Cardiovascular Tissue Engineering Applications Research Articles

A custom-built planar biaxial system for soft tissue material testing

Accurate material characterization of soft tissues is crucial for understanding the physiopathology of cardiovascular diseases. However, commercial biaxial testing systems are expensive, prompting the need for affordable custom solutions. This study aimed to develop a low-cost custom biaxial system capable of accurately characterizing the mechanical behavior of soft tissues. The biaxial system was constructed using 3D printing technology and non-captive linear actuators for precise displacement control. A real-time marker tracking system was implemented to estimate dis-placements without the need for costly hardware. The system's performance was evaluated through tests on a calibration spring and frozen porcine aorta samples. The linear actuators demonstrated excellent response to user position input after motor tuning, showing no discrepancies between commands and actual positions. The experimental testing of the calibration spring showed good agreement with the analytical solution, validating the system's ability to accurately test materials. Testing on porcine aorta samples revealed stress–strain responses consistent with existing literature, accounting for potential variations due to tissue preservation and regional material property heterogeneity. Overall, this custom biaxial system demonstrates promising performance in accurately assessing the mechanical behavior of soft tissues, providing researchers with a valuable tool for cardiovascular disease research and tissue engineering applications.

Bacterial Cellulose-Based Materials: A Perspective on Cardiovascular Tissue Engineering Applications.

Today, a wide variety of bio- and nanomaterials have been deployed for cardiovascular tissue engineering (TE), including polymers, metal oxides, graphene/its derivatives, organometallic complexes/composites based on inorganic-organic components, among others. Despite several advantages of these materials with unique mechanical, biological, and electrical properties, some challenges still remain pertaining to their biocompatibility, cytocompatibility, and possible risk factors (e.g., teratogenicity or carcinogenicity), restricting their future clinical applications. Natural polysaccharide- and protein-based (nano)structures with the benefits of biocompatibility, sustainability, biodegradability, and versatility have been exploited in the field of cardiovascular TE focusing on targeted drug delivery, vascular grafts, engineered cardiac muscle, etc. The usage of these natural biomaterials and their residues offers several advantages in terms of environmental aspects such as alleviating emission of greenhouse gases as well as the production of energy as a biomass consumption output. In TE, the development of biodegradable and biocompatible scaffolds with potentially three-dimensional structures, high porosity, and suitable cellular attachment/adhesion still needs to be comprehensively studied. In this context, bacterial cellulose (BC) with high purity, porosity, crystallinity, unique mechanical properties, biocompatibility, high water retention, and excellent elasticity can be considered as promising candidate for cardiovascular TE. However, several challenges/limitations regarding the absence of antimicrobial factors and degradability along with the low yield of production and extensive cultivation times (in large-scale production) still need to be resolved using suitable hybridization/modification strategies and optimization of conditions. The biocompatibility and bioactivity of BC-based materials along with their thermal, mechanical, and chemical stability are crucial aspects in designing TE scaffolds. Herein, cardiovascular TE applications of BC-based materials are deliberated, with a focus on the most recent advancements, important challenges, and future perspectives. Other biomaterials with cardiovascular TE applications and important roles of green nanotechnology in this field of science are covered to better compare and comprehensively review the subject. The application of BC-based materials and the collective roles of such biomaterials in the assembly of sustainable and natural-based scaffolds for cardiovascular TE are discussed.

Algal-derived macromolecules and their composites: From synthetic biology to biomedical applications in bone and cardiovascular tissue engineering

Algae have shown numerous advantages as biofunctional and bioactive material sources. The development of biosynthetic or synthetic materials has enabled algal-derived macromolecules and their derivatives to be used in biomedical applications. This review examines and analyzes the most recent developments in the production of biomaterials from algal-derived macromolecules and their composites and their potential applications in bone and cardiovascular tissue engineering. Several macromolecules derived from algal polysaccharides, including sulfated polysaccharides, fucoidans, and fucans, have been developed for cartilage, intervertebral disc, bone, and skeletal muscle transplants because of their stable structures. Alginates, fucoidans, chitin, porphyrin, and other algal polysaccharide derivatives have been investigated for engineering blood vessels, heart valves, and even the liver. One advantage of algal-derived macromolecules and composites is their safe immunity properties. This review also highlights cutting-edge developments in applying algal-derived macromolecules with a broader biomedical scope to encourage in-depth research into their potential as biomaterial scaffolds in medical applications.

