tbuckley/cabot-search huggingface dataset:
Integrating 3D Bioprinting and Organoids to Better Recapitulate the Complexity of Cellular Microenvironments for Tissue Engineering
Authors: Yan Hu, Tong Zhu, Haitao Cui, Haijun Cui
Journal: Advanced Healthcare Materials (2024)

Abstract Organoids, with their capacity to mimic the structures and functions of human organs, have gained significant attention for simulating human pathophysiology and have been extensively investigated in the recent past. Additionally, 3D bioprinting, as an emerging bio‐additive manufacturing technology, offers the potential for constructing heterogeneous cellular microenvironments, thereby promoting advancements in organoid research. In this review, the latest developments in 3D bioprinting technologies aimed at enhancing organoid engineering are introduced. The commonly used bioprinting methods and materials for organoids, with a particular emphasis on the potential advantages of combining 3D bioprinting with organoids are summarized. These advantages include achieving high cell concentrations to form large cellular aggregates, precise deposition of building blocks to create organoids with complex structures and functions, and automation and high throughput to ensure reproducibility and standardization in organoid culture. Furthermore, this review provides an overview of relevant studies from recent years and discusses the current limitations and prospects for future development.
Sulfasalazine‐Loaded Copper‐Tannic Acid Coordination Nanozyme Enables ROS Scavenging and Immunomodulation for Inflammatory Bowel Disease Therapy
Authors: Jian‐Hua Yan, Chun‐Xiao Liang, Ran‐Ran Ma, Bo‐Jia Li, Qi‐Wen Chen, Wen Li, Xuan Zeng, Xian‐Zheng Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Inflammatory bowel disease (IBD) is associated with elevated levels of reactive oxygen species (ROS) and an increased expression of proinflammatory cytokines. Anti‐inflammatory drugs, monoclonal antibodies, and immunomodulators are commonly employed to control the inflammatory response in the management of IBD. Here, a copper and tannic acid (TA) coordination nanozyme (CuTA) loaded with sulfasalazine (SSZ‐CuTA) is synthesized for the treatment of IBD by simultaneous scavenging ROS and immunosuppression. The CuTA exhibits both dismutase‐like activity and catalase‐like activity, making it efficient at scavenging ROS. These nanozymes can efficiently traverse gastric acid and subsequently exert their effects within the intestinal tract. It is verified that SSZ‐CuTA can restore intestinal mucosal and goblet cells to a healthy state by effectively eliminating ROS and reducing the pro‐inflammatory factors in a mouse IBD model. Overall, the SSZ‐CuTA will offer a promising alternative treatment for patients suffering from IBD where excessive ROS and high inflammation coexist.
Controlled Synthesis of the FeB Nanometallic Glasses with Stronger Electron Donating Capability to Activate Molecular Oxygen for the Enhanced Ferroptosis Therapy
Authors: Gongyu Shi, Yongxuan Zhang, Wenting Wang, Wanxuan Xiang, Feng Zhang, Xiaojiao Zhu, Hongping Zhou
Journal: Advanced Healthcare Materials (2024)

