Browsing by Author "Vasudev, SC"

Now showing 1 - 16 of 16
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    Changes in pericardial calcification due to antiplatelet agents: In vitro studies
    (ARTIFICIAL ORGANS, 1998) Chandy, T; Vasudev, SC; Rao, GHR
    To develop tissue valves for prolonged use in the cardiovascular system, the complicated process of surface induced calcification must be better understood. Calcification was examined for 60 days on glutaraldehyde treated bovine pericardium (GABP) and enzyme extracted tissues fixed in glutaraldehyde (GATBP) incubated in metastable solutions of calcium phosphate, and the roles of aspirin and persantine in conjunction with vitamins C, B, or E, gentamycin (antibiotic), or pentothal sodium (anesthetic) in the medium were examined. Further, the diffusion of calcium across the GATBP was evaluated using a diffusion cell with 2 compartments. Pericardial calcification was also observed using scanning electron microscopy (SEM) techniques. It seems that the examined antiplatelet agents can modify the pericardial surfaces and subsequently their mineralization processes (GATBP, 31.7 mu g/mg tissue; in the presence of 5 mg% vitamin C, 13.1 mu g/mg tissue; in 1.5 mg% aspirin, 17.2 mu g/mg tissue; and 1 mg% gentamycin, 14.8 mu g/mg tissue) on exposure with the metastable calcium phosphate solution for 60 days. In addition, these agents may modify calcium transport and interfere with the adsorption at the surface, hence reducing calcium nodulation on GATBP. Scanning electron micrographs also revealed a reduction in calcium deposition on the pericardium due to these antiplatelet agents. It may be hypothesized that the influx of calcium on GATBP may be due to the cellular components or the involvement of plasma proteins like the fibrinogen molecule. The exact mechanism of these changes in the calcification of the pericardium are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby for prevention of thrombosis and calcification. However, more in vivo studies are needed to develop applications.
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    Changes in polyurethane calcification due to antibiotics
    (ARTIFICIAL ORGANS, 1996)
    To develop artificial materials for prolonged use in the vascular system, the complicated process of surface-induced calcification must be better understood. Calcification was examined on porous polyurethane incubated in metastable solutions of calcium phosphate, and the role of certain antibiotics in the medium was evaluated. It seems that certain aminoglycoside antibiotics can modify polyurethane surfaces and, subsequently, their mineralization process. In addition, these antibiotics may alter the calcium transport through polyurethanes. Therefore, it is conceivable that certain antibiotics can, in addition to producing their antibacterial effect, modulate surface calcium binding by changing the calcium mobilization and crystallization. Additional studies are needed to develop applications.
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    Controlled release of ferric-magnesium ions from chitosan polyethylene vinyl acetate comatrix for preventing pericardial calcification
    (DRUG DELIVERY, 1999) Vasudev, SC; Chandy, T
    Ferric and magnesium ions mere embedded in chitosan/polyethylene vinyl acetate comatrix to develop a prolonged release form. The in vitro release profiles of these ions from the comatrix system were monitored in Tris-HCl buffer, pH 7.4, using an ultraviolet (UV) spectrophotometer. The amount of Fe3+ and Mg2+ ions released was initially much higher, followed by a constant slow release profile for a prolonged period, The initial burst release was substantially modified with glutaraldehyde cross-linking of chitosan beads and subsequent styrene butadiene (SBR) coatings on the comatrix. Prostaglandin Fl was immobilized on this matrix via free-radical mechanisms, using Nz plasma to improve their biocompatibility. From scanning electron microscopy studies it appears that the Fe3+/Mg2+ ions diffuse out slowly to the dissolution medium through the micropores of the comatrix. The released Fe3+/Mg2+ ions from the comatrix system had substantially inhibited the pericardial tissue associated calcification, in an in vitro model system. The result proposes the possibility of delivering drug combinations having synergestic effects for therapeutic applications.
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    Covalently bonded heparin to alter the pericardial calcification
    (ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY, 2000)
    Calcification is the leading cause of failure of a wide spectrum of cardiovascular and non-cardiovascular medical devices. In this study our aim was to immobilize polyethylene glycol (PEG) and heparin on multiple crosslinked bovine pericardium with Glutaraldehyde (GA) and carbodiimide. Grafting of PEG and heparin through an intermediate tissue bound substrate containing aldehyde and imide functional groups showed reduction in calcification. In this experimental protocol, we used Golomb and Wagner's in vitro model for studying pericardial calcification and a diffusion cell with two compartments for evaluating the diffusion of calcium across the BP. The results showed that heparin immobilization on the surface reduces calcification independent of its concentration in the incubating medium. It is conceivable that inactivation of unpaired aldehydic moieties present in pericardium after exposure to GA act as potential site for PEG grafting and imide functionalities of EDC can covalently bind heparin, would be the key step in the prevention of calcification It is well-established fact that heparin has a potent antithrombotic effect. But the exact role of heparin in the anticalcification process of bioprostheses still remain elusive.