Decellularized bovine aorta as a promising 3D elastin scaffold for vascular tissue engineering applications.

Aim: To evaluate the suitability of using aorta elastin scaffold, in combination with human adipose-derived mesenchymal stem cells (hAd-MSCs), as an approach for cardiovascular tissue engineering. Materials & Methods: Human adipose-derived MSCs were seeded on elastin samples of decellularized bovine aorta. The samples were cultured in vitro to investigate the inductive effects of this scaffold on the cells. The results were evaluated using histological, and immunohistochemical methods, as well as MTT assay, DNA content, reverse transcription-PCR and scanning electron microscopy. Results: Histological staining and DNA content confirmed the efficacy of decellularization procedure (82% DNA removal). MTT assay showed the construct's ability to support cell viability and proliferation. Cell differentiation was confirmed by reverse transcription-PCR and positive immunohistochemistry for alfa smooth muscle actin and von Willebrand. Conclusion: The prepared aortic elastin samples act as a potential scaffold, in combination with MSCs, for applications in cardiovascular tissue engineering. Further experiments in animal models are required to confirm this.

Fabrication, characterization, and in vitro evaluation of electrospun polyurethane-gelatin-carbon nanotube scaffolds for cardiovascular tissue engineering applications.

Myocardial infarction occurs because coronary arteries insufficiency is one of the major causes of mortality worldwide. Recent studies have shown that tissue engineering of myocardial tissue to regenerate infarcted tissue or engineering of the coronary artery may help overcome this problem. In the present research, gelatin and single-walled carbon nanotube were firstly administrated to physico-chemically and biologically modulate polyurethane nanofibers. Electrospinning, as versatile and effective technique for production of functional nanoscale fiber, was applied. Incorporation of both gelatin and SWNTs reduced mean diameter of nanofibrous scaffolds from 210 to 140 nm, which influenced on initial cell behavior. Possible interaction between gelatin and SWNTs with polyurethane chains was evaluated using FTIR and DSC techniques. Regarding the incorporation of both gelatin and SWNTs, it was found that hydrophilicity of nanofibrous scaffolds dramatically improved. Scaffold degradation profile was adjusted by incorporation of gelatin. Biomimetic mechanical properties of composite scaffolds like normal blood vessel were developed and SWNTs improved the Young modulus and ultimate strength of scaffolds up to 16.47 ± 0.5 and 23.73 ± 0.5 MPa, respectively. However, addition of gelatin increased elongation at break due to its softening effect. The incorporation of the SWNTs led to significant enhancement of electrical conductivity of the scaffolds. Biological evaluation using SEM and MTT assay demonstrated that nanofibrous surface was covered by confluent and dense layer of both myocardial myoblast and endothelial cells after 7 days of culture, which is crucial for cardiovascular tissue engineering. Results verified that the fabricated scaffolds could be effective for cardiovascular tissue engineering.

Preparation and optimization of a gelatin-based biomimetic three-layered vascular scaffold.

Electrospinning is promising approach for producing biomimetic vascular scaffolds. In particular, gelatin-based electrospun scaffolds offer excellent biocompatibility. However, gelatin-based vascular scaffolds are difficult to remove from the collector after electrospinning and cross-linking agents such as glutaraldehyde, which is commonly used to improve the strength of water-soluble electrospun gelatin, are highly toxic. Herein, we present a novel electrospinning method for preparing three-layered vascular scaffolds. First, Tween 80 was added to 2,2,2-trifluoroethanol as the polymer electrospinning solution and the gelatin electrospinning solution was mixed with polylactic acid and polycaprolactone, respectively. The three-layered vascular scaffold was fabricated by electrospinning an inner layer of gelatin, a middle layer of polyester, and another outer layer of gelatin. Finally, the electrospun scaffolds were cross-linked with microbial transglutaminase and vacuum dried. Biomechanical properties of the scaffold were determined by tensile testing. Furthermore, the structure and biocompatibility of the scaffolds were assessed by hydrophilicity tests, scanning electron microscopy, and cell seeding experiments. Our results suggest the proposed electrospinning method is suitable for preparing biomimetic vascular scaffolds for cardiovascular tissue engineering applications. Moreover, this paper provides a useful reference for the preparation and optimization of vascular scaffolds.

