engineered heart tissue

UNLABELLED: Familial dilated cardiomyopathy (DCM) is frequently caused by autosomal dominant point mutations in genes involved in diverse cellular processes, including sarcomeric contraction. While patient studies have defined the genetic landscape of DCM, genetics are not currently used in patient care, and patients receive similar treatments regardless of the underlying mutation. It has been suggested that a precision medicine approach based on the molecular mechanism of the underlying mutation could improve outcomes; however, realizing this approach has been challenging due to difficulties linking genotype and phenotype and then leveraging this information to identify therapeutic approaches...

Transparent microelectrodes have received much attention from the biomedical community due to their unique advantages in concurrent crosstalk-free electrical and optical interrogation of cell/tissue activity. Despite recent progress in constructing transparent microelectrodes, a major challenge is to simultaneously achieve desirable mechanical stretchability, optical transparency, electrochemical performance, and chemical stability for high-fidelity, conformal, and stable interfacing with soft tissue/organ systems...

Since cardiovascular diseases (CVDs) are globally one of the leading causes of death, of which myocardial infarction (MI) can cause irreversible damage and decrease survivors' quality of life, novel therapeutics are needed. Current approaches such as organ transplantation do not fully restore cardiac function or are limited. As a valuable strategy, tissue engineering seeks to obtain constructs that resemble myocardial tissue, vessels, and heart valves using cells, biomaterials as scaffolds, biochemical and physical stimuli...

Phthalate esters (PE), a significant class of organic compounds used in industry, can contaminate humans and animals by entering water and food chains. Recent studies demonstrate the influence of PE on the development and progression of heart diseases, particularly in obese people. Di-isobutyl phthalate (DIBP) was administered orally to normal and diet-induced obese mice in this research to assess cardiovascular risk. The modifications in the microbial composition and metabolites were examined using RNA sequencing and mass spectrometry analysis...

Transcatheter heart valve replacements (TVR) are mostly designed in a closed position (c) with leaflets coaptating. However, recent literature suggests fabricating valves in semi-closed (sc) position to minimize pinwheeling. With about 100,000 children in need of a new pulmonary valve each year worldwide, this study evaluates both geometrical approaches in adult as well as pediatric size and condition. Three valves of each geometry were fabricated in adult (30 mm) and pediatric (15 mm) size, using porcine pericardium...

One of the most important medical interventions for individuals with heart valvular disease is heart valve replacement, which is not without substantial challenges, particularly for pediatric patients. Due to their biological properties and biocompatibility, natural tissue-originated scaffolds derived from human or animal sources are one type of scaffold that is widely used in tissue engineering. However, they are known for their high potential for immunogenicity. Being free of cells and genetic material, decellularized xenografts, consequently, have low immunogenicity and, thus, are expected to be tolerated by the recipient's immune system...

Synthetic biomaterials play a crucial role in developing tissue-engineered heart valves (TEHVs) due to their versatile mechanical properties. Achieving the right balance between mechanical strength and manufacturability is essential. Thermoplastic polyurethanes (TPUs) and elastomers (TPEs) garner significant attention for TEHV applications due to their notable stability, fatigue resistance, and customizable properties such as shear strength and elasticity. This study explores the additive manufacturing technique of selective laser sintering (SLS) for TPUs and TPEs to optimize process parameters to balance flexibility and strength, mimicking aortic valve tissue properties...

Background: Mucopolysaccharidoses (MPSs) are rare congenital lysosomal storage disorders due to a deficiency of enzymes metabolising glycosaminoglycans, leading to their accumulation in tissues. This multisystem disease often requires surgical intervention, including valvular cardiac surgery. Adult MPSs have complex airways making anaesthesia risky. Methods: We report novel three-dimensional (3D) modelling airway assessments and multidisciplinary peri-operative airway management. Results: Five MPS adults underwent cardiac surgery at the national MPS cardiac centre (type I = 4, type II = 1; ages 20, 24, 33, 35, 37 years; two males, three females)...

Melanocytes are dendritic cells localized in skin, eyes, hair follicles, ears, heart and central nervous system. They are characterized by the presence of melanosomes enriched in melanin which are responsible for skin, eye and hair pigmentation. They also have different functions in photoprotection, immunity and sound perception. Melanocyte dysfunction can cause pigmentary disorders, hearing and vision impairments or increased cancer susceptibility. This review focuses on the role of melanocytes in homeostasis and disease, before discussing their potential in regenerative medicine applications, such as for disease modeling, drug testing or therapy development using stem cell technologies, tissue engineering and extracellular vesicles...

Viruses elicit long-term adaptive responses in the tissues they infect. Understanding viral adaptions in humans is difficult in organs such as the heart, where primary infected material is not routinely collected. In search of asymptomatic infections with accompanying host adaptions, we mined for cardio-pathogenic viruses in the unaligned reads of nearly one thousand human hearts profiled by RNA sequencing. Among virus-positive cases (∼20%), we identified three robust adaptions in the host transcriptome related to inflammatory NFκB signaling and post-transcriptional regulation by the p38-MK2 pathway...

