Selecting valid in vitro biocompatibility tests that predict the in vivo healing response of synthetic vascular prostheses (original) (raw)
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Studying the biocompatibility of vascular prostheses in experimental in vivo conditions
Today, due to the intensive growth of the total number of patients with the cardiovascular pathology, the number of patients with specific diseases of large vessels is increasing annually. The condition of aid serviced to this category of citizens is undergoing constant perfection and development. Nowadays, to solve several problems related to the shortage of qualitative material for the substitution of the damaged vasculature area, implants and patches based on polymeric fibers are actively developed, and they require detailed studying and experimental validation. Purpose and tasks: to study the tissue response of laboratory animals to the implantation of vascular prostheses used for the correction of defects of large vessels. Results and discussion: A powerful periprosthetic capsule with varying thickness and significant two-layer organization was determined in all experimental groups. The outer layer is represented by the thick fibrous tissue, while the inner one primarily consists of the inflammatory infiltrate cells. Trabeculae dividing the bundles of prosthetic fibers, as well as surrounding its separate filaments pass inside the prosthesis from the fibrous capsule layer. The highest CI parameters are determined on day 60 (4.5±0.68), CI on day 30 is 3.65±0.54, which is 1.7 times higher than CI values on day 15 (2.15±0.32).
Journal of Surgical Research, 2005
Objective. Evaluation of the pig and sheep models for biocompatibility investigations of vascular prostheses (VP). Design. Comparative analysis of animal experimental investigations involving two different animal models. Materials and methods. Commercially available polyester vascular prostheses (PET-VP) were implanted into two different animal models (infrarenal porcine aorta and ovine carotid artery). The costs, surgical handling, patency rate, and healing on the basis of macroscopic, microscopic, and immunohistochemical criteria were analyzed over a period of 3 months. Results. Handling and operating times (63 ؎ 10 versus 76 ؎ 16 min; P ؍ 0.125) did not differ significantly. The cost of the two animal models was comparable. Integration of the VP was complete in the sheep model, but varied in the pig model (two complete, four incomplete). Complete endothelialization of all VPs was observed in the pig, which contrasted with the sheep with complete (circular) endothelialization only in the region of the anastomosis. The thickness of neointima in the region of the anastomosis differed insignificantly; immunohistochemically, only periprosthetic Ki67 was significantly reduced (28.7 ؎ 9.9 versus 6 ؎ 0.9%; P ؍ 0.002) in the sheep. Conclusions. In the porcine model, extremely good endothelialization of the VP was observed, with formation of a rapid neointimal hyperplasia. The ovine model was characterized by the fact that postopera-tive follow-up investigations were easy to perform. Complete endothelialization was not observed.
In vivo Study of a Collagen Impregnated Polyester Arterial Prosthesis: the Arteknit Ra K ® Graft
Cor et vasa
In vivo Study of a Collagen Impregnated Polyester Arterial Prosthesis: the Arteknit Ra K ® Graft. Cor Vasa 2006;48(1):12–18. Purpose: We have previously reported that a transient increase in intracellular Ca 2+ concentrations in endothelial-like cells may reflect the endothelization process on the Arteknit Ra K ® polyester arterial prosthesis implanted in the aorta of mongrel dogs (Physiol Res 51; 217–20:2002). In this study, we further examine early arterial graft healing, i. e. patency, morphology, endothelization and thromboresistance, after short implantation periods in these dogs. Methods: We implanted 12 Arteknit Ra K ® prostheses in the aorta of mongrel dogs for scheduled periods ranging from 48 hours to 6 months. The explanted graft specimens were subjected to histological examination and scanning electron microscopy, analyzed for platelet and fibrinogen uptake as well as prostacyclin (PGI 2) and thromboxane A 2 (TXA 2) concentrations. Results: At the time of sacrifice, all ...
Longterm study of a compliant biological vascular graft
European Journal of Vascular Surgery, 1991
Clinically implanted prostheses of biological origin have recently been shown to develop aneurysms within several years. To study this process, recently developed bovine heterografts that were implanted in canine ilio-femoral arteries for 27 to 45 months, were studied in vivo and in vitro. Seven out of seven grafts were patent with only one showing evidence of focal aneurysm. Measurements of mechanical properties, including water permeability, compliance, and burst pressure, and of heat shrink temperature and dry weight were obtained before and after a period of controlled exposure to bacterial collagenase; all data suggested that much of the original graft had been replaced with host tissue. However, enzyme susceptibility was less than that of fresh bovine arteries, indicating that at least some of the grafts" crosslinked collagen was preserved. The compliance of these explants was similar to that reported for autogenous vein. Histological examination of the graft wall revealed cellular "intimal" and adventitial zones containing host-generated collagen surrounding a central zone devoid of cellular infiltration, which appears to be unmodified graft "'media" highly resistant to degradation. We conclude that, when properly processed, biological prostheses can act as a bioresorbable scaffold for the orderly replacement of structural elements during healing, promoting continued mechanical integrity of the graft. These promising results encourage the further development of prostheses of biological origin.
