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Ozdemir, S.;  Yalcin-Enis, I.;  Yalcinkaya, B.;  Yalcinkaya, F. Design Components for Electrospun Vascular Prosthesis. Encyclopedia. Available online: (accessed on 13 July 2024).
Ozdemir S,  Yalcin-Enis I,  Yalcinkaya B,  Yalcinkaya F. Design Components for Electrospun Vascular Prosthesis. Encyclopedia. Available at: Accessed July 13, 2024.
Ozdemir, Suzan, Ipek Yalcin-Enis, Baturalp Yalcinkaya, Fatma Yalcinkaya. "Design Components for Electrospun Vascular Prosthesis" Encyclopedia, (accessed July 13, 2024).
Ozdemir, S.,  Yalcin-Enis, I.,  Yalcinkaya, B., & Yalcinkaya, F. (2022, October 24). Design Components for Electrospun Vascular Prosthesis. In Encyclopedia.
Ozdemir, Suzan, et al. "Design Components for Electrospun Vascular Prosthesis." Encyclopedia. Web. 24 October, 2022.
Design Components for Electrospun Vascular Prosthesis

The design parameters for electrospun vascular grafts can be divided into two categories: the constructional parameters, which involve fiber diameter, pore size, porosity, fiber orientation, wall thickness, the number of layers, and material selection. The scaffold’s configuration and material choice are both essential because they have a significant impact on mechanical and biological characteristics, including compliance, tensile strength, burst pressure, blood permeability, and suturability, as well as biological processes such as cell phenotype, extracellular matrix (ECM) formation, and cell diffusion.

vascular grafts biopolymers physiological forces compliance burst pressure

1. Constructional Parameters

It is challenging to design ideal 3D scaffolds that replicate the properties of extracellular matrix (ECM); thus, electrospinning is becoming more popular for making vascular grafts due to its potential to create scaffolds with micro/nano-scale topography, high surface area-to-volume proportions, and highly interconnected pores. Researchers can optimize the properties of prostheses and produce scaffolds with higher cell infiltration and proliferation and adequate mechanical properties by modifying the construction parameters of fibrous scaffolds by altering the electrospinning parameters [1].

