3D porous chitosan-chondroitin sulfate scaffolds promote epithelial to mesenchymal transition in prostate cancer cells.

Prostate cancer (PCa) is a common cancer in men that is curable prior to metastasis, when its prognosis worsens. Chondroitin sulfate (CS) is found in the extracellular matrix of normal prostate tissue and PCa, with greater content in metastatic PCa. Biomaterial scaffolds containing CS have yet to be evaluated for tumor microenvironment applications.

Freeze-FRESH: A 3D Printing Technique to Produce Biomaterial Scaffolds with Hierarchical Porosity.

Tissues are organized in hierarchical structures comprised of nanoscale, microscale, and macroscale features. Incorporating hierarchical structures into biomaterial scaffolds may enable better resemblance of native tissue structures and improve cell interaction, but it is challenging to produce such scaffolds using a single conventional scaffold production technique. We developed the Freeze-FRESH (FF) technique that combines FRESH 3D printing (3DP) and freeze-casting to produce 3D printed scaffolds with microscale pores in the struts.

Effect of Mold Geometry on Pore Size in Freeze-Cast Chitosan-Alginate Scaffolds for Tissue Engineering.

Freeze-casting is a popular method to produce biomaterial scaffolds with highly porous structures. The pore structure of freeze-cast biomaterial scaffolds is influenced by processing parameters but has mostly been controlled experimentally. A mathematical model integrating Computational Fluid Dynamics with Population Balance Model was developed to predict average pore size (APS) of 3D porous chitosan-alginate scaffolds and to assess the influence of the geometrical parameters of mold on scaffold pore structure.

3D porous chitosan-alginate scaffold stiffness promotes differential responses in prostate cancer cell lines.

Prostate cancer (PCa) is a leading cause of death for men worldwide. Most PCa patients die from metastasis and bone is the most common metastatic site. Three dimensional (3D) porous chitosan-alginate (CA) scaffolds were developed for bone tissue engineering and demonstrated for culture of cancer cells and enrichment of cancer stem cells.

Direct-Contact Cytotoxicity Evaluation of CoCrFeNi-Based Multi-Principal Element Alloys.

Transition metal multi-principal element alloys (MPEAs) are novel alloys that may offer enhanced surface and mechanical properties compared with commercial metallic alloys. However, their biocompatibility has not been investigated. In this study, three CoCrFeNi-based MPEAs were fabricated, and the in vitro cytotoxicity was evaluated in direct contact with fibroblasts for 168 h.

Modeling, validation and verification of three-dimensional cell-scaffold contacts from terabyte-sized images.

Background: Cell-scaffold contact measurements are derived from pairs of co-registered volumetric fluorescent confocal laser scanning microscopy (CLSM) images (z-stacks) of stained cells and three types of scaffolds (i.e., spun coat, large microfiber, and medium microfiber).

Effect of the scaffold microenvironment on cell polarizability and capacitance determined by probabilistic computations.

In living systems, it is frequently stated that form follows function by virtue of evolutionary pressures on organism development, but in the study of how functions emerge at the cellular level, function often follows form. We study this chicken versus egg problem of emergent structure-property relationships in living systems in the context of primary human bone marrow stromal cells cultured in a variety of microenvironments that have been shown to cause distinct patterns of cell function and differentiation. Through analysis of a publicly available catalog of three-dimensional (3D) cell shape data, we introduce a family of metrics to characterize the 'form' of the cell populations that emerge from a variety of diverse microenvironments.

A Bioinformatics 3D Cellular Morphotyping Strategy for Assessing Biomaterial Scaffold Niches.

Many biomaterial scaffolds have been advanced to provide synthetic cell niches for tissue engineering and drug screening applications; however, current methods for comparing scaffold niches focus on cell functional outcomes or attempt to normalize materials properties between different scaffold formats. We demonstrate a three-dimensional (3D) cellular morphotyping strategy for comparing biomaterial scaffold cell niches between different biomaterial scaffold formats. Primary human bone marrow stromal cells (hBMSCs) were cultured on 8 different biomaterial scaffolds, including fibrous scaffolds, hydrogels, and porous sponges, in 10 treatment groups to compare a variety of biomaterial scaffolds and cell morphologies.

Periodically Patterned Au-TiO Heterostructures for Photoelectrochemical Sensor.

