A hydrogel-fiber-hydrogel composite scaffold based on silk fibroin with the dual-delivery of oxygen and quercetin.

Supplying sufficient oxygen within the scaffolds is one of the essential hindrances in tissue engineering that can be resolved by oxygen-generating biomaterials (OGBs). Two main issues related to OGBs are controlling oxygenation and reactive oxygen species (ROS). To address these concerns, we developed a composite scaffold entailing three layers (hydrogel-electrospun fibers-hydrogel) with antioxidant and antibacterial properties. The fibers, the middle layer, reinforced the composite structure, enhancing the mechanical strength from 4.27 ± 0.15 to 8.27 ± 0.25 kPa; also, this layer is made of calcium peroxide and silk fibroin (SF) through electrospinning, which enables oxygen delivery. The first and third layers are physical SF hydrogels to control oxygen release, containing quercetin (Q), a nonenzymatic antioxidant. This composite scaffold resulted in almost more than 40 mmHg of oxygen release for at least 13 days, and compared with similar studies is in a high range. Here, Q was used for the first time for an OGB to scavenge the possible ROS. Q delivery not only led to antioxidant activity but also stabilized oxygen release and enhanced cell viability. Based on the given results, this composite scaffold can be introduced as a safe and controllable oxygen supplier, which is promising for tissue engineering applications, particularly for bone.

Preliminary evaluation of fish cartilage as a promising biomaterial in cartilage tissue engineering.

Fish cartilage is known as a valuable source of natural biomaterials due to its unique composition and properties. It contains a variety of bioactive components that contribute to its potential applications in different domains such as tissue engineering. The present work aimed to consider the properties of backbone cartilage from fish with a cartilaginous skeleton, including elasmobranch (reticulate whipray: Himantura uarnak and milk shark: Rhizoprionodon acutus) and sturgeon (beluga: Huso huso). The histomorphometric findings showed that the number of chondrocytes was significantly higher in reticulate whipray and milk shark compared to beluga (p < 0.05). The highest GAGs content was recorded in reticulate whipray cartilage compared to the other two species (p < 0.05). The cartilage from reticulate whipray and beluga showed higher collagen content than milk shark cartilage (p < 0.05), and the immunohistochemical assay for type II collagen (Col II) showed higher amounts of this component in reticulate whipray compared to the other two species. Young's modulus of the cartilage from reticulate whipray was significantly higher than that of milk shark and beluga (p < 0.05), while no significant difference was recorded between Young's modulus of the cartilage from milk shark and beluga. The gene expression of ACAN, Col II, and Sox9 showed that the cartilage-ECM from three species was able to induce chondrocyte differentiation from human adipose tissue-derived stem cells (hASCs). From these results, it can be concluded that the cartilage from three species, especially reticulate whipray, enjoys the appropriate biological properties and provides a basis for promoting its applications in the field of cartilage tissue engineering.

Cellulose nanocrystals-reinforced dual crosslinked double network GelMA/hyaluronic acid injectable nanocomposite cryogels with improved mechanical properties for cartilage tissue regeneration.

Improvement of mechanical properties of injectable tissue engineering scaffolds is a current challenge. The objective of the current study is to produce a highly porous injectable scaffold with improved mechanical properties. For this aim, cellulose nanocrystals-reinforced dual crosslinked porous nanocomposite cryogels were prepared using chemically crosslinked methacrylated gelatin (GelMA) and ionically crosslinked hyaluronic acid (HA) through the cryogelation process. The resulting nanocomposites showed highly porous structures with interconnected porosity (>90%) and mean pore size in the range of 130-296 µm. The prepared nanocomposite containing 3%w/v of GelMA, 20 w/w% of HA, and 1%w/v of CNC showed the highest Young's modulus (10 kPa) and excellent reversibility after 90% compression and could regain its initial shape after injection by a 16-gauge needle in the aqueous media. The in vitro results demonstrated acceptable viability (>90%) and migration of the human chondrocyte cell line (C28/I2), and chondrogenic differentiation of human adipose stem cells. A two-month in vivo assay on a rabbit's ear model confirmed that the regeneration potential of the prepared cryogel is comparable to the natural autologous cartilage graft, suggesting it is a promising alternative for autografts in the treatment of cartilage defects.

Bioinspired scaffolds based on aligned polyurethane nanofibers mimic tendon and ligament fascicles.

