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1. Superparamagnetic nanoparticles for the treatment of periodontal disease

   https://doi.org/10.1117/12.2654656  

   Fritz, Shayden; Armijo, Leisha M.; Simpson, Kayla; Lopez, Kimberly; Osinski, Marek; Bandara, Nihal; Smyth, Hugh D.; Sheng, Jian; Xu, Wei (March 2023, Colloidal Nanoparticles for Biomedical Applications XVIII)

   Osiński, Marek; Kanaras, Antonios G. (Ed.)

   Periodontal diseases are prevalent worldwide and are linked to numerous other health conditions due to dysbiosis and chronic inflammatory state. Most periodontal diseases are caused by pathogenic bacteria that colonize dental tissues in the form of biofilm. Eradication of bacterial biofilms can be difficult to achieve due to the complex architecture of the teeth and gums which complicates the removal. Orthodontic wires and dental devices introduce additional hurdles to the adequate removal of biofilms by traditional methods since mechanical disruption via direct contact with toothbrush bristles, floss, and abrasive toothpaste is limited. Magnetically activated nanoparticles (NPs), specifically iron oxide nanoparticles (IONPs) that can be functionalized as antimicrobial particles and remotely controlled by magnetic fields, are of interest for oral biofilm eradication. We present data in multi-species bacterial cultures, established biofilms, human gingival keratinocytes, and human gingival fibroblast cells alone and in the presence of multispecies biofilm co-cultures to determine the safest, most efficacious IONP size ranges and treatment concentrations of active magnetic NPs for removal of dental biofilms. We report enhanced efficacy for IONPs coated with alginate vs. dextran, and small sizes (~8 nm vs. >20 nm in size) appear to exhibit enhanced antimicrobial efficacy. Human gingival keratinocyte (TIGK) cells in co-culture with treated and untreated multispecies biofilms in an in-vitro periodontitis model also exhibited a trend of reduced inflammatory markers in wells with IONP-treated biofilms. 

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2. Engineering anisotropic human stem cell-derived three-dimensional cardiac tissue on-a-chip

   https://doi.org/doi: 10.1016/j.biomaterials.2020.120195  

   Veldhuizen, Jaimeson; Cutts, Joshua; Brafman, David; Migrino, Raymond Q.; Nikkhah, Mehdi (October 2020, Biomaterials)

   Despite significant efforts in the study of cardiovascular diseases (CVDs), they persist as the leading cause of mortality worldwide. Considerable research into human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has highlighted their immense potential in the development of in vitro human cardiac tissues for broad mechanistic, therapeutic, and patient-specific disease modeling studies in the pursuit of CVD research. However, the relatively immature state of hPSC-CMs remains an obstacle in enhancing clinical relevance ofengineered cardiac tissue models. In this study, we describe development of a microfluidic platform for 3D modeling of cardiac tissues, derived from both rat cells and hPSC-CMs, to better recapitulate the native myocardium through co-culture with interstitial cells (specifically cardiac fibroblasts), biomimetic collagen hydrogel encapsulation, and induction of highly anisotropic tissue architecture. The presented platform is precisely engineered through incorporation of surface topography in the form of staggered microposts to enable long-term culture and maturation of cardiac cells, resulting in formation of physiologically relevant cardiac tissues with anisotropy that mimics native myocardium. After two weeks of culture, hPSC-derived cardiac tissues exhibited well-defined sarcomeric striations, highly synchronous contractions, and upregulation of several maturation genes, including HCN1, KCNQ1, CAV1.2, CAV3.1, PLN, and RYR2. These findings demonstrate the ability of the proposed engineered platform to mature animal- as well as human stem cell-derived cardiac tissues over an extended period of culture, providing a novel microfluidic chip with the capability for cardiac disease modeling and therapeutic testing. 

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3. Microfluidic chip-based co-culture system for modeling human joint inflammation in osteoarthritis research

   https://doi.org/10.3389/fphar.2025.1579228  

   Mirazi, Hosein; Wood, Scott T (April 2025, Frontiers in Pharmacology)