Abstract Considering the strong electron‐donating ability and the superior biocompatibility, the integration of zero‐valent iron nanostructure Fe 0 (electron‐reservoir) and zero‐valent boron nanostructure B 0 offers great promise for fabricating novel ferroptosis nanoagents. Nevertheless, the controlled and facile synthesis of alloyed Fe 0 and B 0 nanostructure‐FeB nanometallic glasses (NMGs) has remained a long‐standing challenge. Herein, a complexion‐reduction strategy is proposed for the controlled synthesis of FeB NMGs with greater electron donating capacity to activate the molecular oxygen for improved ferroptosis therapy. In‐depth mechanism reveales that the complexion‐reduction strategy effectively prevent the long‐range diffusion of Fe 0 , resulting in the amorphous alloyed Fe 0 and B 0 nanostructure‐FeB nanoparticles (FeB NPs). The FeB NPs display stronger electron donating capability and electron transfer rate 9.4 times higher than that of the Fe 0 NPs, which effectively activate the molecular oxygen to produce ∙O 2 − , H 2 O 2 and ∙OH. The in vitro cellular experiments confirm the FeB‐ss‐SiO₂ NPs (encapsulation with SiO 2 outlayer containing ‐S‐S‐ bonds) demonstrates the enhanced ferroptosis. The tumor‐bearing mice models shows that FeB‐ss‐SiO₂ NPs exhibited superior biocompatibility and tumor inhibition effect (inhibition rate of 73%), which improve the overall survival rate for 30 days post‐treatment. This study will provide an innovative way to design therapeutic nanoagents for cancer treatments.
Reciprocal tumor‐platelet interaction through the EPHB1‐EFNB1 axis in the liver metastatic niche promotes metastatic tumor outgrowth in pancreatic ductal adenocarcinoma
Authors: Lin‐Li Yao, Wei‐Ting Qin, Li‐Peng Hu, Tie‐Zhu Shi, Jian Yu Yang, Qing Li, Hui‐Zhen Nie, Jun Li, Xu Wang, Lei Zhu, De‐Jun Liu, Yan‐Li Zhang, Shu‐Heng Jiang, Zhi‐Gang Zhang, Xiao‐Mei Yang, Dong‐Xue Li, Xue‐Li Zhang
Journal: Cancer Communications (2024)

Abstract Background The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation. Platelets play pivotal roles in hematogenous cancer metastasis through tumor cell‐platelet interaction in blood vessels. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy distinguished by its notable tendency to metastasize to the liver. However, the role of platelet in the liver metastatic niche of PDAC remains elusive. This study aimed to elucidate the role of platelets and their interactions with tumor cells in the liver metastatic niche of PDAC. Methods An mCherry niche‐labeling system was established to identify cells in the liver metastatic niche of PDAC. Platelet depletion in a liver metastasis mouse model was used to observe the function of platelets in PDAC liver metastasis. Gain‐of‐function and loss‐of‐function of erythropoietin‐producing hepatocellular receptor B1 ( Ephb1 ), tumor cell‐platelet adhesion, recombinant protein, and tryptophan hydroxylase 1 ( Tph1 )‐knockout mice were used to study the crosstalk between platelets and tumor cells in the liver metastatic niche. Results The mCherry metastatic niche‐labeling system revealed the presence of activated platelets in the liver metastatic niche of PDAC patients. Platelet depletion decreased liver metastatic tumor growth in mice. Mechanistically, tumor cell‐expressed EPHB1 and platelet‐expressed Ephrin B1 (EFNB1) mediated contact‐dependent activation of platelets via reverse signaling‐mediated AKT signaling activation, and in turn, activated platelet‐released 5‐HT, further enhancing tumor growth. Conclusion We revealed the crosstalk between platelets and tumor cells in the liver metastatic niche of PDAC. Reciprocal tumor‐platelet interaction mediated by the EPHB1‐EFNB1 reverse signaling promoted metastatic PDAC outgrowth via 5‐HT in the liver. Interfering the tumor‐platelet interaction by targeting the EPHB1‐EFNB1 axis may represent a promising therapeutic intervention for PDAC liver metastasis.
Temporary Nanoencapsulation of Human Intestinal Organoids Using Silk Ionomers
Authors: Brooke Wang, Onur Hasturk, Udathari Kumarasinghe, Sara Rudolph, Cristian Staii, Ying Chen, David L. Kaplan
Journal: Advanced Healthcare Materials (2024)

