Dense Matrix Research Articles

Abstract A049: Collagen-driven kinome reprogramming reveals unique, actionable DDR1-signaling dependencies in pancreatic cancer cells

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDA) is the 3rd most common cause of cancer death in the United States, with a 5-year survival rate of only 13%, in part due to late detection and metastatic dissemination at early stages of progression. Most PDA tumors exhibit a dense fibro-inflammatory stroma consisting of fibroblasts, immune cells, and a dense collagen-rich extracellular matrix (ECM) that regulate disease progression. How distinct collagens (COLs) influence PDA progression remains unclear. COLs signal via specific cell surface receptors, of which the Discoidin Domain Receptors (DDRs) constitute a unique family of collagen-binding receptor tyrosine kinases (RTKs). DDR1 is expressed by PDA cancer cells, while DDR2 is expressed by mesenchymal cells. DDR1 is activated by both basement membrane COL (e.g. COL4) and fibrillar COLs (e.g. COLs 1, 2, 11). Compared to most RTKs, relatively little is understood about differential ligand activation and signaling downstream of DDRs. Our working hypothesis is that switches in ECM collagen composition over the course of PDA progression induce changes in DDR1-intracellular signaling cascades, which may reveal unexplored therapeutic susceptibilities to target and eliminate PDA cancer cells. Methods and Recent Advances: Using genetically engineered mouse models of PDA, we previously found that genetic ablation of Ddr1 impedes tumor progression, blocking the transition from well-differentiated to poorly-differentiated adenocarcinoma and, as a result, metastasis. Moreover, we showed that xenografts of DDR1-expressing human PDA cell lines display enhanced tumor growth exclusively when implanted within a COL1 scaffold. Leveraging an innovative high-throughput kinase-activity mapping (HT-KAM) platform and kinase network resource database (PhosphoAtlas), we started investigating mechanisms of differential activation of DDR1 by distinct COLs, including COL1 and COL11, which is an understudied fibrillar collagen that is prominent in the stroma of late-stage, metastatic PDA. New, Unpublished Findings: Using several PDA cell line models with or without DDR1 expression, our results indicate that DDR1 activates two distinct signaling networks: (1) a conserved, coordinated response that is modestly activated by COL1 but is hyperactivated by COL11 (e.g., ERBB, AKT, MEK/ERK, SRC), and (2) a unique set of phospho-signaling nodes that are only induced by COL11 –and not COL1 (e.g., specific RTKs and PKCs). Several of these kinases are associated with cancer cell proliferation and survival, as well as EMT induction, in part illuminating the malignancy-promoting effects of DDR1 in late-stage PDA in response to changes in COL composition. Conclusion: Differential activation of DDR1 represents a new paradigm on how distinct fibrillar COLs within the TME may drive PDA cell signaling. We are actively exploring how distinct COLs differentially regulate PDA tumor growth and metastatic behavior via DDR1, and how specific kinase-targeting interventions may prevent malignant phenotypes or induce tumor cell death. Citation Format: Anjum Sohail, Yeonjoo Hwang, Denise P Munoz, Yoshihiro Ishikawa, Rafael Fridman, Howard Crawford, Jean-Philippe Coppe. Collagen-driven kinome reprogramming reveals unique, actionable DDR1-signaling dependencies in pancreatic cancer cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A049.

Abstract B081: In situ multi-modal characterization of pancreatic ductal adenocarcinoma reveals tumor cell identity as a defining factor of the surrounding microenvironment

Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is heterogeneous with low tumor purity, prominent microenvironment and complex architecture, which preclude identification of shared tumor intrinsic biology within and across patients. We overcame these challenges by applying complementary spatial omics approaches – providing necessary resolution and context – to primary untreated PDAC tumors from 39 patients capturing 341,949 low-bulk and 531,718 single-cell spatial transcriptomes. Of these, 59,403 low-bulk profiles and 205,665 single-cells represented tumor cells. We leveraged this data to build on prior reports of tumor cell subtypes in PDAC. We identify 5 distinct malignant subtypes, excluding ductal-like and intraepithelial neoplasia cells, that span the classical-to-basal spectrum. One tumor subtype is highly proliferative and enriched for the DNA synthesis-condensation-mitosis transcriptional network suggesting this subset disproportionately contribute to tumor growth. Strikingly, the spectrum of tumor cell subtypes was present within all patients, suggesting that subtype-based treatment stratification may need refinement. We find that each subtype has its own distinct regulators and histology. The classical subtype has extensive cell intrinsic regulation, higher cell density and lower extracellular matrix content. In contrast, the basal subtype phenotype results from a combination of cell intrinsic and tumor microenvironment (TME) interactions, wherein the basal subtype has a lower cell density, is surrounded by activated stroma and dense collagen matrix, and is poised for hypoxic adaptation. We derive the composition of cellular neighborhoods providing an explanation for the complex architecture seen in PDAC. Tumor cell neighborhoods stratified based on which side of the classical-to-basal spectrum they fell. For example, cells towards the classical-side of the spectrum had more homogenous tumor neighborhoods that generally lacked intermediate and basal tumor cells. In contrast, cells towards the basal-side of the spectrum were likely to contain classical neighbors. More broadly, neighborhoods along this continuum also contained different proportions of immune and stromal cells, cell densities, collagen deposition, and TME adaptation. These observations support a model where tumor subtypes exist within disparate niches. Lastly, our atlas unifies the catalog of previously reported stromal cells (fibroblasts and stellate cells versus myofibroblastic and inflammatory cancer associated fibroblasts (CAF)) and describes a novel interferon stimulated gene (ISG) resistance signature (ISG.RS) fibroblast. We map the location of these various stromal cells relative to tumor subtypes. For example, myofibroblast CAFs and ISG.RS fibroblasts are enriched near the basal tumor subtype whereas inflammatory CAF abundance increases with distance away from tumor cells. In sum, our atlas provides a lens for stratifying tumor complexity in a cancer cell centric manner and provides a path for testing therapeutic hypothesis in the right cell subtype and context. Citation Format: Brian Rabe, Anna Lyubetskaya, Andrew Kavran, Yulong Bai, Andrew Fisher, Hannah Pliner, Alba Font-Tello, Anne Lewin, Ruifeng Hu, Alexandre P Alloy, Yelena Cheng, Chao Dai, Yunfan Fan, Constance Brett, Todd Brett, Lauren Giampapa, Soeren Stahlschmidt, Fayaz Seifuddin, Steven Vasquez Grinnell, Daniel Carrera, Carlos Rios, Tom Lila, Pradeep Kar, Abhishek Shukla, Rachael Bashford Rogers, Lara Heij, Mike Mason, Ryan Golhar, Isaac Neuhaus, Enas Abu Shah, Shivan Sivakumar, Jimena Trillo Tinoco, Benjamin J Chen, Konstantinos J Mavrakis, Eugene Drokhlyansky. In situ multi-modal characterization of pancreatic ductal adenocarcinoma reveals tumor cell identity as a defining factor of the surrounding microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B081.

Comparison of Bioengineered Scaffolds for the Induction of Osteochondrogenic Differentiation of Human Adipose-Derived Stem Cells.

Osteochondral lesions may be due to trauma or congenital conditions. In both cases, therapy is limited because of the difficulty of tissue repair. Tissue engineering is a promising approach that relies on designed scaffolds with variable mechanical attributes to favor cell attachment and differentiation. Human adipose-derived stem cells (hASCs) are a very promising cell source in regenerative medicine with osteochondrogenic potential. Based on the assumption that stiffness influences cell commitment, we investigated three different scaffolds: a semisynthetic animal-derived GelMA hydrogel, a combined scaffold made of rigid PEGDA coated with a thin GelMA layer and a decellularized plant-based scaffold. We investigated the role of different biomechanical stimulations in the scaffold-induced osteochondral differentiation of hASCs. We demonstrated that all scaffolds support cell viability and spontaneous osteochondral differentiation without any exogenous factors. In particular, we observed mainly osteogenic commitment in higher stiffness microenvironments, as in the plant-based one, whereas in a dense and softer matrix, such as in GelMA hydrogel or GelMA-coated-PEGDA scaffold, chondrogenesis prevailed. We can induce a specific cell commitment by combining hASCs and scaffolds with particular mechanical attributes. However, in vivo studies are needed to fully elucidate the regenerative process and to eventually suggest it as a potential approach for regenerative medicine.