Characteristics and toxicity assessment of electrospun gelatin/PCL nanofibrous scaffold loaded with graphene in vitro and in vivo.

Background: Electrospun gelatin/polycaprolactone (Gt/PCL) nanofibrous scaffolds loaded with graphene are novel nanomaterials with the uniquely strong property of electrical conductivity, which have been widely investigated for their potential applications in cardiovascular tissue engineering, including in bypass tracts for atrioventricular block.Purpose: Electrospun Gt/PCL/graphene nanofibrous mats were successfully produced. Scanning electron micrography showed that the fibers with graphene were smooth and homogeneous. In vitro, to determine the biocompatibility of the scaffolds, hybrid scaffolds with different fractions of graphene were seeded with neonatal rat ventricular myocytes. In vivo, Gt/PCL scaffolds with different concentrations of graphene were implanted into rats for 4, 8 and 12 weeks.Results: CCK-8 assays and histopathological staining (including DAPI, cTNT, and CX43) indicated that cells grew and survived well on the hybrid scaffolds if the mass fraction of graphene was lower than 0.5%. After implanting into rats for 4, 8 or 12 weeks, there was no gathering of inflammatory cells around the nanomaterials according to the HE staining results.Conclusion: The results indicate that Gt/PCL nanofibrous scaffolds loaded with graphene have favorable electrical conductivity and biological properties and may be suitable scaffolds for use in the treatment of atrioventricular block. These findings alleviate safety concerns and provide novel insights into the potential applications of Gt/PCL loaded with graphene, offering a solid foundation for comprehensive in vivo studies.

Harnessing topographical & biochemical cues to enhance elastogenesis by paediatric cells for cardiovascular tissue engineering applications

The development of tissue-engineered vascular grafts (TEVGs) with a biomimetic extracellular matrix (ECM) structure, including a mature elastic network, remains a key challenge for the production of grafts with long-term functionality. The aim of this study was to investigate the influence of aligned nanofiber substrates on ECM protein synthesis by neonatal smooth muscle cells (SMCs), and to examine the combined effects of this topographical cue in conjunction with transforming growth factor beta-1 (TGF-β1) - a biochemical elastogenic promoter. Glass coverslips were coated in electrospun fibrinogen nanofibers (average diameter < 500 nm) with either a randomly-orientated or aligned topography. Human umbilical artery smooth muscle cells (hUASMCs) were cultured on the electrospun substrates for 7 and 14 days, with or without a 2 ng/ml TGF-β1 supplement. The ECM structure was analysed using immunohistochemistry and the quantity of secreted elastin in the cell layer was measured using a dye-binding assay.Aligned fiber substrates induced a directed orientation of both the seeded cells and cell-synthesized ECM fibers. Cells cultured on aligned fibers exhibited a significant increase in the expression of phenotypic contractile proteins, as well as increases in the secreted elastin content of the cell layer, compared to cells cultured on randomly-orientated substrates. TGF-β1 supplementation was shown to synergistically increase secreted elastin from cells cultured on aligned fiber substrates (p < 0.05). Aligned nanofiber scaffolds can be used to direct cellular orientation, elastin-related protein synthesis and cell phenotype, and consequently there is potential for their application in the development of TEVGs as part of a multi-pronged strategy to promote elastic fiber formation.

