PET Graft Research Articles

Time-programmed release of curcumin and Zn2+ from multi-layered RSF coating modified PET graft for improvement of graft-host integration

Artificial graft serves as the primary grafts used in the clinical management of sports-related injuries. Until now, optimizing its graft-host integration remains a great challenge due to the excessive inflammatory response during the inflammatory phase, coupled with an absence of tissue-inductive capacity during the regeneration phase. Here, a multi-layered regenerated silk fibroin (RSF) coating loaded with curcumin (Cur) and Zn2+ on the surface of the PET grafts (Cur@Zn2+@PET) was designed and fabricated for providing time-matched regulation specifically tailored to address issues arising at both inflammatory and regeneration phases, respectively. The release of Cur and Zn2+ from the Cur@Zn2+@PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn2+@PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1β. Meanwhile, a significant release of Zn2+ was major part during the regeneration phase, serving to induce the osteogenic differentiation of rBMSC. Furthermore, rat model of anterior cruciate ligament reconstruction (ACLR) showed that through time-programmed drug release, Cur@Zn2+@PET could suppress the formation of fibrous interface (FI) caused by inflammatory response, combined with significant new bone (NB) formation during regeneration phase. Consequently, the implementation of the Cur@Zn2+@PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries.

Potential of poly(alkylene terephthalate)s to control endothelial cell adhesion and viability

Poly(ethylene terephthalate) (PET) is known for its various useful characteristics, including its applicability in cardiovascular applications, more precisely as synthetic bypass grafts for large diameter (≥ 6 mm) blood vessels. Although it is widely used, PET is not an optimal material as it is not interactive with endothelial cells, which is required for bypasses to form a complete endothelium. Therefore, in this study, poly(alkylene terephthalate)s (PATs) have been studied. They were synthesized via a single-step solution polycondensation reaction, which requires mild reaction conditions and avoids the use of a catalyst or additives like heat stabilizers. A homologous series was realized in which the alkyl chain length varied from 5 to 12 methylene groups (n = 5–12). Molar masses up to 28,000 g/mol were obtained, while various odd-even trends were observed with modulated differential scanning calorimetry (mDSC) and rapid heat-cool calorimetry (RHC) to access the thermal properties within the homologous series. The synthesized PATs have been subjected to in vitro cell viability assays using Human Umbilical Vein Endothelial Cells (HUVECs) and Human Dermal Microvascular Endothelial Cells (HDMECs). The results showed that HUVECs adhere and proliferate most pronounced onto PAT(n=9) surfaces, which could be attributed to the surface roughness and morphology as determined by atomic force microscopy (AFM) (i.e. Rq = 204.7 nm). HDMECs were investigated in the context of small diameter vessels and showed superior adhesion and proliferation after seeding onto PAT(n=6) substrates. These preliminary results already pave the way towards the use of PAT materials as substrates to support endothelial cell adhesion and growth. Indeed, as superior endothelial cell interactivity compared to PET was observed, time-consuming and costly surface modifications of PET grafts could be avoided by exploiting this novel material class.

Lubricant-Infused PET Grafts with Built-In Biofunctional Nanoprobes Attenuate Thrombin Generation and Promote Targeted Binding of Cells.

New surface coatings that enhance hemocompatibility and biofunctionality of synthetic vascular grafts such as expanded poly(tetrafluoroethylene) (ePTFE) and poly(ethylene terephthalate) (PET) are urgently needed. Lubricant-infused surfaces prevent nontargeted adhesion and enhance the biocompatibility of blood-contacting surfaces. However, limited success has been made in incorporating biofunctionality onto these surfaces and generating biofunctional lubricant-infused coatings that both prevent nonspecific adhesion and enhance targeted binding of biomolecules remains a challenge. Here, a new generation of fluorosilanized lubricant-infused PET surfaces with built-in biofunctional nanoprobes is reported. These surfaces are synthesized by starting with a self-assembled monolayer of fluorosilane that is partially etched using plasma modification technique, thereby creating a hydroxyl-terminated fluorosilanized PET surface. Simultaneously, silanized nanoprobes are produced by amino-silanizing anti-CD34 antibody in solution and directly coupling the anti-CD34-aminosilane nanoprobes onto the hydroxyl terminated, fluorosilanized PET surface. The PET surfaces are then lubricated, creating fluorosilanized biofunctional lubricant-infused PET substrates. Compared with unmodified PET surfaces, the designed biofunctional lubricant-infused PET surfaces significantly attenuate thrombin generation and blood clot formation and promote targeted binding of endothelial cells from human whole blood.

