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Personalized vascular tissue. Tissues are harvested from a patient. Cells and extracellular matrix are isolated from the patient's tissues. The extracellular matrix is manipulated as the self-hydrogel. Adults stem cells are isolated or well-differentiated adult cells are reprogrammed into iPSCs. Diseasecausing genes are modified with CRISPR/Cas9. The gene-fixed stem cells are expanded in vitro and differentiated in the self-hydrogel to produce autologous vascular tissue blocks. The personalized tissue blocks are transplanted back into the patient. CRISPR, clustered regularly interspaced short palindromic repeat; iPSC, induced pluripotent stem cell.
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The common occurrence of cardiovascular diseases and the lack of proper autologous tissues prompt and promote the pressing development of tissue-engineered vascular grafts. Current progress on scaffold production, genetically modified cells and use of nanotechnology-based monitoring has considerably improved the long-term patency of engineered tiss...
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... mathematical model can be used to design the supplemented blood vessels, and a cellularized human heart can be potentially printed. 63 The proper orientation of blood vessels is a key factor in such tissue engineering approaches. The personalized vascular tissue can provide ideal engineering tissue blocks without host immune response in patients (Fig. ...
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... mathematical model can be used to design the supplemented blood vessels, and a cellularized human heart can be potentially printed. 63 The proper orientation of blood vessels is a key factor in such tissue engineering approaches. The personalized vascular tissue can provide ideal engineering tissue blocks without host immune response in patients (Fig. ...
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... These innovations enable more intricate exploration into the effects of nanoscale features on endothelialization. 21 The convergence of these findings and technological advancements holds great promise for cardiovascular biomaterial design, suggesting that the integration of nanoscale roughness alongside hydrophilicity and surface charge into biomaterial surfaces could significantly augment endothelialization. ...
Synthetic small-diameter vascular grafts (<6 mm) are used in the treatment of cardiovascular diseases, including coronary artery disease, but fail much more readily than similar grafts made from autologous vascular tissue. A promising approach to improve the patency rates of synthetic vascular grafts is to promote the adhesion of endothelial cells to the luminal surface of the graft. In this study, we characterized the surface chemical and topographic changes imparted on poly(vinyl alcohol) (PVA), an emerging hydrogel vascular graft material, after exposure to various reactive ion plasma (RIP) surface treatments, how these changes dissipate after storage in a sealed environment at standard temperature and pressure, and the effect of these changes on the adhesion of endothelial colony-forming cells (ECFCs). We showed that RIP treatments including O2, N2, or Ar at two radiofrequency powers, 50 and 100 W, improved ECFC adhesion compared to untreated PVA and to different degrees for each RIP treatment, but that the topographic and chemical changes responsible for the increased cell affinity dissipate in samples treated and allowed to age for 230 days. We characterized the effect of aging on RIP-treated PVA using an assay to quantify ECFCs on RIP-treated PVA 48 h after seeding, atomic force microscopy to probe surface topography, scanning electron microscopy to visualize surface modifications, and X-ray photoelectron spectroscopy to investigate surface chemistry. Our results show that after treatment at higher RF powers, the surface exhibits increased roughness and greater levels of charged nitrogen species across all precursor gases and that these surface modifications are beneficial for the attachment of ECFCs. This study is important for our understanding of the stability of surface modifications used to promote the adhesion of vascular cells such as ECFCs.
... Interestingly, mesenchymal stem cells used in combination with neural stem cells have been proven more effective in animal models than the use of individual therapies [125], while the co-transplantation of MSCs and NCSs in stroke patients has been shown to be a safe and feasible method [112], making it a potential new therapy for ischemic stroke patients [126]. Furthermore, stem cell therapy has also been shown to be effective in combination with gene therapy [127,128], tissue engineering scaffolds [129][130][131][132], and reperfusion therapy [114]. [133], are found in a variety of tissues, such as bone marrow, peripheral blood, connective tissue, and the umbilical cord [134]. ...
Ischemic stroke is one of the major causes of death and disability. Since the currently used treatment option of reperfusion therapy has several limitations, ongoing research is focusing on the neuroprotective effects of microglia and stem cells. By exerting the bystander effect, secreting exosomes and forming biobridges, mesenchymal stem cells (MSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and multilineage-differentiating stress-enduring cells (Muse cells) have been shown to stimulate neurogenesis, angiogenesis, cell migration, and reduce neuroinflammation. Exosome-based therapy is now being extensively researched due to its many advantageous properties over cell therapy, such as lower immunogenicity, no risk of blood vessel occlusion, and ease of storage and modification. However, although preclinical studies have shown promising therapeutic outcomes, clinical trials have been associated with several translational challenges. This review explores the therapeutic effects of preconditioned microglia as well as various factors secreted in stem cell-derived extracellular vesicles with their mechanisms of action explained. Furthermore, an overview of preclinical and clinical studies is presented, explaining the main challenges of microglia and stem cell therapies, and providing potential solutions. In particular, a highlight is the use of novel stem cell therapy of Muse cells, which bypasses many of the conventional stem cell limitations. The paper concludes with suggestions for directions in future neuroprotective research.
