Elastin biosynthesis: The missing link in tissue-engineered blood vessels (original) (raw)
Related papers
Acellular vascular grafts generated from collagen and elastin analogs
Acta Biomaterialia, 2013
Tissue engineered vascular grafts require long fabrication times, in part, due to the requirement of cells from a variety of cell sources to produce a robust load bearing, extracellular matrix. Herein, we propose a design strategy for the fabrication of tubular conduits comprised of collagen fiber networks and elastin-like protein polymers to mimic native tissue structure and function. Dense fibrillar collagen networks exhibited an ultimate tensile strength (UTS) of 0.71 ± 0.06 MPa, strain to failure of 37.1 ± 2.2%, and Young's modulus of 2.09 ± 0.42 MPa, comparing favorably to an UTS and a Young's modulus for native blood vessels of 1.4-11.1 MPa and 1.5 ± 0.3 MPa, respectively. Resilience, a measure of recovered energy during unloading of matrices, demonstrated that 58.9 ± 4.4% of the energy was recovered during loading-unloading cycles. Rapid fabrication of multilayer tubular conduits with maintenance of native collagen ultrastructure was achieved with internal diameters ranging between 1 to 4 mm. Compliance and burst pressures exceeded 2.7 ± 0.3%/100 mmHg and 830 ± 131 mmHg, respectively, with a significant reduction in observed platelet adherence as compared to ePTFE (6.8 ± 0.05 × 10 5 vs. 62 ± 0.05 × 10 5 platelets/mm 2 , p < 0.01). Using a rat aortic interposition model, early in vivo responses were evaluated at 2 weeks via Doppler ultrasound and CT angiography with immunohistochemistry confirming a limited early inflammatory response (n=8). Engineered collagen-elastin composites represent a promising strategy for fabricating synthetic tissues with defined extracellular matrix content, composition, and architecture.
Mitigating challenges and expanding the future of vascular tissue engineering—are we there yet?
Frontiers in Physiology
Atherosclerosis is still a significant cause of death in western societies. The leading cause of this cardiovascular disease is lipid accumulation and inflammation of the large arteries, which may lead to clinical complications such as arterial thrombosis, myocardial infarction, and ischemic stroke (Xenotransplantation, 1997). Drugs are usually the first treatment choice, even in the late stages of atherosclerosis. Sometimes, more aggressive treatment like Coronary artery bypass surgery (CABG) is needed. CABGs are performed by harvesting a vessel from the patient, but the patient undergoing two surgeries only added to their comorbidities. However, long-term results after CABG depend not only on the completeness of revascularization and the initial severity of coronary and myocardial lesions but also on comorbidities like diabetes mellitus, arterial hypertension, and pulmonary and renal disorders. Moreover, the limited availability of autografts was soon realized, and new options proposed by tissue engineering were started exploring to design synthetic grafts (Corridon et al., 2013). Vascular tissue engineering (VTE) is focused on constructing vessels using different biomaterials, cell sources, biomolecules, and mechanical stimuli that can function in physiological environments (Lovett et al., 2009; Pradeep et al., 2019; Wang et al., 2022a). Such vessels replace non-functional vascular compartments and generate networks within bio (artificial) scaffolds. Pioneering efforts in this field date back to 1950, when artificial vascular grafts made from synthetic polymer materials were used to replace occluded arterial vessels (Song et al., 2018). It was perceived that biomaterials could support microvascular function showing great potential in accelerating the transition away from xenogenic materials for clinical application. For example, Li et al. (2017) developed a hyaluronic acid-based hydrogel chemically modified with fibronectin motifs that promote EC binding of α3/α5 b1 integrins, resulting in better vascularization to a non-modified hydrogel in a mouse stroke model. Similarly, advances in nanotechnology can bring additional functionality to vascular scaffolds, optimize internal vascular graft surface, reduce early thrombosis and inflammatory responses, and even direct the differentiation of stem cells into the vascular cell phenotype (Mironov et al., 2008; Wang et al., 2022a).