Development of Small-diameter Polyester Vascular Grafts Coated with Silk Fibroin Sponge

ABSTRACTIn recent years, the demand for functional small-diameter (< 6 mm) artificial vascular grafts has greatly increased due to an increase in the number of patients with vascular heart disease. However, currently, there are no available commercial small-diameter grafts. The objective of this research was to develop a porous silk fibroin (SF)-coated poly(ethylene terephthalate) (PET) graft with a diameter < 6 mm. The graft was compared with a gelatin-coated PET graft because the latter PET graft with a diameter ~ 6 mm was widely used as a commercial vascular graft. Initially, porous SF was prepared using Glyc as the porogen [termed SF(Glyc)] and the PET grafts were prepared through the double-Raschel knitting method. Subsequently, the degradation of the SF coating was monitored using protease XIV in vitro and was compared with that observed in gelatin-coated PET grafts. Finally, these grafts were also implanted into rats for an in vivo comparison. In degradation experiments, after 7 days, the SF was clearly digested by protease XIV, but the gelatin on the graft was still remained at the outer surface. In implantation experiments in rats, the SF(Glyc)-coated PET graft was rapidly degraded in vivo and remodeling to self-tissues was promoted compared with the gelatin-coated PET graft. Thrombus formation and intimal hyperplasia were observed in the gelatin-coated PET graft; however, such side reactions were not observed in the SF(Glyc)-coated PET graft. Thus, the porous SF(Glyc)-coated PET graft with a small diameter < 6 mm may be useful as a commercial vascular graft.

Abstract 132: Application of a Cryogel-Coated Prosthetic Vascular Graft Material for Delivery of Targeted Gene Therapies in a Rabbit Model

Objectives: Long-term success of prosthetic grafts (PG) in peripheral arterial disease is limited by development of anastomotic neointimal hyperplasia. We have constructed a bioactive prosthetic graft material (BPGM) capable of delivering biologic agents in vitro, and evaluate our BPGM in vivo with a rabbit carotid interposition bypass model. Methods: We synthesized our BPGM by cryopolymerization of RGD with methacrylated alginate and heparin, coating 1.5cm by 2mm electrospun PET (ePET) grafts, and dipcoating in fluorescent siRNA for 3 hours. Three rabbits received bare ePET and 3 received cryogel-coated ePET for a carotid interposition bypass (Figure 1). After 24 hours, bypass patency was assessed, and cell toxicity of the proximal anastomosis, mid-graft, and distal anastomosis examined with H&amp;E staining. Confocal microscopy was used to visualize fluorescence, correlating with ability to deliver siRNA in vivo. Results: Graft patency was equal between groups, with no increased cell toxicity in rabbits receiving cryogel-coated ePET. Confocal microscopy demonstrated no difference in retained fluorescence between rabbits receiving cryogel-coated or bare ePET, and no increased transfection of cells at 24 hours (Figure 2). Conclusion: Creation of the optimal PG demands a material that is biocompatible, responsive, and nonthrombogenic. We have constructed a modified PG capable of in vitro delivery of targeted gene therapies, with comparable patency and biocompatibility in our large animal model. Additional optimization to achieve predictable and sustained release is needed to validate this as an effective and practical method to deliver biologic agents in vivo.

Effect of PET graft coated with silk fibroin via EDC/NHS crosslink on graft-bone healing in ACL reconstruction

SF coating via EDC/NHS crosslink improved the osseointegration of PET ligaments within the bone tunnel.