Modulating smooth muscle cell response by the release of TGFβ2 from tubular scaffolds for vascular tissue engineering

Tissue engineering has gained considerable attention in the development of small diameter tissue engineered vascular grafts (TEVGs) for treating coronary heart disease. A properly designed acellular and biodegradable TEVG must encourage the infiltration and growth of vascular smooth muscle cells (SMCs). Our group has previously shown that increasing levels of TGFβ2 can differentially modulate SMC migration and proliferation. In this study, tubular electrospun scaffolds loaded with TGFβ2 were fabricated using various ratios of gelatin/polycaprolactone (PCL), resulting in scaffolds with porous nano-woven architecture suitable for tissue ingrowth. Scaffold morphology, degradation rate, TGβ2 release kinetics, and bioactivity were assessed. TGFβ2 was successfully integrated into the electrospun biomaterial that resulted in a differential release profile depending on the gelatin/PCL ratio over the course of 42 days. Higher TGFβ2 elution was obtained in scaffolds with higher gelatin content, which may be related to the biodegradation of gelatin in culture media. The biological activity of the released TGFβ2 was evaluated by its ability to affect SMC proliferation as a function of its concentration. SMCs seeded on TGFβ2-loaded scaffolds also showed higher densities and infiltration after 5 days in culture as compared to scaffolds without TGFβ2. Our results demonstrate that the ratio of synthetic and natural polymers in electrospun blends can be used to tune the release of TGFβ2. This method can be used to intelligently modulate the SMC response in gelatin/PCL scaffolds making the TGFβ2-loaded conduits attractive for cardiovascular tissue engineering applications.

Nanomaterials for Spinal Cord Injury Recovery

Nanotechnology and nanomaterials have had a significant positive impact within the biomedical field for quite some time, and have included cardiovascular, cartilage, and neural tissue engineering applications. Due to its potential for treating neural tissue, current research is investigating the use of nanomaterials for spinal cord injury (SCI), an injury characterized by tissue damage and the disruption of communication between the brain to the body. To treat such an injury, cell-based therapy has shown promising results, and the following papers are recommended. This communication will focus on nanoparticle, carbon nanotubes, and self-assembling peptide approaches for treating SCI, as well as concerns of toxicity.

Nanomaterials for Cardiac Myocyte Tissue Engineering.

Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials.

The effect of PVDF-TrFE scaffolds on stem cell derived cardiovascular cells.

Recently, electrospun polyvinylidene fluoride (PVDF) and polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE) scaffolds have been developed for tissue engineering applications. These materials have piezoelectric activity, wherein they can generate electric charge with minute mechanical deformations. Since the myocardium is an electroactive tissue, the unique feature of a piezoelectric scaffold is attractive for cardiovascular tissue engineering applications. In this study, we examined the cytocompatibility and function of pluripotent stem cell derived cardiovascular cells including mouse embryonic stem cell-derived cardiomyocytes (mES-CM) and endothelial cells (mES-EC) on PVDF-TrFE scaffolds. MES-CM and mES-EC adhered well to PVDF-TrFE and became highly aligned along the fibers. When cultured on scaffolds, mES-CM spontaneously contracted, exhibited well-registered sarcomeres and expressed classic cardiac specific markers such as myosin heavy chain, cardiac troponin T, and connexin43. Moreover, mES-CM cultured on PVDF-TrFE scaffolds responded to exogenous electrical pacing and exhibited intracellular calcium handling behavior similar to that of mES-CM cultured in 2D. Similar to cardiomyocytes, mES-EC also demonstrated high viability and maintained a mature phenotype through uptake of low-density lipoprotein and expression of classic endothelial cell markers including platelet endothelial cell adhesion molecule, endothelial nitric oxide synthase, and the arterial specific marker, Notch-1. This study demonstrates the feasibility of PVDF-TrFE scaffold as a candidate material for developing engineered cardiovascular tissues utilizing stem cell-derived cells. Biotechnol. Bioeng. 2016;113: 1577-1585. © 2015 Wiley Periodicals, Inc.

Hybrid elastin-like recombinamer-fibrin gels: physical characterization and in vitro evaluation for cardiovascular tissue engineering applications.

In the field of tissue engineering, the properties of the scaffolds are of crucial importance for the success of the application. Hybrid materials combine the properties of the different components that constitute them. In this study hybrid gels of Elastin-Like Recombinamer (ELR) and fibrin were prepared with a range of polymer concentrations and ELR-to-fibrin ratios. The correlation between SEM micrographs, porosities, swelling ratios and rheological properties was discussed and a poroelastic mechanism was suggested to explain the mechanical behavior of the hybrid gels. Applicability as scaffold materials for cardiovascular tissue engineering was shown by the realization of cell-laden matrixes which supported the synthesis of collagens as revealed by immunohistochemical analysis. As a proof of concept, a tissue-engineered heart valve was fabricated by injection moulding and cultivated in a bioreactor for 3 weeks under dynamic conditions. Tissue analysis revealed the production of collagen I and III, fundamental proteins for cardiovascular constructs.

