Browsing by Author "Mohanty, M"
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Item An X-ray micro-fluorescence study to investigate the distribution of Al, Si, P and Ca ions in the surrounding soft tissue after implantation of a calcium phosphate-mullite ceramic composite in a rabbit animal model(JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 2011) Martin, RA; Jaffer, Z; Tripathi, G; Nath, S; Mohanty, M; FitzGerald, V; Lagarde, P; Flank, AM; Stamboulis, A; Basu, BSynthetic calcium phosphates, despite their bioactivity, are brittle. Calcium phosphate-mullite composites have been suggested as potential dental and bone replacement materials which exhibit increased toughness. Aluminium, present in mullite, has however been linked to bone demineralisation and neurotoxicity: it is therefore important to characterise the materials fully in order to understand their in vivo behaviour. The present work reports the compositional mapping of the interfacial region of a calcium phosphate-20 wt% mullite biocomposite/soft tissue interface, obtained from the samples implanted into the long bones of healthy rabbits according to standard protocols (ISO-10993) for up to 12 weeks. X-ray micro-fluorescence was used to map simultaneously the distribution of Al, P, Si and Ca across the ceramic-soft tissue interface. A well defined and sharp interface region was present between the ceramic and the surrounding soft tissue for each time period examined. The concentration of Al in the surrounding tissue was found to fall by two orders of magnitude, to the background level, within similar to 35 mu m of the implanted ceramic.Item Cellular basis for failure of joint prosthesis(BIO-MEDICAL MATERIALS AND ENGINEERING, 1996)In recent times, loosening of joint prosthesis resulting in failure, is of grave concern to orthopedicians. It is estimated that 50% of total hip replacements become loose after 15 years, and most of them require either revision surgery or resection orthoplasty. Neither, newer operative techniques, change in design, use of novel materials, nor surface modifications have helped to circumvent the problem. It is in this context, that attention has been focussed on the role of tissue surrounding the implant, in the loosening of the prosthesis.Tissue response around prosthesis results in either formation of a fibrous layer around the implant, ingrowth into fenestrations on implant or direct bone apposition on prosthesis. Long-term implantation results in implant debris being released into surrounding tissue. These particles initiate a chronic granulonatous inflammation with a significant number of activated macrophages and foreign body type of giant cells, all engaged in attempts to get rid of the debris. These features have been found to be invariably associated with peri-prosthetic lysis of bone. Since such bone resorption is also observed around non-cemented prosthesis, possibly causes other than cement are responsible for the osteolysis.Retrospective studies on failed implants suggest that peri-prosthetic osteolysis is mediated by activated macrophages. Cytokines are capable of stimulating bone resorbing cells, the osteoclasts. Bone resorption results in further loosening of the prosthesis, changes in stress, frictional wear, release of more wear debris and recruitment of more macrophages. Bone death and proliferation of macrophages, thus appear to be the cause for pain and loosening of prosthesis.Item Comparative evaluation of absorbable hemostats: advantages of fibrin-based sheets(BIOMATERIALS, 2004)Bioactive hemostats and wound dressings consist of either inherently active materials or act as delivery vehicles which contain such materials. Fibrin is a natural hemostat and scaffold, guiding the direction of wound contraction and closure. In order to improve the ease of application of liquid fibrin glue, we have made a freeze-dried form of polymerized fibrin that supports hemostasis and wound healing. The bleeding from the middle ear artery of rabbits was found to be arrested instantaneously on application of fibrin sheets, even when the animal was heparinized systemically. As the fibrin sheet was found to be fragile, gelatin was incorporated to the sheet and thus the mechanical stability was improved without compromising the hemostatic effect. The efficacy of the fabricated fibrin and fibrin-gelatin sheets to seal traumatized rat liver was compared with commercially available hemostats, Abgel (cross-linked gelatin) and Surgicel (cross-linked cellulose). Tissue compatibility of all the hemostats was studied by analyzing