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    Development of chitosan/polyethylene vinyl acetate co-matrix: Controlled release of aspirin-heparin for preventing cardiovascular thrombosis
    (BIOMATERIALS, 1997)
    Aspirin and heparin were embedded in chitosan/polyethylene vinyl acetate co-matrix to develop a prolonged release form. The in vitro release profiles of these drugs from the co-matrix system were monitored in Tris HCl buffer pH 7.4, using a UV spectrophotometer. The amount of drug release was initially much higher, followed by a constant slow release profile for a prolonged period. The initial burst release was substantially modified with styrenebutadiene coatings. From scanning electron microscopy studies it appears that the drugs diffuse out slowly to the dissolution medium through the micropores of the co-matrix. The released aspirin-heparin from the co-matrix system had shown their antiplatelet and anticoagulant functions. The results propose the possibility of delivering drug combinations, having synergestic effects for therapeutic applications. (C) 1997 Elsevier Science Limited. All rights reserved.
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    Effect of alternative crosslinking techniques on the enzymatic degradation of bovine pericardia and their calcification
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 1997)
    The in vitro calcification and enzymatic degradation of bovine pericardia (BP) after a series of surface treatments were studied as a function of exposure time. The degradation of these treated surfaces was monitored by scanning electron micrography and tensile strength measurements. Polyethylene glycol-(PEG) grafted BP and glutaraldehyde-(GA) treated BPs retained maximum stability in collagenase digestion compared with SDS-treated BP. The ability of cr, chymotrypsin, bromelain, esterase, trypsin, and collagenase to modulate the degradation of SDS-, GA-, PEG-, Carbodiimide-, and glycidylether-treated BPs also was investigated. Incubation of various enzymes to these crosslinked pericardia variably reduced the tensile strength of these tissues. It is conceivable that chemical treatments of pericardial tissues might have altered their physical and chemical configuration and the subsequent degradation properties. In vitro calcification studies showed a substantial reduction in the calcification profile of PEG-grafted bovine pericardia compared to other treated tissues. Furthermore, the biocompatibility aspects of pericardial tissues were established by platelet adhesion and octane contact angle. In conclusion, it seems that the surface modification of bovine pericardia via GA-PEG grafting may provide new ways of controlling biodegradation and calcification. (C) 1997 John Wiley & Sons, Inc.
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    Effects of double cross-linking technique on the enzymatic degradation and calcification of bovine pericardia
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 2000)
    The strength, resorption rates, and biocompatibility of collagenous biomaterials are profoundly influenced by the method of cross-linking. The in vitro and in viuo calcification and enzymatic degradation of bovine pericardia (BP) after a series of surface modifications were studied as a function of exposure time. Collagenase degradations of modified BP were monitored by scanning electron microscopy and tensile strength measurements. Bovine pericardium was modified by a combination of different tissue fixatives such as glutaraldehyde (GA), carbodiimide (EDC), diisocyanate (HMDIC), and polyethylene glycol (PEG). GA-PEG-EDC-PEG and GA-PEG-HMDIC-PEG combination treated BP retained maximum stability in collagenase digestion compared to GATBP. In vitro calcification studies and in vivo rat subcutaneous implantations of modified pericardium have shown substantial reduction in the calcification of double cross-linked BP with PEG modification. Further, the biocompatibility aspects of pericardial tissues were established by platelet adhesion and octane contact angle. It seems that cross-links involving amino and carboxyl residues may provide new ways of controlling biodegradation and calcification.
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    Glutaraldehyde treated bovine pericardium: Changes in calcification due to vitamins and platelet inhibitors
    (ARTIFICIAL ORGANS, 1997)
    Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common endstage phenomenon affecting a wide variety of bioprostheses. The purpose of the present paper is to study the possibility that some antiplatelet drugs (aspirin and persantine) and certain vitamins (vitamin C, vitamin B-6, and vitamin E) and their combinations might prevent the mineralization of glutaraldehyde treated bovine pericardium (GABP) by modifying the pericardial surface. In this experimental protocol, we used Golomb and Wagner's (1991) in vitro model for studying GABP calcification and a diffusion cell with 2 compartments for evaluating the diffusion of calcium across the GAFF. The results showed that a combination of aspirin and vitamins (0.5 mg% aspirin, 1.5 mg% vitamin C, 4 mg% vitamin B-6, and 2 mg% vitamin E) in a metastable calcium phosphate solution not only reduced the transport of calcium ions through GABP, but along with the combinations of 0.5 mg% aspirin and 5 mg% persantine also produced significant reductions in GABP calcification. The exact mechanism of these changes in the calcification of GABP are still unknown. From these in vitro findings, it appears that a combined vitamin therapy with low doses of aspirin may be beneficial for platelet suppression and thereby prevent thrombosis. In addition, the vitamins may modify calcium transport and interfere with the adsorption at the surface, thus reducing GABP calcification. However, an important question that remains unanswered is whether this inhibitory effect would continue if the antiplatelet drugs and vitamins were discontinued. For the answer, more in vivo studies are needed to develop applications.