Dual-Prodrug-Based Hyaluronic Acid Nanoplatform Provides Cascade-Boosted Drug Delivery for Oxidative Stress-Enhanced Chemotherapy.

Insufficient drug accumulation in tumors severely limits the antitumor efficiency of hyaluronic acid (HA) nanomedicine in solid tumors due to superficial penetration depth, low cell uptake, and nonspecific drug release. Hence, we constructed a dual NO prodrug (alkynyl-JSK) and doxorubicin prodrug (cis-DOX)-conjugated HA nanoparticle (HA-DOX-JSK NPs), which achieved cascade-boosted drug delivery efficiency based on a relay strategy of NO-mediated deep tumor penetration─HA target CD44 tumor cell uptake─tumor microenvironment (TME)-responsive drug release. The nanoparticle demonstrated sustained and locoregionally GSH/GST-triggered NO release and GSH/pH-responsive DOX release in the tumor. The released NO first mediated collagen degradation, causing deep tumor penetration of nanoparticles in the dense extracellular matrix. Immediately, HA was relayed to enhance CD44-targeted tumor cell uptake, and then, the nanoparticles were finally triggered by specific TME to release DOX and NO in the deep tumor. Relying on the relayed delivery strategy, a significant improvement of DOX accumulation in tumors was realized. Moreover, NO depleted GSH-induced intracellular reactive oxygen species, enhancing DOX chemotherapy. Based on this strategy, the tumor inhibition rate in breast cancer was up to 87.8% in vivo. The relay drug-delivery HA system would greatly cascade-boost drug accumulation in deep tumors for efficient solid tumor therapy.

Focal adhesion kinase regulates tendon cell mechanoresponse and physiological tendon development.

Tendons enable locomotion by transmitting high tensile mechanical forces between muscle and bone via their dense extracellular matrix (ECM). The application of extrinsic mechanical stimuli via muscle contraction is necessary to regulate healthy tendon function. Specifically, applied physiological levels of mechanical loading elicit an anabolic tendon cell response, while decreased mechanical loading evokes a degradative tendon state. Although the tendon response to mechanical stimuli has implications in disease pathogenesis and clinical treatment strategies, the cell signaling mechanisms by which tendon cells sense and respond to mechanical stimuli within the native tendon ECM remain largely unknown. Therefore, we explored the role of cell-ECM adhesions in regulating tendon cell mechanotransduction by perturbing the genetic expression and signaling activity of focal adhesion kinase (FAK) through both invitro and invivo approaches. We determined that FAK regulates tendon cell spreading behavior and focal adhesion morphology, nuclear deformation in response to applied mechanical strain, and mechanosensitive gene expression. In addition, our data reveal that FAK signaling plays an essential role in invivo tendon development and postnatal growth, as FAK-knockout mouse tendons demonstrated reduced tendon size, altered mechanical properties, differences in cellular composition, and reduced maturity of the deposited ECM. These data provide a foundational understanding of the role of FAK signaling as a critical regulator of insitu tendon cell mechanotransduction. Importantly, an increased understanding of tendon cell mechanotransductive mechanisms may inform clinical practice as well as lead to the discovery of diagnostic and/or therapeutic molecular targets.