Topographical factors of scaffolds play an important role in regulating cell functions. Although the effects of alignment topography and three-dimensional (3D) configuration of nanofibers as well as surface stiffness on cell behavior have been investigated, there are relatively few reports that attempt to understand the relationship between synergistic effects of these parameters and cell responses. Herein, the influence of biophysical and biomechanical cues of electrospun polyurethane (PU) scaffolds on mesenchymal stem cells (MSCs) activities was evaluated. To this aim, multiscale bundles were developed by rolling up the aligned electrospun mats mimicking the fascicles of tendons/ligaments and other similar tissues. Compared to mats, the 3D bundles not only maintained the desirable topographical features (i.e., fiber diameter, fiber orientation, and pore size), but also boosted tensile strength (∼40 MPa), tensile strain (∼260%), and surface stiffness (∼1.75 MPa). Alignment topography of nanofibers noticeably dictated cell elongation and a uniaxial orientation, resulting in tenogenic commitment of MSCs. MSCs seeded on the bundles expressed higher levels of tenogenic markers compared to mats. Moreover, the biomimetic bundle scaffolds improved synthesis of extracellular matrix components compared to mats. These results suggest that biophysical and biomechanical cues modulate cell-scaffold interactions, providing new insights into hierarchical scaffold design for further studies.

Antibacterial aligned nanofibrous chitosan/PVA patch for repairing chronic tympanic membrane perforations.

Chronic tympanic membrane (TM) perforation is a consequence of trauma or chronic otitis media, and these chronic TM perforations often lead to conduction hearing loss. This study focuses on the development of a patch using a combination of chitosan (CS) and polyvinyl alcohol (PVA) as graft material for repairing chronic tympanic membrane (TM) perforations. Aligned nanofibers were created using a specially designed collector (SDC) through the electrospinning method. The scanning electron microscopy (SEM) analysis revealed that the CS/PVA ratio of (15:85) resulted in uniform and bead-free nanofibers. The aligned nanofibers had a diameter of 131.11 ± 28 nm, indicating that the influence of the electrostatic field introduced by the SDC affected not only the nanofiber alignment but also the nanofiber diameter. The nanofiber angles demonstrated effective alignment. This patch is infused with thyme essential oil (TEO) for antibacterial properties. The results showed that its antibacterial property for Pseudomonas aeruginosa bacteria was enhanced in such a way that the diameter of the antibacterial halo increased from zero to 25 mm. Cell viability assays showed >80 % viability. A preclinical case study on six patients demonstrated the biocompatibility and promising potential of the fabricated patch for eardrum repair.

Hemostatic Electrospun Nanocomposite Containing Poly(lactic acid)/Halloysite Nanotube Functionalized by Poly(amidoamine) Dendrimer for Wound Healing Application: In Vitro and In Vivo Assays.

The main challenge in treating injuries is excessive bleeding whereas intervention is required if the body's hemostatic systems fail to control the bleeding. Herein, a novel nanocomposite consisting of poly(lactic acid) (PLA) and poly(amidoamine) (PAMAM) dendrimer functionalized halloysite nanotube (HNT) with a highly porous structure via electrospinning is developed. HNT is functionalized by PAMAM via divergent synthetic routes from zero to third-generation numbers. The effect of different percentages and generation numbers of PAMAM dendrimer (G1, G2, and G3) functionalized HNT on PLA is studied using physicochemical nanocomposite characteristics. These resultant nanocomposites provide a nanofibrous structure with appropriate physicochemical characteristics such as mechanical properties, surface wettability, and water permeability. The hemostatic assays indicate that nanocomposite with PAMAM G3 functionalized HNT have the quickest blood clotting time due to the abundant amino functional group. Furthermore, the nanocomposites with 10 wt% of nanoparticles significantly promote cellular behavior in vitro. The in vivo study demonstrates that PLA/PAMAM G3 functionalized HNT promotes angiogenesis, collagen deposition, and re-epithelialization in the wound sites of the rat model, as well as inhibiting inflammatory response. The findings indicate that nanofibrous structure and the presence of dendrimer functionalized HNT have a synergetic effect on the enhanced nanocomposite wound healing performance.

A novel substrate based on electrospun polyurethane nanofibers and electrosprayed polyvinyl alcohol microparticles for recombinant human erythropoietin delivery.