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    Influence of polyethylene glycol graftings on the in vitro degradation and calcification of bovine pericardium
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 1997)
    Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). This article reports on various chemical techniques for grafting polyethylene glycol (PEG) on bovine pericardium, their biostability, and calcification. The process of calcification profile was studied by in vitro experiments via the incubation of pericardial samples in a metastable solution of calcium phosphate. The calcification profile of PEG-modified bovine pericardium through glutaraldehyde linkages was significantly reduced compared to other methods of grafting. The mechanical property of these PEG-modified tissues after enzyme (collagenase) digestion and calcification were also investigated. PEG grafting of BP via glutaraldehyde or hexamethylene diisocyanate had shown better mechanical stability compared to other grafting methods used.In conclusion, it seems that the surface modification of bovine pericardium through high molecular weight PEGs via glutaraldehyde linkages may provide new ways of controlling tissue biodegradation and calcification.
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    Influence of steroid hormones on bovine pericardial calcification
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 2001)
    Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GABP). The present investigation describes the influence of steroid hormones in the mineralization of GABP, in an extra-circulatory environment. Calcification was studied on GABP incubation in a metastable solution of calcium phosphate containing steroid hormones such as estrone, progesterone, 7(OH) progesterone, testosterone and beta -estradiol. It is interesting to note that certain steroids can variably increase the GABP calcification. Further, the effect of these steroids in an in vitro hydroxyapatite (HA) formation was investigated. In addition, we observed these steroids alter the calcium transport through GABP in diffusion experiments and also in HA formation. Therefore, it is conceivable that prolonged use of steroids or steroids containing oral contraceptive agents may not be advisable for patients having bioprosthetic implants in contact with blood. A better understanding of the mechanism of these drugs under in vivo conditions is needed to develop applications.
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    Inhibition of bioprosthesis calcification due to synergistic effect of Fe/Mg ions to polyethylene glycol grafted bovine pericardium
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 2001)
    Calcification has limited the durability of bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium (BP). The present study describes calcium antagonistic effect of polyethylene glycol grafted bovine pericardium (PEG-GABP) with Fe2+/Mg2+ delivery from a co-matrix system in rat subcutaneous model. Retrieved samples were biochemically evaluated for calcification and alkaline phosphate (AP) activity. Scanning electron micrographs of 21-day explants had shown excessive calcification with glutaraldehyde treated BP (control). However, the PEG grafting and Fe/Mg release had substantially inhibited the deposition of calcium on BP The extractable alkaline phosphatase activity was also reduced with PEG grafting and metal ion release to BP The extractable AP had shown peak activity at 72 h [for GATBP-250.5 +/-1.2 nm pnp/mg protein/min enzyme activity (unit), PEG-GASP-165.2 +/- 16.6 units], but markedly reduced after 21 days (22.1 +/-1.8 and 12.0 +/-1.5 units, respectively). The initial high levels may be due to tissue injury via surgery, which mitigated with time. It is assumed that ferric ions may slow down or retard the calcification process by the inhibition of proper formation of hydroxy apatite while magnesium ions disrupt the growth of these crystals by replacing Ca2+. In addition it tray be hypothesized that these metal ions may inhibit the key element alkaline phosphatase, which acts as the substrate for mineralization. Hence, it is conceivable that a combination therapy via surface grafting of PEG and local delivery of low levels of ferric and magnesium ions may prevent the bioprosthesis associated calcification.
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    Polyethylene glycol (PEG) modified bovine pericardium as a biomaterial: A comparative study on immunogenicity
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 1998)
    Bioprosthetic heart valves made from glutaraldehyde (GA)-fixed porcine aortic valves or bovine pericardium (BP) are having some advantages over mechanical valves. However, their durability is low due to the calcification and immunological rejection. Study on immunogenicity is an important part in understanding the biocompatibility of materials. Polyethylene glycol (PEG) on pericardium can control biodegradation and calcification. Also, PEG exhibits low immunogenicity. We have studied the complement activation potential and the contribution of complement factors (biologic factors) on the calcification of PEG grafted pericardium samples and compared with standard (control) glutaraldehyde-treated pericardium samples. PEG-grafted BP activated using GA and carbodiimide (EDC) could be selected for further studies since complement activation and calcification observed on these samples has been relatively low.