Simultaneous removal of acidic dyes on binary mixture from aqueous solutions by magnetic basic resin

AbstractThis study, magnetic basic resin (MBR) was synthesized by radical polymerization and modification. Its functional groups, surface morphology, elemental composition, and magnetic value were determined by ATR‐FTIR FE‐ESEM, EDX, and VSM techniques. Subsequently, the usability of MBR as an adsorbent in the simultaneous adsorption of Tartrazine (Tart) and Reactive Blue‐4 (RB4) dye binary mixtures were examined. Maximum adsorption for both dyes, (170 mg/g for Tart and 184 mg/g for RB4), was observed under acidic conditions at a pH range of 1.5–2. It was determined that the adsorption of both dyes onto MBR occurred in a monolayer, and the saturation time was 90 min for Tart and 60 min for RB4. The adsorption of both dyes fitted the pseudo‐second‐order kinetic model. It was also concluded that intra‐particle diffusion was effective. Based on the thermodynamic parameters, it was concluded that the adsorption proceeded spontaneously and endothermically, additionally, the calculated E values led to the conclusion that electrostatic interactions dominated the adsorption of Tart and RB4. The MBR exhibited a notable affinity for Tart and RB4, even within a dense matrix containing both anions and cations. Furthermore, it maintained this high removal affinity across four consecutive uses, involving adsorption and desorption processes.

Reductants supplement boost the antitumor efficacy of nanomedicine

The elevated redox state has become a distinctive characteristic in the tumor environment for designing novel nanomedicines. However, the excessive oxidation stress brought out several plights, such as insufficient reduction-responsive drug release, dense extracellular matrix, and immunosuppressive tumor microenvironment. Here, we explored a potential strategy of replenishing exogenous reductants to boost the efficacy of nanomedicines. Disulfide bond-bridged cabazitaxel prodrug nanoassemblies were developed with high drug loading and reduction responsivity. As relying on endogenous reductants only was not sufficient enough to trigger the activation of prodrug, exogenous reductants were further supplemented to accelerate the activation efficiency. In addition, we found exogenous reductants would increase the tumor penetration of prodrug nanoassemblies, reverse the immunosuppressive system caused by high oxidation stress, and mediate a remarkable antitumor efficacy combined with Anti-PD1. This work elucidated the functions of reductants in cancer treatment, and highlighted their prominent role in combination with nanomedicines.

Fibre hornification improves the long-term properties of hemp fibre-reinforced fly ash-based geopolymer mortar

The study investigates the impact of the fibres’ hornification, subjected to 5 wetting/drying cycles, on the physical and mechanical properties of short hemp fibre-reinforced fly ash-based geopolymer mortars at distinct ages (1, 2.5 and 18 months) cured under laboratory conditions and additionally of the mortars underwent the accelerated ageing of 10 wet/dry cycles. The study reveals that fibres’ hornification induced fibrillation and fibres' cleaner surfaces, most likely enhancing fibres' dispersion within the matrix. This phenomenon leads to suppressing the degradation of all tested mortar’s properties. Considering the curing under laboratory condition, in the case of the density, the suppression is more pronounced in the long term. After 18 months, the hornificated fibre-reinforced mortar nearly matches the water absorption capacity of the plain mortar. Furthermore, the fibres’ hornification contributes to the enhancement in compressive- and flexural strengths of the reinforced mortar at the age of 18 months. In the long term, by increasing the pre-peak segment of the force-displacement curves, the fibres’ hornification slightly increases the energy absorption capacity of the raw fibre-reinforced geopolymer mortar. In the case of the mortars’ curing under wet/dry cycles, the hornification proves to slightly (10 %) improve the physical (increase in density, decrease in water absorption) and mechanical properties (increase in compressive- and flexural strength, as well as energy absorption capacity) of the fibre-reinforced mortar. Due to the mortars’ exposure to the dry cycles (happen at 60 °C), the further geopolymerisation speeds up, which results in the denser matrix, increase in its compressive- and flexural strengths, but a general fibre/matrix bond deteriorates and therefore the fibre-reinforced mortars’ energy absorption capacity decreases, when compared to their counterpart tested at the same age but cured under laboratory condition.

Comparison of Antigen Retrieval Methods for Immunohistochemical Analysis of Cartilage Matrix Glycoproteins Using Cartilage Intermediate Layer Protein 2 (CILP-2) as an Example.