After myocardial infarction caused by a heart attack, endothelial cells need to be preserved in order to regenerate new capillaries. Moreover, sufficient mechanical support is necessary for the infarcted myocardium to pump the blood. Herein, we designed a novel substrate containing polyurethane (PU) nanofibrous layers and recombinant human erythropoietin (rhEPO)-loaded microparticles for both controlled releases of rhEPO and mechanical support of myocardium. In this system, the single-layer (SL) and double-layer (DL) PU nanofibers were electrospun, and then microparticles with different rhEPO:polyvinyl alcohol (PVA) ratios were electrosprayed on the layers. The in vitro release behavior of rhEPO from SL substrates was not satisfactory, and then the study focused on DL patches in which the release profile was in accordance with Korsmeyer-Peppas model. The release exponent of 0.89 for the DL PU/120PVA:1rhEPO represented zero-order release. The results inferred that these substrates possessed highly tailored mechanical properties; Young's modulus and ultimate tensile strength of the substrates were 74-172 kPa and 7.4-9.9 MPa, respectively. The rhEPO release from the substrates was leading to the proper adhesion of endothelial cells and more than 95% cell viability. The results indicated that the patch of elastic nanofibers and microparticles offered a potential substrate for simultaneous rhEPO delivery to endothelial cells and also mechanically supporting the infarcted myocardium.

Application of plasma surface modification techniques to improve hemocompatibility of vascular grafts: A review.

Surface modification using plasma processing can significantly change the chemical and physical characteristics of biomaterial surfaces. When used in combination with additional modification techniques such as direct chemical or biochemical methods, it can produce novel biomaterial surfaces, which are anticoagulant, bioactive, and biomimetic in nature. This article reviews recent advances in improving hemocompatibility of biomaterials by plasma surface modification (PSM). The focus of this review is on PSM of the most commonly used polymers for vascular prostheses such as expanded polytetrafluoroethylene (PTFE), polyethylene terephthalate (Dacron(®) ), and next generation of biomaterials, including polyhedral oligomeric silsesquioxane nanocomposite.

Surface modification of POSS-nanocomposite biomaterials using reactive oxygen plasma treatment for cardiovascular surgical implant applications.

In this study, central composite design (CCD) was used to develop predictive models to optimize operating conditions of plasma surface modification. It was concluded that out of the two process variables, power and duration of plasma exposure, the latter was significantly affecting the surface energy (γ(s) ), chemistry, and topography of polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU) films. On the basis of experimental data, CCD was used to model the γ(s) using a quadratic modeling of the process variables to achieve optimum surface energy to improve the interaction between endothelial cells (ECs). It was found that optimal water θ for EC adhesion and retention, which was reported 55° from supporting literature (equivalent to γ(s) = 51 mN/m), was easily achievable using the following experimental conditions: (1) power output at 30 W for 75 Sec, (2) 90 W for 40 Sec, and (3) 90 W for 55 Sec in oxygen. In vitro cell culture and metabolic activity studies on optimized films [as in (1)] demonstrate increased adhesion, coverage, and growth of human umbilical vein endothelial cells that were confluent over a shorter time period (<24 H) than controls. Such materials enhanced the EC response and promoted endothelialization on optimized films, thus demonstrating their use as bypass graft materials.

Amine-terminated dendritic polymers as promising nanoplatform for diagnostic and therapeutic agents' modification: A review.

It is often challenging to design diagnostic and therapeutic agents that fulfill all functional requirements. So, bulk and surface modifications as a common approach for biomedical applications have been suggested. There have been considerable research interests in using nanomaterials to the prementioned methods. Among all nanomaterials, dendritic materials with three-dimensional structures, host-guest properties, and nano-polymeric dimensions have received considerable attention. Amine-terminated dendritic structures including, polyamidoamine (PAMAM), polypropyleneimine (PPI), and polyethyleneimine (PEI), have been enormously utilized in bio-modification. This review briefly described the structure of these three common dendritic polymers and their use to modify diagnostic and therapeutic agents in six major applications, including drug delivery, gene delivery, biosensor, bioimaging, tissue engineering, and antimicrobial activity. The current review covers amine-terminated dendritic polymers toxicity challenging and improvement strategies as well.

Ionic conductive nanocomposite based on poly(l-lactic acid)/poly(amidoamine) dendrimerelectrospun nanofibrous for biomedical application.