1.1. Fiber Diameter, Pore Size, Porosity, and Permeability

Ideal scaffolds are frequently fabricated to be very porous for cell diffusion, nutrient and oxygen delivery, and metabolic disposal of wastes to promote the development of targeted neotissues [2]. Small pore sizes are the major issue concerning electrospinning because they result in inadequate cell penetration and compliance mismatch [3][4]. This issue can be resolved by regulating porosity using various techniques, including salt/polymer leaching, collector modification, post-treatment with laser radiation, and adjusting the electrospinning conditions. It has been demonstrated that the pore size of electrospun webs is directly associated with the fiber diameter, suggesting that the pore size increases with an increase in fiber diameter. Thus, the diameter of the fiber can be easily modified by changing electrospinning variables such as the polymer concentration, voltage, and solvent type [4]. Even though electrospun prostheses made of nanofibers have a greater capacity for cell adhesion and proliferation than scaffolds made of microfibers, they frequently have lower cell infiltration levels. This is typically due to the small pore sizes, complex distribution, and lack of pore connectivity of scaffolds made of nanofibers, which have an impact on long-term matrix regeneration. Thus, using microfibers and nanofibers together encourages cell adhesion and proliferation with the help of nanofibers and gives more void areas for cell penetration through less dense microfibers [5].
The pore size of vascular grafts is recognized as an essential design parameter in the production of tissue-engineered vascular grafts (TEVGs) because the vascular cells must be effectively settled with endothelial cells (ECs) on the lumen surface and smooth muscle cells (SMCs) in the outer layers. While ECs on the luminal surface prevent thrombosis, SMCs on the outer wall of vascular scaffolds support the scaffolds’ activities such as vasoconstriction and vasodilatation [6]. It is claimed that electrospun scaffolds with fiber diameters of more than 1 μm allow larger pore diameters and encourage cell penetration, whereas smaller fiber diameters of less than 1 μm dramatically restrict diffusion for the majority of cell types, and so the ideal pore diameter necessary for sufficient cellular penetration is greater than 10 μm [6][7][8]. Small pore diameters are acceptable for the ECs to accumulate, proliferate, and infiltrate on the graft surface, which encourages ECM regeneration; however, they hinder SMCs’ infiltration and colonization around the neo-vessel [6]. It has also been stated that the optimum scaffold pore diameter ranges from 5 to 500 μm since distinct cell types have unique dimensions and morphologies [9][10]. Large pores are ideal for better cell diffusion but can also promote blood leakage through the graft wall. With a homogeneous design, it is challenging to achieve a balance among enhanced tissue regeneration, decreased blood leakage, and sufficient mechanical characteristics; for this reason, multilayered vascular prostheses with different pore diameters have been thought to be useful [9]. Additionally, it is claimed that grafts with a porosity of 90% and pore sizes between 100 and 300 μm can effectively support cell adhesion and matrix development. When SMCs are cultured on these scaffolds, the mechanical behavior can be changed from elastic to viscoelastic, more closely approximating the mechanical characteristics of the native vessels [11].
The mechanical characteristics of the vascular scaffolds are also greatly influenced by the fiber diameter, pore size, and porosity, in addition to their biological impacts. Fluid permeability, thermal conductivity, diffusion coefficient, elastic modulus, yield, rupture, stiffness, fatigue resistance, and ductile strength are all significantly affected by porosity, a microstructural feature [12][13]. The superior mechanical properties are often seen in scaffolds with low porosity [14]. In nanofibrous scaffolds, mechanical characteristics are typically reported to decrease as porosity and pore diameter increase [15][16]. The stiff porous nanofibers located in the nanofibrous webs with strongly packed structures and enhanced molecular orientation have high tensile modulus and strength and low elongation at breakage. Reduced porosity and smaller pore sizes also improve the ductility of the material [17]. On the other hand, larger pore sizes lead to massive surrounding fibrous tissue accumulation post-implantation, which significantly reduces compliance, whereas low porosity limits endothelialization, negatively impacting antithrombogenicity [18]. The graft’s flexibility is reduced due to the extensive fibrous accumulation caused by the large pore diameters, and high-porosity scaffolds are weaker than low-porosity ones. On the other hand, sufficient porosity (>80%) is usually necessary to simulate vascular distensibility. A detailed examination of burst strength is also essential to bring a promising graft through the stages of in vivo investigation and further clinical studies [19][20]. Interestingly, it has been demonstrated that the burst strength can decrease significantly after a certain porosity level because the low-porosity scaffolds are too fragile to withstand high pressures [21]. The more flexible high-porosity scaffold had a larger strain at rupture, burst pressure, and suture retention strength than the low-porosity scaffold with more closely packed fibers. When Young’s modulus of the two grafts was compared, the low porosity graft had higher maximum stress and was stiffer than the high porosity grafts. On the other hand, bilayered grafts having layers of both high and low porosity exhibited performance outcomes that were comparable to those of monolayer grafts. Therefore, despite the use of the same polymer, different microarchitectures may provide mechanical properties that are noticeably different [22]. Additionally, the in vitro and in vivo mechanical performances of the grafts should be considered.
In addition to the porosity, pore size, and inner connectivity of pores, static permeability is another critical parameter that influences the penetration and proliferation of cells as vascular graft performance. The permeability affects the molecular exchange between the enclosed graft and the surrounding blood environment. Permeability depends on the electrospun scaffolds’ packing density, porosity, and pore size. Densely packed fibers result in poor porosity and permeability, which hinder cellular infiltration inside the scaffolds, thus limiting the penetration distance of cells. In these circumstances, the oxygen and nutrient diffusion is limited, and cells can survive only on the surface. A perfectly permeable vascular graft should prevent immunogenic molecules from entering and permit the free transportation of oxygen, essential nutrients, and metabolic waste of cells [23]. To maintain a cell’s expected growth, the permeability of TEVGs must be sufficient to transport oxygen and nutrients and export waste between the microenvironment of cells and the blood.