the liver tissue 15 days after application. While the hemostatic effect was best with fibrin and fibrin-gelatin sheets, both Surgicel and Abgel were not capable of arresting the bleeding quickly. Gross analysis of tissue on the 15th day of application, visibly, Abgel was not only degraded but resulted in severe adhesions of internal organs and histologically capsule formation around the implant was evident. Though Surgicel was also seen as cream soft material on the site of application that joined two pieces of liver, there was no adhesion of other internal organs and histologically, immune reaction and foreign-body-type giant cells were present in large amounts. Fibrin was not found grossly on application site whereas fibrin-gelatin was seen as a small white spot. Granulation tissue formation and cell migration into the fibrin-based sheets were evident, and therefore, fibrin-based sheets are not only efficient hemostats but showed optimum degradation and wound healing. (C) 2004 Elsevier Ltd. All rights reserved.Item Effect of 980-nm diode laser and 1064-nm Nd:YAG laser on the intervertebral disc--in vitro and in vivo studies(Photomed Laser Surg., 2009) Jayasree, RS; Gupta, AK; Bodhey, NK; Mohanty, MItem 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.Item Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin(BIOMATERIALS, 2005)Wound dressings that can be formed in situ offer several advantages over the use of preformed dressings such as conformability without wrinkling or fluting in the wound bed, ease of application and improved patient compliance and comfort. Here we describe such an in situ forming hydrogel wound dressing from gelatin, oxidized alginate and borax. Periodate oxidized alginate rapidly cross-links proteins such as gelatin in the presence of borax to give in situ forming hydrogels that are both non-toxic and biodegradable. The composite matrix has the haemostatic effect of gelatin, the wound healing-promoting feature of alginate and the antiseptic property of borax to make it a potential wound dressing material. The hydrogel was found to have a fluid uptake of 90% of its weight which would prevent the wound bed from accumulation of exudates. The water vapour transmission rate (WVTR) of the hydrogel was found to be 2686 + 124 g/m(2)/day indicating that the hydrogel can maintain a moist environment over wound bed in moderate to heavily exuding wound which would enhance epithelial cell migration during the healing process. The wound healing efficacy of hydrogel was evaluated in experimental full thickness wounds using a rat model which demonstrated that within 2 weeks, the wound covered with gel was completely filled with new epithelium without any significant adverse reactions. These in situ forming hydrogels fulfil many critical elements desirable in a wound dressing material. (c) 2005 Elsevier Ltd. All rights reserved.Item Evaluation of the effect of incorporation of dibutyryl cyclic adenosine monophosphate in an in situ-forming hydrogel wound dressing based on oxidized alginate and gelatin(BIOMATERIALS, 2006)Cyclic adenosine monophosphate (cAMP) has long been regarded as a second messenger and a regulator of human keratinocyte proliferation. To explore more effective wound management, dibutyryl cyclic adenosine monophosphate (DBcAMP), a lipophilic analog of cAMP was incorporated into an in situ-forming hydrogel wound dressing based on periodate-oxidized alginate and gelatin. In vitro release of DBcAMP from the matrix into phosphate buffered saline was slow and increased with time. Only 50-60% of the compound was released into the medium over a period of 2 days suggestive of a sustained release into the wound bed over a period of few days. The wound-healing efficacy of the DBcAMP-incorporated dressing was evaluated on experimental full-thickness wounds in a rat model. It was found that dressing promoted wound healing leading to complete re-epithelialization of wounds within 10 days, whereas control wounds took 15 days for complete re-epithelialization. Data obtained in this Study showed that the presence of DBcAMP accelerated healing and re-epithelialization of full-thickness wounds. (c) 2005 Elsevier Ltd. All rights reserved.Item F-actin and alpha-actinin reorganization mediates initial fibroblast interaction with CoCr alloy particles in vitro(MICROSCOPY RESEARCH AND TECHNIQUE, 2012) Madathil, BK; Damodaran, V; Thrikkovil, KV; Mohanty, MAsceptic loosening remains the primary cause for failure of joint implant. The active role of fibroblasts in mediating asceptic loosening is however not well