The aim of this study was to compare different antigen retrieval methods to improve the outcome of immunohistochemistry (IHC) performed on osteoarthritic (OA) cartilage obtained from total knee replacement operation. A voluminous and dense extracellular matrix of articular cartilage inhibits antibody penetration, and therefore, proteins present at low concentrations and masked during fixation may need antigen retrieval to enhance an IHC outcome. We focused on the IHC detection of a minor but diagnostically promising cartilage glycoprotein, CILP-2 (cartilage intermediate layer protein 2), to demonstrate the effect of four different protocols: (1) heat-induced epitope retrieval (HIER), (2) proteolytic-induced epitope retrieval applying proteinase K and hyaluronidase (PIER), (3) HIER combined with PIER, and (4) no antigen retrieval (control). A semi-quantitative staining assessment based on the CILP-2 staining extent was applied. Out of the tested antigen retrieval protocols, the best CILP-2 IHC staining results were achieved by PIER. Combining PIER with HIER did not improve CILP-2 staining in the given experimental setting. Rather the opposite, the application of heat reduced the positive effect of PIER on CILP-2 staining and resulted in the frequent detachment of sections from the slides. Our findings emphasize the need for proper adaptation of antigen retrieval protocols for IHC to maximize the quantitative evaluation of minor matrix proteins in OA articular cartilage samples.

Significant impact of carbon source on microstructure and water–oxygen corrosion behavior of Si–Y alloy modified SiC/SiC composite

This study investigated the influence of carbon source on the microstructure and water–oxygen corrosion behavior of Si–Y alloy modified SiC/SiC composites. The results indicated that incorporating a small-sized and diffusely distributed carbon source within the matrix not only facilitates the preparation of a highly dense matrix, but also enables a uniform dispersion of the reaction-generated SiC. Furthermore, with the assistance of residual Si–Y alloy, the dispersed SiC enhanced the matrix strength, leading to a stepwise fracture behavior of the composites. Yttrium silicate with a gradient structure formed around the dispersed SiC could effectively exert its water–oxygen corrosion resistance. After 100 h of water–oxygen corrosion test at 1300 °C, the flexural strength of the composites with this structure reached 416 MPa, with a retention rate of 85 %. Both bending strength and retention were found to be at a high level in the current research on matrix modification.

Delivery Systems Developed for Treatment Combinations to Improve Adoptive Cell Therapy.

Adoptive cell therapy (ACT) has shown great success in the clinic for treating hematologic malignancies. However, solid tumor treatment with ACT monotherapy is still challenging, owing to insufficient expansion and rapid exhaustion of adoptive cells, tumor antigen downregulation/loss, and dense tumor extracellular matrix. Delivery strategies for combination cell therapy have great potential to overcome these hurdles. The delivery of vaccines, immune checkpoint inhibitors, cytokines, chemotherapeutics, and photothermal reagents in combination with adoptive cells, have been shown to improve the expansion/activation, decrease exhaustion, and promote the penetration of adoptive cells in solid tumors. Moreover, the delivery of nucleic acids to engineer immune cells directly in vivo holds promise to overcome many of the hurdles associated with the complex ex vivo cell engineering strategies. Here, these research advance, as well as the opportunities and challenges for integrating delivery technologies into cell therapy s are discussed, and the outlook for these emerging areas are criticlly analyzed.

Efficient Mixed-Precision Matrix Factorization of the Inverse Overlap Matrix in Electronic Structure Calculations with AI-Hardware and GPUs.

In recent years, a new kind of accelerated hardware has gained popularity in the artificial intelligence (AI) community which enables extremely high-performance tensor contractions in reduced precision for deep neural network calculations. In this article, we exploit Nvidia Tensor cores, a prototypical example of such AI-hardware, to develop a mixed precision approach for computing a dense matrix factorization of the inverse overlap matrix in electronic structure theory, S-1. This factorization of S-1, written as ZZT = S-1, is used to transform the general matrix eigenvalue problem into a standard matrix eigenvalue problem. Here we present a mixed precision iterative refinement algorithm where Z is given recursively using matrix-matrix multiplications and can be computed with high performance on Tensor cores. To understand the performance and accuracy of Tensor cores, comparisons are made to GPU-only implementations in single and double precision. Additionally, we propose a nonparametric stopping criteria which is robust in the face of lower precision floating point operations. The algorithm is particularly useful when we have a good initial guess to Z, for example, from previous time steps in quantum-mechanical molecular dynamics simulations or from a previous iteration in a geometry optimization.

