Long-term evaluation of a new selectively biodegradable vascular graft coated with polyethylene oxide-polylactic acid for right ventricular conduit. An experimental study

Low-porosity woven Dacron grafts have been used extensively as an extracardiac conduit in the surgical treatment of congenital and acquired heart diseases involving total heparinization. Caution is still warranted in their use, however, because of long-term complications, including calcification and development of obstructive fibrous peel. In contrast, high-porosity grafts offer much better tissue anchorage and healing but cannot be used under heparinization. We have developed a compound vascular prosthesis in which a knitted Dacron graft is coated with a polymeric biodegradable sealant. Polyethylene oxide-polylactic acid-segmented copolymers comprised the degradable component of the graft. In vitro studies showed that the coated prosthesis exhibited a highly flexible elastomer-like mechanical response. The prostheses were completely watertight, and significant degradation started after 1 week, with absorption completed after 3 weeks. Seven woven and six knitted polyethylene oxide-polylactic acid-coated Dacron grafts used as extracordiac conduits (16 mm), connecting the right ventricle and the pulmonary artery were implanted in dogs. The dogs were killed after 12 to 18 months, and the results are reported. Scanning electron microscopy examination showed peel detachment and nonhomogenous intimal surface with fenestrations in the woven graft group, but complete healing and incorporation of the pseudointima with homogenous, thin lining of the luminal surface in the polyethylene oxide-polylactic acid-coated group. Histologic studies indicated much superior healing and anchorage of the periprosthetic tissue and the pseudointima in the polyethylene oxide-polylactic acid-coated grafts. The biodegradable polymer was fully degraded and exhibited a complete incorporation of the compound vascular prosthesis. This study indicates the superior healing properties of these selectively biodegradable grafts, which might increase long-term patency and decrease complications of right ventricular conduits.     

An experimental study of the strength in arterial prosthetic anastomoses: relationship between anastomotic tensile strength and its organization]

Five types of 6-mm diameter arterial prostheses, i.e.m woven Teflon, woven Dacron, velour woven Dacron, velour knitted Dacron and expanded polytetrafluoroethylene (E-PTFE), were studied in the dog to assess anastomotic tensile strength and its organization. Five types of composite grafts, about 3.0cm in length, were implanted in the abdominal aorta of fifty-two adult mongrel dogs using absorbable polyglycolic acid suture. At 16 weeks after the implantation, if the composite graft was patent, tensile strength of the bilateral anastomoses were measured and its organizations were examined microscopically. The mean forces required to disrupt the anastomoses of velour woven Dacron, velour knitted Dacron and E-PTFE were greater than those of woven Teflon and woven Dacron. At the disrupted sites of woven Teflon and woven Dacron, which were non-velour grafts, fibrous outer sheath were remarkably separated from the grafts. This results indicate that organization and fixation of fibrous outer sheath are the most important factors in the strength of arterial prosthetic anastomoses and velour grafts have superiority over non-velour grafts. The organization of E-PTFE was poor, but its tensile strength was equal to velour grafts. It is considered E-PTFE has an advantage due to non-crimped structure and requires further evaluation over longer period.     

Differential effect of the retropleural and retroperitoneal environments on healing of the inner wall of porous fabric prostheses in the thoracic and abdominal aorta of the same dog

Healing of the inner wall of the same preclotted knitted Dacron arterial prostheses was compared in the descending thoracic aorta (DTA) and the abdominal aorta (AA) of the same dog. Each of 16 dogs received this dual implantation with study periods of 4 weeks for five dogs, 8 weeks for five dogs, and 16 weeks for six dogs. Healing was studied with light microscopy, scanning electron microscopy, transmission electron microscopy, and immunocytochemistry identification. The outer capsule was firmly adherent to the Dacron framework of all grafts implanted in the DTA; advanced healing of the inner wall of all thoracic grafts was present by 4 weeks, nearly complete healing by 8 weeks, and complete healing by 16 weeks. In contrast, the outer capsule was either not attached or only loosely adherent to the Dacron framework in eight AA grafts (50%), and in these implants no healing of the inner wall occurred beyond the limited perianastomotic pannus zone. In the other eight implants in which the outer capsule was firmly adherent to the Dacron framework, healing was roughly comparable to that in the grafts implanted in the DTA. This study demonstrated that (1) DTA grafts heal faster and more completely than AA grafts, (2) healing and endothelialization are related to the tightness of the outer capsule, (3) there is a high incidence of loose tissue attachment in the AA, and (4) healing of aortic grafts is site specific.We appreciate the help of David Criss, medical photographer Mary Ann Harvey, medical editor; and Mary-Ann Nelson, medical illustrator.     