documented. In this study the initial interactions of fibroblasts with metal particles was studied by evaluating changes in the cytoskeletal structure and cytokine level. Murine L929 fibroblasts cultured with cobalt chromium particles were observed by phase contrast and scanning electron microscopy (SEM). Changes in the cytoskeletal rearrangement of F-actin and a-actinin focal adhesion plaques were studied by confocal microscopy. Expression of the proinflammatory cytokines IL-6 and IL-1a were analyzed by ELISA. The role of actin filaments and microtubules in particle uptake were determined at low temperature and in presence of colchicine and cytochalasin B. Phase contrast and SEM studies reveal that the metal particles adhere to the fibroblasts. The cellular cytoplasm was observed to grow over the particles and is suggestive of particle uptake. Confocal microscopy shows the presence of voids within the F-actin cytoskeletal framework corresponding to areas occupied by the metal particles, indicating the possible uptake of these particles. Aggregates of a-actinin into patches at the cell surface were also noted. Adherence and uptake of particles did not occur at low temperature and in presence of cytochalasin B, indicating that it is an active energy-dependent process involving actin filaments. Changes in the levels of cytokine IL-6 and IL-1a were not observed suggesting the role of other cytokine molecules in mediating the inflammatory response to wear debri by fibroblasts. Microsc. Res. Tech. 2012. (c) 2012 Wiley Periodicals, Inc.Item Fibrinolysis inhibitors adversely affect remodeling of tissues sealed with fibrin glue(BIOMATERIALS, 2003)Experiments have been carried out to determine if aprotinin and epsilon-amino caproic acid increases the quality of Fibrin glue. A rat model was used for tissues such as liver and skin while rabbits were used for application of glue in dura mater. Apposition of all the tissues, glued with fibrin was found to be good and remnants of the polymerized fibrin were seen even on the seventh day of application, though inhibitors were not incorporated with the glue. In skin, excessive amounts of fibrin remained as a result of addition of aprotinin and epsilon-amino caproic acid, as compared to the glue applied without any inhibitor. After dural sealing, the wound repair and new bone formation at cramotomy site progressed well in the fibrin glue applied area as compared to the commercially available glue that contained aprotinin. The adhesive strength of the glue without or with fibrinolysis inhibitors was found to be similar, after 1 h grafts on rat back. The observations from this study suggests that the use of aprotinin with fibrin glue may not be required because, even liver tissue that is known to have high fibrinolytic activity was sealed and repaired well in the absence of plasminogen inhibitors. On the other hand, it was found that if inhibitors were added, nondegraded matrix remained in the tissue even after 15 days and affected migration of repair cells. Thus, the inhibition of fibrinolysis after fibrin glue application is found detrimental to wound healing. (C) 2002 Elsevier Science Ltd. All rights reserved.Item In vitro and in vivo performance of a dual drug-eluting stent (DDES)(BIOMATERIALS, 2010) Huang, YY; Venkatraman, SS; Boey, FYC; Lahti, EM; Umashankar, PR; Mohanty, M; Arumugam, S; Khanolkar, L; Vaishnav, SThis study reports on a dual drug-eluting stent (DDES) that has an anti-proliferative and an anti-thrombotic in a biodegradable polymer-coated onto a cobalt-chromium stent. The DDES was prepared by spray coating the bare metal stent with a biodegradable polymer loaded with sirolimus and triflusal, to treat against restenosis and thrombosis, respectively. The 2-layered dual-drug coated stent was characterized in vitro for surface properties before and after expansion, as well as for possible delamination by cross-sectioning the stent in vitro. The in vitro anti-platelet behavior of the triflusal-loaded films was investigated by using dynamic platelet adhesion measurements. Additionally, the in vitro degradation and release study of the films and the stents w/single sirolimus and dual sirolimus-triflusal in different formulations were examined. Finally, in vivo studies (in a porcine carotid artery model) were performed for acute thrombosis, inflammation and restenosis at 30 days. The in vitro results show DDES can sustain release both anti-proliferation drug (sirolimus) and anti-thrombosis drug (triflusal), two drugs were controlled in different rates to effectively reduce