Induced pluripotent stem cell-derived cardiomyocyte in vitro models: benchmarking progress and ongoing challenges.

Recent innovations in differentiating cardiomyocytes from human induced pluripotent stem cells (hiPSCs) have unlocked a viable path to creating in vitro cardiac models. Currently, hiPSC-derived cardiomyocytes (hiPSC-CMs) remain immature, leading many in the field to explore approaches to enhance cell and tissue maturation. Here, we systematically analyzed 300 studies using hiPSC-CM models to determine common fabrication, maturation and assessment techniques used to evaluate cardiomyocyte functionality and maturity and compiled the data into an open-access database.

Computational Model for Early-Stage Aortic Valve Calcification Shows Hemodynamic Biomarkers.

Heart disease is a leading cause of mortality, with calcific aortic valve disease (CAVD) being the most prevalent subset. Being able to predict this disease in its early stages is important for monitoring patients before they need aortic valve replacement surgery. Thus, this study explored hydrodynamic, mechanical, and hemodynamic differences in healthy and very mildly calcified porcine small intestinal submucosa (PSIS) bioscaffold valves to determine any notable parameters between groups that could, possibly, be used for disease tracking purposes.

Structural and biomechanical characterizations of acellular porcine mitral valve scaffolds: anterior leaflets, posterior leaflets, and chordae tendineae.

Mitral valve (MV) tissue engineering is still in its early stage, and one major challenge in MV tissue engineering is to identify appropriate scaffold materials. With the potential of acellular MV scaffolds being demonstrated recently, it is important to have a full understanding of the biomechanics of the native MV components and their acellular scaffolds. In this study, we have successfully characterized the structural and mechanical properties of porcine MV components, including anterior leaflet (AL), posterior leaflet (PL), strut chordae, and basal chordae, before and after decellularization.

Stem Cell-Secreted Allogeneic Elastin-Rich Matrix with Subsequent Decellularization for the Treatment of Critical Valve Diseases in the Young.

Critical valve diseases in infants have a very poor prognosis for survival. Particularly challenging is for the valve replacement to support somatic growth. From a valve regenerative standpoint, bio-scaffolds have been extensively investigated recently.

Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model.

Researchers have shown that adult zebrafish have the potential to regenerate 20% of the ventricular muscle within two months of apex resection, and neonatal mice have the capacity to regenerate their heart after apex resection up until day 7 after birth. The goal of this study was to determine if large mammals (porcine heart model) have the capability to fully regenerate a resected portion of the left ventricular apex during the neonatal stage, and if so, how long the regenerative potential persists. A total of 36 piglets were divided into the following groups: 0-day control and surgical groups and seven-day control and surgical groups.

Importance of Non-Newtonian Computational Fluid Modeling on Severely Calcified Aortic Valve Geometries-Insights From Quasi-Steady State Simulations.

The Newtonian model has commonly been used to represent the viscosity of blood in the aorta, despite blood itself being a non-Newtonian fluid. This is justified where shear rates tend to be large. However, we hypothesized that using the Newtonian model to predict the hemodynamics on the aortic valve, particularly in those with severe calcifications, is inaccurate owing to valve leaflet geometry irregularities inducing multiple regions of low shear rates, <100 s-1, where a Newtonian model is invalid.

Directional dependence on concomitant pressure and volume increases during left ventricular filling.

Myocardial infarction continues to be a leading cause of mortality and morbidity globally. A major challenge post-myocardial infarction is scar tissue growth, which eventually can lead to heart failure. Cardiovascular regenerative strategies to minimize scar tissue growth and promote cardiac tissue formation are currently being actively pursued via the development of cardiac patches.

De Novo Valve Tissue Morphology Following Bioscaffold Mitral Valve Replacement in a Juvenile Non-Human Primate Model.

The utility of implanting a bioscaffold mitral valve consisting of porcine small intestinal submucosa (PSIS) in a juvenile baboon model (12 to 14 months old at the time of implant; = 3) to assess their in vivo tissue remodeling responses was investigated. Our findings demonstrated that the PSIS mitral valve exhibited the robust presence of de novo extracellular matrix (ECM) at all explantation time points (at 3-, 11-, and 20-months). Apart from a significantly lower level of proteoglycans in the implanted valve's annulus region ( < 0.

Oscillatory fluid-induced mechanobiology in heart valves with parallels to the vasculature.

Forces generated by blood flow are known to contribute to cardiovascular development and remodeling. These hemodynamic forces induce molecular signals that are communicated from the endothelium to various cell types. The cardiovascular system consists of the heart and the vasculature, and together they deliver nutrients throughout the body.

Physiologically Relevant Fluid-Induced Oscillatory Shear Stress Stimulation of Mesenchymal Stem Cells Enhances the Engineered Valve Matrix Phenotype.

Support of somatic growth is a fundamental requirement of tissue-engineered valves. However, efforts thus far have been unable to maintain this support long term. A key event that will determine the valve's long-term success is the extent to which healthy host tissue remodeling can occur on the valve soon after implantation.

Uncovering the Mechanical, Thermal, and Chemical Characteristics of Biodegradable Mushroom Leather with Intrinsic Antifungal and Antibacterial Properties.