... Finally, it shou also be able to sustain the surgical grafting process, which involves stitching [16,27,28] In order to achieve these complex properties and fully recapitulate the physiologi environment, appropriate cell sources, optimal biomaterial, and fabrication a maturation techniques are important elements to consider; as a result, these constitute t fundamentals of VTE ( Figure 2). Understanding these elements and the rationale behi the choice is essential; thus, a synopsis of each of these components will follow [19,27]. In order to achieve these complex properties and fully recapitulate the physiological environment, appropriate cell sources, optimal biomaterial, and fabrication and maturation techniques are important elements to consider; as a result, these constitute the fundamentals of VTE (Figure 2). ...
... In order to achieve these complex properties and fully recapitulate the physiological environment, appropriate cell sources, optimal biomaterial, and fabrication and maturation techniques are important elements to consider; as a result, these constitute the fundamentals of VTE (Figure 2). Understanding these elements and the rationale behind the choice is essential; thus, a synopsis of each of these components will follow [19,27]. Thus, an ideal graft should have adequate biological and mechanical characteristics [14,25]. ...
... In order to achieve these complex properties and fully recapitulate the physiological environment, appropriate cell sources, optimal biomaterial, and fabrication and maturation techniques are important elements to consider; as a result, these constitute the fundamentals of VTE ( Figure 2). Understanding these elements and the rationale behind the choice is essential; thus, a synopsis of each of these components will follow [19,27]. ...
The clinical demand for tissue-engineered vascular grafts is still rising, and there are many challenges that need to be overcome, in particular, to obtain functional small-diameter grafts. The many advances made in cell culture, biomaterials, manufacturing techniques, and tissue engineering methods have led to various promising solutions for vascular graft production, with available options able to recapitulate both biological and mechanical properties of native blood vessels. Due to the rising interest in materials with bioactive potentials, materials from natural sources have also recently gained more attention for vascular tissue engineering, and new strategies have been developed to solve the disadvantages related to their use. In this review, the progress made in tissue-engineered vascular graft production is discussed. We highlight, in particular, the use of natural materials as scaffolds for vascular tissue engineering.
... These strategies aim to stimulate a body's innate repair mechanisms for regenerating damaged blood vessels. Growth factors, cytokines, or signaling molecules that promote angiogenesis are employed (Chen et al. 2021). Natural polymers like collagen and chitosan have also been employed in the development of vascular grafts. ...
Natural polymers, or biopolymers, are widely utilized in regenerative medicine and tissue engineering. These polymers, derived from proteins, polysaccharides, and nucleic acids, serve as biomaterials for scaffolds, drug delivery systems, and bioactive materials that mimic the extracellular matrix. They offer advantages such as biocompatibility, biodegradability, versatility, and integration with gene therapy. Collagen, gelatin, chitosan, hyaluronic acid, fibrin, and alginate are commonly used natural polymers in regenerative medicine. They promote cell growth, tissue formation, wound healing, and tissue regeneration. Natural polymers also play a crucial role in controlled drug and gene delivery systems, providing safe and effective alternatives to synthetic polymers. Moreover, they contribute to developing bioactive and bio-functional materials, including hydrogels, which mimic natural biological processes and have applications in tissue engineering, drug delivery, and wound healing. Overall, natural polymers hold great promise for advancing regenerative medicine and tissue engineering. However, several challenges impede the widespread adoption and utilization of natural polymers in regenerative medicine. These challenges include variations in batch-to-batch composition, limited mechanical strength, rapid degradation rates, immunogenicity concerns, and difficulties achieving precise control over their properties. Overcoming these challenges necessitates a comprehensive understanding of the structure-function relationships of natural polymers and the development of innovative processing techniques to enhance their mechanical properties and stability. The future of natural polymers in regenerative medicine holds immense potential. Ongoing research efforts focus on refining their properties, tailoring their degradation rates, and integrating them with advanced technologies like 3D bioprinting and nanotechnology. By leveraging these advancements, natural polymers can be further optimized for specific tissue engineering applications, enabling the creation of patient-specific scaffolds, enhanced wound healing materials, and personalized drug delivery systems. Additionally, harnessing the innate bioactivity of natural polymers and their interactions with cells and tissues opens new avenues for the development of bioactive materials that promote tissue regeneration and healing.