thrombosis and proliferation at the same time. In vivo results show a significant reduction in restenosis with dual-drug eluting stent compared with the controls (a bare metal stent, a sirolimus coated and a pure polymer-coated stent). The reduction in restenosis with a dual sirolimus-triflusal eluting stent is associated with an inhibition of inflammation, especially thrombus formation, suggesting that such dual-drug eluting stents have a role to play for the treatment of coronary artery disease. (C) 2010 Elsevier Ltd. All rights reserved.Item In Vivo Response of Novel Calcium Phosphate-Mullite Composites: Results Up to 12 Weeks of Implantation(JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, 2009) Nath, S; Basu, B; Mohanty, M; Mohanan, PVIn this paper, the in vivo response, in particular, the histocompatibility of newly developed CaP-mullite composites is reported. In the present experiments, the bioceramic implants were inserted in the long bones of healthy rabbits according to standard protocols (ISO-10993) and the tissue response was studied at different time intervals of up to 12 weeks. Ultra high-molecular weight polyethylene (UHMWPE) was used as control samples. The postimplant bone-material interfaces were analyzed by staining of histological sections, following bone tissue histopathology protocols. The interface zones were critically observed by fluorescent optical microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). Importantly, no inflammation, necrosis was observed during this tenure. New bone formation was observed at all the implantation time intervals (1-12 weeks). However, the bone integrity with the material was increased after 12 weeks of implantation. Although macrophages and fibrous tissue were present during the first week of implantation, they were not observed on histology sections after 12 weeks postimplantation. More importantly, foci of chondrocytes could be observed after 12 weeks of implantation. Remodeling of Haversian canal was observed at the interfacial area of natural bone and implant material. All the observations were assessed critically to analyze the in vivo biocompatibility of this novel composite material. (C) 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 90B: 547-557, 2009Item Influence of curing agent on fibrosis around silicone implants(JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, 2013) Joseph, J; Mohanty, MSevere capsular contracture around silicone expander breast implants leading to pain and failure is a major clinical problem. Even though earlier studies have implicated the immunogenicity of silicone, the role of physical and chemical properties of the silicone material in excessive collagen deposition and fibrosis has been less addressed. The present study investigates whether there is any correlation between the type of curing systems i.e. addition and free radical curing and the fibrosis around silicone elastomer. The experiment carried out uses commercially available silicone ventriculo-peritoneal shunt material elastomer cured by platinum and the results are compared with results obtained in a similar study carried out by the authors using commercially available silicone tissue expander material cured by peroxide. Ultra-high molecular weight poly-ethylene (UHMWPE), the standard reference for biocompatibility evaluation, was used as the control material. The materials were implanted in rat skeletal muscle for 30 and 90days. Inflammatory cells, myofibroblasts, cytokines, and collagen deposition at the material-tissue interface were identified by haematoxylin-eosin and Masson's Trichrome stains and semi-quantitated based on immunohistochemical studies. Results indicate that even though the cellular response in the initial phase of wound healing was similar in both platinum and peroxide-cured materials, the collagen deposition in the proliferative phase was more around peroxide-cured material in comparison to the platinum-cured silicone elastomer. There is a need to look into the molecular mechanisms of this interaction and the possibility of using curing systems other than free radical peroxide in the manufacture of silicone elastomer expanders for breast prosthesis.Item Long term tissue response to titanium coated with diamond like carbon(BIOMOLECULAR ENGINEERING, 2002)Diamond like carbon (DLC) coatings were deposited on to Ti substrates by plasma enhanced chemical vapor deposition technique. Ti and DLC/Ti samples were implanted in skeletal muscle of rabbits. The samples were explanted after 1, 3, 6 and 12 months and the tissue-cell