Abstract Human intestinal organoids (HIOs) are vital for modeling intestinal development, disease, and therapeutic tissue regeneration. However, their susceptibility to stress, immunological attack, and environmental fluctuations limits their utility in research and therapeutic applications. This study evaluated the effectiveness of temporary silk protein‐based layer‐by‐layer (LbL) nanoencapsulation technique to enhance the viability and functions of HIOs against common biomedical stressors, without compromising their native functions. Cell viability and differentiation capacity are assessed, finding that nanoencapsulation significantly improved HIO survival under the various environmental perturbations studied without compromising cellular functionality. Post‐stress exposures, the encapsulated HIOs still successfully differentiated into essential intestinal cell types such as enterocytes, goblet cells, enteroendocrine cells, and Paneth cells. Moreover, the silk nanocoatings effectively protected against environmental stressors such as ultraviolet (UV) light exposure, protease degradation, antibody binding, and cytokine‐induced inflammation. This nanoencapsulation technique shows promise for advancing HIO applications in disease modeling, drug testing, and potential transplantation therapies.
HBV and HCV testing outcomes among marginalized communities in Italy, 2019–2024: a prospective study
Authors: Monica Monti, Teresita Caruso, Alice Castellaccio, Irene De Giorgi, Gabriella Cavallini, Maria Laura Manca, Serena Lorini, Silvia Marri, Luisa Petraccia, Francesco Madia, Cristina Stasi, Laura Carraresi, Elisabetta Lorefice, Sara Irene Bonelli, Alessandro Nerli, Mouheb M A Mudalal, Lorenzo Martini, Stefano Gitto, Eleonora Carradori, Adela Xheka, Irene Bendini, Samuele Lukolic', Lorenzo Latella, Donatella Aquilini, Pierluigi Blanc, Anna Linda Zignego, Laura Gragnani
Journal: The Lancet Regional Health - Europe (2024)
3D‐Bioprinting for Precision Microtissue Engineering: Advances, Applications, and Prospects
Authors: Jinrun Liu, Qi Wang, Yinpeng Le, Min Hu, Chen Li, Ni An, Qingru Song, Wenzhen Yin, Wenrui Ma, Mingyue Pan, Yutian Feng, Yunfang Wang, Lu Han, Juan Liu
Journal: Advanced Healthcare Materials (2024)

Abstract Microtissues, engineered to emulate the complexity of human organs, are revolutionizing the fields of regenerative medicine, disease modelling, and drug screening. Despite the promise of traditional microtissue engineering, it has yet to achieve the precision required to fully replicate organ‐like structures. Enter 3D bioprinting, a transformative approach that offers unparalleled control over the microtissue's spatial arrangement and mechanical properties. This cutting‐edge technology enables the detailed layering of bioinks, crafting microtissues with tissue‐like 3D structures. It allows for the direct construction of organoids and the fine‐tuning of the mechanical forces vital for tissue maturation. Moreover, 3D‐printed devices provide microtissues with the necessary guidance and microenvironments, facilitating sophisticated tissue interactions. The applications of 3D‐printed microtissues are expanding rapidly, with successful demonstrations of their functionality in vitro and in vivo. This technology excels at replicating the intricate processes of tissue development, offering a more ethical and controlled alternative to traditional animal models. By simulating in vivo conditions, 3D‐printed microtissues are emerging as powerful tools for personalized drug screening, offering new avenues for pharmaceutical development and precision medicine.
Coupling Probiotics with CaO<sub>2</sub> Nanoparticle‐Loaded CoFeCe‐LDH Nanosheets to Remodel the Tumor Microenvironment for Precise Chemodynamic Therapy
Authors: Ruxue Si, Tingting Hu, Gareth R. Williams, Yu Yang, Shuqing Yang, Dan Yan, Ruizheng Liang, Weiping Ji
Journal: Advanced Healthcare Materials (2024)