1.2. Fiber Orientation

Recent studies on the electrospinning of aligned fibers mainly concentrate on the configuration of the collector system, such as parallel electrodes, metal rotating discs, and mandrels. The main concerns of researchers are the linear velocity of the collector surface and the effects of the collection settings on the electric field. It has been stated that the electrical properties of the solvent, along with the collector speed, have a significant impact on the level of fiber orientation [24]. It is challenging to achieve the high speeds greater than 10,000 min−1 required to obtain fiber orientation by using rotating mandrels with diameters less than 6 mm. As a result, large-diameter rotating collectors (630 mm, 100 mm, 32 mm, and 640 mm) were used in many studies to achieve high rotational speeds and eliminate the resonance frequency concern [25]. It has also been shown in the literature that the polymer type is another factor that affects the aligned fiber morphology. Some polymers can align crimp-like, whereas others are oriented in the flat form [26].
Fiber orientation has been regarded as one of the most important characteristics of scaffolds since it affects both cellular orientation and the mechanical characteristics of prostheses used as vascular grafts [27][28]. The main factor influencing cell development behavior is fiber orientation, and cells on scaffolds typically create a phenotypic morphology and grow effectively based on fiber alignment [29][30]. Furthermore, it has been demonstrated in studies that radially oriented fibers encourage SMC penetration and alignment [31].
On the other hand, there is a significant correlation between the radial elastic modulus of the tubular scaffolds and the direction of fiber orientation. Circumferentially aligned fibers provide higher radial elastic modulus, and the Poisson effect confirms the distribution of fiber orientations in terms of mechanical characteristics [32]. In contrast to their orientated counterparts, randomly distributed fibers significantly improve the suture retention strength (SRS). This result is unexpected as efficient scaffold designs are usually approached with orientation to enhance mechanical properties. Thus, a multilayer strategy for vascular substitutes with carefully selected fiber orientations is necessary to provide the ideal balance of compliance, burst pressure strength, and SRS, particularly at the anastomotic site [33]. Modifying fiber orientation enables the control of graft compliance [34]. Oriented fibers display better modulus, tensile strength, and burst strength values, as well as reduced compliance when strained in the direction of orientation, which is related to the stiff structure of the material [35].

1.3. Wall Thickness

Along with the previously mentioned factors, wall thickness is a crucial factor in designing vascular grafts since it affects the biomechanical characteristics, compliance, burst pressure resistance, and biological activities. Native vessels are reported to have walls with thicknesses ranging between 400 and 1000 μm [36]. Increasing the electrospinning duration will result in larger walls for the vascular scaffolds, significantly enhancing their circumferential tensile strength and suture retention strength [37]. Suture movement is more challenging in grafts with thicker walls, which provide increased fiber overlapping and enhanced binding force. However, the increased wall thickness is unfavorable for graft porosity and compliance [38]. Vascular grafts with a thinner wall thickness are more permeable and have greater mass transfer than the ones with a greater wall thickness in vivo. Hence, they have better cell proliferation and attachment performance than grafts constructed with thick layers [39]. Additionally, studies have demonstrated that as wall thickness is increased, vascular graft compliance decreases [40]. Compliance mismatch among the synthetic vascular scaffold and the native blood vessel also causes a change in hemodynamics, which then affects wall shear stress (WSS) and creates irregular flow patterns. Thus, undesirable biological responses are triggered by inconsistent mechanical signals that result in intimal hyperplasia [41]. In several investigations, the wall thickness has been decreased to produce compliant grafts similar to the native vessels; nevertheless, this can lead to poor bursting strength, which might not be adequate for implantation. The thickness of the graft wall also has an impact on blood permeability and graft handling during surgical procedures. Hence, it may be challenging to achieve a proper balance between all mechanical and biological properties and design parameters, especially blood leakage, cell permeability, burst strength, and compliance, when deciding on the wall thickness of the vascular grafts [42]. This makes determining the ideal wall thickness for vascular grafts extremely important.