... Then, seed cells onto synthetic or natural polymer to shape a tubular mold. Reprinted from ref. [131]. Vascular cells, mainly ECs, are the cells that cover the lumen of the vessels and prevent the blood from clotting. ...
Cardiovascular diseases remain the leading cause of mortality worldwide. Although new therapies are actively being developed and used for cardiovascular pathologies, these attempts have not significantly decreased mortality rates. Regenerative medicine has made enormous progress and set promising approaches over the past half-century. However, since autologous (donor-derived) vascular grafts are lacking, an alternative prosthesis must be constructed for cardiovascular disease patients. In vascular tissue manufacturing and regenerative medicine, scientists seek to improve this significant clinical challenge using bio-fabrication techniques combining additive manufacturing, biomaterials science, and advanced cellular biology. In the last few decades, many improvements and changes in various approaches have helped develop bioengineered concepts that reflect native blood vessels’ structure and function. However, numerous challenges must be overcome to clinically translate the next generation of tissue-engineered vascular transplants. This review provides update on the cell sources, scaffold essential for cardiovascular tissue engineering, and tissue engineering approaches as prospective options for curative therapy for blood vessel disease.
... Furthermore, using novel nanotechnology applications that involve nanofibers and nanoparticles, it will be possible to modify several features of the grafts' materials providing, for example, a greater antibiotic-loading capacity to prevent VGEI. In this context, 3D bioprinting, and even 4D bioprinting, may be an effective technology with the potential to produce patient-tailored grafts with major resistance to several biological assaults, thus, overcoming a series of complications [149][150][151][152][153][154]. Thus, the ideal engineered graft should have the biomechanical, morphologic, and cellular characteristics of a human vessel [155]. ...
Citation: Costa, D.; Andreucci, M.; Ielapi, N.; Serraino, G.F.; Mastroroberto, P.; Bracale, U.M.; Serra, R. Infection of Vascular Prostheses: A Comprehensive Review. Prosthesis 2023, 5, 148-166. Abstract: Vascular graft or endograft infection (VGEI) is a complex disease that complicates vascular-surgery and endovascular-surgery procedures and determines high morbidity and mortality. This review article provides the most updated general evidence on the pathogenesis, prevention, diagnosis, and treatment of VGEI. Several microorganisms are involved in VGEI development, but the most frequent one, responsible for over 75% of infections, is Staphylococcus aureus. Specific clinical, surgical, radiologic, and laboratory criteria are pivotal for the diagnosis of VGEI. Surgery and antimicrobial therapy are cornerstones in treatment for most patients with VGEI. For patients unfit for surgery, alternative treatment is available to improve the clinical course of VGEI.
... 3D bioprinting is an emerging approach to directly print cells and supporting material (referred to as bioink) to create 3D structures with high precision and curated spatial distribution [75]. Liguori et al. used a DAG hydrogel to bioprint the tunica media of a small-diameter blood vessel [76]. ...
Cardiovascular disease is a globally prevalent disease with far-reaching medical and socio-economic consequences. Although improvements in treatment pathways and revascularisation therapies have slowed disease progression, contemporary management fails to modulate the underlying atherosclerotic process and sustainably replace damaged arterial tissue. Direct cellular reprogramming is a rapidly evolving and innovative tissue regenerative approach that holds promise to restore functional vasculature and restore blood perfusion. The approach utilises cell plasticity to directly convert somatic cells to another cell fate without a pluripotent stage. In this narrative literature review, we comprehensively analyse and compare direct reprogramming protocols to generate endothelial cells, vascular smooth muscle cells and vascular progenitors. Specifically, we carefully examine the reprogramming factors, their molecular mechanisms, conversion efficacies and therapeutic benefits for each induced vascular cell. Attention is given to the application of these novel approaches with tissue engineered vascular grafts as a therapeutic and disease-modelling platform for cardiovascular diseases. We conclude with a discussion on the ethics of direct reprogramming, its current challenges, and future perspectives.
... 12 Due to the limit of cell proliferation in culture, it remains difficult to harvest large amounts of these vascular cells. 13 Second, is the lack of a well-defined culture system to support the regenerate functional microvessels. The suitable scaffold, cytokines, and culture system remain to be established. ...