Chemodynamic therapy (CDT) has become an emerging cancer treatment strategy with advantages of tumor-specificity, high selectivity, and low systemic toxicity. However, it usually suffers from low therapeutic efficacy. This is caused by low hydroxyl radical (·OH) yield arising because of the relatively high pH, overexpressed glutathione, and low H2O2 concentration in the tumor microenvironment (TME). Herein, a probiotic metabolism-initiated pH reduction and H2O2 supply-enhanced CDT strategy is reported to eradicate tumors by generating ·OH, in which Lactobacillus acidophilus is coupled with CoFeCe-layered double hydroxide nanosheets loaded with CaO2 nanoparticles (NPs) as a chemodynamic platform for high-efficiency CDT (CaO2/LDH@L. acidophilus). Owing to the hypoxia tropism of L. acidophilus, CaO2/LDH@L. acidophilus exhibits increased accumulation at tumor sites compared with the CaO2/LDH. The CaO2 NPs loaded on CoFeCe-LDH nanosheets are decomposed into H2O2 in the TME. L. acidophilus metabolite-induced pH reduction (<5.5) and CaO2-mediated in situ H2O2 generation synergistically boost ·OH generation activity of the CoFeCe-LDH nanosheets, effectively damaging cancer cells and ablating tumors with a tumor inhibition rate of 96.4%, 2.32-fold higher than that of CaO2/LDH. This work demonstrates that probiotics can function as a tumor-targeting platform to remodel the TME and amplify ROS generation for highly efficient and precise CDT.
Probiotic‐Based Mineralized Living Materials to Produce Antimicrobial Yogurts
Authors: Gloria B. Ramírez‐Rodríguez, Laura Sabio, Laura Cerezo‐Collado, Víctor Garcés, Jose M. Domínguez‐Vera, José M. Delgado‐López
Journal: Advanced Healthcare Materials (2024)

Abstract Mineralization of living cells represents an evolutionary adaptation that enhances cellular resilience to physicochemical stress. Inspired by this strategy, we have here developed hybrid living materials (HLMs), incorporating probiotics into mineralized collagen 3D matrices, with the aim of protecting and promoting the successful oral delivery of the bacteria. Collagen fibrils are simultaneously self‐assembled and mineralized in the presence of the probiotics ( Lactobacillus acidophilus , La , was used as model), resulting in the integration of the probiotics into the hybrid matrix (i.e., bulk encapsulation). During this process, probiotics are also coated with a nanofilm of apatite mineral (single‐cell encapsulation), which provides them with extra protection and reinforces their viability and activity. In fact, the resulting HLM is metabolically active, and maintain the capacity to ferment milk into yogurt with antibacterial activity against the two major foodborne pathogens Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) . Interestingly, the HLM provides probiotics an additional protection in the gastrointestinal environment (i.e., simulated gastric fluid), which is of special interest for healthcare materials for oral administration. The results pave the way for the creation of innovative healthcare materials with enhanced functionalities and the potential to produce probiotic foods with notable antimicrobial properties.
Mn and Zn‐Doped Multivariate Metal–Organic Framework as a Metalloimmunological Adjuvant to Promote Protection Against Tuberculosis Infection
Authors: Thomas S. Howlett, Sneha Kumari, Ryanne N. Ehrman, Jesse Masson, Linda Izzo, Trixie Wang, Humera Gull, Ikeda Trashi, Wendy Tang, Orikeda Trashi, Neha Satish, Yalini H. Wijesundara, Fabian C. Herbert, Angelo A. Izzo, Jeremiah J. Gassensmith
Journal: Advanced Healthcare Materials (2024)