Cell adhesion on NiTi thin film sputter-deposited meshes

Scaffolds for tissue engineering enable the possibility to fabricate and form biomedical implants in vitro, which fulfill special functionality in vivo. In this study, free-standing Nickel–Titanium (NiTi) thin film meshes were produced by means of magnetron sputter deposition. Meshes contained precisely defined rhombic holes in the size of 440 to 1309μm2 and a strut width ranging from 5.3 to 9.2μm. The effective mechanical properties of the microstructured superelastic NiTi thin film were examined by tensile testing. These results will be adapted for the design of the holes in the film. The influence of hole and strut dimensions on the adhesion of sheep autologous cells (CD133+) was studied after 24h and after seven days of incubation. Optical analysis using fluorescence microscopy and scanning electron microscopy showed that cell adhesion depends on the structural parameters of the mesh. After 7days in cell culture a large part of the mesh was covered with aligned fibrous material. Cell adhesion is particularly facilitated on meshes with small rhombic holes of 440μm2 and a strut width of 5.3μm. Our results demonstrate that free-standing NiTi thin film meshes have a promising potential for applications in cardiovascular tissue engineering, particularly for the fabrication of heart valves.

Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine.

Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted.

Carbon nanotubes reinforced chitosan films: mechanical properties and cell response of a novel biomaterial for cardiovascular tissue engineering

Carbon nanotubes have been proposed as fillers to reinforce polymeric biomaterials for the strengthening of their structural integrity to achieve better biomechanical properties. In this study, a new polymeric composite material was introduced by incorporating various low concentrations of multiwalled carbon nanotubes (MWCNTs) into chitosan (CS), aiming at achieving a novel composite biomaterial with superior mechanical and biological properties compared to neat CS, in order to be used in cardiovascular tissue engineering applications. Both mechanical and biological characteristics in contact with the two relevant cell types (endothelial cells and vascular myofibroblasts) were studied. Regarding the mechanical behavior of MWCNT reinforced CS (MWCNT/CS), 5 and 10 % concentrations of MWCNTs enhanced the mechanical behavior of CS, with that of 5 % exhibiting a superior mechanical strength compared to 10 % concentration and neat CS. Regarding biological properties, MWCNT/CS best supported proliferation of endothelial and myofibroblast cells, MWCNTs and MWCNT/CS caused no apoptosis and were not toxic of the examined cell types. Conclusively, the new material could be suitable for tissue engineering (TE) and particularly for cardiovascular TE applications.

In vitrofabrication of autologous living tissue-engineered vascular grafts based on prenatally harvested ovine amniotic fluid-derived stem cells

Amniotic fluid cells (AFCs) have been proposed as a valuable source for tissue engineering and regenerative medicine. However, before clinical implementation, rigorous evaluation of this cell source in clinically relevant animal models accepted by regulatory authorities is indispensable. Today, the ovine model represents one of the most accepted preclinical animal models, in particular for cardiovascular applications. Here, we investigate the isolation and use of autologous ovine AFCs as cell source for cardiovascular tissue engineering applications. Fetal fluids were aspirated in vivo from pregnant ewes (n = 9) and from explanted uteri post mortem at different gestational ages (n = 91). Amniotic non-allantoic fluid nature was evaluated biochemically and in vivo samples were compared with post mortem reference samples. Isolated cells revealed an immunohistochemical phenotype similar to ovine bone marrow-derived mesenchymal stem cells (MSCs) and showed expression of stem cell factors described for embryonic stem cells, such as NANOG and STAT-3. Isolated ovine amniotic fluid-derived MSCs were screened for numeric chromosomal aberrations and successfully differentiated into several mesodermal phenotypes. Myofibroblastic ovine AFC lineages were then successfully used for the in vitro fabrication of small- and large-diameter tissue-engineered vascular grafts (n = 10) and cardiovascular patches (n = 34), laying the foundation for the use of this relevant pre-clinical in vivo assessment model for future amniotic fluid cell-based therapeutic applications.