Optimization of Gene Selection for Cancer Classification in High-Dimensional Data Using an Improved African Vultures Algorithm

This study presents a novel method, termed RBAVO-DE (Relief Binary African Vultures Optimization based on Differential Evolution), aimed at addressing the Gene Selection (GS) challenge in high-dimensional RNA-Seq data, specifically the rnaseqv2 lluminaHiSeq rnaseqv2 un edu Level 3 RSEM genes normalized dataset, which contains over 20,000 genes. RNA Sequencing (RNA-Seq) is a transformative approach that enables the comprehensive quantification and characterization of gene expressions, surpassing the capabilities of micro-array technologies by offering a more detailed view of RNA-Seq gene expression data. Quantitative gene expression analysis can be pivotal in identifying genes that differentiate normal from malignant tissues. However, managing these high-dimensional dense matrix data presents significant challenges. The RBAVO-DE algorithm is designed to meticulously select the most informative genes from a dataset comprising more than 20,000 genes and assess their relevance across twenty-two cancer datasets. To determine the effectiveness of the selected genes, this study employs the Support Vector Machine (SVM) and k-Nearest Neighbor (k-NN) classifiers. Compared to binary versions of widely recognized meta-heuristic algorithms, RBAVO-DE demonstrates superior performance. According to Wilcoxon’s rank-sum test, with a 5% significance level, RBAVO-DE achieves up to 100% classification accuracy and reduces the feature size by up to 98% in most of the twenty-two cancer datasets examined. This advancement underscores the potential of RBAVO-DE to enhance the precision of gene selection for cancer research, thereby facilitating more accurate and efficient identification of key genetic markers.

Intelligent micelles for on-demand drug delivery targeting extracellular matrix of pancreatic cancer

As a key pathological feature of pancreatic ductal adenocarcinoma(PDAC), the dense extracellular matrix(ECM) limits the penetration of chemotherapy drugs and is involved in the formation of immunosuppressive microenvironment. Meanwhile, clinical practice has shown that the treatment strategy for ECM should consider its restriction of tumor cell metastasis, and the need for in-depth chemotherapy without destroying ECM is proposed. STAT3 inhibitors have been reported to regulate tumor microenvironment including interrupt the form of ECM. Therefore, we designed and established a micelle system MP@HA with in vivo targeting and responsive drug release function co-loading gemcitabine monophosphate and STAT3 inhibitor silibinin. The hyaluronic acid on the surface of the micelle can bind specifically to the CD44 molecule on the surface of tumor cells and help micelles accumulate at the tumor site. The nitroimidazole used to modify the polymeric skeleton can make the micellar structure collapse in response to hypoxia reduction conditions in the tumor environment, and release silibinin to widely regulate STAT3 molecules in the PDAC microenvironment. The polymer fragment attached with gemcitabine monophosphate can penetrate deep into PDAC tumors due to its small size and positive charge exposed, achieving deep chemotherapy. This research indicates a promising micelle system meeting complicated demands proposed in PDAC treatment to improve antitumor efficacy.

Experimental study on hybrid fiber reinforced high performance concrete properties: Investigatingcomprehensive energy consumption capacity

The brittleness of concrete in tension increases with higher compressive strength, necessitating the study of cementitious composites that combine high strength and ductility. This study investigated the fresh and mechanical properties of high-strength concrete (HPC) incorporating fibers: steel, basalt, and polyethylene (PE). Hybrid fiber reinforced high performance concrete (HyFHPC) was created by tailoring mix proportions, with eight series of specimens cast, each carrying different fiber combinations alongside plain HPC as a reference. Compressive, tensile, and flexural tests were conducted, and results were analyzed. The electron microscopy techniques were employed to observe the microstructural morphology and perform elemental analysis of the composites. Findings revealed a dense HPC matrix with 1.5 % total fiber content, exhibiting uniform dispersion and ideal bonding. Digital image correlation (DIC) technique was utilized to analyze strain distribution and crack development of specimens in tension and bending, proving effective in tracking the strain and crack evolution. Statistical analysis of five influencing elements—cubic compressive strength, axial compressive strength, tensile energy dissipation, tensile fracture energy, and energy release rate—revealed Series F9 (S0.5P1) as optimal for comprehensive energy consumption performance. HyFHPC demonstrated enhanced strength, ductility, and toughness compared to HPC with mono fiber or none. The hybridization achieved positive synergy and improved reinforcing efficiency while conserving resources.

