tbuckley/cabot-search huggingface dataset:
Bioprinted Fibroblast Mediated Heterogeneous Tumor Microenvironment for Studying Tumor‐Stroma Interaction and Drug Screening
Authors: You Chen, Yifan Xue, Cong Yan, Jinlong Jin, Yadong Liu, Jing Li, Shuai Han, Jie Liu
Journal: Advanced Healthcare Materials (2025)

Abstract Cancer‐associated fibroblasts (CAFs) are crucial stromal cells in the tumor microenvironment, affecting cancer growth, angiogenesis, and matrix remodeling. Developing an effective in vitro tumor model that accurately recapitulates the dynamic interplay between tumor and stromal cells remains a challenge. In this study, a 3D bioprinted fibroblast ‐ mediated heterogeneous breast tumor model was created, with tumor cells and fibroblasts in a bionic matrix. The impact of transforming growth factor‐β （TGF‐β） on the dynamic transformation of normal fibroblasts into CAFs and its subsequent influence on tumor cells is further investigated. These findings reveales a profound correlation between CAFs and several critical biological processes, including epithelial‐mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, gene expression profiles, and tumor progression. Furthermore, tumor models incorporating CAFs exhibits reduced drug sensitivity compared to models containing tumor cells alone or models co‐cultured with normal fibroblasts. These results underscore the potential of the in vitro fibroblast‐mediated heterogeneous tumor model to simulate real‐life physiological conditions, thereby offering a more effective drug screening platform for elucidating tumor pathogenesis and facilitating drug design prior to animal and clinical trials. This model's establishment promotes the understanding of tumor‐stromal interactions and their therapeutic implications.
Masquelet Inspired in Vivo Engineered Extracellular Matrix as Functional Periosteum for Bone Defect Repair and Reconstruction
Authors: Chen Jiang, Tianfeng Miao, Xiaojie Xing, Kevin J. Schilling, Nicholas Lenhard, Lichen Wang, Susan McDowell, Bradley L. Nilsson, Hongjun Wang, Xinping Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract The Masquelet technique that combines a foreign body reaction (FBR)‐induced vascularized tissue membrane with staged bone grafting for reconstruction of segmental bone defect has gained wide attention in Orthopedic surgery. The success of Masquelet hinges on its ability to promote formation of a “periosteum‐like” FBR‐induced membrane at the bone defect site. Inspired by Masquelet's technique, here a novel approach is devised to create periosteum mimetics from decellularized extracellular matrix (dECM), engineered in vivo through FBR, for reconstruction of segmental bone defects. The approach involved 3D printing of polylactic acid (PLA) template with desired pattern/architecture, followed by subcutaneous implantation of the template to form tissue, and depolymerization and decellularization to generate dECM with interconnected channels. The dECM matrices produces from the same mice (autologous) or from different mice (allogenic) are used as a functional periosteum for repair of structural bone allograft in a murine segmental bone defect model. This study shows that autologous dECM performed better than allogenic dECM, further permitting local delivery of low dose BMP‐2 to enhance allograft incorporation. The success of this current approach can establish a new line of versatile, patient‐specific, and periosteum‐like autologous dECM for bone regeneration, offering personalized therapeutics to patients with impaired healing.
Challenges and recommendations for enhancing digital data protection in Indian Medical Research and Healthcare Sector
Authors: Anubhuti Sood, Deepika Mishra, Varun Surya, Harpreet Singh, Rajesh Sundaresan, Debnath Pal, Raghu Dharmaraju, Rohit Satish, Shashwat Mishra, Nishant A. Chavan, Soham Mondal, Pavan Duggal, Venkateswaran K. Iyer
Journal: npj Digital Medicine (2025)

The Digital Personal Data Protection Act (DPDPA), 2023 of India provides a regulatory framework for use and security of personal digital data. However, instances, wherein the patients consult the clinicians via digital means of communication: the implications of DPDPA, 2023 for the medical personnel remain unclear. This paper critically discusses the gray areas encountered in the Indian medical ecosystem and DPDPA, 2023 and; lists the recommendations to address them.
Periodontal response to nonsurgical accelerated orthodontic tooth movement
Authors: Fatma Oner, Alpdogan Kantarci
Journal: Periodontology 2000 (2025)

