A novel method for engineering autologous non-thrombogenic in situ tissue-engineered blood vessels for arteriovenous grafting

Geelhoed, Wouter J.; Bogt, Koen E.A. van der; Rothuizen, T.C.; Damanik, Febriyani; Hamming, Jaap F.; Mota, Carlos; Agen, M.S. van; Boer, Hetty C. de; Restrepo, Mauricio Tobón; Hinz, Boris; Kislaya, Ankur; Poelma, Christian; Zonneveld, Anton Jan van; Rabelink, Ton J.; Moroni, Lorenzo; Rotmans, Joris I.

doi:10.1016/j.biomaterials.2019.119577

Cited by 28 publications

(25 citation statements)

References 44 publications

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“…An interesting new alternative could be the use of tissue-engineered blood vessels (TEBV) as grafts. Several variants of TEBV are described, usually based on the use of a scaffold to which vascular (precursor) cells are attracted to or seeded on [103][104][105].…”

Section: Alternatives For Vein Grafting: Tissue-engineered Graftsmentioning

confidence: 99%

“…This delicate balance between nanofiber degradation and neovessel tissue is different between species and requires optimization for the enhancement of translational capacity [103]. An alternative can be the in situ TEBV, where fibroblast and progenitor vascular cells form a vascular-like tube around a solid scaffold that can be used as a conduit for (arterio) venous grafting [104]. Together, this highlights that TEBVs may serve as arterial bypass grafts and represent a potential solution for future vascular surgery but still require optimization before large-scale clinical application is to be expected.…”

Section: Alternatives For Vein Grafting: Tissue-engineered Graftsmentioning

confidence: 99%

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The Role of Immunomodulation in Vein Graft Remodeling and Failure

Baganha

Jong

Jukema

et al. 2020

J. of Cardiovasc. Trans. Res.

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Obstructive arterial disease is a major cause of morbidity and mortality in the developed world. Venous bypass graft surgery is one of the most frequently used revascularization strategies despite its considerable short and long time failure rate. Due to vessel wall remodeling, inflammation, intimal hyperplasia, and accelerated atherosclerosis, vein grafts may (ultimately) fail to revascularize tissues downstream to occlusive atherosclerotic lesions. In the past decades, little has changed in the prevention of vein graft failure (VGF) although new insights in the role of innate and adaptive immunity in VGF have emerged. In this review, we discuss the pathophysiological mechanisms underlying the development of VGF, emphasizing the role of immune response and associated factors related to VG remodeling and failure. Moreover, we discuss potential therapeutic options that can improve patency based on data from both preclinical studies and the latest clinical trials. This review contributes to the insights in the role of immunomodulation in vein graft failure in humans. We describe the effects of immune cells and related factors in early (thrombosis), intermediate (inward remodeling and intimal hyperplasia), and late (intimal hyperplasia and accelerated atherosclerosis) failure based on both preclinical (mouse) models and clinical data.

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Section: Alternatives For Vein Grafting: Tissue-engineered Graftsmentioning

confidence: 99%

Section: Alternatives For Vein Grafting: Tissue-engineered Graftsmentioning

confidence: 99%

The Role of Immunomodulation in Vein Graft Remodeling and Failure

Baganha

Jong

Jukema

et al. 2020

J. of Cardiovasc. Trans. Res.

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“…Interestingly, our findings are in line with recent results reported by Geelhoed et al., who found maximum stenosis of about 50% in a tissue‐engineered graft implanted as carotid‐jugular shunt in goats, as compared to the control group implanted with 6 mm‐diameter ePTFE grafts which featured average stenosis values of 85% already after two months. [ 21 ] Endoluminal stenosis at the venous anastomosis with ePTFE grafts was found to reach 50% already after 8 weeks also by Kohler et al. in a sheep model of dialysis access failure.…”

Section: Discussionmentioning

confidence: 79%

“…Interestingly, our findings are in line with recent results reported by Geelhoed et al, who found maximum stenosis of about 50% in a tissue-engineered graft implanted as carotid-jugular shunt in goats, as compared to the control group implanted with 6 mm-diameter ePTFE grafts which featured average stenosis values of 85% already after two months. [21] Endoluminal stenosis at the venous anastomosis with ePTFE grafts was found to reach 50% already after 8 weeks also by Kohler et al in a sheep model of dialysis access failure. [22] Notably, in our study, the endoluminal matrix adhering to the graft inner wall, appearing upon SEM imaging as a dense fibrin matrix entrapping platelets and red blood cells, seemed to represent the ideal pavement for a gradual endothelialization of the graft lumen, starting at day 60 from the venous anastomosis (G4) and lining 50% to 70% of the fibrous pavement in the mid-graft region (G2/G3) at day 90 ( Figure 6,7).…”

