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Biomaterials, cells, and biomolecules constitute the tissue engineering triad to promote tissue regeneration
Source publication
Despite the introduction of new drugs and innovative devices contributing in the last years to improve patients’ quality of life, morbidity and mortality from cardiovascular diseases remain high. There is an urgent need for addressing the underlying problem of the loss of cardiac or vascular tissues and therefore developing new therapies. Autologou...
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Purpose of Review
Tissue engineering has expanded into a highly versatile manufacturing landscape that holds great promise for advancing cardiovascular regenerative medicine. In this review, we provide a summary of the current state-of-the-art bioengineering technologies used to create functional cardiac tissues for a variety of applications in vit...
Citations
... In the study, a canine model was utilized to effectively rebuild a significant defect in the pulmonary artery using collagen thrombin as a triggering agent. Specifically, a collagen thrombin-based fibrinogen/thrombin combination known as Tach Combo was employed (Simon-Yarza et al., 2017). Consequently, this biological material exhibits the potential to be utilized in the reconstruction of low-pressure pulmonary arteries in the context of cardiac surgery, with the aim of restoring the totality of the anomalous lung or substituting for substantial vessels. ...
Myocardial infarction (MI) stands as a prominent contributor to global cardiovascular disease (CVD) mortality rates. Acute MI (AMI) can result in the loss of a large number of cardiomyocytes (CMs), which the adult heart struggles to replenish due to its limited regenerative capacity. Consequently, this deficit in CMs often precipitates severe complications such as heart failure (HF), with whole heart transplantation remaining the sole definitive treatment option, albeit constrained by inherent limitations. In response to these challenges, the integration of bio-functional materials within cardiac tissue engineering has emerged as a groundbreaking approach with significant potential for cardiac tissue replacement. Bioengineering strategies entail fortifying or substituting biological tissues through the orchestrated interplay of cells, engineering methodologies, and innovative materials. Biomaterial scaffolds, crucial in this paradigm, provide the essential microenvironment conducive to the assembly of functional cardiac tissue by encapsulating contracting cells. Indeed, the field of cardiac tissue engineering has witnessed remarkable strides, largely owing to the application of biomaterial scaffolds. However, inherent complexities persist, necessitating further exploration and innovation. This review delves into the pivotal role of biomaterial scaffolds in cardiac tissue engineering, shedding light on their utilization, challenges encountered, and promising avenues for future advancement. By critically examining the current landscape, we aim to catalyze progress toward more effective solutions for cardiac tissue regeneration and ultimately, improved outcomes for patients grappling with cardiovascular ailments.
... Despite considerable progresses in prevention and treatment, cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally, seriously threatening to human health [1,2]. The incidence of CVDs has been increasing in recent years and is predicted to rise to 23.6 million by 2030 [3][4][5]. The traditional Chinese medicine (TCM) have been applied in the prevention and treatment of CVDs with a long history, according to the therapeutic methods and concepts of promoting blood circulation, dissipating blood stasis, detoxifying, dredging collaterals and tonifying qi [6,7]. ...
Despite continued advances in prevention and treatment strategies, cardiovascular diseases (CVDs) remain the leading cause of death worldwide, and more effective therapeutic methods are urgently needed. Polygonatum is a traditional Chinese herbal medicine with a variety of pharmacological applications and biological activities, such as antioxidant activity, anti-inflammation, antibacterial effect, immune-enhancing effect, glucose regulation, lipid-lowering and anti-atherosclerotic effects, treatment of diabetes and anticancer effect. There has also been more and more evidence to support the cardioprotective effect of Polygonatum in recent years. However, up to now, there has been a lack of comprehensive studies on the active ingredients and their pharmacotoxicological effects related to cardiovascular diseases. Therefore, the main active components of Polygonatum (including Polysaccharides, Flavonoids, Saponins) and their biological activities were firstly reviewed in this paper. Furthermore, we summarized the pharmacological effects of Polygonatum ’s active components in preventing and treating CVDs, and its relevant toxicological investigations. Finally, we emphasize the potential of Polygonatum in the prevention and treatment of CVDs.
