang He

Jing Zhang

Zhanhai Yin

Bioprinted living tissue constructs with layer-specific, growth factor-loaded microspheres for improved enthesis healing of a rotator cuff.

Cuproptosis is an emerging form of programmed cell death and shows enormous prospect in cancer treatment. Excessive generation of reactive oxygen species (ROS), metal ion accumulation, and the tricarboxylic acid (TCA) cycle collapse are pivotal elements in the triggering of cell death via mitochondrial pathways. Herein, a cascade nanoreactor CaCuZC has been constructed by incorporating nanosonosensitizer IR780 carbon dots (IR780 CD) and calcium peroxide (CaO2) into metal-organic frameworks (MOF) for synergistic cuproptosis-ferroptosis and Ca2+overload mediated immunotherapy. Within tumor cells, CaCuZC dissociates into CaO2, Cu2+and sonosensitizer IR780 CD. The decomposition of CaO2 could generate H2O2 to strengthen the Cu2+-based chemodynamic therapy and Ca2+overload induces amplified intracellular oxidative stress, thus leading to mitochondrial dysfunction. As a result, the combination of Cu2+and Ca2+ overload together induce cascade mitochondrial damage. Moreover, the sonosensitizer IR780 CD generates ROS under ultrasound irradiation to amplify intracellular oxidative stress. In addition, the overloaded Cu2+ released from CaCuZC leads to the aggregation of lipoylated protein dihydrolipoamide S-acetyltransferase, thus resulting in cuproptosis. Furthermore, ferroptosis could been concomitantly induced by CaCuZC with intracellular glutathione (GSH) consumption and lipid peroxidation (LPO) accumulation. The cuproptosis-ferroptosis and Ca2+overload-enhanced synergistic therapy also activates robust immunogenic cell death. CaCuZC enhances the infiltration and activation of tumor-specific cytotoxic T cells to transform a "cold" tumor into a "hot" tumor, activating the anti-tumor immune response. This study provides a cascade of mitochondrial damage strategy for triggering cuproptosis-ferroptosis and Ca2+overload-enhanced immunotherapy and achieving improved therapeutic effects. STATEMENT OF SIGNIFICANCE: To improve the efficacy of tumor immunotherapy, a cascade nanoreactor CaCuZC was successfully constructed based on a self-assembly strategy for cuproptosis-ferroptosis and Ca2+ overload mediated immunotherapy. Upon decomposition within the acidic and GSH-overexpressing tumor microenvironment, CaCuZC released CaO2 and Cu2+ and sonosensitizer IR780 CD. The CaO2 further produced H2O2/O2 and Ca2+ in a weakly acidic environment to strengthen the Cu2+-based CDT and IR780 CD-mediated SDT, respectively. The overload copper ions not only led to cuproptosis, but also efficiently induced ferroptosis. The cuproptosis-ferroptosis and Ca2+overload-enhanced synergistic therapy also activates robust immunogenic cell death. This study presents a cascade of mitochondrial damage strategy for cuproptosis-ferroptosis and Ca2+overload-enhanced immunotherapy.

Cong Tang

Kairui Liu

Xiaoning Gao

Hanmeixuan Kang

Weijie Xie

Jin Chang

Linling Yin

Jun Kang

A metal-organic framework functionalized CaO2-based cascade nanoreactor induces synergistic cuproptosis/ferroptosis and Ca2+ overload-mediated mitochondrial damage for enhanced sono-chemodynamic immunotherapy

金属有机框架功能化的CaO2基级联纳米反应器诱导协同铜死亡/铁死亡及Ca2+超载介导的线粒体损伤以增强声动力化学免疫治疗

Zhen Zhao

John Fetse

Umar-Farouk Mamani

Yuhan Guo

Yuanke Li

Pratikkumar Patel

Yanli Liu

Chien-Yu Lin

Yongren Li

Bahaa Mustafa

Kun Cheng

Development of a Peptide-Based Tumor-Activated Checkpoint Inhibitor for Cancer Immunotherapy

基于肽的肿瘤激活型检查点抑制剂在癌症免疫治疗中的开发

Jianqin Yan

Dengshuai Wei

Zijian Zhao

Kaichuang Sun

Yong Sun

Osteosarcoma-Targeting PtIV Prodrug Amphiphile for Enhanced Chemo-Immunotherapy via Ca2+ trapping