Abstract Tooth movement is a complex process involving the vascularization of the tissues, remodeling of the bone cells, and periodontal ligament fibroblasts under the hormonal and neuronal regulation mechanisms in response to mechanical force application. Therefore, it will inevitably impact periodontal tissues. Prolonged treatment can lead to adverse effects on teeth and periodontal tissues, prompting the development of various methods to reduce the length of orthodontic treatment. These methods are surgical or nonsurgical interventions applied simultaneously within the orthodontic treatment. The main target of nonsurgical approaches is modulating the response of the periodontal tissues to the orthodontic force. They stimulate osteoclasts and osteoclastic bone resorption in a controlled manner to facilitate tooth movement. Among various nonsurgical methods, the most promising clinical results have been achieved with photobiomodulation (PBM) therapy. Clinical data on electric/magnetic stimulation, pharmacologic administrations, and vibration forces indicate the need for further studies to improve their efficiency. This growing field will lead to a paradigm shift as we understand the biological response to these approaches and their adoption in clinical practice. This review will specifically focus on the impact of nonsurgical methods on periodontal tissues, providing a comprehensive understanding of this significant and understudied aspect of orthodontic care.
Delivery of Islatravir via High Drug‐Load, Long‐acting Microarray Patches for the Prevention or Treatment of Human Immunodeficiency Virus
Authors: Qonita Kurnia Anjani, Ashley R. Johnson, Akmal H. Sabri, Ryan Lutz, Steven Tignor, Jeanine Ballard, Nathan Rudd, Li Zhao, Lalitkumar K. Vora, Stephanie E. Barrett, Angela Wagner, Ryan F. Donnelly
Journal: Advanced Healthcare Materials (2025)

Abstract This research focuses on developing and characterizing islatravir‐loaded dissolving microarray patches (MAPs) to provide an effective, minimally invasive treatment option for human immunodeficiency virus (HIV‐1) prevention and treatment. The research involves manufacturing these MAPs using a double‐casting approach, and conducting in vitro and in vivo evaluations. Results show that the MAPs have excellent needle fidelity, structural integrity, and mechanical strength. in vitro studies demonstrate that the MAPs can penetrate skin up to 580 µm and dissolve within 2 hours. Permeation studies reveal that the delivery efficiency of islatravir across the skin is around 40%. In rodent models, these dissolving MAPs sustain islatravir delivery for up to 3 months. Scaling up the MAPs and increasing drug loading produced detectable levels in minipig. Projections from animal data suggest that these dissolving MAPs can achieve effective islatravir levels for a month after a single application in humans. These findings indicate dissolving MAPs as a minimally invasive approach to sustained release of islatravir.
Double‐Dynamic‐Bond Cross‐Linked Hydrogel Adhesive with Cohesion‐Adhesion Enhancement for Emergency Tissue Closure and Infected Wound Healing
Authors: Ming Yan, Shi‐Yu Hu, Hao‐Jie Tan, Rui Dai, Haibo Wang, Xu Peng, Zhi‐Guo Wang, Jia‐Zhuang Xu, Zhong‐Ming Li
Journal: Advanced Healthcare Materials (2025)

Abstract The hydrogel adhesives with strong tissue adhesion and biological characteristics adhm202404447are urgently needed for injury sealing and tissue repair. However, the negative correlation between tissue adhesion and the mechanical strength poses a challenge for their practical application. Herein, a bio‐inspired cohesive enhancement strategy is developed to prepare the hydrogel adhesive with simultaneously enhanced mechanical strength and tissue adhesion. The double cross‐linked network is achieved through the cooperation between polyacrylic acid grafted with N‐hydroxy succinimide crosslinked by tannic acid and cohesion‐enhanced ion crosslinking of sodium alginate and Ca 2+ . Such a unique structure endows the resultant hydrogel adhesive with excellent tissue adhesion strength and mechanical strength. The hydrogel adhesive is capable of sealing various organs in vitro, and exhibits satisfactory on‐demand removability, antibacterial, and antioxidant properties. As a proof of concept, the hydrogel adhesive not only effectively halts non‐compressible hemorrhages of beating heart and femoral artery injury models in rats, but also accelerates the healing of infected wound by inhibiting bacteria and reducing inflammation. Overall, this advanced hydrogel adhesive is promising as an emergency rescue adhesive that enables robust tissue closure, timely controlling bleeding, and promoting damaged tissue healing.
Navigating Tumor Microenvironment Barriers with Nanotherapeutic Strategies for Targeting Metastasis
Authors: Mahima Rachel Thomas, Anjana Kaveri Badekila, Vishruta Pai, Nijil S, Yashodhar Bhandary, Ankit Rai, Sudarshan Kini
Journal: Advanced Healthcare Materials (2025)