The modification of poly (l-lactic acid) (PLLA) electrospun nanofibrous scaffolds was carried out by blending with second-generation poly amidoamine (PAMAM) for enhancement of their ionic conductivity. The samples containing PLLA and various amounts of PAMAM (1%, 3%, 5%, and 7% by wt.) were fabricated by electrospinning techniques. The electrospun fibers were characterized using scanning electron microscopy (SEM), porosity, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry, contact angle measurement, water uptake measurement, mechanical properties, and electrical properties. Furthermore,in vitrodegradation study and cell viability assay were investigated in biomaterial applications. Creating amide groups through aminolysis reaction was confirmed by FTIR analysis successfully. The results reveal that adding PAMAM caused an increase in fiber diameter, crystallinity percentage, hydrophilicity, water absorption, elongation-at-break, and OE-mesenchymal stem cell viability. It is worth mentioning that this is the first report investigating the conductivity of PLLA/PAMAM nanofiber. The results revealed that by increasing the amount of PAMAM, the ionic conductivity of scaffolds was enhanced by about nine times. Moreover, the outcomes indicated that the presence of PAMAM could improve the limitations of PLLA like hydrophobicity, lack of active group, and poor cell adhesion.

Electrospun polyurethane/carbon nanotube composites with different amounts of carbon nanotubes and almost the same fiber diameter for biomedical applications.

The aim of this study was to investigate the net effect of raw carbon nanotube (CNTs) on the final properties of polyurethane (PU)/CNT composites considering their biomedical applications. So, neat PU and PU/CNT composites containing different amounts of CNTs (0.05%, 0.1%, 0.5%, and 1%) were prepared by electrospinning. Electrospinning parameters optimized to have a bead-free structure with no significant difference between their mean fiber diameter and porosity percentage. The results showed adding CNTs caused an increase in crystallinity percentage, water absorption ratio, young modulus, toughness, conductivity, degradation time in an accelerated medium, clotting time, and human umbilical vein endothelial cells adhesion. But a direct relationship between CNT percentage and the calcium adsorption was not detected. Moreover, no significant cytotoxicity was observed for 7-day extracts of all samples. These nanocomposites have a vast range of properties which make them a good candidate as neural, cardiovascular, osseous biomaterials or tendon, and ligament substitute.

Fabrication of nanocomposite/nanofibrous functionally graded biomimetic scaffolds for osteochondral tissue regeneration.

One of the main challenges in treating osteochondral lesions via tissue engineering approach is providing scaffolds with unique characteristics to mimic the complexity. It has led to application of heterogeneous scaffolds as a potential candidate for engineering of osteochondral tissues, in which graded multilayered-structure should promote bone and cartilage growth. By designing three-dimensional (3D)-nanofibrous scaffolds mimicking the native extracellular matrix's nanoscale structure, cells can grow in controlled conditions and regenerate the damaged tissue. In this study, novel 3D-functionality graded nanofibrous scaffolds composed of five layers based on different compositions containing polycaprolactone(PCL)/gelatin(Gel)/nanohydroxyapatite (nHA) for osteoregeneration and chitosan(Cs)/polyvinylalcohol(PVA) for chondral regeneration are introduced. This scaffold is fabricated by electrospinning technique using spring as collector to create 3D-nanofibrous scaffolds. Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, scanning electron microscopy, mechanical compression test, porosimetry, and water uptake studies were applied to study each layer's physicochemical properties and whole functionally graded scaffold. Besides, biodegradation and biological studies were done to investigate biological performance of scaffold. Results showed that each layer has a fibrous structure with continuous nanofibers with improved pore size and porosity of novel 3D scaffold (6-13 µm and 90%) compared with two-dimensional (2D) mat (2.2 µm and 19.3%) with higher water uptake capacity (about 100 times of 2D mat). Compression modulus of electrospun scaffold was increased to 78 MPa by adding nHA. The biological studies revealed that the layer designed for osteoregeneration could improve cell proliferation rate in comparison to the layer designed for chondral regeneration. These results showed such structure possesses a promising potential for the treatment of osteochondral defects.

Crosslinking strategies for silk fibroin hydrogels: promising biomedical materials.