interaction was studied. Our data indicate both DLC/Ti and bare Ti to be compatible with skeletal muscle. (C) 2002 Elsevier Science B.V. All rights reserved.Item Mediatory role of interleukin-6 in alpha smooth muscle actin induction and myofibroblast formation around silicone tissue expander(JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2013) Joseph, J; Variathu, KT; Mohanty, MMaterials used for medical devices are usually tested for their biocompatibility, before use. However, it is known that long-term implantation in the body may lead to degradation of the material leading to an adverse tissue response. The failure of silicone breast implants due to excessive fibrosis and contracture has led to studies to delineate the cause of fibrosis around this material. To detect the biological moieties involved, conditioned media from RAW 264.7 macrophages seeded over commercially available silicone tissue expander material was added to L929 fibroblasts. Ultrahigh-molecular-weight polyethylene and tissue culture grade polystyrene served as the control materials. The gene expression of fibrogenic cytokines, interleukin-6 (IL-6), and transforming growth factor beta (TGF) in the RAW macrophages and myofibroblast marker alpha smooth muscle actin (SMA) in L929 cells were quantitated by real time polymerase chain reaction. Protein expression analysis of SMA was carried out by immunocytochemical staining and confocal microscopy. An in vitro degradation study of silicone expander material in pseudoextracellular fluid (PECF) and the SMA expression in fibroblasts incubated with the silicone extract containing PECF has revealed the role of silicone leachants in induction of myofibroblasts. This in vitro expression study revealed the additional profibrotic role of IL-6 in fibroblast to myofibroblast transition and the synergy between material aspects and biomolecules in regulating fibrosis around Silicone implants. These findings may help in targeting newer biological moieties in the profibrotic pathway and in devising better manufacturing processes aiding the life of millions of patients. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2967-2973, 2013.Item Pulsed electromagnetic field therapy results in healing of full thickness articular cartilage defect(INTERNATIONAL ORTHOPAEDICS, 2011) Boopalan, PRJVC; Arumugam, S; Livingston, A; Mohanty, M; Chittaranjan, SThis study aimed to determine the efficacy of PEMF (pulsed electromagnetic field) treatment in experimental osteochondral defect healing in a rabbit model. The study was conducted on 12 New Zealand white rabbits. Six rabbits formed the study group and six rabbits the control group. The right knee joints of all 12 animals were exposed and a 3.5-mm diameter osteochondral defect was created in the trochlear groove. The defect was filled with calcium phosphate scaffold. Six animals from the study group were given PEMF of one hour duration once a day for six weeks with set parameters for frequency of 1 Hz, voltage 20 V, sine wave and current +/- 30 mA. At six weeks the animals were sacrificed and histological evaluation was done using H&E, Safranin O, Maissons trichrome staining and immunohistochemistry for type 2 collagen. The quality of the repair tissue was graded and compared between groups with the Wakitani histological grading scale and a statistical analysis was done. The total histological score was significantly better in the study group (p = 0.002) with regeneration similar to adjacent normal hyaline cartilage. Immunohistochemistry for collagen type II was positive in the study group. PEMF stimulation of osteochondral defects with calcium phosphate scaffold is effective in hyaline cartilage formation. PEMF is a non-invasive and cost effective adjuvant treatment with salvage procedures such as abrasion chondroplasty and subchondral drilling.Item Safety and efficacy of Chitra-CPC calcium phosphate cement as bone substitute(CURRENT SCIENCE, 2006) Fernandez, AC; Mohanty, M; Varma, HK; Komath, MCalcium phosphate cements (CPCs) have gained importance in orthopaedics and dentistry as repair materials for bony/dentinal defects. They are aqueous based, mouldable and osteoconductive materials which set into hydroxyapatite, the basic mineral of bone and teeth. A CPC product 'Chitra-CPC' has been developed. This communication compiles the safety and efficacy evaluation of Chitra-CPC. The evaluation plan consisted of acute systemic toxicity test (in mice for systemic response), intracutaneous reactivity test (in rabbits for skin response), pyrogen test (in rabbits for presence of