Periodically patterned Au nanorods in TiO nanocavities (Au NRs@TiO) were fabricated via magnetron sputtering followed by a thermal dewetting process. This innovative Au NRs@TiO heterostructure was used as a plasmonic sensing platform for photoelectrochemical detection of glucose and lactose. This Au NRs@TiO patterned heterostructure possesses superior sensing properties to other Au nanoparticle-based sensors because (i) localized surface plasmon resonance (LSPR) generated at Au/TiO interfaces enhanced sensitivity of glucose (lactose) amperometric detection; (ii) periodic Au nanocrystals in TiO nanocavities accelerated charge separation and transfer rate, especially under monochromatic blue light irradiation; (iii) discrete planar architectures comprising Au NRs immobilized on TiO substrates significantly improved stability and reusability of the sensors.

3D Porous Chitosan-Alginate Scaffolds Promote Proliferation and Enrichment of Cancer Stem-Like Cells.

Cancer stem cells are increasingly becoming a primary target for new cancer treatment development. The ability to study their transient behavior in vitro will provide the opportunity for high-throughput testing of more effective therapies. We have previously demonstrated the use of 3D porous chitosan-alginate (CA) scaffolds to promote cancer stem-like cell (CSC) proliferation and enrichment in glioblastoma.

Machine learning based methodology to identify cell shape phenotypes associated with microenvironmental cues.

Cell morphology has been identified as a potential indicator of stem cell response to biomaterials. However, determination of cell shape phenotype in biomaterials is complicated by heterogeneous cell populations, microenvironment heterogeneity, and multi-parametric definitions of cell morphology. To associate cell morphology with cell-material interactions, we developed a shape phenotyping framework based on support vector machines.

3D Porous Chitosan-Alginate Scaffolds as an In Vitro Model for Evaluating Nanoparticle-Mediated Tumor Targeting and Gene Delivery to Prostate Cancer.

Cationic nanoparticles (NPs) for targeted gene delivery are conventionally evaluated using 2D in vitro cultures. However, this does not translate well to corresponding in vivo studies because of the marked difference in NP behavior in the presence of the tumor microenvironment. In this study, we investigated whether prostate cancer (PCa) cells cultured in three-dimensional (3D) chitosan-alginate (CA) porous scaffolds could model cationic NP-mediated gene targeted delivery to tumors in vitro.

Proliferation and enrichment of CD133(+) glioblastoma cancer stem cells on 3D chitosan-alginate scaffolds.

Emerging evidence implicates cancer stem cells (CSCs) as primary determinants of the clinical behavior of human cancers, representing an ideal target for next-generation anti-cancer therapies. However CSCs are difficult to propagate in vitro, severely limiting the study of CSC biology and drug development. Here we report that growing cells from glioblastoma (GBM) cell lines on three dimensional (3D) porous chitosan-alginate (CA) scaffolds dramatically promotes the proliferation and enrichment of cells possessing the hallmarks of CSCs.

CCL21 and IFNγ recruit and activate tumor specific T cells in 3D scaffold model of breast cancer.

Effective elicitation of endogenous immunity is associated with improved prognosis for cancer patients. Clinical evidence in hematological and solid cancers shows that intratumoral injection of immunostimulatory genes primes and augments endogenous T cell responses. The ability of pro-inflammatory chemokines/cytokines to facilitate migration/activation of antigen-presenting cells (APC) and lymphocytes prompted our modeling of intratumoral delivery of a chemokine/cytokine combination for breast cancer treatment.

Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM.

Cancer therapeutics are developed through extensive screening; however, many therapeutics evaluated with 2D in vitro cultures during pre-clinical trials suffer from lower efficacy in patients. Replicating the in vivo tumor microenvironment in vitro with three-dimensional (3D) porous scaffolds offers the possibility of generating more predictive pre-clinical models to enhance cancer treatment efficacy. We developed a chitosan and hyaluronic acid (HA) polyelectrolyte complex 3D porous scaffold and evaluated its physical properties.

Evaluation of three-dimensional porous chitosan-alginate scaffolds in rat calvarial defects for bone regeneration applications.

This study investigated the use of three-dimensional porous chitosan-alginate (CA) scaffolds for critical size calvarial defect (diameter, 5.0 mm) repair in Sprague-Dawley rats. CA scaffolds have been used for in vitro culture of many cell types and demonstrated osteogenesis in ectopic locations in vivo, but have yet to be evaluated for functional bone tissue engineering applications.

Three-dimensional scaffolds to evaluate tumor associated fibroblast-mediated suppression of breast tumor specific T cells.