Are we approaching the development of a novel calcium phosphate-based bioceramic dental material?

ObjectivesDevelop a sustainable bovine hydroxyapatite dental ceramic with the addition of titanium dioxide (TiO2) nanoparticles (5 % and 8 % by weight), analyzing the outcome of this addition to the microstructure, as well as its mechanical and chemical properties, in order to evaluate whether they satisfy the International Organization for Standardization (ISO) 6872:2015 for dental ceramics or not. MethodsDisks were obtained through uniaxial followed by isostatic pressing from bovine hydroxyapatite powder and TiO2 nanoparticles and sintered at 1300ºC for 2 h. Three experimental groups were developed (HA, HA+5 %TiO2 and HA+8 %TiO2) and subjected to X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), indentation fracture (IF), biaxial flexural strength (BFS) and chemical solubility test. ResultsXRD revealed, for HA group, the appearance of a peak corresponding to b-tricalcium phosphate (ß-TCP). For HA+ 5 %TiO2 and HA+ 8 %TiO2, the entire composition was converted into ß-TCP and calcium titanate (CaTiO3). The SEM images showed a dense ceramic matrix and a uniform distribution of another phase in groups with TiO2 nanoparticles. HA+ 5 %TiO2 (1.40 ± 0.18 MPa.m1/2) and HA+ 8 %TiO2 (1.32 ± 0.18 MPa.m1/2) showed significantly higher fracture toughness values than HA (0.67 ± 0.09 MPa.m1/2). HA showed significantly higher characteristic stress (295.8 MPa) in comparison to groups with 5 % (235.1 MPa) and 8 % (214.4 MPa) TiO2 nanoparticles. Differences were not observed between the Weibull modulus values. The solubility results indicated that all experimental ceramics were above the 2000 ug/cm2 limit set by the ISO 6872:2015. SignificanceThis study proposed the development and characterization of a new ceramic for dental prosthesis made from HA extracted from bovine bones, with the intention of reusing these solids waste and transforming them into a sustainable and low-cost material. Although the experimental calcium phosphate ceramic with additions of 5 % and 8 % of TiO2 achieved desirable mechanical properties, the chemical solubility values were very high.

Direct ink writing of non-sintered ceramic with biomimetic cellular structure

Cellular ceramics are highly valued for their exceptional mechanical properties and low density, making them suitable for applications like thermal insulation, impact absorption, and biomedical implants. However, high-temperature sintering required for densification can cause issues like shrinkage, loss of precision, and degradation of functional additives. This work reports a novel approach for fabricating 3D printed cellular ceramics under ambient conditions using CO2-cured γ-C2S ink via direct ink writing. The printed green body is converted into a dense matrix of CaCO3 and silica gel upon exposure to a CO2-rich environment without high temperature sintering. The non-sintered cellular ceramics achieve high compressive and specific strength comparable to sintered counterparts, with the square-shaped structure exhibiting the best performance of 104 and 171 MPa in terms of in-plane and out-of-plane compressive strength, respectively. Further, the in-situ analysis reveals distinct deformation modes and crack propagation patterns across structures, providing insights into structure-property relationships to guide the design of high-strength non-sintered cellular ceramics.

