Development of a Growing Rat Model for the In Vivo Assessment of Engineered Aortic Conduits

Assmann, Alexander; Akhyari, Payam; Delfs, Christofer; Flögel, Ulrich; Jacoby, Christoph; Kamiya, Hiroyuki; Lichtenberg, Artur

doi:10.1016/j.jss.2011.10.009

Cited by 42 publications

(52 citation statements)

References 34 publications

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“…36 After initially confirming the feasibility of the dECM functionalization strategy, biological effects were assessed in vitro in a standardized model system for cell adhesion onto dPVCs, as previously described, 37 and in vivo in a functional rodent aortic graft (AoG) transplantation model, a standardized vascular graft model system allowing the in vivo evaluation under systemic pressure, as previously described. 7 Decellularization of ECM. All ECM materials (except for the chemically preserved cBP) were decellularized on a detergent basis, as previously described.…”

Section: Ecm Substrates and Model Systemsmentioning

confidence: 99%

“…All ECM materials (except for the chemically preserved cBP) were decellularized on a detergent basis, as previously described. 2,7,36 Briefly, decellularization was achieved through dynamic tissue incubation in four repetitive 12-h cycles with 0.5% sodium dodecyl sulfate (SDS) and 0.5% deoxycholate (DCA), followed by 24 h of incubation in distilled water containing 0.05% sodium azide and three repetitive 24-h rinsing cycles with phosphatebuffered saline (PBS) and 1% penicillin/streptomycin. Decellularization quality was controlled as previously described.…”

Section: Ecm Substrates and Model Systemsmentioning

confidence: 99%

“…Rodent AoGs were harvested from donor Wistar rats (male, 200-250 g), essentially following a recent publication, with minor modifications. 7 Briefly, following CO 2 euthanization and thoracotomy, the thoracic and upper abdominal aorta were explanted in toto and thoroughly rinsed with heparinized PBS. A U-shaped AoG was prepared by dissection of adjacent connective tissue and clipping of the supra-aortal arteries.…”

Section: Ecm Substrates and Model Systemsmentioning

confidence: 99%

“…Heterotopic implantation of the functionalized dAoGs into the systemic circulation of recipient rats was conducted according to a recent publication, with minor modifications. 7 Briefly, recipient rats were anesthetized with 2.0-2.5% isoflurane, orally intubated, and machine ventilated. After insertion of a central venous jugular vein catheter and systemic heparanization (100 IU/kg), a median laparotomy was performed, and the infrarenal aorta was dissected from the inferior vena cava.…”

Section: In Vivo Endothelialization Studiesmentioning

confidence: 99%

“…3 Therefore, decellularized ECM (dECM) is widely used as a platform for bioengineering of medical implants, having shown its suitability in a variety of preclinical as well as clinical models. [4][5][6][7][8] In the cardiovascular field, dECM-based approaches are particularly pursued in heart valve and vascular graft engineering. 4 Here, experimental models have already successfully been translated into the preclinical and clinical settings, with, for example, a first clinical series of decellularized allogenic valves implanted in the pulmonary as well as aortic positions showing promising mid-and long-term results.…”

Section: Introductionmentioning

confidence: 99%

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Customized Interface Biofunctionalization of Decellularized Extracellular Matrix: Toward Enhanced Endothelialization