Compliance Study of Endovascular Stent Grafts Incorporated with Polyester and Polyurethane Graft Materials in both Stented and Unstented Zones.

Compliance mismatch between stent graft and host artery may induce complications and blood flow disorders. However, few studies have been reported on stent graft compliance. This study aims to explore the deformation and compliance of stent graft in stented and unstented zones under three pressure ranges. Compliance of two stent grafts incorporated with polyurethane graft (nitinol-PU) and polyester graft (nitinol-PET) materials respectively were tested; the stents used in the two stent grafts were identical. For the circumferential deformation of the stent grafts under each pressure range, the nitinol-PET stent graft was uniform in both zones. The nitinol-PU stent graft was circumferentially uniform in the stented zone, however, it was nonuniform in the unstented zone. The compliance of the PU graft material was 15 times higher than that of the PET graft. No significant difference in compliance was observed between stented and unstented zones of the nitinol-PET stent graft regardless of the applied pressure range. However, for the nitinol-PU stent graft, compliance of the unstented PU region was approximately twice that of the stented region; thus, compliance along the length of the nitinol-PU stent graft was not constant and different from that of the nitinol-PET stent graft.

Covalent immobilization of lysozyme onto woven and knitted crimped polyethylene terephthalate grafts to minimize the adhesion of broad spectrum pathogens.

Graft-associated infections entirely determine the short-term patency of polyethylene terephthalate PET cardiovascular graft. We attempted to enzymatically inhibit the initial bacterial adhesion to PET grafts using lysozyme. Lysozyme was covalently immobilized onto woven and knitted forms of crimped PET grafts by the end-point method. Our figures of merit revealed lysozyme immobilization yield of 15.7 μg/cm(2), as determined by the Bradford assay. The activity of immobilized lysozyme on woven and knitted PET manifested 58.4% and 55.87% using Micrococcus lysodeikticus cells, respectively. Noteworthy, the adhesion of vein catheter-isolated Staphylococcus epidermidis decreased by 6- to 8-folds and of Staphylococcus aureus by 11- to 12-folds, while the Gram-negative Escherichia coli showed only a decrease by 3- to 4-folds. The anti-adhesion efficiency was specific for bacterial cells and no significant effect was observed on adhesion and growth of L929 cells. In conclusion, immobilization of lysozyme onto PET grafts can inhibit the graft-associated infection.

Mussel-Inspired Artificial Grafts for Functional Ligament Reconstruction.

The development of an artificial graft with distinct osteogenetic activity to enhance osseointegration and to induce the formation of biomimetic tissue structure for ligament reconstruction remains a significant challenge. Inspired by mussels, biomimetic calcium phosphate apatite/polydopamine hybridized-polyethylene terephthalate (APA/PDA-PET) grafts were successfully prepared. The efficacy and mechanism of APA/PDA-PET grafts to induce osseointegration were systematically investigated. The results from the in vitro study indicated that the prepared APA/PDA-PET grafts support the attachment of bone marrow stromal cells (BMSCs) and stimulate the proliferation and osteogenic/angiogenic differentiation of BMSCs via activation of the PKC/p-ERK1/2 signaling pathway. In vivo, histological and radiological results further demonstrate that the APA/PDA-PET grafts significantly improve osseointegration by inducing the formation of new bone tissue and the fibrocartilage transitional zone compared with pure PET grafts. In addition, the pull-out strength of the APA/PDA-PET grafts is significantly higher than that of the pure PET grafts 12 weeks after surgery. These results suggest that this mussel-inspired biomimetic method is an effective strategy for modifying artificial grafts, and the prepared APA/PDA-PET grafts, which possess a beneficial interface, can significantly improve in vivo osseointegration for ligament reconstruction via the synergistic effect of polydopamine and apatite.