1.4. Number of Layers

As previously mentioned, vascular tissue engineering aims to imitate the construction and activities of native vessels that are composed of three layers known as the tunica intimatunica media, and tunica adventitia, which provide high strength, elasticity, and compliance as well as outstanding hemodynamic function and anti-thrombogenicity [43]. Different roles are accomplished by each layer within the blood vessels. For instance, the endothelium layer of a native blood vessel is a well-organized monolayer, and the alignment of endothelial cells can regulate biological signaling such as intracellular protein expression, cytoskeleton development, and cellular interactions, whereas the middle layer involves spindle-shaped and circumferentially oriented SMCs that significantly affect the elasticity, mechanical strength, and vasoactive reactivity of blood vessels [44]. The reported mechanical and biological incompatibility of monolayered electrospun vascular scaffolds has led to the development of vascular prostheses with multilayers as an alternative technique for mimicking the characteristics of these layers [45]. In this regard, the middle and outermost layers should have a higher porosity to encourage SMC migration, whereas the inner layer should have a lower porosity to promote EC proliferation and limit blood permeability [46]. According to the researchers, creating multi-layered vascular scaffolds that imitate the mechanical and structural features of the native vessel walls is a useful way to mimic the functions of the media and intima layers [44][47]. Additionally, fabricating synthetic vascular scaffolds consisting of multiple layers with unique mechanical characteristics enables achieving a particular J-shaped stress–strain curve as in native blood vessels that show non-linear stress–strain behavior that provides the vessel’s resilience and, as a result, helps prevent aneurysms [48]. Due to the integrated mechanical features of the layers, the composite effect has been observed in stress–strain graphs in the work by Yalcin Enis et al. [25] by creating bilayered scaffolds with layers of random and orientated fibers of PCL and PLC polymers with various molecular weights. Therefore, by optimizing the fiber diameter, fiber alignment, pore size, wall thickness, material type, or their combinations, multilayer designs should be created to meet the requirements of vascular grafts in separate layers.

