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Biomedical subjects

M Rabaud

Publications and source records attributed to M Rabaud.

At least 19 recordsLinked to original sources

Elastin-derived protein coating onto poly(ethylene terephthalate). Technical, microstructural and biological studies.

Recently, it has been shown in our laboratory that certain proteins solubilized from elastin (ESP) formed a tight association with certain polymers such as elastin or polyethylene glycol terephthalate (PET) ... . The present paper deals with the description of the optimal chemical conditions of this unexpected association, its microstructure and its biological properties. A microstructural study of the composite ESP-PET material was performed using scanning and transmission electron microscopy. The thickness of the yield composite was evaluated (0.4-2 microm) but its imperviousness was unsatisfactory using ESP alone. So, we tentatively coated PET with the elastin-ESP complex. The microscopic views confirmed that the polymer was better filled by the organic matrix, the thickness of the layer being markedly improved (3 microm). Simultaneously, we attempted to verify whether the yielded composite retains the biological properties previously demonstrated with the 'Biopatches' and probably due to ESP. Thus, the culture of endothelial cells on an ESP-coating (with elastin or not) showed that a 100 microg/cm2 ESP concentration was able to promote endothelial cell growth in perfect conditions, maintaining their phenotypic character. While several physico-chemical determinations are in progress in our laboratory to identify and characterize the protein involved, a prototype of small-calibre vascular prosthesis was elaborated with elastin-ESP-PET composite and will be placed in a dog at the abdominal femoral junction to evaluate the in vivo performance of such an attractive material in artery restoration.

Adsorption↗

Rejection of islets differing by a single antigen is dependent on donor MHC.

To study the effect of expression of a single foreign antigen on the outcome of otherwise compatible mouse islet grafts, we have used transgenic mice expressing the human complement receptor 2 (CR2, CD21, C3d/EBV receptor) on their pancreatic beta-cells (RIP-CR2 mice). Donors were RIP-CR2 mice, typed at the major histocompatibility complex (MHC) as H-2(k), H-2(b), or H-2(bxk), and recipients were streptozotocin-treated nontransgenic B6 x CBA F1 mice (H-2(bxk)). H-2(b) or H-2(bxk) CR2-expressing islets were not rejected (mean survival time [MST] >100 days) but induced a peri-insulitis and an antibody response to CR2. In contrast, H-2(k) CR2-expressing islets were rejected in 80% of the cases with a MST of 65 +/- 23 days and were massively infiltrated by a destructive insulitis. In both cases, the infiltrate was mainly made of CD4+ cells, with few CD8+ cells. The isotype of IgG antibody response to CR2 was studied: recipients of H-2(k) grafts had a predominantly IgG1 response, while recipients of H-2(b) grafts had a balanced IgG2a and IgG1 response. To further evaluate the mechanism of differential rejection of the two types of grafts, recipients were immunized with CR2-expressing rat insulinoma cells before transplantation. Preimmunization with CR2 did not affect the outcome of H-2(b) grafts but greatly accelerated the rejection of H-2(k) grafts. These experiments indicate that expression of a single foreign antigen on beta-cells triggers an immune response leading to rejection or to peri-insulitis, depending on the MHC of donor islets.

Animals↗

New preparation and microstructure of the EndoPatch elastin-collagen containing glycosaminoglycans.

Several improvements of the basic reaction between elastin-solubilized peptides and type I + III collagens are presented. They concern the prior incubation of the proteins in an adequate medium as well as the addition of heparan sulphate or hyaluronic acid (HA) and the consequent effects on the physical properties of yielded matrices. The addition of HA in small amounts enabled us to make membranes with good performances.

Biocompatible Materials↗

Use of a biodegradable elastin-fibrin material, Neuroplast, as a dural substitute.

Since the new Neuroplast biomaterial is now commonly used in several domains of restorative and curative surgery, its preliminary evaluation as a dura mater substitute in the rabbit was performed and is described herein. Whereas the importance of prosthesis thickness was implicated and solved (0.2 rather than 1.0 mm), both macroscopic examination and histological studies revealed for the neotissue an effective patency, a good continuity and especially no or almost no adherence at all. As Neuroplast is now available for use everywhere in humans, this material is being developed in several fields of neurosurgery.

Animals↗

Colonization of a calcium phosphate/elastin-solubilized peptide-collagen composite material by human osteoblasts.

The evaluation of the suitability of a new biomaterial as a possible substitute for bone tissue is described here. This biomaterial is based on calcium phosphate particles linked to an artificial connective matrix, the elastin-solubilized peptides (ESP) associated with type I and III collagens. This work demonstrates the feasibility of shaping this composite material into discs, describes its microstructural characteristics, and evaluates its capacity as a substrate for the proliferation of human osteoblasts without loss of their phenotypic expression.

Adsorption↗

Evaluation of bioabsorbable elastin-fibrin matrix as a barrier in surgical periodontal treatment.