Pseudointima formation in woven and knitted dacron grafts. A comparative ultrastructural analysis

Twelve specially designed crimped aortobifurcated grafts (aorta, woven 200 porosity; right limb, woven 500 porosity; left limb, knitted 1200 porosity) were implanted into mongrel dogs that were sacrificed at two, six, eight and twelve-month intervals. Pseudointima from the mid portion of each type of graft was studied with light (LM) and transmission electron microscopy (TEM). An ocular micrometer was used to determine the thickness of the pseudointima. A trilaminar cytoarchitecture resembling the wall of a medium-sized artery existed in the pseudointima. This was characterized by an inner cellular layer, outer fibrocollagenous layer, and multi-interlamination of cells and glycosaminoglycan in the middle layer. The cellular inner layer was thickest in the knitted and thinnest in the woven 200 porosity. A zone of acellularity separated the luminal cells from the underlying myoblasts and myofibroblasts. Specificity of varying types of cell distribution occurred in the pseudointima. Myoblasts and myofibroblasts were located near the lumen while fibroblasts and mesenchymoid cells were situated near the graft. The luminal cells had the combined features of endothelial cells and myofibroblasts. Collagen and glycosaminoglycans were the dominant extracellular matrix. Despite the difference of fluid permeability in high porosity woven and knitted dacron grafts, the pseudointima was well formed and revealed no striking general cytoarchitectural difference between these two types of grafts.     

Seeding arterial prostheses with vascular endothelium. The nature of the lining.

Arterial prostheses seeded with autogenous vascular endothelium demonstrate a well-organized, cellular, inner lining. To determine the nature of the lining cells, six animals underwent replacement of the infrarenal aorta with Dacron prostheses. During the preparation of three such grafts, endothelium was scraped from the saphenous vein with a steel wool pledget, suspended in chilled Sack's solution, and mixed with blood used to preclot the graft. This suspension was omitted from the three control grafts. After six weeks, the grafts were removed, rinsed and examined. Fluorescent Factor VIII related antigen (F VIII-RA) strongly stained the lining cells. Silver nitrate Haütchen and electron microscopy preparations revealed a lining pattern characteristic of vascular endothelium. Endothelial cell-specific Weibel-Palade bodies were identified in the lining cell cytoplasm. Masson's trichrome staining revealed a relatively collagen-poor connective tissue within the seeded fabric. Transmission electron microscopy disclosed vascular smooth muscle cells between the seeded graft fabric and the lining cells. Vasa vasorum, arising from the outer capsule, penetrated the fabric to supply the inner capsules of the seeded grafts. It is concluded that the cells lining seeded canine arterial prostheses are true vascular endothelium supported by vascular smooth muscle cells, that the lining contains minimal connective tissue, and that vasa vasorum develop. Unseeded control grafts lacked these features.     

Evaluation of the healing of precoated vascular dacron prostheses

Summary Knitted and woven Dacron grafts commercially coated with bovine collagen, gelatin and human albumin were implanted end-to-side between the infrarenal aorta and the bifurcation in 35 growing pigs. Grafts were explanted after 4, 8 and 12 weeks and compared to 6 uncoated knitted prostheses preclotted with blood that served as a control. Uncoated grafts rapidly developed a firmly attached neointima lined with endothelium. Compared with coated grafts the thrombus-free area of uncoated grafts was significantly larger (P < 0.05). The slow resorption of albumin resulted in a delayed and incomplete neointimal healing and failing graft incorporation. Although the bovine collagen was only minimally cross-linked by formaldehyde, healing of the neointima was compromised in a thin woven graft that demonstrated peeling of the inner capsule even after 12 weeks. The identical collagen as well as bovine gelatin were quickly degraded in knitted grafts and both types showed transprosthetic infiltration at 4 weeks. All knitted grafts coated with either collagen or gelatin, however, were occluded after 8 and 12 weeks. Light microscopy revealed hyperplasia of smooth-muscle cells within the thickened distal anastomotic region. These results demonstrate that a timely return of porosity is mandatory for the development and maintenance of an intact neointima. Both the structure of the fabric as well as the method of preparing the coating are crucial variables to determine the rate of biodegradation.