The growing demand for a sustainable leather industry with a low environmental impact has prompted the development of alternative vegetable-based materials. In this study, a biodegradable mushroom-based leather derived from the fruiting body of is investigated. The biodegradable leather proves to be thermally stable up to 250 °C.

Porcine Small Intestinal Submucosa Mitral Valve Material Responses Support Acute Somatic Growth.

Conceptually, a tissue engineered heart valve would be especially appealing in the pediatric setting since small size and somatic growth constraints would be alleviated. In this study, we utilized porcine small intestinal submucosa (PSIS) for valve replacement. Of note, we evaluated the material responses of PSIS and subsequently its acute function and somatic growth potential in the mitral position.

Elastin-Dependent Aortic Heart Valve Leaflet Curvature Changes During Cyclic Flexure.

The progression of calcific aortic valve disease (CAVD) is characterized by extracellular matrix (ECM) remodeling, leading to structural abnormalities and improper valve function. The focus of the present study was to relate aortic valve leaflet axial curvature changes as a function of elastin degradation, which has been associated with CAVD. Circumferential rectangular strips (L × W = 10 × 2.

Stem Cell Cytoskeletal Responses to Pulsatile Flow in Heart Valve Tissue Engineering Studies.

Heart valve replacement options remain exceedingly limited for pediatric patients because they cannot accommodate somatic growth. To overcome this shortcoming, heart valve tissue engineering using human bone marrow stem cells (HBMSCs) has been considered a potential solution to the treatment of critical congenital valvular defects. The mechanical environments during culture are key regulators of progenitor cell fate.

Use of combined polarization-sensitive optical coherence tomography and Mueller matrix imaging for the polarimetric characterization of excised biological tissue (Erratum).

This erratum corrects two errors in the original paper.

A "sweet-spot" for fluid-induced oscillations in the conditioning of stem cell-based engineered heart valve tissues.

Fluid-induced shear stresses are involved in the development of cardiovascular tissues. In a tissue engineering framework, this stimulus has also been considered as a mechanical regulator of stem cell differentiation. We recently demonstrated that the fluid-oscillating effect in combination with a physiologically-relevant shear stress magnitude contributes to the formation of stem cell-derived de novo heart valve tissues.

Hydrodynamic Assessment of Aortic Valves Prepared from Porcine Small Intestinal Submucosa.

Infants and children born with severe cardiac valve lesions have no effective long term treatment options since currently available tissue or mechanical prosthetic valves have sizing limitations and no avenue to accommodate the growth of the pediatric patient. Tissue engineered heart valves (TEHVs) which could provide for growth, self-repair, infection resistance, and long-term replacement could be an ideal solution. Porcine small intestinal submucosa (PSIS) has recently emerged as a potentially attractive bioscaffold for TEHVs.

Use of combined polarization-sensitive optical coherence tomography and Mueller matrix imaging for the polarimetric characterization of excised biological tissue.

Mueller matrix polarimetry and polarization-sensitive optical coherence tomography (PS-OCT) are two emerging techniques utilized in the assessment of tissue anisotropy. While PS-OCT can provide cross-sectional images of local tissue birefringence through its polarimetric sensitivity, Mueller matrix polarimetry can be used to measure bulk polarimetric properties such as depolarization, diattenuation, and retardance. To this day true quantification of PS-OCT data can be elusive, partly due to the reliance on inverse models for the characterization of tissue birefringence and the influence of instrumentation noise.

Integration of Stem Cell to Chondrocyte-Derived Cartilage Matrix in Healthy and Osteoarthritic States in the Presence of Hydroxyapatite Nanoparticles.

We investigated the effectiveness of integrating tissue engineered cartilage derived from human bone marrow derived stem cells (HBMSCs) to healthy as well as osteoarthritic cartilage mimics using hydroxyapatite (HA) nanoparticles immersed within a hydrogel substrate. Healthy and diseased engineered cartilage from human chondrocytes (cultured in agar gels) were integrated with human bone marrow stem cell (HBMSC)-derived cartilaginous engineered matrix with and without HA, and evaluated after 28 days of growth. HBMSCs were seeded within photopolymerizable poly (ethylene glycol) diacrylate (PEGDA) hydrogels.

Relative Effects of Fluid Oscillations and Nutrient Transport in the In Vitro Growth of Valvular Tissues.

Engineered valvular tissues are cultured dynamically, and involve specimen movement. We previously demonstrated that oscillatory shear stresses (OSS) under combined steady flow and specimen cyclic flexure (flex-flow) promote tissue formation. However, localized efficiency of specimen mass transport is also important in the context of cell viability within the growing tissues.

Differentiation and Distribution of Marrow Stem Cells in Flex-Flow Environments Demonstrate Support of the Valvular Phenotype.

For treatment of critical heart valve diseases, prosthetic valves perform fairly well in most adults; however, for pediatric patients, there is the added requirement that the replacement valve grows with the child, thus extremely limiting current treatment options. Tissue engineered heart valves (TEHV), such as those derived from autologous bone marrow stem cells (BMSCs), have the potential to recapitulate native valve architecture and accommodate somatic growth. However, a fundamental pre-cursor in promoting directed integration with native tissues rather than random, uncontrolled growth requires an understanding of BMSC mechanobiological responses to valve-relevant mechanical environments.