Selecting valid in vitro biocompatibility tests that predict the in vivo healing response of synthetic vascular prostheses (original) (raw)
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.
Experimental evaluation of a gelatin-coated polyester graft used as an arterial sstitute
Biomaterials, 1989
Protein coating and endothelial cell preseeding have been proposed and studied as improvements to arterial prostheses. In this paper, an impervious polyester vascular graft which had been coated with cross-linked gelatin was compared to a porous one over a period of up to 8 month in dogs. This evaluation involved in viva methods using radio tracers to study patency and thrombogenicity and in vitro controls of the healing processes. The main advantages offered by coated grafts over uncoated include the absence of preclotting and better biointegration. Numerous clinical and experimental studies show the reliability of polyester arterial prostheses. Amongst the desired improvements of knitted Dacron@, the availability of blood-tight grafts appears to be interestingle7. The first bioprostheses made of polyester fibres cross-linked with a biological substance date back more than 25 yrESg. Elastin'"-'2, fibrin13 and more recently albumin14,15 and collageng,'6 have been studied. This kind of prosthesis was proposed to avoid preclotting, which causes blood loss and can initiate intramural thrombus formation and infection' 7-1g. In addition to blood tightness, protein impregnation aims for reinforcement of mechanical properties, better healing and an improvement of the blood material interface to reduce prosthesis thrombogenicity. Numerous studies have been added to the work of Chvapil" and Krajicek et al. and
Novel Synthetic Selectively Degradable Vascular Prostheses: A Preliminary Implantation Study
Journal of Surgical Research, 2001
Background. Vascular grafts perform less well than autologous arterial or vein grafts. The purpose of this study was to evaluate the short-term performance of selectively biodegradable filament-wound vascular prostheses, comprising elastomeric poly(ether urethane) (Lycra) scaffolds and flexible, hydrophilic biodegradable coatings. Materials and methods. Two types of selectively biodegradable vascular grafts were manufactured, comprising a filament-wound Lycra scaffold, subsequently coated with a biodegradable poly(ethylene glycol)/ poly(lactic acid) (PELA) block copolymer. The two types of grafts differed in both the overall porosity of the scaffold and the hydrophilicity of the biodegradable constituent. A 60-mm-long and 6-mm-diameter filament-wound and polytetrafluoroethylene (ePTFE) grafts were implanted as interposition prostheses, randomly, at the right-and left-side carotid arteries. Results. Implantation studies proved the grafts to be patent and pulsatile for periods of up to 3 months. Increasing the scaffold porosity and enhancing the hydrophilicity of the biodegradable component improved both the transmural tissue ingrowth process and the vascularization of the prosthesis wall. Also, a well-adhered peripheral tissue and a thin, uniform intima and endothelial lining were obtained. All ePTFE graft controls, although patent, were rather stiff and nonpulsatile. A thick pseudointima, poorly attached to the prosthesis inner surface, was observed. The compliance of the wet grafts was significantly higher than in the dry state, stemming mainly from the water-plasticizing effect on the biodegradable component. The grafts explanted after a period of 6 weeks exhibited compliance only slightly lower than that of the wet grafts. After 12 weeks, however, the hoop compliance was 20% lower than that prior to implantation. At 100 mm Hg, for example, the original compliance of the wet graft was 2.5%/100 mm Hg decreasing to 2.0%/100 mm Hg after a 3-month implantation. The compliance reduction with implantation is attributed to the ingrowth of the perigraft tissue as revealed by the histological study. A compliance of 2.0%/100 mm Hg is slightly better than that of a standard PTFE graft with an original compliance of 1.6%/ 100 mm Hg. Yet it is still an order of magnitude smaller than that of a canine carotid artery. Conclusions. The improved mechanical properties and enhanced healing of the highly porous filament-wound Lycra scaffold graft coated with hydrophilic biodegradable PELA has the potential of being a highly effective small caliber prosthetic graft.
Morpho-Pathological Review on the Healing of Synthetic Vascular Grafts
Acta Medica Marisiensis, 2016
Objective: Tissue integration of vascular grafts partially depends on the host response to injury, which immediately begins after implantation and restoration of the circulation. In an infected environment, the inflammation changes the incorporation patterns. The aim of the study was to observe the tissue incorporation process, in a normal and an infected environment. Methods: We have created an experimental model by performing subfascial implantation of four types of vascular grafts, in rats (woven Dacron®, knitted Dacron®, silver coated Dacron® and expanded Polytetrafloroethylene -ePTFE) and by infecting some of them with three different bacterial strains. We have retrieved the noninfected grafts at two and four weeks after implantation, whilst the infected ones at one, two and three weeks. Results: Detailed microscopic appearences were analysed. The control and infected groups were compared. Statistical significance was calculated for various corelations. Conclusions: The morphopathological findings showed that the ePTFE graft's structure was best preserved. Statistical significance existed between the bacterial strain and the degree of inflammation. The silver coated Dacron® was not shown to be superior to the knitted Dacron®. The poorest incorporation was the one of the woven Dacron®.
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...
Experimental evaluation of ten clinically used arterial prostheses
Annals of Vascular Surgery, 1992
The arterial grafts currently in use are classified into five basic categories; 10 different commercially available prostheses were chosen to represent these categories. The Vascutek and Bionit are made from knitted Dacron and have medium porosity, requiring preclotting by the surgeon. The DeBakey Soft Woven and Plasma TFE grafts are made from woven Dacron and have low porosity, not requiring preclotting under most circumstances. Also studied were woven and knitted grafts with leakage resistance referred to as “impervious” Dacron grafts: the Vascutek Gelseal, the Bard Albumin Coated DeBakey Vasculour II, the Microvel with Hemashield, and the albumin saturated, autoclaved DeBakey Soft Woven graft. Gore-Tex and Impra are expanded polytetrafluoroethylene grafts which do not require preclotting. For each type, five grafts 6 cm long and 8 mm in diameter were implanted in the descending thoracic aorta of healthy adult dogs for 16 weeks. The physical characteristics, biocompatibility, and healing patterns varied according to the structure and treatment of the grafts. Pretreatment with biomaterials during manufacture is quite effective in preventing transinterstices blood loss during implantation, but results in altered physical qualities, increased thrombogenicity and delayed healing in comparison to the effects of preclotting with autogenous blood at the time of implantation.
New polyester arterial prostheses from great britain: an in vitro and in vivo evaluation
Annals of Biomedical Engineering, 1986
Two models of knitted velour polyester prostheses have been developed in Great Britain, i.e. the VP1200K and the VP50K Triaxial. The evaluation of these new devices in vitro and in vivo in dogs has demonstrated that, while the first model has similar surgical, mechanical and healing characteristics in the short term to other commercial knitted velour prostheses, the second model has lower water permeability and superior strength and dimensional stability. On the basis of these results, clinical investigations can be undertaken.