---

Untersuchung zur Einheilung vorbeschichteter Dacrongefaäßprothesen

Zusammenfassung Gestrickte und gewebte Dacronprothesen mit kommerzieller Vorbeschichtung aus bovinem Kollagen, Gelatine oder humanem Albumin wurden bei 35 Schweinen End-zu-Seit zwischen infrarenaler Aorta und der Bifurkation implantiert. Die Prothesen wurden nach 4, 8 und 12 Wochen explantiert und mit 6 unbeschichteten gestrickten Dacronprothesen verglichen. Unbeschichtete Dacronprothesen entwickelten rasch eine fest haftende Neointima mit Endothelauskleidung, wobei die thrombusfreie Fläche gegenüber beschichteten Prothesen signifikant größer war (P<0,05). Die verlangsamte Albuminresorption führte zu einer verzögerten und inkompletten Neointimaausbildung sowie zu einer ausbleibenden Protheseneinheilung. Obwohl das bovine Kollagen nur schwach vernetzt war, war auch bei gewebten beschichteten Dacronprothesen die Neointimaausbildung verzögert, wobei noch nach 12 Wochen die Neointima nur locker mit der Prothese verbunden war. Das identische Kollagen sowie die bovine Gelatine waren bei gestrickter Prothesenstruktur bereits nach 4 Wochen resorbiert und die Prothesen waren komplett eingeheilt. Diese beiden Prothesentypen zeigten jedoch nach 8 bzw. 12 Wochen konstant einen organisierten thrombotischen Verschluß. Hier wies die Histologic eine Hyperplasie glatter Muskelzellen innerhalb der verdickten distalen Anastomosenregion nach. Diese Ergebnisse zeigen, daß die zeitgerechte Wiederkehr der Porosität unverzichtbar ist für die regelrechte Entwicklung sowie für die Aufrechterhaltung einer intakten Neointima. Hier sind sowohl die Struktur der Prothese als auch die Art der Beschichtungsverarbeitung entscheidende Parameter, die die Resorptionsrate der Imprdgnierung beeinflussen.

     

Partially bioresorbable vascular grafts in dogs.

Previous studies have shown the effectiveness of partially resorbable arterial prostheses in the rabbit. This study compares these same compound prostheses with commercial graft materials in the dog. Conduits 4 mm inner diameter X 50 mm in length were woven from composite yarns containing 69% polyglactin 910 (PG910)/31% polypropylene or containing 70% polydioxanone/30% polypropylene. Nonresorbable controls were woven Dacron and expanded polytetrafluoroethylene (ePTFE). Baseline platelet aggregometry to 10(-5) mol/L adenosine diphosphate was performed. Seventy prostheses were implanted into the aorto-ilac positions, and the prosthesis/tissue complexes were harvested serially from 2 weeks to 1 year. Explanted specimens were photographed and fixed for light microscopy and for scanning and transmission electron microscopy. Results showed no aneurysms or perigraft hematomas. Overall patency for the PG910/polypropylene grafts was 18 of 20 (90%) and for polydioxanone/polypropylene was 19 of 22 (86%). For Dacron and ePTFE, 13 of 19 (68%) and 6 of 11 (54%) remained patent at time of explantation. The partially resorbable grafts, as a group, had significantly greater patency than the control grafts (p less than 0.03). Platelet aggregometry was not predictive of graft patency. Histologic analysis of the partially bioresorbable groups showed inner capsules (IC) composed of myofibroblasts and collagen beneath confluent endothelialized surfaces by 1 month. Kinetics of IC formation paralleled the rates of resorption of the resorbable components. IC cellularity and thickness were greater than those within Dacron or ePTFE. This study suggests an enhanced transinterstitial endothelial cell and myofibroblast ingrowth into the ICs of partially resorbable grafts and shows the effectiveness of these prostheses in the dog.     