pyrogens) and maximization sensitization test (in guinea pigs for allergic skin response). Soft tissue response was tested by implantation in rabbit paravertebral muscle, with histological evaluation at 1, 4 and 12 weeks post-implantation. The efficacy of the product to heal bone defects was investigated by implanting in rabbit femur with hydroxyapatite ceramic granules as the control. Local effects at macroscopic and microscopic levels were assessed at time periods of 4, 12, 26 and 52 weeks post implantation. The cement did not show any adverse effects in the acute systemic toxicity. Nor did it elicit any erythemic or edematous reactivity in the intracutaneous reactivity test. The maxindzation sensitization study did not show any adverse skin response and the pyrogen test did not evoke undue temperature rise. In the muscle implantaion test, there was no haemorrhage, infection or necrosis. Localized vascularization was present near the implanted region. Chronic inflammation was observed in 1 week, which became mild by 12 weeks with the evidence of repair. Bone implantation studies showed that efficacy of Chitra-CPC and hydroxyapatite granules in bone healing is comparable. Both materials were found to be osteoconductive, but with the difference that Chitra-CPC resorbed progressively allowing simultaneous new bone formation. This proves the osteotransductivity of Chitra-CPC, which is the ideal property for a bone substitute.Item Short term tissue response to carbon fibre: A preliminary in vitro and in vivo study(BULLETIN OF MATERIALS SCIENCE, 1998) Mohanty, M; Kumary, TV; Lal, AV; Sivakumar, RCarbon in the form of pyrolytic carbon coating is used in a number of implantable medical devices. Carbon-reinforced carbon composite and other forms of diamond-like carbon coatings are being evaluated for their many potential biomedical applications. There is also a possibility of using carbon in fibre form. Though the possibility of using the fibre form of carbon in skeletal and dental implants has been recognized, a detailed study of tissue reaction to carbon fibre has not been reported so far. In this paper, we describe in vitro and irt vivo evaluation of carbon fibre in bone and muscle. Good cell and tissue biocompatibility of the material was observed in bone and muscle. New bone was present in contact with the fibres. Results of this study indicate that carbon fibre has potential in non-load bearing applications, such as skeletal repair and as ligament prosthesis.Item Spinal fixation device: A 6-year postimplantation study(JOURNAL OF BIOMATERIALS APPLICATIONS, 2003)Long-term tissue response to a metal device is described here. The components of a spinal fixation device were removed 6 years after implantation, following the need for revision surgery after a fall. Scanning electron microscopy (SEM) revealed changes in surface topography of the metal. Examination of the adjacent tissue showed a chronic inflammatory response with occasional metal debris. Immunohistochemistry identified the predominant macrophages and abundant neovascularization. The presence of macrophages in tissues adjacent to the implants, in an otherwise asymptomatic person, is noteworthy.Item Structural studies on bovine bioprosthetic tissues and their in vivo calcification: Prevention via drug delivery(BIOMATERIALS, 1996)Cardiovascular calcification, the formation of calcium phosphate deposits in cardiovascular tissue, is a common end-stage phenomenon affecting a wide variety of bioprostheses. To study the process of calcification in tissue prosthetics, glutaraldehyde-treated bovine pericardium, dura mater and fascialata were implanted subcutaneously in rats and retrieved 21 days later and thereby morphological findings were correlated with biochemically determined levels of calcium. Transmission electron microscopy showed that calcification primarily involved the surface of collagen fibrils and the interfibrillar spaces. The deposition of calcium was higher with dura and fascia prostheses compared to pericardium. However, the release of Fe3+ ions from chitosan matrix had substantially inhibited the deposits of calcium in all implanted tissues. It seems that the structural and anatomical features of the tissue is one of the important factors for tissue-associated calcification. It is also confirmed that glutaraldehyde-preserved pericardium is the most suitable material for the development of cardiac prosthesis, with an appropriate drug combination therapy for prevention of pathological calcification.Item 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.