Abstract Therapeutic strategy for efficiently targeting cancer cells needs an in‐depth understanding of the cellular and molecular interplay in the tumor microenvironment (TME). TME comprises heterogeneous cells clustered together to translate tumor initiation, migration, and proliferation. The TME mainly comprises proliferating tumor cells, stromal cells, blood vessels, lymphatic vessels, cancer‐associated fibroblasts (CAFs), extracellular matrix (ECM), and cancer stem cells (CSC). The heterogeneity and genetic evolution of metastatic tumors can substantially impact the clinical effectiveness of therapeutic agents. Therefore, the therapeutic strategy shall target TME of all metastatic stages. Since the advent of nanotechnology, smart drug delivery strategies are employed to deliver effective drug formulations directly into tumors, ensuring controlled and sustained therapeutic efficacy. The state‐of‐the‐art nano‐drug delivery systems are shown to have innocuous modes of action in targeting the metastatic players of TME. Therefore, this review provides insight into the mechanism of cancer metastasis involving invasion, intravasation, systemic transport of circulating tumor cells (CTCs), extravasation, metastatic colonization, and angiogenesis. Further, the novel perspectives associated with current nanotherapeutic strategies are highlighted on different stages of metastasis.
Universal Hydrogel Carrier Enhances Bone Graft Success: Preclinical and Clinical Evaluation
Authors: Dax Calder, Farshad Oveissi, Simin Maleknia, Tom Huang, Bernard Koong, Terence Abrams, Andrew Oar, Wojciech Chrzanowski, Fariba Dehghani, Ali Fathi
Journal: Advanced Healthcare Materials (2025)

Abstract Orthopedic, maxillofacial, and complex dentoalveolar bone grafting procedures that require donor‐site bone harvesting can be associated with post‐surgical complications. There has been widespread adoption of exogenously sourced particulate bone graft materials (BGM) for bone regenerative procedures; however, the particulate nature of these materials may lead to compromised healing outcomes, mainly attributed to structural collapse of the BGM, prolonged tissue healing. In this study, a fully synthetic thermoresponsive hydrogel‐based universal carrier matrix (TX) that forms flowable and shapable putties with different BGMs while spatially preserving the particles in a 3D scaffold at the implantation site is introduced. The potential synergistic effect of the carrier is investigated in combination with particulate demineralized bone matrix (DBM) in a standard muscle pouch nude mice model (n = 24) as well as in a rabbit femoral critical‐sized cortico‐cancellous bone defect model (n = 9). Finally, the clinical usability, safety, and efficacy of the carrier for the delivery of deproteinized bovine bone mineral (DBBM) are evaluated in a controlled clinical trial for extraction socket alveolar ridge preservation (ARP) (n = 11 participants). Overall, the TX carrier improved the delivery of different types of BGMs, maintaining these spatially at the implantation site with minimal inflammatory responses, resulting in favorable bone regenerative outcomes.
A Highly Bioactive Organic–Inorganic Nanoparticle for Activating Wnt10b Mediated Osteogenesis by Specifically Anchor CCN3 Protein
Authors: Yonghao Qiu, Chunhui Wang, Yulian Yang, Shijing Xu, Haohui Huang, Liuyang Zhang, Bo Lei, Fujian Zhao
Journal: Advanced Healthcare Materials (2025)