Section: Discussionmentioning

confidence: 84%

A Novel Hybrid Silk Fibroin/Polyurethane Arteriovenous Graft for Hemodialysis: Proof‐of‐Concept Animal Study in an Ovine Model

Riboldi

Tozzi

Bagardi

et al. 2020

Adv Healthcare Materials

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To solve the problem of vascular access failure, a novel semi-degradable hybrid vascular graft, manufactured by electrospinning using silk fibroin and polyurethane (Silkothane), has been previously developed and characterized in vitro. This proof-of-concept animal study aims at evaluating the performances of Silkothane grafts in a sheep model of arteriovenous shunt, in terms of patency and short-term remodeling. Nine Silkothane grafts are implanted between the common carotid artery and the external jugular vein of nine sheep, examined by palpation three times per week, by echo-color Doppler every two weeks, and euthanized at 30, 60, and 90 days (N = 3 per group). At sacrifice, grafts are harvested and submitted for histopathology and/or scanning electron microcopy (SEM). No cases of graft-related complications are recorded. Eight of nine sheep (89%) show 100% primary unassisted patency at the respective time of sacrifice (flow rate 1.76 ± 0.61 L min −1 , one case of surgery-related thrombosis excluded). Histopathology and SEM analysis evidence signs of inflammation and pseudointima inside the graft lumen, especially at the venous anastomosis; however, endoluminal stenosis never impairs the functionality of the shunt and coverage by endothelial cells is observed. In this model, Silkothane grafts grant safety and 100% patency up to 90 days.

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“…Subcutaneous implantation of a cylindrical polymeric rod originates a tube‐shape tissue capsule, forming the basis for a TEBV. [ 7 ]…”

Section: Introductionmentioning

confidence: 99%

Control Delivery of Multiple Growth Factors to Actively Steer Differentiation and Extracellular Matrix Protein Production

et al. 2021

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In tissue engineering, biomaterials have been used to steer the host response. This determines the outcome of tissue regeneration, which is modulated by multiple growth factors (GFs). Hence, a sustainable delivery system for GFs is necessary to control tissue regeneration actively. A delivery technique of single and multiple GF combinations, using a layer‐by‐layer (LBL) procedure to improve tissue remodeling, is developed. TGF‐β1, PDGF‐ββ, and IGF‐1 are incorporated on tailor‐made polymeric rods, which could be used as a tool for potential tissue engineering applications, such as templates to induce the formation of in situ tissue engineered blood vessels (TEBVs). Cell response is analyzed in vitro using rat and human dermal fibroblasts for cellular proliferation, fibroblast differentiation, and extracellular matrix (ECM) protein synthesis. Results revealed a higher loading efficiency and control release of GFs incorporated on chloroform and oxygen plasma‐activated (COX) rods. Single PDGF‐ββ and IGF‐1 release, and dual release with TGF‐β1 from COX rods, showed higher cell proliferation when compared to COX rods alone. A substantial increase in α‐smooth muscle actin (α‐SMA) is also observed in GF releasing COX rods, with TGF‐β1 COX rods providing the most pronounced differentiation. A significant increase in collagen and elastin synthesis is observed on all GF releasing COX rods compared to control, with COX rods releasing TGF‐β1 and IGF‐1 providing the highest secretion. TGF‐β1 and IGF‐1 releasing COX rods induced higher Glycosaminoglycan (GAG)/DNA amounts than the other GF releasing COX rods. As PDGF‐ββ and TGF‐β1/PDGF‐ββ COX rods displayed the highest fibroblast attachment, these rods provided the highest total collagen and elastin production. The attractive results from efficiently incorporating single and multiple GFs on COX rods and their sustainable release to steer cellular behavior suggest a promising route to enrich the formation of in situ engineered tissues.

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A novel method for engineering autologous non-thrombogenic in situ tissue-engineered blood vessels for arteriovenous grafting

Cited by 28 publications

References 44 publications

The Role of Immunomodulation in Vein Graft Remodeling and Failure

The Role of Immunomodulation in Vein Graft Remodeling and Failure

A Novel Hybrid Silk Fibroin/Polyurethane Arteriovenous Graft for Hemodialysis: Proof‐of‐Concept Animal Study in an Ovine Model

Control Delivery of Multiple Growth Factors to Actively Steer Differentiation and Extracellular Matrix Protein Production

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