Novel porous aortic elastin and collagen scaffolds for tissue engineering
Biomaterials, 2004
Decellularized vascular matrices are used as scaffolds in cardiovascular tissue engineering because they retain their natural biological composition and three-dimensional (3-D) architecture suitable for cell adhesion and proliferation. However, cell infiltration and subsequent repopulation of these scaffolds was shown to be unsatisfactory due to their dense collagen and elastic fiber networks. In an attempt to create more porous structures for cell repopulation, we selectively removed matrix components from decellularized porcine aorta to obtain two types of scaffolds, namely elastin and collagen scaffolds. Histology and scanning electron microscopy examination of the two scaffolds revealed a well-oriented porous decellularized structure that maintained natural architecture of the aorta. Quantitative DNA analysis confirmed that both scaffolds were completely decellularized. Stressstrain analysis demonstrated adequate mechanical properties for both elastin and collagen scaffolds. In vitro enzyme digestion of the scaffolds suggested that they were highly biodegradable. Furthermore, the biodegradability of collagen scaffolds could be controlled by crosslinking with carbodiimides. Cell culture studies showed that fibroblasts adhered to and proliferated on the scaffold surfaces with excellent cell viability. Fibroblasts infiltrated about 120 mm into elastin scaffolds and about 40 mm into collagen scaffolds after 4 weeks of rotary cell culture. These results indicated that our novel aortic elastin and collagen matrices have the potential to serve as scaffolds for cardiovascular tissue engineering. r
The Evolution of Vascular Tissue Engineering and Current State of the Art
Cells Tissues Organs, 2012
more biology-driven strategies. In this article, we review the preclinical and clinical efforts in the quest for a tissue-engineered blood vessel that is free of permanent synthetic scaffolds but has the mechanical strength to become a successful arterial graft. Special emphasis is given to the tissue engineering by self-assembly (TESA) approach, which has been the only one to reach clinical trials for applications under arterial pressure.
Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges
2011
Vascular disease results in the decreased utility and decreased availability of autologus vascular tissue for small diameter (< 6 mm) vessel replacements. While synthetic polymer alternatives to date have failed to meet the performance of autogenous conduits, tissue-engineered replacement vessels represent an ideal solution to this clinical problem. Ongoing progress requires combined approaches from biomaterials science, cell biology, and translational medicine to develop feasible solutions with the requisite mechanical support, a non-fouling surface for blood flow, and tissue regeneration. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. This review will highlight the current inadequacies of autologus and synthetic grafts, the engineering requirements for implantation of tissue-engineered grafts, and the current status of tissue-engineered blood vessel research.
Development of a reinforced porcine elastin composite vascular scaffold
… Research Part A, 2006
Elastin, a principal structural component of native arteries, has distinct biological and mechanical advantages when used as a biomaterial; however, its low ultimate tensile strength has limited its use as an arterial conduit. We have developed a scaffold, consisting of a purified elastin tubular conduit strengthened with fibrin bonded layers of acellular small intestinal submucosa (aSIS) for potential use as a small diameter vascular graft. The addition of aSIS increased the ultimate tensile strength of the elastin conduits nine-fold. Burst pressures for the elastin composite vascular scaffold (1396 Ϯ 309 mmHg) were significantly higher than pure elastin conduits (162 Ϯ 36 mmHg) and comparable to native saphenous veins. The average suture pullout strength of the elastin composite vascular scaffolds was 14.612 Ϯ 3.677 N, significantly higher than the pure elastin conduit (0.402 Ϯ 0.098 N), but comparable to native porcine carotid arteries (13.994 Ϯ 4.344 N). Cyclic circumferential strain testing indicated that the composite scaffolds were capable of withstanding physiological loading conditions for at least 83 h. Implantation of the elastin composites as carotid interposition grafts in swine demonstrated its superiority to clinically acceptable ePTFE with significantly longer average patency times of 5.23 h compared to 4.15 h. We have developed a biologically based elastin scaffold with suitable mechanical properties and low thrombogenicity for in vivo implantation, and with the potential for cellular repopulation and host integration reestablishing an appropriate elastic artery.
Journal of Biomedical Materials Research Part A, 2009
Small-diameter blood vessel substitutes are urgently needed for patients requiring replacements of their coronary and below-the-knee vessels and for better arteriovenous dialysis shunts. Circulatory diseases, especially those arising from atherosclerosis, are the predominant cause of mortality and morbidity in the developed world. Current therapies include the use of autologous vessels or synthetic materials as vessel replacements. The limited availability of healthy vessels for use as bypass grafts and the failure of purely synthetic materials in small-diameter sites necessitate the development of a biological substitute. Tissue engineering is such an approach and has achieved promising results, but reconstruction of a functional vascular tunica media, with circumferentially oriented contractile smooth muscle cells (SMCs) and extracellular matrix, appropriate mechanical properties, and vasoactivity has yet to be demonstrated. This review focuses on strategies to effect the switch of SMC phenotype from synthetic to contractile, which is regarded as crucial for the engineering of a functional vascular media. The synthetic SMC phenotype is desired initially for cell proliferation and tissue remodeling, but the contractile phenotype is then necessary for sufficient vasoactivity and inhibition of neointima formation. The factors governing the switch to a more contractile phenotype with in vitro culture are reviewed. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009