Dilation of woven and knitted aortic prosthetic grafts: CT scan evaluation

Because there are few reports in the literature concerning short- and medium-term outcome of woven and knitted aortic prosthetic grafts, we conducted CT evaluations in 58 asymptomatic patients (53 males and five females with a mean age of 63.5 years) undergoing infrarenal aortic reconstruction between June 1988 and June 1991. Joined CT slices after contrast enhancement, centered on the proximal anastomoses, prosthetic bodies, and prosthetic limbs, were obtained in the early (mean 19 days) and late (mean 19 months, range 6 to 40 months) postoperative periods. In end-to-side aortoprosthetic anastomoses (n=28), early and late CT examinations revealed that the anteroposterior diameter increased 1.9% (p=NS) and 8.8% (p<0.0001) for woven and knitted grafts, respectively. In end-to-end aortoprosthetic anastomoses, the diameter of the prosthetic body on early CT scans increased 12.6% (p<0.0001) and 28% (p<0.0001) for woven and knitted prosthetic grafts, respectively, as compared with diameter values provided by the manufacturer. Dilation continued to progress 2.2% (p<0.04) for woven and 6.2% (p<0.0002) for knitted prosthetic grafts on late CT scans. The mean diameter of the prosthetic graft limbs (n=96) increased 22.3% (p<0.0001) and 34.6% (p<0.0001) for woven and knitted prosthetic grafts, respectively, on early CT scans as compared with manufacturers' values. Secondary increases were 3.2% (p<0.002) and 7.7% (p<0.007) for woven and knitted prosthetic grafts, respectively. These data show that dilation of aortic prostheses occurs early in most cases, most likely soon after declamping of the graft, as shown by recent intraoperative measurements. Secondary progression is slow but more marked for knitted prostheses.Presented at the Annual Meeting of the Société de Chirurgie Vasculaire de Langue Française, Reims, France, June 19– 20, 1992.     

Indium 111-labeled platelet deposition in woven and knitted Dacron bifurcated aortic grafts with the same patient as a clinical model

A study was designed to compare platelet deposition between knitted and woven Dacron grafts in the same patient. Twenty patients received aortoiliac or aortofemoral bifurcated Dacron grafts, each composed of one woven and one double-velour knitted limb. External nuclear graft imaging was carried out after injection of autologous platelets labeled with indium 111. The patients were studied postoperatively in time periods ranging from 6 days to 42 months. Platelet accumulation was almost identical in knitted and woven limbs in all patients. This study appears to indicate that there is no difference in thrombogenicity between knitted and woven bifurcated Dacron grafts in the aortoiliac or aortofemoral positions measured by platelet accumulation.     

Postoperative dilation of knitted Dacron aortic bifurcation graft

Dilation is the most common inherent "failure mode" of knitted Dacron aortic prostheses. However, the incidence of graft failure related to dilation is unknown because of insufficient data regarding the occurrence, degree, and prognostic significance of postoperative alterations in graft size. In 1979 we reported that postoperative ultrasonic examinations in 95 asymptomatic patients, selected at random after aortic surgery, revealed dilation of the aortic portion of knitted Dacron bifurcation grafts. The average follow-up was 33 months, and the mean dilation was 18%. This article provides the results of a later follow-up, averaging 175 months, in 32 patients from the 1979 study. CT scanning, rather than ultrasonic imaging, was used to evaluate all parts of the grafts. CT scans disclosed that the three parts of each graft dilated, but the parts did not always dilate uniformly. Mean percent dilation values for the entire series were aortic portion 67% +/- 38% SD; right limb 77% +/- 66% SD; left limb 54% +/- 26% SD. Maximum percent dilation for any part of the grafts ranged from 26% to 367% with a mean of 94%. At least one part of the grafts dilated 100% or greater in 12 patients. Three patients had generalized and saccular dilation of the aortic portion of the prostheses and an anastomotic aortic aneurysm; one patient had a localized aneurysm in the midportion of the right limb. Three of the latter grafts were replaced with woven Dacron prostheses.     