Abstract A first‐in‐class vaccine adjuvant delivery system, Mn‐ZIF, is developed by incorporating manganese (Mn) into the zinc‐containing zeolitic‐imidazolate framework‐8 (ZIF‐8). The mixed metal approach, which allowed for tunable Mn doping, is made possible by including a mild reducing agent in the reaction mixture. This approach allows up to 50% Mn, with the remaining 50% Zn within the ZIF. This multivariate approach exhibits significantly decreased cytotoxicity compared to ZIF‐8. The porous structure of Mn‐ZIF enables the co‐delivery of the STING agonist cyclic di‐adenosine monophosphate (CDA) through post‐synthetic loading, forming CDA@Mn‐ZIF. The composite demonstrated enhanced cellular uptake and synergistic activation of the cGAS‐STING pathway, producing proinflammatory cytokines and activating antigen‐presenting cells (APCs). In a preclinical Mycobacterium tuberculosis ( Mtb ) model, CDA@Mn‐ZIF formulates with the CysVac2 fusion protein elicited a potent antigen‐specific T‐cell response and significantly reduced the mycobacterial burden in the lungs of infected mice. These findings highlight the potential of CDA@Mn‐ZIF as a promising adjuvant for subunit vaccines, offering a novel approach to enhancing vaccine efficacy and protection against infectious diseases such as tuberculosis.
Charge Engineering of Star‐Shaped Organic Photosensitizers Enables Efficient Type‐I Radicals for Photodynamic Therapy of Multidrug‐Resistant Bacterial Infection
Authors: Jie Yu, Wenchang Xu, Huan Chen, Haitao Yuan, Yu Wang, Xiandie Qian, Jie Zhang, Yu Ji, Qi Zhao, Shengliang Li
Journal: Advanced Healthcare Materials (2024)

Abstract Infection induced by multidrug‐resistant bacteria is now the second most common cause of accidental death worldwide. However, identifying a high‐performance strategy with good efficiency and low toxicity is still urgently needed. Antibacterial photodynamic therapy (PDT) is considered a non‐invasive and efficient approach with minimal drug resistance. Whereas, the precise molecular design for highly efficient oxygen‐independent type‐I photosensitizers is still undefined. In this work, the regulation of the positive charge of star‐shaped NIR‐emissive organic photosensitizers can boost radical generation for the efficient treatment of wounds infected with multidrug‐resistant bacteria. With positive charge engineering, TPAT‐DNN, which has six positive charges, mainly produces hydroxyl radicals via the type‐I pathway, while TPAT‐DN, which has three positive charges, tends to generate singlet oxygen and superoxide radicals. For multidrug‐resistant bacteria, TPAT‐DNN exhibited specific killing effects on multidrug‐resistant gram‐positive bacteria at low concentrations, while TPAT‐DN is similar antibacterial effects on both multidrug‐resistant gram‐negative and gram‐positive bacteria. Furthermore, the efficiency and safety of TPAT‐DNN for eradicating multidrug‐resistant bacteria methicillin‐resistant S. aureus (MRSA) infection and accelerating wound healing in an MRSA‐infected mouse model are demonstrated. This work offers a new approach toward manipulating efficient type‐I photosensitizers for MRSA treatment.
Self‐Driven Janus Ga/Mg Micromotors for Reducing Deep Bacterial Infection in the Treatment of Periodontitis
Authors: Hang Chi, Wei Wu, Hongxia Bao, Yingjie Wu, Narisu Hu
Journal: Advanced Healthcare Materials (2024)

A self-propulsion Janus gallium (Ga)/magnesium (Mg) bimetallic micromotor is designed with favorable biocompatibility and antimicrobial properties as a therapeutic strategy for periodontitis. The Janus Ga/Mg micromotors are fabricated by microcontact printing technique to asymmetrically modify liquid metallic gallium onto magnesium microspheres. Hydrogen bubbles produced by the magnesium-water reaction can provide the driving performance of up to 31.03 µm s-1 (pH 6.8), prompting the micromotor to actively breakthrough the biological barrier of saliva and gingival crevice fluid (GCF) into the bottom of periodontal pockets. In addition, the Janus Ga/Mg micromotors are effectively converted by degradation into the built-in antimicrobial ion Ga(III) to eliminate deep-seated Porphyromonas gingivalis (P.gingivalis), with bactericidal efficiencies of over 99.8%. The developed Janus Ga/Mg micromotors have demonstrated potent antimicrobial and anti-inflammatory activity both in vitro and in vivo studies. Crucially, it reduces alveolar bone resorption, demonstrating the superior efficacy of liquid metal gallium in treating periodontitis. Therefore, Ga/Mg bimetallic micromotors hold great promise to be an innovative and translational drug delivery system to treat periodontitis or other inflammation-related diseases in the near future.
Embedded Bioprinting of Breast Cancer–Adipose Composite Tissue Model for Patient‐Specific Paracrine Interaction Analysis
Authors: Wonwoo Jeong, Jonghyeuk Han, Jeonghan Choi, Hyun‐Wook Kang
Journal: Advanced Healthcare Materials (2024)