Abstract The rapid and efficient bone regeneration is still in unsatisfactory outcomes, demonstrating alternative strategy and molecular mechanism is necessary. Nanoscale biomaterials have shown some promising results in enhancing bone regeneration, however, the detailed interaction mechanism between nanomaterial and cells/tissue formation is not clear. Herein, a molecular‐based inorganic–organic nanomaterial poly(citrate‐siloxane) (PCS) is reported which can rapidly enhance osteogenic differentiation and bone formation through a special interaction with the cellular surface communication network factor 3 (CCN3), further activating the Wnt10b/β‐catenin signaling pathway. Further studies revealed that the CCN3 is a key bridge protein for transmitting the osteoinductive effects of nano PCS into the intracellular compartment and activating Wnt10b. Specifically, the molecular mechanism studies confirmed that the inorganic silicon hydroxyl and the organic ester group can bound to the Thrombospondin‐1 (TSP‐1) and von Willebrand factor type C repeat module (vWC) structural domains of CCN3 respectively. The special material‐protein interaction induced a conformational change of CCN3 and activated the function of the TSP‐1 structural domain, which is further associated with the binding and activation of Wnt10b signaling. This study reveals the first targets of nanobiomaterials to promote tissue regeneration through cellular interactions and provides new ideas for the development of materiobiology.
FXa‐Responsive Hydrogels to Craft Corneal Endothelial Lamellae
Authors: Mikhail V. Tsurkan, Juliane Bessert, Rabea Selzer, Sarah D. Tsurkan, Dagmar Pette, Manfred F. Maitz, Petra B. Welzel, Carsten Werner
Journal: Advanced Healthcare Materials (2025)

Abstract Cell‐instructive polymer hydrogels are instrumental in tissue engineering for regenerative therapies. Implementing defined and selective responsiveness to external stimuli is a persisting challenge that critically restricts their functionality. Addressing this challenge, this study introduces a versatile, modular hydrogel system composed of four‐arm poly(ethylene glycol)(starPEG)‐peptide and glycosaminoglycan(GAG)‐maleimide conjugates. The gel system features a small peptide sequence that is selectively cleaved by the coagulation factor FXa. In a cell culture environment, where active FXa is absent, the hydrogel remains stable, providing a conducive matrix for the growth of complex tissue structures or organoids. Upon the introduction of FXa, the hydrogel is designed to disintegrate rapidly, enabling the gentle release of the cultivated tissues without impairing their functionality. The efficacy of this approach is demonstrated through the ex vivo development, detachment, and transplantation of human corneal endothelial lamellae, achieving sizes relevant for clinical application in Descemet Membrane Endothelial Keratoplasty (DMEK). Furthermore, the practicality of the hydrogel system is validated in vitro using a de‐endothelialized porcine cornea as a surrogate recipient. Since the FXa‐cleavable peptide can be integrated into a variety of multifunctional hydrogels, it can pave the way for next‐generation scaffold‐free tissue engineering and organoid regenerative therapies.
In vivo CRISPR–Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington’s disease
Authors: Ricardo Mouro Pinto, Ryan Murtha, António Azevedo, Cameron Douglas, Marina Kovalenko, Jessica Ulloa, Steven Crescenti, Zoe Burch, Esaria Oliver, Maheswaran Kesavan, Shota Shibata, Antonia Vitalo, Eduarda Mota-Silva, Marion J. Riggs, Kevin Correia, Emanuela Elezi, Brigitte Demelo, Jeffrey B. Carroll, Tammy Gillis, James F. Gusella, Marcy E. MacDonald, Vanessa C. Wheeler
Journal: Nature Genetics (2025)

Huntington's disease, one of more than 50 inherited repeat expansion disorders1, is a dominantly inherited neurodegenerative disease caused by a CAG expansion in HTT2. Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the disease is driven by the CAG length-dependent propensity of the repeat to further expand in the brain3–9. Routes to slowing somatic CAG expansion, therefore, hold promise for disease-modifying therapies. Several DNA repair genes, notably in the mismatch repair pathway, modify somatic expansion in Huntington's disease mouse models10. To identify novel modifiers of somatic expansion, we used CRISPR–Cas9 editing in Huntington's disease knock-in mice to enable in vivo screening of expansion-modifier candidates at scale. This included testing of Huntington's disease onset modifier genes emerging from human genome-wide association studies as well as interactions between modifier genes, providing insight into pathways underlying CAG expansion and potential therapeutic targets. A novel in vivo screening strategy identifies new modifiers of somatic CAG repeat expansion that contribute to age of onset in Huntington's disease.
Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification
Authors: Chin Yee Ho, Meng-Ying Wu, Jirapath Thammaphet, Sadia Ahmad, James Ho C.S., Lilia Draganova, Grace Anderson, Umesh S. Jonnalagadda, Robert Hayward, Rukshana Shroff, Wilson Tan Lek Wen, Anja Verhulst, Roger Foo, Catherine M. Shanahan
Journal: Circulation Research (2025)