Does porosity matter?

Patients who had survived at least four years after aortic aneurysmectomy were divided into two groups depending on the prosthesis being of woven or knitted fabric. Such prostheses do not develop an endothelial lining in man, and remain thrombogenic despite their great practical success. A comparison of the persistence versus the loss of palpable pulses distal to the prosthesis, was taken as an index of thrombogenicity and the formation of micro-emboli. There was a statistically significant difference in the persistence of distal pulses in patients with knitted grafts in the 5th, 6th and 7th years of the study, suggesting that such grafts are less prone to thromboembolic activity than the woven prostheses.     

Dacron arterial grafts: the influence of porosity, velour, and maturity on thrombogenicity

It has been claimed that the neointimal healing of Dacron arterial prostheses can be enhanced by increasing porosity and including both an internal and an external velour layer. To test this, 24 patients received at random either woven (USCI, DeBakey, C. R. Bard, Inc.) or more porous, double-velour, knitted (Microvel, Meadox Medicals, Inc.) Dacron aortobifemoral prostheses. Graft thrombogenicity was measured using autogenous 111In-labeled platelets shortly following surgery and 6 to 9 months later. The thrombogenicity index was defined as the mean daily rise in the ratio of emissions over the graft to emissions over a reference area (aortic arch) and is a measure of platelet deposition. At early study the mean (+/- SE) thrombogenicity index was similar in woven and knitted graft patients at 0.19 +/- 0.4 and 0.14 +/- 0.2, respectively. In both groups it was lower (P less than 0.05) 6 to 9 months later at 0.06 +/- 0.2 (woven( and 0.08 +/- 0.1 (knitted), with again no difference between materials. Although platelet survival was restored to near normal values in both groups by 6 to 9 months, only one woven graft failed to demonstrate continued platelet accumulation by gamma-imaging. Thrombogenicity in Dacron grafts diminishes in the early months of maturation but is not affected by porosity and velour. Moreover, this thrombogenicity persists beyond the period of altered platelet survival.     

The influence of inner wall filamentousness on the performance of small- and large-caliber arterial grafts

Dacron prostheses with differing degrees of inner wall filamentousness were implanted in the canine descending thoracic aorta for 56 days (n = 14) and the carotid arteries for 21 days (n = 40). In the thoracic aorta the healed inner capsule of 8 mm internal velour grafts was approximately three times as thick as the inner capsule of external velour knitted prostheses. However, the early patency and rapidity of healing of these two types of prostheses were essentially the same. In the carotid arteries the patency of the 4 mm external velour prostheses was greater than that of the internal velour prostheses and the mean thrombus-free surface area of the external velour grafts was significantly greater than that of the internal velour grafts. These observations suggest that an internal velour surface is not deleterious to early patency in a large-caliber, high-flow artery but that it may be in a small-caliber, low-flow artery.     

Influence of prosthetic graft fabrication on graft healing,I

The object of this report was to analyze graft healing by comparing the content of collagen and noncollagen protein among seven commonly used prostheses: light-weight knitted dacron concentric crimp (USCI), Sauvage filimentous external velour knitted dacron with concentric crimp, random crimp, or no crimp (USCI), microvel double-velour knitted dacron concentric crimp (Meadox), PTFE Impra, and PTFE Gortex. Grafts (6 mm) were used to replace 4-cm segments of infrarenal abdominal aorta in 85 experimental dogs and five autograft aorta control animals. At 3 and 6 months postimplantation the grafts were aseptically harvested, inspected for completeness of neointimal healing and submitted for biochemical analysis. After 3 months implantation, uncrimped external velour grafts had less hydroxyproline than all dacron grafts except random crimp external velour (P < 0.05) but not less than both PTFE grafts and most dacron and PTFE grafts were not significantly different in noncollagen protein. After 6 months implantation, all dacron grafts had more hydroxyproline than both PTFE grafts (P < 0.03) and most dacron grafts had significantly more noncollagen protein than PTFE Impra (P < 0.05). Of all the grafts analyzed, only uncrimped external velour knitted dacron grafts had both rapid neoendothelial healing and a significant increase in both hydroxyproline and noncollagen protein between 3 and 6 months after graft implantation (P < 0.01). These data indicate that dacron prostheses heal in a manner different from that of PTFE grafts, that there may be differences among the various types of dacron prostheses, and that external velour uncrimped grafts would appear to have the best healing characteristics.     