In the tumor microenvironment, the signals from tumor-associated fibroblasts (TAF) that suppress antitumor immunity remain unclear. Here, we develop and investigate an in vitro three-dimensional (3D) scaffold model for the novel evaluation of TAF interaction with breast tumor cells and breast specific, neu antigen (p98) reactive T cells. Breast cancer cells seeded on 3D chitosan-alginate (CA) scaffolds showed productive growth and formed distinct tumor spheroids.

Integrated bi-layered scaffold for osteochondral tissue engineering.

Osteochondral tissue engineering poses the challenge of combining both cartilage and bone tissue engineering fundamentals. In this study, a sphere-templating technique was applied to fabricate an integrated bi-layered scaffold based on degradable poly(hydroxyethyl methacrylate) hydrogel. One layer of the integrated scaffold was designed with a single defined, monodispersed pore size of 38 μm and pore surfaces coated with hydroxyapatite particles to promote regrowth of subchondral bone while the second layer had 200 μm pores with surfaces decorated with hyaluronan for articular cartilage regeneration.

3D porous chitosan-alginate scaffolds: a new matrix for studying prostate cancer cell-lymphocyte interactions in vitro.

The treatment of castration-resistant prostate cancer (CRPC) remains palliative. Immunotherapy offers a potentially effective therapy for CRPC; however, its advancement into the clinic has been slow, in part because of the lack of representative in vitro tumor models that resemble the in vivo tumor microenvironment for studying interactions of CRPC cells with immune cells and other potential therapeutics. This study evaluates the use of 3D porous chitosan-alginate (CA) scaffolds for culturing human prostate cancer (PCa) cells and studying tumor cell interaction with human peripheral blood lymphocytes (PBLs) ex vivo.

Enhanced bone tissue formation by alginate gel-assisted cell seeding in porous ceramic scaffolds and sustained release of growth factor.

Increasing cell seeding efficiency in a tissue engineering construct can enhance cellular activity and tissue formation in vivo. Here, we demonstrate the use of alginate gel as a secondary phase material in 3D porous β-tricalcium phosphate scaffolds to improve cell seeding and provide controlled release of growth factors for bone tissue engineering. Cells were seeded in scaffolds in three ways: conventional seeding (CS), alginate gel-assisted seeding (GS), and alginate GS with bone morphogenetic protein-2 (BMP-2, GSB).

Influence of processing parameters on pore structure of 3D porous chitosan-alginate polyelectrolyte complex scaffolds.

Fabrication of porous polymeric scaffolds with controlled structure can be challenging. In this study, we investigated the influence of key experimental parameters on the structures and mechanical properties of resultant porous chitosan-alginate (CA) polyelectrolyte complex (PEC) scaffolds, and on proliferation of MG-63 osteoblast-like cells, targeted at bone tissue engineering. We demonstrated that the porous structure is largely affected by the solution viscosity, which can be regulated by the acetic acid and alginate concentrations.

Chitosan-alginate scaffold culture system for hepatocellular carcinoma increases malignancy and drug resistance.

Purpose: Hepatocellular carcinoma (HCC) is a prevalent solid malignancy. Critically needed discovery of new therapeutics has been hindered by lack of an in vitro cell culture system that can effectively represent the in vivo tumor microenvironment. To address this need, a 3D in vitro HCC model was developed using a biocompatible, chitosan-alginate (CA) scaffold cultured with human HCC cell lines.

Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment.

Despite recent advances in the understanding of its cell biology, glioma remains highly lethal. Development of effective therapies requires a cost-effective in vitro tumor model that more accurately resembles the in vivo tumor microenvironment as standard two-dimensional (2D) tissue culture conditions do so poorly. Here we report on the use of a three-dimensional (3D) chitosan-alginate (CA) scaffold to serve as an extracellular matrix that promotes the conversion of cultured cancer cells to a more malignant in vivo-like phenotype.

Manufacture of nanoparticles from bone: a preliminary study.

This study investigated a mechanical processing method using vibratory milling to reduce the particle size of bone ash to produce hydroxyapatite (HA) nanoparticles from bovine bone. Bovine femurs were cleaned of soft tissue, cut into small pieces, heated to 600 deg for 24 h, and ground into a coarse powder. A 50 wt% suspension was prepared, vibratory milled for 18 h, and then the milled suspension was filter pressed, dried, and ground into powder.

Ethical issues in nanotechnology.

Nanotechnology is a rapidly developing area in science involved with manipulating matter at the atomic or molecular level. Nanotechnology is typically defined at a scale on the order of less than approximately 100 nm. Matter possesses unique properties at these size levels that are neither Newtonian nor quantum, but between the two regimes.