Large Scale Expansion of Human Umbilical Cord Cells in a Rotating Bed System Bioreactor for Cardiovascular Tissue Engineering Applications

Widespread use of human umbilical cord cells for cardiovascular tissue engineering requires production of large numbers of well-characterized cells under controlled conditions. In current research projects, the expansion of cells to be used to create a tissue construct is usually performed in static cell culture systems which are, however, often not satisfactory due to limitations in nutrient and oxygen supply. To overcome these limitations dynamic cell expansion in bioreactor systems under controllable conditions could be an important tool providing continuous perfusion for the generation of large numbers of viable pre-conditioned cells in a short time period. For this purpose cells derived from human umbilical cord arteries were expanded in a rotating bed system bioreactor for up to 9 days. For a comparative study, cells were cultivated under static conditions in standard culture devices.Our results demonstrated that the microenvironment in the perfusion bioreactor was more favorable than that of the standard cell culture flasks. Data suggested that cells in the bioreactor expanded 39 fold (38.7 ± 6.1 fold) in comparison to statically cultured cells (31.8 ± 3.0 fold). Large-scale production of cells in the bioreactor resulted in more than 3 x 108 cells from a single umbilical cord fragment within 9 days. Furthermore cell doubling time was lower in the bioreactor system and production of extracellular matrix components was higher. With this study, we present an appropriate method to expand human umbilical cord artery derived cells with high cellular proliferation rates in a well-defined bioreactor system under GMP conditions.

Synthesis and Characterization of Hybrid Hyaluronic Acid-Gelatin Hydrogels

Biomimetic hybrid hydrogels have generated broad interest in tissue engineering and regenerative medicine. Hyaluronic acid (HA) and gelatin (hydrolyzed collagen) are naturally derived polymers and biodegradable under physiological conditions. Moreover, collagen and HA are major components of the extracellular matrix (ECM) in most of the tissues (e.g., cardiovascular, cartilage, neural). When used as a hybrid material, HA-gelatin hydrogels may enable mimicking the ECM of native tissues. Although HA-gelatin hybrid hydrogels are promising biomimetic substrates, their material properties have not been thoroughly characterized in the literature. Herein, we generated hybrid hydrogels with tunable physical and biological properties by using different concentrations of HA and gelatin. The physical properties of the fabricated hydrogels including swelling ratio, degradation, and mechanical properties were investigated. In addition, in vitro cellular responses in both two and three-dimensional culture conditions were assessed. It was found that the addition of gelatin methacrylate (GelMA) into HA methacrylate (HAMA) promoted cell spreading in the hybrid hydogels. Moreover, the hybrid hydrogels showed significantly improved mechanical properties compared to their single component analogs. The HAMA-GelMA hydrogels exhibited remarkable tunability behavior and may be useful for cardiovascular tissue engineering applications.

Amniotic Fluid-Derived Stem Cells for Cardiovascular Tissue Engineering Applications

Recent research has demonstrated that a population of stem cells can be isolated from amniotic fluid removed by amniocentesis that are broadly multipotent and nontumorogenic. These amniotic fluid-derived stem cells (AFSC) could potentially provide an autologous cell source for treatment of congenital defects identified during gestation, particularly cardiovascular defects. In this review, the various methods of isolating, sorting, and culturing AFSC are compared, along with techniques for inducing differentiation into cardiac myocytes and endothelial cells. Although research has not demonstrated complete and high-yield cardiac differentiation, AFSC have been shown to effectively differentiate into endothelial cells and can effectively support cardiac tissue. Additionally, several tissue engineering and regenerative therapeutic approaches for the use of these cells in heart patches, injection after myocardial infarction, heart valves, vascularized scaffolds, and blood vessels are summarized. These applications show great promise in the treatment of congenital cardiovascular defects, and further studies of isolation, culture, and differentiation of AFSC will help to develop their use for tissue engineering, regenerative medicine, and cardiovascular therapies.