Compound polyglactin 910/polypropylene small vessel prostheses

This study evaluated morphologic and functional characteristics of tissue reactions to compound prostheses of 69% absorbable polyglactin 910 (PG910) and 31% nonabsorbable polypropylene in the rabbit. Forty-two woven PG910/polypropylene prostheses (24 X 4 mm internal diameter) implanted into rabbit infrarenal aortas were harvested after 2 weeks to 12 months. Each explant was photographed and sectioned for light microscopy and transmission and scanning electron microscopy. Randomly selected explants underwent either compliance and bursting strength measurements or assays of production of prostacyclin and thromboxane metabolites by luminal surfaces of both regenerated conduits and normal control aortas in response to administered sodium arachidonate. Results showed 100% patency with no aneurysms and 2% stenoses (1 of 42 prostheses). Confluent endothelial-like cellular luminal surfaces covering oriented smooth muscle-like myofibroblasts comprised the inner capsules whose thicknesses stabilized at 1 to 2 months. Only residual polypropylene remained in the prostheses after 2 months. Compliance studies reflected a 0.65 mm (14%) change over a pressure range of 0 to 160 mm Hg. All regenerated prosthesis-tissue complexes had bursting strengths greater than the proximal perianastomotic native aortas, which burst between 600 and 2000 mm Hg. At 1 month the rate of production of 6-keto-PGF1 alpha per square millimeter of surface area of experimental segments was normal. Production of 6-keto-PGF1 alpha by experimental segments at 3 months had increased fourfold whereas thromboxane B2 (TxB2) production remained unchanged. The 6-keto-PGF1 alpha/TxB2 ratio increased from 1 to 4 months. This study demonstrates clinically efficacious morphologic, mechanical, and biochemical characteristics of PG910/polypropylene-elicited vascular prosthesis-tissue complexes.     

Patency rate of bifurcated aortic grafts: comparative analysis of woven versus knitted prostheses in the same patient

To investigate the difference in patency rate between woven and knitted aortofemoral or aortoiliac prosthetic grafts, a special vascular prosthesis was manufactured with one limb of the graft knitted and the other, woven. The prosthesis was implanted in 143 consecutive patients with occlusive aortoiliac arteriosclerotic disease or aneurysms. Detailed statistical analysis failed to reveal any difference in the patency rate between the woven and knitted limbs of the grafts during an observation period ranging from one month to two years.     

New prostheses for venous substitution

In 81 Beagle dogs, 6 cm long segments of the inferior vena cava were replaced end-to-end by artificial vascular grafts (10 mm in diameter) without an av-fistula and anticoagulant drugs. Different graft materials have been used, such as various e-PTFE (30-90 microns fiber length) and polyurethane with low and increased microporosity. e-PTFE with 75 microns fiber length and polyurethane with increased porosity showed the best tissue incorporation, complete endothelialization of the whole length and a high patency rate of 80-85% after a follow-up of 12 months. In contrast to other commercially available vascular grafts (textile woven or knitted, e-PTFE 30 microns) tested in previous series, polyurethane and e-PTFE with increased microporosity had already achieved complete endothelialization after 6-12 weeks. Therefore, these optimized prostheses should be introduced into clinical practice for large venous substitution. Thereafter, an adjunctive av-fistula as protection is probably no longer necessary.     