Due to their strong biomimetic potential, silk fibroin (SF) hydrogels are impressive candidates for tissue engineering, due to their tunable mechanical properties, biocompatibility, low immunotoxicity, controllable biodegradability, and a remarkable capacity for biomaterial modification and the realization of a specific molecular structure. The fundamental chemical and physical structure of SF allows its structure to be altered using various crosslinking strategies. The established crosslinking methods enable the formation of three-dimensional (3D) networks under physiological conditions. There are different chemical and physical crosslinking mechanisms available for the generation of SF hydrogels (SFHs). These methods, either chemical or physical, change the structure of SF and improve its mechanical stability, although each method has its advantages and disadvantages. While chemical crosslinking agents guarantee the mechanical strength of SFH through the generation of covalent bonds, they could cause some toxicity, and their usage is not compatible with a cell-friendly technology. On the other hand, physical crosslinking approaches have been implemented in the absence of chemical solvents by the induction of ß-sheet conformation in the SF structure. Unfortunately, it is not easy to control the shape and properties of SFHs when using this method. The current review discusses the different crosslinking mechanisms of SFH in detail, in order to support the development of engineered SFHs for biomedical applications.

Electrospun PET/PCL small diameter nanofibrous conduit for biomedical application.

In recent years, the mortality rate caused by cardiovascular diseases has increased dramatically around the world. Tissue engineering is considered as a novel and efficient approach to offer a substituent of engineered tissues for defective body tissues. For this purpose, fabrication of the scaffold that resembles the physical and mechanical properties of natural body vessels, and culturing appropriate cells seems to be a promising approach. Due to the fibrous structure of the vascular wall, the nanofibrous scaffold produced by electrospinning could be a proper choice for vascular tissue engineering. One of the main properties of artificial vessels is its mechanical properties consistency with the native one in order to mimic its natural characteristics. To do so, in present study two biocompatible polymers, polyethylene terephthalate (PET) and polycaprolactone (PCL) with different blend ratio were electrospun into a tubular nanofibrous structure with 6 mm internal diameter and the mechanical properties such as tensile strength, modulus, compliance, bursting pressure, elastic recovery, and suture retention were investigated. The results revealed that PET/PCL (1:3) had better similar properties with the reported natural one as its longitudinal and transverse tensile strength was about 9.47 and 6.38 MPa, respectively. The longitudinal strain at break, compliance, bursting pressure, and suture retention were 205.88 ± 51.12%, 4.19 ± 0.78%/100 mmHg, 6378.76 ± 2159.20 mmHg, and 287.73 ± 13.10 gmf, respectively. The elasticity of this studied sample was 60.21 ± 12.49% as it was relieved, and this may be a good candidate for the artificial vessel in this size, as the MTT test confirmed its appropriate substrate for cell culture.

Biomimetic double-sided polypropylene mesh modified by DOPA and ofloxacin loaded carboxyethyl chitosan/polyvinyl alcohol-polycaprolactone nanofibers for potential hernia repair applications.

Polypropylene (PP) meshes are the most widely used as hernioplasty prostheses. As far as hernia repair is concerned, bacterial contamination and tissue adhesion would be the clinical issues. Moreover, an optimal mesh should assist the healing process of hernia defect and avoid undesired prosthesis displacements. In this present study, the commercial hernia mesh was modified to solve the mentioned problems. Accordingly, a new bi-functional PP mesh with anti-adhesion and antibacterial properties on the front and adhesion properties (reduce undesired displacements) on the backside was prepared. The backside of PP mesh was coated with polycaprolactone (PCL) nanofibers modified by mussel-inspired L-3,4-dihydroxyphenylalanine (L-DOPA) bioadhesive. The front side was composed of two different nanofibrous mats, including hybrid and two-layered mats with different antibacterial properties, drug release, and biodegradation behavior, which were based on PCL nanofibers and biomacromolecule carboxyethyl-chitosan (CECS)/polyvinyl alcohol (PVA) nanofibers containing different ofloxacin amounts. The anti-adhesion, antibacterial, and biocompatibility studies were done through in-vitro experiments. The results revealed that DOPA coated PCL/PP/hybrid meshes containing ofloxacin below 20 wt% possessed proper cell viability, AdMSCs adhesion prevention, and excellent antibacterial efficiency. Moreover, DOPA modifications not only enhanced the surface properties of the PP mesh but also improved cell adhesion, spreading, and proliferation.

Multilayer nanofibrous patch comprising chamomile loaded carboxyethyl chitosan/poly(vinyl alcohol) and polycaprolactone as a potential wound dressing.