通过钙离子捕获增强化学免疫疗法的骨肉瘤靶向PtIV前药两亲物

Dynamic therapies such as photodynamic therapy (PDT) and sonodynamic therapy (SDT) have potential in cancer treatment. Microalgae have attracted increasing attention because of their high active mobility, flexibility in terms of functionality, and good biocompatibility. In this study, surface-engineered microalgae Chlorella vulgaris (Chl) modified with metal‒organic framework (MOF) nanoparticles (denoted Chl-MOF) are successfully developed for synergistic photo-sonodynamic therapy and immunotherapy. The resulting Chl-MOF can be used as an oxygenator for O2 generation through Chl-mediated photosynthesis, alleviating tumor hypoxia. Furthermore, Chl-MOF produces reactive oxygen species (ROS) during laser and ultrasound (US) irradiation, further augmenting the photo-sonodynamic effects and enhancing tumor cell apoptosis. Owing to the high mobility of Chl, cellular uptake efficiency and accumulation in deep tumor sites are 5.2-fold and 3.3-fold higher, respectively, for Chl-MOF than for the MOF. Owing to the immunomodulatory effects of Chl, Chl-MOF can increase natural killer (NK) cell cytotoxic activity, increase dendritic cell (DC) antigen-presenting ability, reverse the establishment of an immunosuppressive tumor microenvironment (TME), and induce a relatively strong antitumor immune response. Chl-MOF can effectively reduce breast cancer size by 88.8% in vitro and in vivo via synergistic photo-sonodynamic therapy and immunotherapy. These intriguing properties of the combination of Chl and a MOF provide promising platform for cancer theranostic applications. STATEMENT OF SIGNIFICANCE: : • Chl acts as an O2 generator for alleviating hypoxia in tumors. • The high mobility of Chl resulted in 3.3-folds higher tumor accumulation. • The Chl-MOF can induce a relatively strong antitumor immune response. • Chl-MOF effectively reduce breast cancer size by 88.8% via synergistic therapies.

Chaoli Xu

Jinhao Dong

Xuzhi Shi

Jiaxin Rui

Meng Chen

Wei Lu

Aihua Zhang

Shouju Wang

Zhaogang Teng

Xinhua Ye

Engineered Microalgae for Photo-Sonodynamic Synergistic Therapy in Breast Cancer Treatment

工程微藻用于乳腺癌治疗的光声动力协同疗法

Implantable medical devices have played a significant role in improving both medical care and patients' quality of life. Urinary Catheters (UCs) are commonly utilized as a substitute for bladder drainage and urine collection to prevent urinary retention in patients. However, bacterial colonization and biofilm formation on the catheter surface are prone to occur, leading to catheter-associated urinary tract infections (CAUTIs) and other complications. In recent years, UC coatings have garnered increasing attention. In this review, various antifouling and antibacterial materials for UC coatings are summarized and their impacts on bacterial activities are linked to potential mechanisms of action. Additionally, this review provides an in-depth understanding of the current advancements in UC coatings by presenting the advantages, limitations, notable achievements, and latest research findings. Finally, it anticipates the prospective design and development trajectories of UC coatings in this domain. This holds paramount significance in advancing medical device technology. STATEMENT OF SIGNIFICANCE: Combating catheter-associated urinary tract infections is a major healthcare challenge, and urinary catheter (UC) coatings are considered promising candidates to counter these infections. In this review, various antifouling and antibacterial materials for UCs are summarized, and their impacts on bacterial activities are linked to potential mechanisms of action. Additionally, the review provides an in-depth understanding of the current advancements in UC coatings by presenting the advantages, limitations, notable achievements, and latest research findings. This holds paramount significance in advancing medical device technology. This review not only contributes to the scientific research but also sparks interest among readerships and other researchers in the study of safer and more effective UC coatings for improved patient outcomes.

Abbreviation	Acta Biomater.
Journal Impact	9.29
Quartiles(Global)	MATERIALS SCIENCE, BIOMATERIALS(Q1)

ISSN	1742-7061, 1878-7568
h-index	245
Top Journals	Yes

Publication Information	Publisher: Acta Materialia Inc，Publishing cycle: Bimonthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2005，Proportion of original research papers: 89.82%，Self Citation Rate:3.20%， Gold OA Rate: 27.88%
Average review cycle	网友分享经验：平均2.8个月来源Elsevier官网：平均6.2周
Average recruitment ratio	网友分享经验：较难

Acta Biomaterialia

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