   Here we present a microfluidic model that allows for co-culture of human osteoblasts, chondrocytes, fibroblasts, and macrophages of both quiescent (M0) and pro-inflammatory (M1) phenotypes, maintaining initial viability of each cell type at 24 h of co-culture. We established healthy (M0-based) and diseased (M1-based) joint models within this system. An established disease model based on supplementation of IFN-γ and lipopolysaccharide in cell culture media was used to induce an M1 phenotype in macrophages to recapitulate inflammatory conditions found in Osteoarthritis. Cell viability was assessed using NucBlue™ Live and NucGreen™ Dead fluorescent stains, with mean viability of 83.9% ± 14% and 83.3% ± 12% for healthy and diseased models, respectively, compared with 93.3% ± 4% for cell in standard monoculture conditions. Cytotoxicity was assessed via a lactate dehydrogenase (LDH) assay and showed no measurable increase in lactate dehydrogenase release into the culture medium under co-culture conditions, indicating that neither model promotes a loss of cell membrane integrity due to cytotoxic effects. Cellular metabolic activity was assessed using a PrestoBlue™ assay and indicated increased cellular metabolic activity in co-culture, with levels 5.9 ± 3.2 times mean monolayer cell metabolic activity levels in the healthy joint model and 5.3 ± 3.4 times mean monolayer levels in the diseased model. Overall, these findings indicate that the multi-tissue nature ofin vivohuman joint conditions can be recapitulated by our microfluidic co-culture system at 24 h and thus this model serves as a promising tool for studying the pathophysiology of rheumatic diseases and testing potential therapeutics. 

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4. Fibroblasts Promote Proliferation and Matrix Invasion of Breast Cancer Cells in Co‐Culture Models

   https://doi.org/10.1002/adtp.201900121  

   Plaster, Madison; Singh, Sunil; Tavana, Hossein (September 2019, Advanced Therapeutics)

   Abstract Fibroblasts are an abundant cell type in tumor microenvironments. Activated fibroblasts, known as carcinoma‐associated fibroblasts (CAFs), interact with cancer cells through biochemical signaling and render cancer cells proliferative, invasive, and resistant to therapeutics. Targeting CAFs–cancer cells interactions offers a strategy to block cancer progression. 2D and 3D co‐cultures of human mammary fibroblasts and triple negative breast cancer (TNBC) cells are used to investigate the impact of heterotypic cellular interactions on the proliferation of matrix invasion of TNBC cells. The results show that fibroblasts secreting a chemokine, CXCL12, significantly enhance proliferation of TNBC cells expressing the chemokine receptor, CXCR4. Disrupting this interaction with a receptor antagonist normalizes cancer cell proliferation to that of a co‐culture model lacking this signaling. When co‐culture spheroids are embedded in collagen, fibroblasts producing CXCL12 promote collagen invasion of TNBC cells. Although co‐cultures containing normal fibroblasts also lead to TNBC cell spreading into the matrix, a morphological analysis of cells and inhibition of chemokine‐receptor signaling shows that this spreading is due to the incompatibility of fibroblasts and cancer cells leading to the segregation of the two cell types from the spheroid. 

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5. Novel Fabrication Approach of a Porous Silicon Biocompatible Membrane Evaluated within a Alveolar Coculture Model

   https://doi.org/10.31224/osf.io/mztyc  

   Williams, Marcus_A C; Wiens, Cooper; Hamilton, Adam; Mancha, Sophie; Stalder, Madeline; Vargas, Koby; Crawford, Jerry; Li, Yiyan; Schreiner, Sarah; Blake, David J; et al (October 2021, Engrxiv Engineering Archive)

   The use of conventional in vitro and preclinical animal models often fail to properly recapitulate the complex nature of human diseases and hamper the success of translational therapies in humans [1-3] Consequently, research has moved towards organ-on-chip technology to better mimic human tissue interfaces and organ functionality. Herein, we describe a novel approach for the fabrication of a biocompatible membrane made of porous silicon (PSi) for use in organ-on-chip technology that provides key advantages when modeling complex tissue interfaces seen in vivo. By combining well-established methods in the semiconductor industry with organ-on-chip technology, we have developed a novel way of producing thin (25 μm) freestanding PSi biocompatible membranes with both nano (~15.5 nm diameter pores) and macroporous (~0.5 μm diameter pores) structures. To validate the proposed novel membrane, we chose to recapitulate the dynamic environment of the alveolar blood gas exchange interface in alveolar co-culture. Viability assays and immunofluorescence imaging indicate that human pulmonary cells remain viable on the PSi membrane during long-term culture (14 days). Interestingly, it was observed that macrophages can significantly remodel and degrade the PSi membrane substrate in culture. This degradation will allow for more intimate physiological cellular contact between cells, mimicking a true blood-gas exchange interface as observed in vivo. Broadly, we believe that this novel PSi membrane may be used in more complex organ-on-chip and lab-on-chip model systems to accurately recapitulate human anatomy and physiology to provide further insight into human disease pathology and pre-clinical response to therapeutics. 

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