Failure of dacron arterial prostheses caused by structural defects

We have observed unusual aneurysmal complications associated with structural defects of Dacron fabrics in three patients. The first patient had beadshape aneurysms along the course of the bilateral axillo-femoral prosthetic bypasses 4 or 5 years after surgery. Round defects or longitudinal rents in the lower third of the prostheses (Vascular-D knitted Dacron graft of high porosity, USCI) were the source of the aneurysmal complications. In the second patient, the transverse diameter of the aorto-femoral Dacron graft (Vascular-D, USCI) was increased to twice that of the original graft with formation of an anastomotic false aneurysm in the groin 3 1/2 years after surgery. The defective prostheses in these two cases were successfully replaced by Cooley double velour knitted Dacron grafts. The third patient developed an arterio-ureteral fistula originating from a round defect of the aorto-femoral prosthesis (Tetoron that is woven Dacron graft with a low porosity, Nakao-Filter, Japan) 8 years postoperatively and died from massive hematuria and subsequent disseminated intravascular coagulopathy. Microscopic examination of the removed prostheses revealed a complete loss of the conformation of the weave with fragmentation and disruption of the graft fibers. Therefore, patients with Dacron arterial prostheses should be followed up regularly and with great care.     

Autologous tissue-fragmented extracardiac conduit with rapid, stable endothelialization due to angiogenesis.

OBJECTIVES: Autologous angiogenic cytokines are known to activated by mincing stimulation, and well regulated in vivo. We applied this tissue fragmentation technique to a low-pressure pulmonary extracardiac conduit to obtain rapid endothelialization and stable neointima formation due to angiogenesis. METHODS: Subcutaneous adipose tissue was obtained, minced, suspended, and sieved through highly porous fabric vascular prosthesis by pressurized injection. The adipose tissue fragmented graft with an autologous fresh pericardial monocusp valve was implanted between the right ventricle and the pulmonary artery in 13 dogs. The same grafts without fragments were implanted in 8 dogs as controls. No anticoagulation therapy was given. RESULTS: Grafts were removed 6 to 1,128 days after implantation. In the developed grafts, angiogenesis occurred throughout the interstices of the graft wall from the adventitial side, and host cells proliferated and migrated. Endothelialization was completed throughout developed grafts at 2 weeks. The intima was still thin up to 1,128 days and free of degenerative changes. In control grafts, however, capillary infiltration was limited to perigraft tissue at 2 weeks and endothelialization was not completed by 3 months. Under the endothelial cell layer, laminal elastic fibers were formed through the developed graft wall by 4 months and still maintained at 1,128 days. CONCLUSIONS: The results demonstrated that adipose tissue fragmented extracardiac conduits induce rapid endothelialization and maintained thin intima with laminal elastic fibers. Long-term durability is expected based on results from using this technique in a low-pressure pulmonary system in dogs.     

Development of a "leak-proof," knitted Dacron vascular prosthesis

We have developed a technique to render knitted Dacron prostheses totally impervious to blood leak by impregnating the cloth with collagen. These grafts were prepared by the manufacturer, sterilized, and have an indefinite shelf life. The objective of this study was to determine whether collagen impregnation has a deleterious effect on surface thrombogenicity and graft healing. The infrarenal aortas of 30 mongrel dogs were replaced with 6 cm X 6 mm Dacron grafts (15 collagen-impregnated and 15 control). The collagen-impregnated prostheses were visibly indistinguishable from the control. After blood flow was restored, no interstitial bleeding occurred in the collagen grafts, in contrast to the control grafts that initially leaked profusely. When they recovered, the dogs were divided into three groups: group I (five collagen, five control), group II (five collagen, four control), and group III (five collagen, three control). The grafts were harvested at 3, 6, and 9 months, respectively. Retroperitoneal healing response, capsular thickness and adherence, completeness of neointimal healing, surface fibrinolytic activator activity, and sections taken for light and scanning electron microscopy were studied and compared in a blinded fashion. In a separate set of experiments, experimental and control grafts were compared for in vivo surface thrombogenicity. The healing data were identical in the experimental and control prostheses in all parameters. Of particular interest was that initial capsule adherence was better and surface thrombogenicity less in the collagen-impregnated prosthesis. We conclude that collagen impregnation of a knitted Dacron prosthesis has no deleterious effect for the term of observation of this experiment.