... However, Nomura et al. [34] reconstructed the cardiomyocyte remodeling and elucidated the cardiomyocyte gene programs encoding, morphological and functional characteristics in cardiac hypertrophy and failure, correlating single-cardiomyocyte transcriptome with a cell morphology, epigenomic state and heart function. In addition, it is essential to understand and elucidate the gene programs in stimulating cardiomyocytes for cardiac cell regeneration using the scaffolds on the infarcted myocardium [34,35]. ...
Cardiovascular diseases (CVD), such as myocardial infarction (MI), constitute one of the world’s leading causes of annual deaths. This cardiomyopathy generates a tissue scar with poor anatomical properties and cell necrosis that can lead to heart failure. Necrotic tissue repair is required through pharmaceutical or surgical treatments to avoid such loss, which has associated adverse collateral effects. However, to recover the infarcted myocardial tissue, biopolymer-based scaffolds are used as safer alternative treatments with fewer side effects due to their biocompatibility, chemical adaptability and biodegradability. For this reason, a systematic review of the literature from the last five years on the production and application of chitosan scaffolds for the reconstructive engineering of myocardial tissue was carried out. Seventy-five records were included for review using the “preferred reporting items for systematic reviews and meta-analyses” data collection strategy. It was observed that the chitosan scaffolds have a remarkable capacity for restoring the essential functions of the heart through the mimicry of its physiological environment and with a controlled porosity that allows for the exchange of nutrients, the improvement of the electrical conductivity and the stimulation of cell differentiation of the stem cells. In addition, the chitosan scaffolds can significantly improve angiogenesis in the infarcted tissue by stimulating the production of the glycoprotein receptors of the vascular endothelial growth factor (VEGF) family. Therefore, the possible mechanisms of action of the chitosan scaffolds on cardiomyocytes and stem cells were analyzed. For all the advantages observed, it is considered that the treatment of MI with the chitosan scaffolds is promising, showing multiple advantages within the regenerative therapies of CVD.
... CVDs are the main causes of mortality worldwide and are currently difficult to treat (36). CVD was the primary cause of 17.7 million deaths worldwide in 2015, which is predicted to increase to 23.6 million by 2030 (37,38). SFR, the main active substance extracted from saffron, has been proven to have cardio-protective properties (30)(31)(32). ...
Safranal (SFR), an active ingredient extracted from saffron, exhibits a protective effect on the cardiovascular system. However, the mechanism of SFR against hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury has previously not been investigated in vitro. The aim of the present study was therefore to observe the protective effects of SFR on H/R-induced cardiomyocyte injury and to explore its mechanisms. A H/R injury model of H9c2 cardiac myoblasts was established by administering 800 µmol/l CoCl2 to H9c2 cells for 24 h and reoxygenating the cells for 4 h to induce hypoxia. H9c2 cardiac myoblasts were pretreated with SFR for 12 h to evaluate the associated protective effects. A Cell Counting Kit-8 assay was used for cell viability detection, and the expression levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), glutathione peroxidase (GSH-px), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and caspase-3, and the intracellular Ca2+ concentration were measured using the corresponding commercial kits. Levels of reactive oxygen species (ROS) in the cells were detected using 2,7-dichlorodihydrofluorescein diacetate. Flow cytometry was used to determine the degree of apoptosis and the level of mitochondrial membrane potential (MMP). Moreover, the expression levels of phosphorylated (p-)PI3K, AKT, p-AKT, glycogen synthase kinase 3β (GSK3β), p-GSK3β, Bcl-2, Bax, caspase-3 and cleaved caspase-3 were measured using western blot analysis. Results of the present study demonstrated that the H9c2 cardiac myoblasts treated with SFR exhibited significantly improved levels of viability and significantly reduced levels of ROS, compared with the H/R group. Furthermore, compared with the H/R group, SFR treatment significantly increased the MMP levels and antioxidant enzyme levels, including CAT, SOD and GSH-px; whereas the levels of CK-MB, LDH, MDA and intracellular Ca2+ concentration were significantly decreased. Moreover, the results of the present study demonstrated that SFR significantly reduced caspase-3, cleaved caspase-3 and Bax protein expression levels, but upregulated the Bcl-2 protein expression levels. SFR also increased the protein expressions of PI3K/AKT/GSK3β. In summary, the results suggested that SFR may exert a protective effect against H/R-induced cardiomyocyte injury, which occurs in connection with the inhibition of oxidative stress and apoptosis via regulation of the PI3K/AKT/GSK3β signaling pathway.