Aubin

Mas‐Moruno

Iijima

et al. 2016

Tissue Engineering Part C: Methods

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Interface biofunctionalization strategies try to enhance and control the interaction between implants and host organism. Decellularized extracellular matrix (dECM) is widely used as a platform for bioengineering of medical implants, having shown its suitability in a variety of preclinical as well as clinical models. In this study, specifically designed, custom-made synthetic peptides were used to functionalize dECM with different cell adhesive sequences (RGD, REDV, and YIGSR). Effects on in vitro endothelial cell adhesion and in vivo endothelialization were evaluated in standardized models using decellularized ovine pulmonary heart valve cusps (dPVCs) and decellularized aortic grafts (dAoGs), respectively. Contact angle measurements and fluorescent labeling of custommade peptides showed successful functionalization of dPVCs and dAoGs. The functionalization of dPVCs with a combination of bioactive sequences significantly increased in vitro human umbilical vein endothelial cell adhesion compared to nonfunctionalized controls. In a functional rodent aortic transplantation model, fluorescent-labeled peptides on dAoGs were persistent up to 10 days in vivo under exposure to systemic circulation. Although there was a trend toward enhanced in vivo endothelialization of functionalized grafts compared to nonfunctionalized controls, there was no statistical significance and a large biological variability in both groups. Despite failing to show a clear biological effect in the used in vivo model system, our initial findings do suggest that endothelialization onto dECM may be modulated by customized interface biofunctionalization using the presented method. Since bioactive sequences within the dECM-synthetic peptide platform are easily interchangeable and combinable, further control of host cell proliferation, function, and differentiation seems to be feasible, possibly paving the way to a new generation of multifunctional dECM scaffolds for regenerative medicine.

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Section: Ecm Substrates and Model Systemsmentioning

confidence: 99%

Section: Ecm Substrates and Model Systemsmentioning

confidence: 99%

Section: Ecm Substrates and Model Systemsmentioning

confidence: 99%

Section: In Vivo Endothelialization Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Customized Interface Biofunctionalization of Decellularized Extracellular Matrix: Toward Enhanced Endothelialization

Aubin

Mas‐Moruno

Iijima

et al. 2016

Tissue Engineering Part C: Methods

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Mechanocompatible Polymer‐Extracellular‐Matrix Composites for Vascular Tissue Engineering

Jiang

Suen

Wang

et al. 2016

Adv Healthcare Materials

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Small-diameter vascular grafts developed from vascular extracellular matrix (ECM) can potentially be used for bypass surgeries and other vascular reconstruction and repair procedures. The addition of heparin to the ECM improves graft hemocompatibility but often involves chemical crosslinking, which increases ECM mechanical stiffness compared to native arteries. Herein, we demonstrate the importance of maintaining ECM mechanocompatibility, and describe a mechanocompatible strategy to immobilize heparin onto the ECM via a biodegradable elastomer. Specifically, poly (1,8-octamethylene citrate)-co-cysteine (POC-Cys) was hybridized to the ECM, forming a polymer-ECM composite that allows for heparin immobilization via maleimide-thiol “click” chemistry. Heparinized composites reduced platelet adhesion by >60% in vitro, without altering the elastic modulus of the ECM. In a rat abdominal aortic interposition model, intimal hyperplasia in heparinized mechanocompatible grafts was 65% lower when compared to ECM-only control grafts at 4 weeks. In contrast, grafts that were heparinized with carbodiimide chemistry exhibited increased intimal hyperplasia (4.2 fold) and increased macrophage infiltration (3.5 fold) compared to ECM-only control grafts. All grafts showed similar, partial endothelial cell coverage and little to no ECM remodeling. Overall, we describe a mechanocompatible strategy to improve ECM thromboresistance and highlight the importance of ECM mechanical properties for proper in vivo graft performance.

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Transcatheter treatment of tricuspid regurgitation by caval valve implantation—experimental evaluation of decellularized tissue valves in central venous position

Lauten

Laube

Schubert

et al. 2014

Cathet Cardio Intervent

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Development of a Growing Rat Model for the In Vivo Assessment of Engineered Aortic Conduits

Cited by 42 publications

References 34 publications

Customized Interface Biofunctionalization of Decellularized Extracellular Matrix: Toward Enhanced Endothelialization

Customized Interface Biofunctionalization of Decellularized Extracellular Matrix: Toward Enhanced Endothelialization

Mechanocompatible Polymer‐Extracellular‐Matrix Composites for Vascular Tissue Engineering

Transcatheter treatment of tricuspid regurgitation by caval valve implantation—experimental evaluation of decellularized tissue valves in central venous position

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