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1. Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue Engineering

   https://doi.org/10.3390/jcdd8110137  

   Khanna, Astha; Zamani, Maedeh; Huang, Ngan F. (November 2021, Journal of Cardiovascular Development and Disease)

   Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic scaffolding structure characterized by tissue-specific biochemical, biophysical, and mechanical properties that modulates cellular behavior and activates highly regulated signaling pathways. In light of technological advancements, biomaterial-based scaffolds have been developed that better mimic physiological ECM properties, provide signaling cues that modulate cellular behavior, and form functional tissues and organs. In this review, we summarize the in vitro, pre-clinical, and clinical research models that have been employed in the design of ECM-based biomaterials for cardiovascular regenerative medicine. We highlight the research advancements in the incorporation of ECM components into biomaterial-based scaffolds, the engineering of increasingly complex structures using biofabrication and spatial patterning techniques, the regulation of ECMs on vascular differentiation and function, and the translation of ECM-based scaffolds for vascular graft applications. Finally, we discuss the challenges, future perspectives, and directions in the design of next-generation ECM-based biomaterials for cardiovascular tissue engineering and clinical translation. 

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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. Vasculature-on-a-chip technologies as platforms for advanced studies of bacterial infections

   https://doi.org/10.1063/5.0179281  

   Gaudreau, Lily Isabelle; Stewart, Elizabeth J. (March 2024, Biomicrofluidics)

   Bacterial infections frequently occur within or near the vascular network as the vascular network connects organ systems and is essential in delivering and removing blood, essential nutrients, and waste products to and from organs. In turn, the vasculature plays a key role in the host immune response to bacterial infections. Technological advancements in microfluidic device design and development have yielded increasingly sophisticated and physiologically relevant models of the vasculature including vasculature-on-a-chip and organ-on-a-chip models. This review aims to highlight advancements in microfluidic device development that have enabled studies of the vascular response to bacteria and bacterial-derived molecules at or near the vascular interface. In the first section of this review, we discuss the use of parallel plate flow chambers and flow cells in studies of bacterial adhesion to the vasculature. We then highlight microfluidic models of the vasculature that have been utilized to study bacteria and bacterial-derived molecules at or near the vascular interface. Next, we review organ-on-a-chip models inclusive of the vasculature and pathogenic bacteria or bacterial-derived molecules that stimulate an inflammatory response within the model system. Finally, we provide recommendations for future research in advancing the understanding of host–bacteria interactions and responses during infections as well as in developing innovative antimicrobials for preventing and treating bacterial infections that capitalize on technological advancements in microfluidic device design and development. 

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4. Extracellular Mechanical Stimuli Alters the Metastatic Progression of Prostate Cancer Cells within 3D Tissue Matrix

   https://doi.org/10.3390/bioengineering10111271  

   Ditto, Maggie; Jacho, Diego; Eisenmann, Kathryn M; Yildirim-Ayan, Eda (November 2023, Bioengineering)

   This study aimed to understand extracellular mechanical stimuli’s effect on prostate cancer cells’ metastatic progression within a three-dimensional (3D) bone-like microenvironment. In this study, a mechanical loading platform, EQUicycler, has been employed to create physiologically relevant static and cyclic mechanical stimuli to a prostate cancer cell (PC-3)-embedded 3D tissue matrix. Three mechanical stimuli conditions were applied: control (no loading), cyclic (1% strain at 1 Hz), and static mechanical stimuli (1% strain). The changes in prostate cancer cells’ cytoskeletal reorganization, polarity (elongation index), proliferation, expression level of N-Cadherin (metastasis-associated gene), and migratory potential within the 3D collagen structures were assessed upon mechanical stimuli. The results have shown that static mechanical stimuli increased the metastasis progression factors, including cell elongation (p < 0.001), cellular F-actin accumulation (p < 0.001), actin polymerization (p < 0.001), N-Cadherin gene expression, and invasion capacity of PC-3 cells within a bone-like microenvironment compared to its cyclic and control loading counterparts. This study established a novel system for studying metastatic cancer cells within bone and enables the creation of biomimetic in vitro models for cancer research and mechanobiology. 

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5. SOUTHERN BIOMEDICAL ENGINEERING CONFERENCE

   Yeoheung Yun (August 2022, Vascularized Cortical Organoid Microphysiological System To Model Alzheimer’s Disease)

   Human induced pluripotent stem cell (hiPSC)-derived brain organoids can recapitulate the complex cytoarchitecture of the brain as well as the genetic and epigenetic footprint of human brain development. Although the brain organoids are able to mimic the structures and functions of brain in vitro, the 3D models have difficulty in integrating a complex vascular network that can provide the interaction with organoids. Here we report on a microfluidicbased three-dimensional, vascularized cortical organoid tissue construct consisting of 1) a perfused micro-vessel against an extracellular matrix (ECM), dynamic flow and membrane-free culture of the endothelial layer, 2) a sprouted vascular network using a combination of angiogenic factors, and 3) a vascularized hiPSCderived cortical organoid. We report on an optimization of density/stiffness of ECM to induce angiogenic sprouting and effect of angiogenic factors to trigger robust, rapid, and directional angiogenesis for concentration-driven and repetitive sprout formation. Vascularized network in the microfluidic device was further characterized in terms of morphology, directional alignment under perfusion, lumen formation, and permeability. HiPSCderived cortical organoid was generated, placed, and integrated into a vascularized network in the vascularized microfluidic device. We investigate how vascularized micro-vessels interact with cortical organoid. This paper further demonstrates the potential utility of a membrane-free vascularized cortical organoid in perfusion used to model Alzheimer’s disease and for toxicity screening of nerve agents. 

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