... Dental disorders (i.e., genetic abnormalities, periodontal diseases, and trauma) may damage the dental tissue or even lead to its ultimate loss [252]. Current treatments for oral pathologies include switching damaged tissues with combinatorial materials such as dental amalgams, titanium screws, endodontic sealers, and glass-ionomer cement. ...
... Current treatments for oral pathologies include switching damaged tissues with combinatorial materials such as dental amalgams, titanium screws, endodontic sealers, and glass-ionomer cement. Another therapeutic option is tooth regeneration [252,253]. However, these approaches cannot fully restore dental functions in terms of enduring mechanical stresses due to the lack of cementum and periodontal tissues. ...
The tissue engineering of hard organs and tissues containing cartilage, teeth, and bones is a widely used and rapidly progressing field. One of the main features of hard organs and tissues is the mineralization of their extracellular matrices (ECM) to enable them to withstand pressure and weight. Recently, a variety of printing strategies have been developed to facilitate hard organ and tissue regeneration. Fundamentals in three-dimensional (3D) printing techniques are rapid prototyping, additive manufacturing, and layered built-up and solid-free construction. This strategy promises to replicate the multifaceted architecture of natural tissues. Nowadays, 3D bioprinting techniques have proved their potential applications in tissue engineering to construct transplantable hard organs/tissues including bone and cartilage. Though, 3D bioprinting methods still have some uncertainties to fabricate 3D hard organs/tissues. In the present review, most advanced technical improvements, experiments, and future outlooks of hard tissue engineering are discussed, as well as their relevant additive manufacturing techniques.
... Cardiovascular diseases (CVDs) are the major causes of mortality worldwide and currently provide a considerable challenge for clinical treatments [23].CVDs were the primary cause of 17.7 million deaths worldwide in 2015, which is predicted to increase to 23.6 million by 2030 [24,25]. In recent years, the introduction of novel drugs and innovative devices has contributed to protecting patients with cardiopathy from CVDs. ...
Saffron is commonly used in traditional medicines and precious perfumes. It contains pharmacologically active compounds with notably potent antioxidant activity. Saffron has a variety of active components, including crocin, crocetin, and safranal. Oxidative stress plays an important role in many cardiovascular diseases, and its uncontrolled chain reaction is related to myocardial injury. Numerous studies have confirmed that saffron exact exhibits protective effects on the myocardium and might be beneficial in the treatment of cardiovascular disease. In view of the role of oxidative stress in cardiovascular disease, people have shown considerable interest in the potential role of saffron extract as a treatment for a range of cardiovascular diseases. This review analyzed the use of saffron in the treatment of cardiovascular diseases through antioxidant stress from four aspects: antiatherosclerosis, antimyocardial ischemia, anti-ischemia reperfusion injury, and improvement in drug-induced cardiotoxicity, particularly anthracycline-induced. Although data is limited in humans with only two clinically relevant studies, the results of preclinical studies regarding the antioxidant stress effects of saffron are promising and warrant further research in clinical trials. This review summarized the protective effect of saffron in cardiovascular diseases and drug-induced cardiotoxicity. It will facilitate pharmacological research and development and promote utilization of saffron.
... Different nano-or microcarriers (e.g., liposomes, polymeric, magnetic nano-& microparticles, quantum dots, nanotubes, dendrimers) are similarly researched in the therapeutic area of CVD [37]. Nanotechnology plays a role for wide-ranging cardiovascular applications, such as hypertension [38], atherosclerosis [39], prevention of restenosis following interventional cardiology [40], ablation for atrial fibrillation [41], cardiac tissue engineering [42], but also in the management of aneurysms [43] as well as CVD prevention [44]. ...