The establishment of effective vascularization represents a key challenge in regenerative medicine. Adequate sources of vascular cells and intact vessel fragments have not yet been explored. We herein examined the potential application of microvessels induced from hiPSCs for rapid angiogenesis and tissue regeneration. Microvessels were generated from human pluripotent stem cells (iMVs) under a defined induction protocol and compared with human adipose tissue-derived microvessels (ad-MVs) to illustrate the similarity and differences of the alternative source. Then, the therapeutic effect of iMVs was detected by transplantation in vivo. The renal ischemia-reperfusion model and skin damage model were applied to explore the potential effect of vascular cells derived from iMVs (iMVs-VCs). Besides, the subcutaneous transplantation model and muscle injury model were established to explore the ability of iMVs for angiogenesis and tissue regeneration. The results revealed that iMVs had remarkable similarities to natural blood vessels in structure and cellular composition, and were potent for vascular formation and self-organization. The infusion of iMVs-VCs promoted tissue repair in the renal and skin damage model through direct contribution to the reconstruction of blood vessels and modulation of the immune microenvironment. Moreover, the transplantation of intact iMVs could form a massive perfused blood vessel and promote muscle regeneration at the early stage. The infusion of iMVs-VCs could facilitate the reconstruction and regeneration of blood vessels and modulation of the immune microenvironment to restore structures and functions of damaged tissues. Meanwhile, the intact iMVs could rapidly form perfused vessels and promote muscle regeneration. With the advantages of abundant sources and high angiogenesis potency, iMVs could be a candidate source for vascularization units for regenerative medicine.
... The study was conducted by Edenfield L. et al. to define the effects of carotid endarterectomy based on patch bovine pericardium patch showed superior results up to 1 year approach has an attractive alternative cell-based tactic to vascular graft preparation (Edenfield et al. 2020). The basic approach of tissue engineering is to develop an engineered vessel by seeding autologous cells with a natural, synthetic, or hybrid cylindrical scaffold under appropriate culture conditions (Chen et al. 2021;Ju et al. 2017). For over half a century Synthetic grafts have been used for the replacement of damaged or diseased vessels (Ju et al. 2017). ...
Small diameter vascular graft is a clinical need in cardiovascular disease (CAD) and peripheral atherosclerotic diseases (PAD). Autologous graft has limitations in availability and harvesting surgery. To make luminal surface modification with heparin coating in xenogeneic small diameter vascular graft. We constructed a conduit from decellularized human saphenous vein (HSV) matrices in small diameter vascular graft (< 0.8 mm diameter). Luminal surface modification was done with heparin coating for transplantation in the rat femoral artery. Biocompatibility of conduit was checked in Chorioallantoic Membrane (CAM) assay and in vivo. The blood flow rate in conduit grafts was measured, and immuno-histological analysis was performed. CAM assay and in vivo biocompatibility test showed cellular recruitment in the HSV scaffold. Heparin binding was achieved on the luminal surface. After three months of transplantation surgery neo-intimal layer was formed in the graft. The graft was patent for two weeks after surgery. There were no statistically differences between blood flow rate in graft (at proximal end 0.5 ± 0.01 m/s and at distal end 0.4 ± 0.01 m/s (n = 6)) and native artery (0.6 ± 0.1 m/second, (n = 3)). Biomarkers of endothelial cells, medial smooth muscle cells, and angiogenesis were observed in the transplanted graft. Our study demonstrates that xenogeneic decellularized vascular grafts with surface modification with heparin coating could be useful for the replacement of small diameter vessels.
... Naturally derived polymers, constituting a temporary scaffold and their other replacement with a complete biological vascular conduit, are promising candidates in VTE. 146 An ideal scaffold for ECM-mimicking blood vessels should have bioactive functional groups to bind with cell ligands and potentially guide cellular behavior towards regeneration patterns. 147 The normal physiologic responses of the blood vessel wall have a key role in controlling thrombotic, inflammation and long-term patency. ...
The main objective of the present review article is to investigate the in-vitro and in-vivo biocompatibility behavior of hybrid PCL-based scaffolds with collagen, gelatin, and chitosan to improve endothelialization for VTE applications. It is reported that the high-rate failure of small diameters vascular grafts (SDVGs, <6 mm) due to adhesion of platelets and plasma protein and aggregation, over-proliferation of smooth muscle cells (SMCs), and neointimal hyperplasia at the implantation site is main challenge in vascular tissue engineering (VTE). The fast re-establishment of a functional endothelial cell (EC) layer representing a crucial importance strategy has been proposed to reduce these adverse outcomes. Polycaprolactone (PCL), with optimum mechanical properties, it showed great potential in biomedical applications, but its biocompatibility is still highly concerned in VTE. Modifications of the PCL vascular grafts by developing the hybrid structures using natural polymers with optimum hydrophilicity and biocompatibility properties in order to speed up the re-endothelialization process have been proposed over the last years. Analyzing the mentioned results in the present study can offer a better understanding of the benefits and challenges of applying the natural polymer as a thrombotic response upon implantation in clinical trials. Also, it can suggest the PCL-Collagen as the best framework for the fabrication of rationally designed SDVGs for VTE.