The purpose of this investigation was to test clinically the efficiency of a recently described bioabsorbable matrix as a guided tissue regeneration membrane. This matrix was prepared from an original reaction between elastin and fibrin monomers and is now extensively used in several domains of surgery. The study group was composed of 26 patients, with a total of 35 lesions (22 intrabony defects, 8 Class II furcations and 5 Class III furcations) presenting moderate to advanced adult periodontitis. After initial therapy, measurements were made with a calibrated periodontal probe. Probing depth (PD) and gingival margin location (GM) measurements were taken twice: immediately before surgery and after 6 months before re-entry. Clinical attachment level (CAL), vertical osseous level (VOL) and alveolar crest location (AC) measurements were taken during surgery and after 6 months with re-entry procedures for all the patients. Color change of the gingival margin was only observed in 4 defects and device exposure occurred in the proportion of 2 out of the 35 defects. No foreign body reaction was observed in any case. At the intrabony defects mean PD reduction was 5 mm (P < 0.001), and mean gain of CAL was 4 mm (P < 0.001). Mean VOL was 4.3 mm (P < 0.001), mean gingival recession was 0.9 mm (P < 0.05) and mean AC was 0.2 mm (NS). At the Class II furcation defects the mean PD reduction was 4.5 mm (P < 0.001), mean gain CAL vertical was 3.2 mm and CAL horizontal was 4.5 mm (P < 0.001). Gingival recession averaged 1 mm (NS). A complete closure was observed in 2 out of the 8 defects. At the Class III furcation defects the mean PD reduction was 3.6 mm (P < 0.05) and mean CAL-V gain was 1.5 mm (P < 0.02). However the 5 sites showed no horizontal attachment gain and none were unchanged. A very low gingival recession, gingival reaction, crestal bone loss, and device exposure occurred during this study. This preliminary study suggests that the use of a biosynthetic barrier may have beneficial effects in the treatment of intrabony defects and Class II furcation defects. Randomized controlled trials are necessary to evaluate the efficacy and safety of this bioabsorbable membrane in periodontal therapy.

Adult↗

New artificial connective matrix made of fibrin monomers, elastin peptides and type I + III collagens: structural study, biocompatibility and use as tympanic membranes in rabbit.

Experiments leading to the conception and development of a new artificial connective matrix based on collagen-elastin-fibrin associations are presented. Preliminary evaluation of this biomaterial as an artificial tympanic membrane is described. Morphological evaluation was performed by histopathological and scanning electron microscopic studies. Biocompatibility was documented by subcutaneous implantation and experimental grafting in rabbits was performed with histopathological studies of the tympanic grafted membranes. The positive results obtained in this experimental study enable future studies in humans to be prepared.

Animals↗

New bioactivation mode for vascular prostheses made of Dacron polyester.

The performance of vascular prostheses, especially those of small calibre, still presents several problems. The use of polyesters such as the well-known poly(ethylene terephthalate) (Dacron) and, more recently, poly(tetrafluoroethylene) and polyurethanes provides a marked improvement. We have developed a process to increase the efficiency of such prostheses, using the ability of the Dacron polyester to be covalently modified by proteins under mild chemical conditions. The biomaterial is obtained from the particular interaction of elastin-solubilized peptides with type I + III collagens under very precise conditions. We have obtained an irreversible covalent bonding on Dacron. These biological conditions and the addition of connective proteins and glycosaminoglycans conferred on the resulting material a composition and a three-dimensional structure equivalent to the subendothelium, providing bioactive properties suitable for the development of a vascular prosthesis.

Biocompatible Materials↗

[Preliminary results of the evaluation of the Endopatch E-F in digestive surgery].

Endopatch E-F is a new product elaborated with natural human and animal proteins. Its synthesis originates in a covalent link between elastin and fibrin monomers. Numerous experimental studies carried out in animal have previously shown its ability to reinforce healing process of digestive wall. The results reported herein have been obtained in very selected patients in whom a digestive anastomosis had to be done in spite of unfavorable circumstances, such as intra-abdominal infection, radiated bowel or ascitis. From October 1990 to October 1992, 21 digestive anastomosis have been performed in 18 patients. All were reinforced by Endopatch E-F. Two deaths have been observed (mortality: 11.1%), which do not look like a consequence of the use of the product (One myocardial infarction and one cirrhotic failure). There were 2 post-operative fistulas (9.5% of the whole anastomosis). No patients had any reaction of intolerance. These preliminary results confirm experimental data, and suggest that Endopatch EF can be used in order to reinforce digestive sutures when performed under unfavorable circumstances.

Adult↗

Elastin patches.

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Biocompatible Materials↗

Oxidized alpha 1-proteinase inhibitor: a fast-acting inhibitor of human pancreatic elastase.

Unlike human neutrophil elastase or porcine and rat pancreatic elastases, human pancreatic elastase is rapidly inhibited by oxidized alpha 1-proteinase inhibitor. The second-order association-rate constant for the reaction of the oxidized inhibitor with this enzyme (kass = 10(5) M-1 s-1) is only 8-fold lower than that measured with native alpha 1-proteinase inhibitor. Elastase releases faster from its complex with the oxidized inhibitor (t1/2 approximately 0.7 days) than from its complex with the native inhibitor (t1/2 approximately 5 days). Oxidized alpha 1-proteinase inhibitor is as efficient as the native inhibitor in inhibiting the elastolytic activity of elastase. Oxidized alpha 1-proteinase inhibitor may thus be considered as a physiological inhibitor of human pancreatic elastase which may prevent degradation of blood vessel elastin during acute hemorrhagic pancreatis.

Humans↗

New artificial connective matrix-like structure made of elastin solubilized peptides and collagens: elaboration, biochemical and structural properties.

Several improvements of the basic reaction between elastin peptides and type III collagen, specially the addition of heparan sulphate proteoglycans, are presented. The consequent elaboration of either cell culture support or membranes are described and illustrated by scanning electron microscopy. The material produced possesses composition, very well organized lamellar structure and some properties quite close to natural membranes such as subendothelial tissue.

Biocompatible Materials↗

New artificial connective matrix-like structure: thrombogenicity and use as endothelial cell culture support.

The recently described artificial connective matrix made of elastin solubilized peptides, type I+III collagens and connective proteins is shown to have structural and biological properties very close to the natural arterial subendothelium: the capacity to promote endothelial cell cultures maintaining their phenotype expression and its non-thrombogenicity. This new bioactive composite material could be used to replace arteries.

Biocompatible Materials↗