Thrombotic occlusion of blood vessels is responsible for life-threatening cardiovascular disorders such as myocardial infarction, ischemic stroke, and venous thromboembolism. Current thrombolytic therapy, the injection of Plasminogen Activators (PA), is yet limited by a narrow therapeutic window, rapid drug elimination, and risks of hemorrhagic complications. Nanomedicine-based vectorization of PA protects the drug from the enzymatic degradation, improves the therapeutic outcomes, and diminishes adverse effects in preclinical models. Herein, we review the pathophysiology of arterial and venous thrombosis and summarize clinically approved PA for the treatment of acute thrombotic diseases. We examine current challenges and perspectives in the recent key research on various (lipid, polymeric, inorganic, biological) targeted nanocarriers intended for the site-specific delivery of PA. Microbubbles and ultrasound-assisted sonothrombolysis that demonstrate thrombolysis enhancement in clinical trials are further discussed. Moreover, this review features strategies for the rational design of nanocarriers for targeted thrombolysis and effective PA encapsulation in view of interactions between nanomaterials and biological systems. Overall, nanomedicine represents a valued approach for the precise treatment of acute thrombotic pathologies.
... To overcome these limitations, tissue engineering strategies aim at improving the graft biocompatibility [1][2][3]. Decellularization is a method of removing cells from donor tissue or organs so that only extracellular matrix remains. Such a construct allows low immunogenicity and allows for in vivo migration of host cells into the scaffolds [1,2]. ...
... However, since an approach of rapid and complete in vivo recellularization of decellularized vascular grafts has not been established yet, the performance of various kinds of biomaterials has been studied [3,4]. Original content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. ...
Optimized biocompatibility is crucial for the durability of cardiovascular implants. Previously, a combined coating with fibronectin and stromal cell-derived factor 1α (SDF1α) has been shown to accelerate the in vivo cellularization of synthetic vascular grafts and to reduce the calcification of biological pulmonary root grafts. In this study, we evaluate the effect of side-specific coating with SDF1α and fibronectin on the in vivo cellularization and degeneration of decellularized rat aortic implants. Aortic arch vascular donor grafts were detergent-decellularized. The luminal graft surface was coated with SDF1α, while the adventitial surface was coated with fibronectin. SDF1α-coated and uncoated grafts were infrarenally implanted (n=20) in rats and followed up for up to 8 weeks.Cellular intima population was accelerated by luminal SDF1α coating at 2 weeks (92.4 ± 2.95% vs. 61.1 ± 6.51% in controls, p<0.001). SDF1α coating inhibited neo-intimal hyperplasia, resulting in a significantly decreased intima-to-media ratio after 8 weeks (0.62 ± 0.15 vs. 1.35 ± 0.26 in controls, p<0.05). Furthermore, at 8 weeks, media calcification was significantly decreased in the SDF1α group as compared to the control group (area of calcification in proximal arch region 1,092 ± 517 µm2 vs. 11,814 ± 1,883 µm2, p<0.01). Luminal coating with SDF1α promotes early autologous intima recellularization in vivo and attenuates neo-intima hyperplasia as well as calcification of decellularized vascular grafts.
... Specifically, it is thinner than bovine pericardium and collagen content is highly undulated [4]. In addition, the decellularization must behave as a scaffold to be repopulated with patient's own cells [25,26]. We hereby propose a comparative analysis of donkey pericardium treated with glutaraldehyde to the same material after soft decellularization. ...
Background
The donkey pericardium is considered a good candidate to manufacture percutaneous heart valves based upon its thinness, low cellularity and undulating collagen bundles and laminates. Decellularization represents an avenue worth exploring, should its superiority to glutaraldehyde-treated pericardium be demonstrated.
Materials and methods
Donkey pericardium was divided into two groups: regular glutaraldehyde fixation and mild decellularization. The treated pericardia were observed using scanning electron microscopy, histology and transmission electron microscopy. Tensile tests were performed along the axial and perpendicular directions, with the data fitted into both the Gasser–Ogden–Holzapfel (GOH) material model and the Fung’s anisotropic one.
Results
The microstructures of the pericardia processed by the two protocols were similar, showing collagen bundles and laminates free of flaws. The decellularization eliminated most of the cells, however leaving the structure somehow compressed. The collagen filaments in bundles were slightly blurry. The anisotropy rates of the non-decellularized specimens were almost identical to the decellularized ones. The decellularized pericardium appeared stiffer.