Electrospun multilayer nanofibrous patches with a new design were developed using poly(ε-caprolactone) (PCL) and chamomile loaded carboxyethyl chitosan (CECS) and polyvinyl alcohol (PVA) in which chamomile extract was used as an antioxidant/antibacterial agent. To prepare an aqueous solution (water as solvent) from chitosan and PVA along with the herbal extract, chitosan was modified to CECS by Michael reaction and proved by 1H NMR and FTIR. Multilayer patches composed of a hydrophilic chamomile loaded CECS/PVA nanofibrous layer to be in contact with the wound and a hydrophobic PCL nanofibrous layer to provide the strength were electrospun. Hybrid nanofibers made of PCL and chamomile/CECS/PVA were electrospun as cohesion promoter between the hydrophilic and hydrophobic layers due to their different chemical nature and weak cohesion. SEM showed continuous, smooth, and bead-free nanofibers with excellent compatibility between polymers and chamomile. The mats exhibited satisfactory tensile strength (8.2-16.03 MPa), and antioxidant characteristics (6.60-38.01%). Furthermore, 15, 20, and 30 wt% chamomile loaded mats possessed high antibacterial efficiency, which enhanced with increasing chamomile content. The results demonstrated that chamomile sustained-release significantly controlled by Fickian-Diffusion mechanism. MTT assay revealed proper cell viability for all mats except one contained 30 wt% chamomile.

A comparison of the material properties of natural and synthetic vascular walls.

Characterization of the mechanical properties of native and synthetic vascular grafts is an essential task in the process of designing novel vascular constructs. The aim in this study was to compare the mechanical behavior of ovine left Subclavian artery with that of POSS-PCU (a commercial biomaterial which is currently under clinical investigation. ClinicalTrials.gov Identifier: NCT02301312). We used Delfino's strain energy potential within the framework of quasilinear viscoelasticity theory to capture the viscoelastic response of the considered materials. The material parameters of the quasilinear viscoelastic constitutive equation were determined through a combination of experimental and computational method. First, a uniaxial tensile testing device was used to perform a series of stress relaxation tests on ring samples. Then, the derived quasilinear viscoelastic models were implemented into finite element system. With the aid of mechanical experimentation and finite element simulation, the material parameters were obtained, modified and used for comparison of the mechanical properties of vascular walls. The results showed that the stiffness and the long term viscoelastic parameters of POSS-PCU may lead to different stress responses of the vascular walls. These two factors can be improved by modifications in manufacturing parameters of the synthetic vessel.

Biomimetic modification of polyurethane-based nanofibrous vascular grafts: A promising approach towards stable endothelial lining.

The emerging demand for small caliber vascular grafts to replace damaged vessels has attracted research attention. However, there is no perfect replacement in clinical use yet, mainly due to low patency rate of synthetic small caliber grafts. The main pathology behind low patency rate include thrombosis and graft/vessel hemodynamic mismatch, leading to intimal hyperplasia. Rapid in-situ endothelialization of vascular grafts is considered as one of the best strategies to overcome these complications. In the present study, Heparin and VEGF were immobilized via self-polymerization and deposition of polydopamine (PDA) on polyurethane (PU) nanofibrous scaffolds to improve endothelialization. Polyurethane nanofibrous scaffold (PUNF) that mimics vascular extracellular matrix (ECM) was chosen owing to its biocompatibility, biodegradability. Scanning electron microscopy (SEM), water contact angle (CA) measurement and Raman spectroscopy were used to characterize the surface, and tensile test was used to analyze mechanical properties before and after surface modification of the scaffolds. It was found that tensile strength and young's modulus were significantly increased after PDA coating on PUNF membranes. The hemocompatibility tests revealed that surface heparinization significantly inhibited the adhesion of platelet on the scaffolds. Immobilization of VEGF on the scaffolds significantly enhanced the proliferation of human umbilical vein endothelial cells (HUVECs) through enhanced cells adhesion and improved cell-scaffold interactions. The results suggest that dual-factor immobilization resulted in not only confluent monolayer of endothelial cells but also conferred excellent antithrombotic properties to the surface. This method of surface modification (immobilization of Heparin, VEGF by PDA layer) is suggested as a promising modification technique to increase hemocompatibility of small-diameter vascular grafts.