Multifunctional network-structured film coating for woven and knitted polyethylene terephthalate against cardiovascular graft-associated infections

Multifunctional network-structured polymeric coat for woven and knitted forms of crimped polyethylene terephthalate PET graft was developed to limit graft-associated infections. A newly synthesized antibacterial sulfadimethoxine polyhexylene adipate-b-methoxy polyethylene oxide (SD-PHA-b-MPEO) di-block copolymer was employed. Our figures of merit revealed that the formed coat showed a porous topographic architecture which manifested paramount properties, mostly bacterial anti-adhesion efficiency and biocompatibility with host cells. Compared to untreated grafts, the coat presented marked reduction of adhered Gram-positive Staphylococcus epidermidis previously isolated from a patient's vein catheter by 2.6 and 2.3 folds for woven and knitted grafts, respectively. Similarly, bacterial anti-adhesion effect was observed for Staphylococcus aureus by 2.3 and 2.4 folds, and by 2.9 and 2.7 folds for Gram-negative Escherichia coli for woven and knitted grafts, respectively. Additionally, adhesion and growth characteristics of L929 cells on the modified grafts revealed no significant effect on the biocompatibility. In conclusion, coating of PET with (SD-PHA-b-MPEO) is a versatile approach offers the desired bacterial anti-adhesion effect and host biocompatibility.

Gene silencing in human aortic smooth muscle cells induced by PEI–siRNA complexes released from dip-coated electrospun poly(ethylene terephthalate) grafts

An excessive tissue response to prosthetic arterial graft material leads to intimal hyperplasia (IH), the leading cause of late graft failure. Seroma and abnormal capsule formation may also occur after prosthetic material implantation. The matricellular protein Thrombospondin-2 (TSP-2) has shown to be upregulated in response to biomaterial implantation. This study evaluates the uptake and release of small interfering RNA (siRNA) from unmodified and surface functionalized electrospun PET graft materials. ePET graft materials were synthesized using electrospinning technology. Subsets of the ePET materials were then chemically modified to create surface functional groups. Unmodified and surface-modified ePET grafts were dip-coated in siRNAs alone or siRNAs complexed with transfection reagents polyethyleneimine (PEI) or Lipofectamine RNAiMax. Further, control and TSP-2 siRNA–PEI complex treated ePET samples were placed onto a confluent layer of human aortic smooth muscle cells (AoSMCs).Complexation of all siRNAs with PEI led to a significant increase in adsorption to unmodified ePET. TSP-2 siRNA-PEI released from unmodified-ePET silenced TSP-2 in AoSMC. Regardless of the siRNA–PEI complex evaluated, AoSMC migrated into the ePET. siRNA–PEI complexes delivered to AoSMC from dip-coated ePET can result in gene knockdown. This methodology for siRNA delivery may improve the tissue response to vascular and other prosthetics.

Layer-by-layer hyaluronic acid-chitosan coating promoted new collagen ingrowth into a poly(ethylene terephthalate) artificial ligament in a rabbit medical collateral ligament (MCL) reconstruction model

The ideal artificial ligament graft should have favorable biocompatibility to facilitate cell adhesion, proliferation, and collagen regeneration. In this present study, surface modification was performed on a poly(ethylene terephthalate) (PET) artificial ligament graft by layer-by-layer (LBL) self-assembly coating of hyaluronic acid (HA) and chitosan (CS). The surface characterization of the ligament was examined using scanning electron microscopy, atomic force microscopy, and energy-dispersive X-ray spectroscopy. The results of in vitro culturing of human foreskin fibroblast cells supported the hypothesis that the LBL coating of CS-HA could promote the cell proliferation and adhesion on the sheets. A rabbit medical collateral ligament reconstruction model was used to evaluate the effect of this LBL coating in vivo. The final results proved that this LBL coating could significantly promote and enhance new collagen formation among the graft fibers. On the basis of these results, we conclude that such CS-HA assembly coating could enhance PET graft biocompatibility in vitro and in vivo, and a CS-HA-coated PET graft has considerable potential as a desirable substitute for ligament reconstruction.