Conclusion
The decellularization proved to be effective. However, it makes the tissue stiffer, which may lead to higher shear concentration during cardiac cycles and reduce its wavy microstructure. Therefore, it appears premature to select decellularized donkey pericardium to manufacture heart valves.
... The shortage of donor organs grows as the general patient life-span increases and medical treatments that can prolong the life of even poorer condition patients needing transplants are developed [Lechler et al., 2005]. Multiple treatment and prevention methods are constantly being studied to alleviate the effects of cardiovascular disease, and clinical cardiac TE is one of the methods [Simon-Yarza et al., 2017, Duan, 2017. The main application of clinical cardiac TE is the treatment of myocardial damage caused by ischemia or heart failure due to some other causes [Madonna et al., 2016]. ...
... In either case, the regenerative effect of these cell transplantations has thus far been largely attributed to the paracrine effect of the cells' secreted biomolecules and not on actual regeneration. [Farouz et al., 2014, Madonna et al., 2016, Duan, 2017, Menasché et al., 2018 Similar to neural TE, the injection of regeneration stimulating growth factors alone, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), has been studied [Simon-Yarza et al., 2017]. And other molecules, even the oxygen radical scavengingbioamines mentioned in Chapter 2.2.2. ...
... have been tested as injectable drugs to the infarcted site [Han et al., 2007, Wei et al., 2016. Based on these, the actual regeneration of ischemic cardiac tissue still seems to require a full TE product with cell-supporting scaffold and stem cells combined, possibly with added growth factor release. [Madonna et al., 2016, Simon- Yarza et al., 2017 Even though the mechanical properties of CNS and heart are very different, there is high similarity within the biomaterial choices for both of these tissues. In fact, one of the earliest studies on the effect of substrate stiffness on cell response was done with muscle cells on top of collagen coated PAA hydrogels [A. ...
The aim of tissue engineering (TE) is the production of live and functional tissues by combining a biomaterial scaffold, living cells, and a relevant bioactive stimulus. The engineering of soft tissues, such as brain and heart, requires a scaffold material that represents the natural tissue, meaning that it needs to be soft, elastic, flexible, and possibly strain hardening. Additionally, a scaffold material must allow the diffusion of nutrients and the penetration of migrating cells inside the microstructure. Furthermore, the scaffold must provide the encapsulated cells with enough attachment sites to ensure the cells can function in their natural way.
Hydrogels are promising scaffold candidates for soft tissue engineering applications. They are crosslinked, hydrophilic polymer networks with a high water content in the structure. Hydrogels can be produced from a large variety of natural or synthetic polymers by implementing a variety of physical and chemical crosslinking strategies. Here, hydrogels based on the polysaccharide gellan gum are studied in a conclusive manner from both the materials science and biological perspective. The gelation process and chemistry of modified hydrogel-forming biopolymers are characterized. The mechanical properties of the hydrogels as well as their microstructure and the effects of different functionalization strategies on these characteristics are studied in detail. Novel imaging methods are applied for the analysis of hydrogel microstructure. Similarly, the mechanical properties of the hydrogels are studied using methods that have never before been applied to gels in hydrated form. Then, the newly developed hydrogel formulations are used with human cells for the soft tissue engineering of the two most vital and poorly regenerating organs of the human body – the central nervous system and the heart.
The developed gellan gum-based hydrogels have biomimicking mechanical properties with adjustable stiffness corresponding to either brain or heart muscle tissue, depending on the exact composition used. The elasticity of the hydrogel network enables the spontaneous beating of human induced pluripotent stem cell-derived cardiomyocytes in three-dimensional culture. The polymer network creating the hydrogels is loose enough so that the cells can grow inside and that nutrients and waste products of cell metabolism can also be transported in and out of the hydrogel. The functionalization of gellan gum with extracellular matrix proteins, such as laminin and collagen-derived gelatin, enhances the cytocompatibility, growth, and elongation of cells cultured in the novel three-dimensional microenvironments.