Hyaluronic acid-targeted dual-bubble/photothermal-driven nanomissile for enhanced “four-in-one” anti-tumor strategy

The dense extracellular matrix and high interstitial pressure affect the diffusion of nanodrug in tumor tissue, resulting in a small range of action of the active components in nanodrug, thereby affecting its anticancer efficacy. In order to enhance the diffusion ability of nanodrug, a dual-bubble/photothermal-driven nanomissile (HA@MnO2@TA/Fe/ICG/TPZ, HMTAFIT) was designed through “four in one” anti-tumor strategy. Harnessing the capabilities of hyaluronic acid, a biomacromolecule, the nanomotor transforms into a nanomissile, targeting cancer cells with precision. The oxygen generated by the reaction of manganese dioxide with hydrogen peroxide and the local temperature rise of indocyanine green under near-infrared light endow HMTAFIT with the ability of bubble/photothermal dual-driven, and the outermost layer of modified hyaluronic acid incubates the targeting properties of HMTAFIT which could avoid damage to normal cells. The bubble/photothermal-dual-driven increases motion speed of HMTAFIT by 13.8 μm/s, and the enhanced “four in one” anti-tumor strategy effectively improved the anticancer efficacy. The precision-guided nanomissile boasts the capability to eliminate deep-seated cancer cells and overcome multidrug resistance via optimized diffusion and a cutting-edge “four-in-one” approach.

Synthesis of eco-sustainable seawater sea-sand geopolymer mortars from ternary solid waste: Influence of microstructure evolution on mechanical performance

To fully utilize abundant marine resources and reduce the carbon footprint in the construction sector, this study developed a seawater sea-sand geopolymer mortar (SSGM) using seawater, sea-sand, and ternary solid waste. Three different alkaline content levels (4%, 5%, and 7%) were tailored for the SSGM, in addition to freshwater river sand mixed geopolymer mortars (FRGM), seawater sea-sand ordinary Portland cement mortar (SSCM), and SSGM without additional fibres (SSGM-0). The workability, setting time, mechanical performance, and drying shrinkage of all samples were studied. The microstructural characteristics of each mortar were meticulously scrutinized through techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and mercury intrusion porosimetry (MIP). The results showed that as alkaline content increased, SSGM formed more hybrid sodium, calcium aluminosilicate hydrate (N, C-A-S-H) gels, resulting in a denser matrix. Under the influence of magnesium ions and sulfate ions in seawater, the formation of magnesium aluminosilicate hydrates, magnesium silicate hydrates, and silica gels filled the pores, making SSGM has more mesopores and gel pores compared to FRGM, thus exhibiting superior mechanical properties. However, the Ca/Si ratio of the primary hydration products of SSGM was lower than that of SSCM and FRGM, indicating a more disordered microstructure of SSGM, leading to greater shrinkage. Despite moisture migration reaching a stable state, SSGM exhibited persistent shrinkage, revealing their inherent time-dependent (creep) response to drying conditions, indicative of typical viscoelastic/visco-plastic matrix behavior.

Trash into Treasure: Nano-coating of Catheter Utilizes Urine to Deprive H2S Against Persister and Rip Biofilm Matrix.

Bacteria-derived hydrogen sulfide (H2S) often contributes to the emergence of antibiotic-recalcitrant bacteria, especially persister (a sub-population of dormant bacteria), thus causing the treatment failure of Catheter-associated urinary tract infection (CAUTI). Here, an H2S harvester nanosystem to prevent the generation of persister bacteria and disrupt the dense biofilm matrix by the self-adaptive ability of shape-morphing is prepared. The nanosystem possesses a core-shell structure that is composed of liquid metal nanoparticle (LM NP), AgNPs, and immobilized urease. The nanosystem decomposes urea contained in urine to generate ammonia for eliminating bacteria-derived H2S. Depending on the oxidative layer of liquid metal, the nanosystem also constitutes a long-lasting reservoir for temporarily storing bacteria-derived H2S, when urease transiently overloads or in the absence of urine in a catheter. Depriving H2S can prevent the emergence of persistent bacteria, enhancing the bacteria-killing efficiency of Ga3+ and Ag+ ions. Even when the biofilm has formed, the urine flow provides heat to trigger shape morphing of the LM NP, tearing the biofilm matrix. Collectively, this strategy can turn trash (urea) into treasure (H2S scavengers and biofilm rippers), and provides a new direction for the antibacterial materials application in the medical field.