BACKGROUND: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined. METHODS: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array. Epigenetic findings were verified in vivo using immunohistochemistry in human vessels, in a mouse model of inducible prelamin A expression, and in a rat model of chronic kidney disease–induced calcification. Transcriptomic and chromatin immunoprecipitation followed by sequencing analyses were used to identify gene targets impacted by changes in the epigenetic landscape. Molecular tools and antibody arrays were used to monitor the effects of mineral dysregulation on heterochromatin, inflammation, aging, and calcification. RESULTS: Here, we report that depletion of the repressive heterochromatin marks, H3K9me3 and H3K27me3, is an early hallmark of vascular aging induced by both nuclear lamina dysfunction and dysregulated mineral metabolism, which act to modulate the expression of key epigenetic writers and erasers. Global analysis of H3K9me3 and H3K27me3 marks and pathway analysis revealed deregulation of insulin signaling and autophagy pathways as well as cross-talking DNA damage and NF-κB (nuclear factor κB) inflammatory pathways consistent with early activation of the senescence-associated secretory phenotype. Expression of prelamin A in vivo induced loss of heterochromatin and promoted inflammation and osteogenic differentiation which preceded aging indices, such as DNA damage and senescence. Vessels from children on dialysis and rats with chronic kidney disease showed prelamin A accumulation and accelerated loss of heterochromatin before the onset of calcification. CONCLUSIONS: Dysregulated mineral metabolism drives changes in the epigenetic landscape and nuclear lamina dysfunction that together promote early induction of inflammaging pathways priming the vasculature for downstream pathological change.
Gut Microbiota Metabolites Sensed by Host GPR41/43 Protect Against Hypertension
Authors: Rikeish R. Muralitharan, Tenghao Zheng, Evany Dinakis, Liang Xie, Anastasia Barbaro-Wahl, Hamdi A. Jama, Michael Nakai, Madeleine Patterson, Kwan Charmaine Leung, Zoe McArdle, Katrina Mirabito Colafella, Chad Johnson, Wendy Qin, Ekaterina Salimova, Natalie Bitto, Maria-Kaparakis Liaskos, David M. Kaye, Joanne A. O’Donnell, Charles R. Mackay, Francine Z. Marques
Journal: Circulation Research (2025)

BACKGROUND: Fermentation of dietary fiber by the gut microbiota leads to the production of metabolites called short-chain fatty acids, which lower blood pressure and exert cardioprotective effects. Short-chain fatty acids activate host signaling responses via the functionally redundant receptors GPR41 and GPR43, which are highly expressed by immune cells. Whether and how these receptors protect against hypertension or mediate the cardioprotective effects of dietary fiber remains unknown. METHODS: Cardiovascular phenotype was assessed in untreated and Ang II (angiotensin II) treated hypertensive wild-type and GPR41/43 knockout (KO) double knockout male mice fed diets with different levels of fiber content. Some mice received TLR4-antagonist treatment and bone marrow chimeras. Single-nucleotide polymorphisms associated with GPR41 and GPR43 expression were assessed in UK Biobank participants. RESULTS: Untreated GPR41/43KO mice had unaltered blood pressure but had greater cardiac and renal collagen deposition with higher macrophage numbers in the kidney compared with wild-type mice. Ang II–treated GPR41/43KO mice showed higher systolic blood pressure, cardiorenal weights and collagen deposition, and increased gut permeability, which allows the translocation of gastrointestinal bacterial components such as lipopolysaccharides into the circulation. The use of an antagonist to the lipopolysaccharide receptor, TLR4, a potent proinflammatory signaling molecule, restored the cardiovascular phenotype in GPR41/43KO mice. The lack of GPR41/43 expression in the immune compartment was sufficient to lead to a worsened hypertensive phenotype. We also demonstrate that GPR41/43 is, at least partially, responsible for the blood pressure–lowering and cardioprotective effects of a high-fiber diet. Finally, using the UK Biobank, we provide translational evidence that variants associated with lower expression of both GPR41 and GPR43 are more prevalent in participants with hypertension. CONCLUSIONS: Our findings highlight that lack of short-chain fatty acid-receptor signaling via both GPR41 and GPR43 increases risk of high blood pressure, suggesting treatments that target these receptors could be a novel strategy to prevent or treat hypertension.