2. Material Selection

Synthetic vascular grafts made of non-biodegradable materials, including expanded polytetrafluoroethylene (ePTFE), Dacron, and PU, which are commercially utilized, are not suitable for manufacturing grafts with diameters smaller than 6 mm, which are required to replace the saphenous vein, internal mammary artery, or radial artery as a vascular substitute because of poor patency, compliance mismatch, thrombosis, and ineffective neo-vessel development [31][49][50]. The drawbacks of currently available materials have prompted scientists to design biodegradable synthetic vascular grafts to enhance native vessel regeneration and reconstitute a functional arterial composition. However, when employed in animal experiments, these grafts have shown severe failure because of aneurysms, intimal hyperplasia, and thrombosis. These outcomes are probably brought on by the regenerated grafts with an insufficient amount of elastin [51].
Multiple biopolymers, including synthetic and natural ones, can be used to construct vascular grafts from electrospun fibers [52]. These materials are utilized to create a vascular scaffold that is physiologically suitable, and they should be chosen based on the graft structure, desirable biodegradation rate, and capacity for cell adhesion [53]. The material and architecture of small-caliber TEVGs have a significant impact on their biocompatibility, non-toxicity, non-immunogenicity, mechanical properties, ease of handling, and storability [54]. Furthermore, the scaffolds need to support host tissue remodelling and tissue regeneration during biodegradation and withstand inherent biological stresses as in biological systems to resist long-term issues including infection, intimal hyperplasia, stenosis, calcification, and aneurysmal dilatation [55]. While a rapid degradation rate may improve regeneration efficiency, it may also diminish tissue performance and damage mechanical qualities. In contrast, a slow degradation rate may hinder the development of neo-tissues. Therefore, it is essential to maintain a balance between the rates of vascular regeneration and biodegradation [56]. Additionally, the significance of in vivo foreign body responses of monocytes and macrophages to biomaterials is crucial for developing neo-vessels and thrombosis; as a result, strategies for material choice and manufacturing that control macrophage phenotype have drawn considerable attention [57]. Since it is normally impossible for one material to satisfy all of these qualities, mixing several polymers to form a hybrid graft seems to be an effective way to fabricate TEVGs [58]. These composite scaffolds can be thought of as innovative smart biomaterials that have the potential to produce TEVGs since they blend the advantages of natural polymers, including biocompatibility and biochemical capabilities, with the benefits of synthetic polymers, consisting of high strength, modifiability, and processability [59]. Some of the most commonly used biopolymers in vascular tissue engineering applications are given in Table 1, with their advantages and disadvantages.
Table 1. Some of the advantages and disadvantages of natural and synthetic biopolymers used in tissue engineering.
An ideal vascular graft should possess mechanical strength, compliance, suture retention strength, and a J-shaped mechanical response close to physiological levels. The mechanical responses of both passive (elastin and collagen fibers) and active components (SMCs) affect the mechanical reaction of the artery wall. When arteries are subjected to blood pressure, non-linear elastic behavior is seen as a J-shaped curve [89]. Many biomaterials and biological tissues have what is known as a J-shaped strain–stress curve, which illustrates how small increases in stress initially lead to enormous elongation, but as the material stretches further, it stiffens and becomes more difficult to stretch [90]. Elastin fibers are mainly responsible for the compliance of vessel walls at low pressures, whereas high stiffness is mainly caused by the mechanical reaction of collagen at high pressures. As pressure increases, collagen fibers start aligning and orienting, lowering arterial compliance. Therefore, utilizing collagen and elastin and mimicking their crimpy architecture appears to be a suitable method for creating a small-caliber vascular graft that simulates this mechanical reaction [89]. In order to provide sufficient compliance and structural integrity of TEVGs, the co-spinning of both elastin and collagen has been used as a strategy to imitate the artery’s three-layered architecture [91].
A natural contractile-like SMC phenotype can be differentiated to resemble the composition of native blood vessels by using ECM proteins such as collagen type I and insoluble elastin, which have superior viscoelastic capabilities. In addition to their outstanding biological features, natural polymers can be easily modified in terms of their mechanical characteristics and biodegradation rates through the change in their degree of crosslinking [92]. The polymers derived from ECM components collagen, elastin, fibrin, and gelatin are utilized to create TEVGs. There are many studies targeting the improvement of the integrity of collagen-based grafts to overcome the inadequate mechanical qualities, including anastomosis strength, burst pressure, and tensile strength. Elastin and gelatin grafts have similar behavior. In addition, dynamic culture has enhanced the mechanical behavior of fibrin grafts developed from in vitro-produced fibroblasts, providing compliance close to natural blood vessels [58]. The J-shaped mechanical behavior is generally achieved when natural biopolymers such as collagen, elastin, or fibrin are used.
However, natural polymers’ properties differ from sample to sample, and it might be challenging to find consistently suitable production conditions. They are also weak, which makes it tricky to withstand intense physiological forces. Although synthetic biopolymers with mechanical properties similar to collagen and elastin appear to be promising materials for replacement, using them in a neat form causes a decrease in compliance as stress increases. This makes achieving J-shaped reactions in vascular grafts difficult [89]. Some of the most studied synthetic biopolymers for vascular scaffolds are biodegradable polyesters, including PGA, PLA, PLLA, their copolymer PLGA, and PCL [93]. When compared to natural polymers, synthetic polymers have several advantages. First, they are simple to produce due to their physical and chemical characteristics. Despite their ability to help restore damaged tissue structure and activity, these biomaterials have limited cell attachment locations and thus need chemical modifications. The tensile strength, Young’s modulus, and degradation rate can be predicted and repeated over a wide range. These polymers vary in their degree of biodegradability, biocompatibility, and mechanical characteristics, but no single polymer provides the ideal mix of all of these crucial characteristics [94]. Therefore, utilizing various polymers to construct hybrid grafts that may offer ideal features similar to native vessels is considered a promising technique.
Tissue engineers have been able to adjust TEVG features thanks to various polymers and production methods, but choosing the ideal mix of graft properties is still difficult to accomplish [95]. Therefore, the design and material selection should be considered together rather than individually, as the scaffold’s characteristics depend on its morphology and material.


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