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    Polyethylene glycol-grafted bovine pericardium: a novel hybrid tissue resistant to calcification
    (JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 1999)
    Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). An investigation was made of the grafting of different molecular weight polyethylene glycol (PEG 600, 1500, 4000 and 6000) via glutaraldehyde (GA) linkages to bovine pericardium (BP) and of their stability and calcification. The process of the calcification profile was studied by in vitro experiments via incubating pericardial samples in a metastable solution of calcium phosphate. Calcification of bovine pericardium grafted with PEG 6000 was significantly decreased compared to low molecular weight PEG grafts or Sodium dodecyl sulphate- (SDS) and GA-treated tissues. The mechanical properties of these modified tissues after enzyme (Trypsin) digestion and calcification were investigated. The biocompatibility aspects of grafted tissues were also established by monitoring the platelet adhesion, octane contact angle and water of hydration. PEG 6000-grafted tissues retained the maximum strength in trypsin buffer and calcium phosphate solutions. Scanning electron micrographs revealed that the PEG-grafted bovine pericardium had substantially inhibited the platelet-surface attachment and their spreading. It is conceivable that high molecular weight polyethylene glycol-grafted pericardium (a hybrid tissue) may be a suitable calcium-resistant material for developing prosthetic valves due to their stability and biocompatibility. (C) 1999 Kluwer Academic Publishers.
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    Synergistic effect of released aspirin/heparin for preventing bovine pericardial calcification
    (ARTIFICIAL ORGANS, 2000)
    Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). Aspirin, a potent antiplatelet drug, and heparin, an anticoagulant, are commonly used for postimplant complications such as thrombosis and thromboembolism. Aspirin and heparin were embedded in chitosan/polyethylene vinylacetate co-matrix to develop a prolonged release form. The effect of these drugs towards the bioprosthetic calcification was investigated by in vitro and in vivo models. In vitro and in vivo evaluation suggest that the released aspirin/heparin from the co-matrix had a synergistic effect in inhibiting GATBP calcification. In vivo subcutaneous coimplantation was performed with PEG-20,000 grafted bovine pericardium (PEG-GABP), aspirin, and heparin. Biochemical, histological, and scanning electron microscopic evaluation of retrieved samples demonstrated a significant reduction in calcium deposition and alkaline phosphatase activity on PEG-GABP compared to GATBP. It seems that the aspirin/heparin combination synergistically inhibits the pericardial calcification in addition to their antithrombotic function.
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    The anticalcification effect of polyethylene glycol - Immobilized on hexamethylene diisocyanate treated pericardium
    (ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY, 2000)
    Pathologic calcification is thought to be the main cause of failure in the present generation tissue valves fabricated from glutaraldehyde pretreated bovine pericardium (BP). The present investigation describes the in vitro calcification and enzymatic degradation of bovine pericardia after hexamethylene diisocyanate (HMDIC) crosslinking and subsequent modification with polyethylene glycol. The enzymatic degradation of these treated surfaces were monitored by scanning electron micrography and tensile strength measurements. Various proteases, such as proportional to-chymotrypsin, bromelain, esterase, trypsin and collagenase were investigated for tissue stability. Incubation of these enzymes with crosslinked pericardia had variably reduced their tensile strength. Among these treated surfaces, polyethylene glycol (PEG) grafted BP via isocyanate functionalities had retained maximum strength. The PEG modified tissues had also indicated a substantial reduction in calcification, when compared to other treated tissues. Further, the biocompatibility of various pericardial tissues were established by platelet adhesion and octane contact angle measurements. It is assumed that the PEG modification of pericardium may interfere with the cellular activation of injury (platelets) to reduce tissue associated calcification. In conclusion, it seems the PEG modification of bovine pericardium via HMDIC may provide new ways or controlling tissue biodegradation and calcification. However, more in vivo studies are needed to develop applications.
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    The antithrombotic versus calcium antagonistic effects of polyethylene glycol grafted bovine pericardium
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 1999)
    Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common end stage phenomenon affecting a wide variety of bioprosthesis. This study proposes a novel approach of reducing pericardial calcification and thrombosis via coupling polyethylene glycols (PEG) to glutaraldehyde treated bovine pericardium via acetal linkages. The calcification of the PEG modified tissue and the control pericardium (extracted and glutaraldehyde treated) was investigated by in vivo rat subcutaneous implantation models and by in vitro meta stable calcium phosphate solutions. Scanning electron microscopy showed that calcification primarily involved the surface of collagen fibrils and the intrafibrillar spaces. However, the grafting of pericardium with PEG-20,000 had dramatically modified the surface and subsequently inhibited the deposits of calcium. Further, the modified tissue had also reduced the platelet surface attachment. Such a reduced calcification of PEG modified tissues can be explained by decrease of free aldehyde groups, a space filling effect and therefore improved biostability and synergistic blood compatible effects of PEG after coupling to the tissues. This simple method can be a useful anticalcification treatment for implantable tissue valves.