Low Thrombogenicity Coating of Nonwoven PET Fiber Structures for Vascular Grafts

Vascular PET grafts (Dacron) have shown good performance in large vessels (≥ 6 mm) applications. To address the urgent unmet need for small-diameter (2-6 mm) vascular grafts, proprietary high-compliance nonwoven PET fiber structures were modified with various PEG concentrations using PVA as a cross-linking agent, to fabricate non-thrombogenic mechanically compliant vascular grafts. The blood compatibility assays measured through platelet adhesion (SEM and mepacrine dye) and platelet activation (morphological changes, P-selectin secretion, and TXB2 production) demonstrate that functionalization using a 10% PEG solution was sufficient to significantly reduce platelet adhesion/activation close to optimal literature-reported levels observed on carbon-coated ePTFE.

Titanium Dioxide Particle-induced Alkaline Degradation of Poly(ethylene Terephthalate): Application to Medical Textiles

Titanium dioxide induced degradation of bright high-tenacity poly(ethylene terephthalate) (PET:2GT) used in medical applications was investigated under both relaxed and stressed conditions. It was found that successive layers of the polymers were removed by hydrolysis as weight loss (%) was linear with the treatment time. However, owing to the presence of titanium dioxide, tenacity loss occurred and, therefore, at a given time of hydrolysis treatment, the breaking load loss (%) was greater than the weight loss (%). Scanning electron microscopy of the hydrolyzed PET showed that surface pitting occurred due to the presence of titanium dioxide. Larger pits formed on the surface of the stressed fibers than on the relaxed fibers. The findings suggest that the failure of numerous PET (Dacron) grafts, which have been responsible for many deaths, is due to the penetration of hydroxyl ions through the surface defects caused by titanium dioxide.

Computational mechanics of Nitinol stent grafts

A finite element analysis of tubular, diamond-shaped stent grafts under representative cyclic loading conditions for abdominal aortic aneurysm (AAA) repair is presented. Commercial software was employed to study the mechanical behavior and fatigue performance of different materials found in commercially available stent–graft systems. Specifically, the effects of crimping, deployment, and cyclic pressure loading on stent–graft fatigue life, radial force, and wall compliances were simulated and analyzed for two types of realistic but different Nitinol materials (NITI-1 and NITI-2) and grafts (expanded polytetrafluoroethylene—ePTFE and polyethylene therephthalate—PET). The results show that NITI-1 stent has a better crimping performance than NITI-2. Under representative cyclic pressure loading, both NITI-1 and NITI-2 sealing stents are located in the safe zone of the fatigue-life diagram; however, the fatigue resistance of an NITI-1 stent is better than that of an NITI-2 stent. It was found that the two types of sealing stents do not damage a healthy neck artery. In the aneurysm section, the NITI-1&ePTFE, NITI-1&PET, and NITI-2&PET combinations were free of fatigue fracture when subjected to conditions of radial stress between 50 and 150 mmHg. In contrast, the safety factor for the NITI-2&ePFTE combination was only 0.67, which is not acceptable for proper AAA stent–graft design. In summary, a Nitinol stent with PET graft may greatly improve fatigue life, while its compliance is much lower than the NITI–ePTFE combination.

Dyeing properties of poly(methyl vinyl pyridine)-poly(ethylene terephthalate) graft copolymers

Grafting of poly(ethylene terephthalate) fibers (PET) with 2-methyl-5-vinylpyridine (MVP) was carried out using γ rays and benzoyl peroxide independently for the initiation of grafting. The poly(MVP)-PET graft copolymers were analyzed for density, moisture regain, and dyeability. Radiation-induced grafting yielded copolymers with densities and moisture regain appreciably higher than those produced by benzoyl peroxide. The same results occurred when acid dyes were used. The behavior of (MVP)-PET graft copolymers towards some reactive dyes was also studied. The extent and rate of dyeing were dependent of pH of the dye bath, nature of the dye and the magnitude of grafting. Dyeing occurs through formation of salt linkages between the pyridine moieties and the solubilizing groups (usually sulfonate groups) in the dye molecule.