Tissue engineering, a crucial approach in medical research and clinical applications, aims to regenerate damaged organs. Combining stem cells, biochemical factors, and biomaterials, it encounters challenges in designing complex 3D structures. Artificial intelligence (AI) enhances tissue engineering through computational modeling, biomaterial design, cell culture optimization, and personalized medicine. This review explores AI applications in organ tissue engineering (bone, heart, nerve, skin, cartilage), employing various machine learning (ML) algorithms for data analysis, prediction, and optimization...

We developed a 96-well plate assay which allows fast, reproducible, and high-throughput generation of 3D cardiac rings around a deformable optically transparent hydrogel (polyethylene glycol [PEG]) pillar of known stiffness. Human induced pluripotent stem cell-derived cardiomyocytes, mixed with normal human adult dermal fibroblasts in an optimized 3:1 ratio, self-organized to form ring-shaped cardiac constructs. Immunostaining showed that the fibroblasts form a basal layer in contact with the glass, stabilizing the muscular fiber above...

Blood vessels are subjected to complex biomechanical loads, primarily from pressure-driven blood flow. Abnormal loading associated with vascular grafts, arising from altered hemodynamics or wall mechanics, can cause acute and progressive vascular failure and end-organ dysfunction. Perturbations to mechanobiological stimuli experienced by vascular cells contribute to remodeling of the vascular wall via activation of mechanosensitive signaling pathways and subsequent changes in gene expression and associated turnover of cells and extracellular matrix...

Here, we present a protocol for 3D printing heart tissues using thiol-norbornene photoclick collagen (NorCol). We describe steps for synthesizing NorCol, preparing bioink and the support bath, and cell-laden printing. We then detail procedures for the loading of C2C12 cells into NorCol, ensuring structural integrity and cell viability after printing. This protocol is adaptable to various cell lines and allows for the printing of diverse complex structures, which can be used in drug screening and disease modeling...

Tissue engineering heart valves (TEHVs) are expected to address the limitations of mechanical and bioprosthetic valves used in clinical practice. Decellularized heart valve (DHV) is an important scaffold of TEHVs due to its natural three-dimensional structure and bioactive extracellular matrix, but its mechanical properties and hemocompatibility are impaired. In this study, DHV was cross-linked with three different molecular weights of oxidized hyaluronic acid (OHA) by a Schiff base reaction and presented enhanced stability and hemocompatibility, which could be mediated by the molecular weight of OHA...

Systemic lupus erythematosus (SLE) is a highly heterogenous autoimmune disease that affects multiple organs, including the heart. The mechanisms by which myocardial injury develops in SLE, however, remain poorly understood. Here we engineered human cardiac tissues and cultured them with IgG fractions containing autoantibodies from SLE patients with and without myocardial involvement. We observed unique binding patterns of IgG from two patient subgroups: (i) patients with severe myocardial inflammation exhibited enhanced binding to apoptotic cells within cardiac tissues subjected to stress, and (ii) patients with systolic dysfunction exhibited enhanced binding to the surfaces of viable cardiomyocytes...

Valvular heart disease (VHD) is becoming more prevalent in an ageing population, leading to challenges in diagnosis and management. This two-part Series offers a comprehensive review of changing concepts in VHD, covering diagnosis, intervention timing, novel management strategies, and the current state of research. The first paper highlights the remarkable progress made in imaging and transcatheter techniques, effectively addressing the treatment paradox wherein populations at the highest risk of VHD often receive the least treatment...

In the last 30 years, there have been nearly 60, 000 publications about electrospun nanofibers, but it is still unclear whether nanoscale fibers are really necessary for electrospun tissue engineering scaffolds. The present report puts forward this argument and reveals that compared with electrospun nanofibers, microfibers with diameter of about 3 μm (named as "oligo-micro fiber" by us) is more appropriate for tissue engineering scaffolds owing to its better cell infiltration ability caused by larger pores with available nuclear deformation...

Today, adeno-associated virus (AAV)-based vectors are arguably the most promising in vivo gene delivery vehicles for durable therapeutic gene expression. Advances in molecular engineering, high-throughput screening platforms, and computational techniques have resulted in a toolbox of capsid variants with enhanced performance over parental serotypes. Despite their considerable promise and emerging clinical success, there are still obstacles hindering their broader use, including limited transduction capabilities, tissue/cell type-specific tropism and penetration into tissues through anatomical barriers, off-target tissue biodistribution, intracellular degradation, immune recognition, and a lack of translatability from preclinical models to clinical settings...

The pathogenesis of aortic aneurysm and dissection continues to be under discussion. Extracellular matrix (ECM) remodeling processes in the aortic wall are hypothesized to be involved in the development of the disorders. Therefore, in a histological study, we investigated the expression of metalloproteases 1 and 9 (MMP1 and MMP9) and their inhibitors (TIMP 1 and TIMP 2) in cardiac surgery patients. In parallel, we studied the aortic roots by echocardiography. Clinical reports of 111 patients (30 women and 81 men) who suffered from aortic aneurysms and aortic dissection were evaluated and studied by transesophageal echocardiography...