Abstract The interaction between breast cancer and stromal tissues varies significantly from patient to patient, greatly impacting cancer prognosis. However, conventional models struggle to accurately replicate these patient‐specific interactions. Herein, a novel breast cancer–adipose composite tissue model capable of precisely adjusting the inter‐tissue interaction is developed. The composite tissue model is produced through precise embedded bioprinting of breast‐cancer spheroids and live‐adipose‐tissue ink. This model possessed not only precisely patterned cancer spheroids but also well‐preserved intrinsic extracellular matrices (ECMs) and heterogeneous cell populations of adipose tissue (AT). Evaluation results successfully demonstrated that the bioprinted composite model can precisely regulate adipokine secretion, drug resistance, and cancer‐cell invasion characteristics by adjusting the distance between the cancer spheroids and adipose tissue. The utility of the model is validated using adipokine‐targeted therapies (C‐compound/SC600125 (SC), AG 490 (AG), and Metformin (MET)). Interestingly, the inhibition of cancer cell proliferation and invasion by these adipokine‐targeted drugs nearly doubled as the tissue distance decreased. This suggests that the efficacy of the drugs can be precisely evaluated using the new model. These findings underscore the potential of the developed composite model to replicate patient‐specific crosstalk, thereby offering a promising platform for the sophisticated evaluation of various breast‐cancer therapies.
Outcome of lupus nephritis patients treated with an anti‐CD40 monoclonal antibody according to kidney biopsy features
Authors: Martina Uzzo, Helmut Schumacher, Juergen Steffgen, Simone Deutschel, David Jayne, Ingeborg Bajema
Journal: Arthritis & Rheumatology (2024)

Objective A phase II trial tested different doses of the anti‐CD40 monoclonal antibody BI655064 as add‐on therapy to the standard of care in class III or IV Lupus Nephritis (LN) patients with active disease. A post‐hoc analysis showed a potential benefit of the higher tested doses (180mg/240mg) versus low dose (120mg)/placebo. We investigated whether the treatment effect of BI655064 on kidney outcomes may be modified by the presence of glomerular monocytes, a target for this drug with a well‐known role in LN pathogenesis. Methods 101 renal biopsies of LN patients enrolled in the BI655064 trial were scored centrally. eGFR and spot urine protein/urine creatinine ratio (UP/UC) and Complete Renal Response (CRR) were evaluated over 52 weeks. Patients were divided according to a “Better” or “Worse” performance than the average of all patients in the cohort, predicted by a mixed model for repeated measurements. Logistic regression models adjusted for potential confounders assessed the association between different treatment doses and outcomes according to the presence or absence of monocytes. Results A higher BI655064 dose (180/240mg) was associated with better outcomes of UP/UC and CRR when glomerular monocytes were present in kidney biopsies (OR 3.66[1.09‐12.3], P=0.04; OR 4.58[1.24‐16.9], P=0.02). A trend toward improved eGFR was also observed in these patients (P 52‐weeks=0.08). Conclusions In LN kidney biopsies with glomerular monocytes, high‐dose BI655064 treatment improved proteinuria at 52 weeks and resulted in a higher CRR compared to biopsies without glomerular monocytes. Histologic features may guide the choice of treatment for individual LN patients.