Healing of prosthetic arterial grafts
Scanning microscopy, 1990
Numerous synthetic biomaterials have been developed as vascular substitutes. In vitro, ex vivo and in vivo studies have demonstrated that in animals, selected materials, i.e., Dacron and ePTFE (expanded polytetrafluoroethylene) grafts, are successfully incorporated in both the large and the small caliber host arteries through a process which is generally referred to as graft healing. Morphologically, this process consists of a series of complex events including fibrin deposition and degradation, monocyte-macrophage recruitment and flow-oriented cell-layer generation, this last event being the complete endothelialization of the arterial substitute. In contrast to experimental animals, the flow surface of synthetic vascular grafts remains unhealed in humans, particularly in the small caliber conduits. Healing in man consists of graft incorporation by the perigraft fibrous tissue response with a surface covered by more or less compacted, cross-linked fibrin. It is therefore obvious tha...
Prosthetic vascular grafts: Wrong models, wrong questions and no healing
Biomaterials, 2007
In humans, prosthetic vascular grafts remain largely without an endothelium, even after decades of implantation. While this shortcoming does not affect the clinical performance of large bore prostheses in aortic or iliac position, it contributes significantly to the high failure rate of small-to medium-sized grafts (SMGs). For decades intensive but largely futile research efforts have been under way to address this issue. In spite of the abundance of previous studies, a broad analysis of biological events dominating the incorporation of vascular grafts was hitherto lacking. By focusing on the three main contemporary graft types, expanded polytetrafluoroethylene (ePTFE), Dacron and Polyurethane (PU), accumulated clinical and experimental experience of almost half a century was available. The main outcome of this broad analysis-supported by our own experience in a senescent non-human primate model-was twofold: Firstly, inappropriate animal models, which addressed scientific questions that missed the point of clinical relevance, were largely used. This led to a situation where the vast majority of investigators unintentionally studied transanastomotic rather than transmural or blood-borne endothelialization. Given the fact that in patients transanastomotic endothelialization (TAE) covers only the immediate perianastomotic region of sometimes very long prostheses, TAE is rather irrelevant in the clinical context. Secondly, transmural endothelialization seems to have a time window of opportunity before a build-up of an adverse microenvironment. In selecting animal models that prematurely terminate this build-up through the early presence of an endothelium, the most significant 'impairment factor' for physiological tissue regeneration in vascular grafts remained ignored. By providing insight into mechanisms and experimental designs which obscured the purpose and scope of several decades of vascular graft studies, future research may better address clinical relevance.
Endothelial Cell Culture and Seeding of Prosthetic Vascular Grafts: An Experimental Study
Medical Journal Armed Forces India, 1999
Current synthetic vascular prostheses do not acquire lining of vascular endothelium in humans or dogs. Endothelial seeding of vascular grafts has been proposed as a means of reducing the thrombogenicity of these grafts. We examined feasibility of cultivating endothelial cells (EC) by tissue culture technique and their subsequent seeding onto small diameter polytetra fluoroethylene (PTFE) grafts. Twenty adult dogs underwent common carotid artery interposition with 4 mm PTFE grafts. Ten dogs received seeded and the remaining ten received unseeded grafts. Grafts were removed at 4 and 12 weeks and their gross/morphological features compared. Cumulative patency rates for seeded grafts were 70% as compared to unseeded ones 30%. Seeded grafts were completely surfaced with a mono•layer of endothelium by 4 weeks. Small graft patency appears to be related to the establishment of an endothelial surface, the development of which is clearly facilitated by seeding with autogenous endothelium.
In vivo evaluation of modified mandrel-grown vascular prostheses
Journal of Biomedical Materials Research, 1999
The Omniflow™ Vascular Prosthesis (OVP) has been manufactured and extensively tested in animal and human trials. It has mechanical and biological qualities superior to synthetic and biological conduits, particularly in low flow conditions. For further development into the smaller diameter coronary prostheses, the inner luminal surface is of paramount importance. In a previous study this inner surface was modified to produce a more uniformly thicker nonundulating surface. In this study the mandrels of these modified OVPs were treated with either collagen or heparin; the OVPs were evaluated for patency, tissue integration and wound healing, and endothelialization using a dog model comparable to that used to evaluate the unmodified OVP. In all instances, each of the modified prostheses were fully patent and had no signs of any deleterious effects caused by these modifications; no thrombus or aneurysms were visible. The tissue response was rapid with excellent new host collagen deposition within the vessel wall and minimal inflammatory and foreign body giant cells. Endothelialization was noted at the earliest explant time point in central regions of the prostheses, albeit that the histological picture at this time point appeared to reflect a complex atypical intimal layer.
Annals of biomedical engineering, 2016
Following the implantation of biodegradable vascular grafts, macrophages and fibroblasts are the major two cell types recruited to the host-biomaterial interface. In-vitro biocompatibility assessment usually involves one cell type, predominantly macrophages. In this study, macrophage and fibroblast mono- and co-cultures, in paracrine and juxtacrine settings, were used to evaluate a new biodegradable thermoplastic polyurethane (TPU) vascular graft. Expanded-polytetrafluoroethylene (ePTFE) grafts served as controls. Pro/anti-inflammatory gene expression of macrophages and cytokines was assessed in vitro and compared to those of an in vivo rat model. Host cell infiltration and the type of proliferated cells was further studied in vivo. TPU grafts revealed superior support in cell attachment, infiltration and proliferation compared with ePTFE grafts. Expression of pro-inflammatory TNF-α/IL-1α cytokines was significantly higher in ePTFE, whereas the level of IL-10 was higher in TPU. Init...