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Biomedical subjects

C M Agrawal

Publications and source records attributed to C M Agrawal.

At least 37 records · Page 2Linked to original sources
PubMed1999

Short-term effects of bisphosphonates on the biomechanical properties of canine bone.

Periprosthetic osteolysis and aseptic loosening of total joint replacements are believed to be initiated often by abnormal bone resorption induced by prosthetic wear debris. Bisphosphonates can inhibit bone resorption and have been successfully used clinically to treat osteoporosis and Paget's disease. In a recent study it also was shown that a third generation bisphosphonate (alendronate) is effective in preventing wear debris-induced periprosthetic osteolysis. Since inhibition of bone resorption by alendronate may disrupt the delicate balance between bone resorption and formation in normal bone remodeling, it is possible that continuous alendronate therapy may have an adverse effect on the biomechanical properties of bone. Thus the purpose of the present study was to examine the effects of systemic alendronate administration on the biomechanical properties of normal bone using a canine total hip arthroplasty model. We evaluated the biomechanical properties of femora from canines that had received total hip replacements on one side and had been given oral alendronate daily for 23 weeks. The biomechanical properties assessed were fracture toughness, elastic modulus, tensile strength, microhardness, porosity, and weight fractions of the mineral and organic phases of bone. Also, bone microstructure was examined using optical microscopy. Our results indicate that in the short term alendronate therapy does not have any adverse effects on the intrinsic biomechanical properties of canine bone. However, the long-term effects of alendronate therapy still need to be investigated.

Alendronate↗
PubMed1999

Morphology of in vitro generated ultrahigh molecular weight polyethylene wear particles as a function of contact conditions and material parameters.

Osteolysis in total joint replacements has been linked to ultrahigh molecular weight polyethylene (UHMWPE) wear particles. Although the biological response to these UHMWPE particles is poorly understood at present, it has been demonstrated that particle size and morphology are important factors in such a response. The goal of the present study was twofold: to develop a comprehensive set of particle size and shape descriptors, and to use these descriptors to analyze the effects of different contact conditions and material parameters during the wear process on the size and morphology of UHMWPE wear debris. The three parameters studied were average contact stress (6.9 and 13.8 MPa), macromolecular orientation of the UHMWPE with respect to the wear direction (0 degrees , 45 degrees , and 90 degrees ), and UHMWPE initial surface roughness (Ra = 1 and 3 microm). Tests were performed using pin on disk or cylinder on plate systems for 3 million cycles each. The results indicated that the initial surface roughness of the UHMWPE test samples had no effect on the morphology of UHMWPE wear particles. However, particle size and morphology were a function of the average contact stress and molecular orientation of the UHMWPE.

Biocompatible Materials↗
PubMed1999

Ultrahigh molecular weight polyethylene particles have direct effects on proliferation, differentiation, and local factor production of MG63 osteoblast-like cells.

Small particles of ultrahigh molecular weight polyethylene stimulate formation of foreign-body granulomas and bone resorption. Bone formation may also be affected by wear debris. To determine if wear debris directly affects osteoblasts, we characterized a commercial preparation of ultrahigh molecular weight polyethylene (GUR4150) particles and examined their effect on MG63 osteoblast-like cells. In aliquots of the culture medium containing ultrahigh molecular weight polyethylene, 79% of the particles were less than 1 microm in diameter, indicating that the cells were exposed to particles of less than 1 microm. MG63 cell response to the particles was measured by assaying cell number, [3H]thymidine incorporation, alkaline phosphatase specific activity, osteocalcin production, [35S]sulfate incorporation, and production of prostaglandin E2 and transforming growth factor-beta. Cell number and [3H]thymidine incorporation were increased in a dose-dependent manner. Alkaline phosphatase specific activity, a marker of cell differentiation for the cultures, was significantly decreased, but osteocalcin production was not affected. [35S]sulfate incorporation, a measure of extracellular matrix production, was reduced. Prostaglandin E2 release was increased, but transforming growth factor-beta production was decreased in a dose-dependent manner. This shows that ultrahigh molecular weight polyethylene particles affect MG63 proliferation, differentiation, extracellular matrix synthesis, and local factor production. These effects were direct and dose dependent. The findings suggest that ultrahigh molecular weight polyethylene wear debris particles with an average size of approximately 1 microm may inhibit bone formation by inhibiting cell differentiation and reducing transforming growth factor-beta production and matrix synthesis. In addition, increases in prostaglandin E2 production may not only affect osteoblasts by an autocrine pathway but may also stimulate the proliferation and activation of cells in the monocytic lineage. These changes favor decreased bone formation and increased bone resorption as occur in osteolysis.

Alkaline Phosphatase↗
PubMed1999

Exercise affects the mechanical properties and histological appearance of equine articular cartilage.

Dorsal carpal osteochondral injury is a major cause of reduced performance in horses undergoing high-intensity training. It was hypothesised that the mechanical behaviour and histology of cartilage are influenced by the intensity of exercise and by location within a joint. Relationships between histology and mechanical behaviour were identified in 2-year-old horses undergoing 19 weeks of high-intensity treadmill training or low-intensity exercise and then compared between groups. Dorsal and palmar test sites were identified on radial, intermediate, and third carpal articular surfaces after euthanasia. The mechanical properties of cartilage were determined with an automated creep indentation apparatus as previously described for equine cartilage. Cartilage morphology was assessed with use of sections stained with haematoxylin and eosin and toluidine blue. Dorsal cartilage was less permeable, thinner, and had a loss of chondrocyte alignment compared with palmar cartilage. Cartilage from strenuously trained horses showed more fibrillation and chondrocyte clusters than did cartilage from gently exercised animals. Dorsal radial carpal cartilage and third carpal cartilage of strenuously trained animals were significantly less stiff than that from gently exercised animals, and the former had reduced superficial toluidine blue staining compared with that from the gently exercised group. These results indicate that topographical and exercise-related differences exist in the morphology and mechanical properties of carpal cartilage and suggest that strenuous training may lead to deterioration of cartilage at sites with a high clinical incidence of lesions.

Animals↗
PubMed1999

Development of the cytodetachment technique to quantify mechanical adhesiveness of the single cell.

Adhesion of cells to biomaterials or to components of the extracellular matrix is fundamental in many tissue engineering and biotechnological processes, as well as in normal development and tissue maintenance. Many cells on adhesive molecules will spread and form an organized actin cytoskeleton and complex transmembrane signaling regions called focal adhesions. Focal adhesions appear to function as both signaling and stabilizing components of normal adherent cell activity. To better understand adhesion formations between cells and their underlying substrata, we have designed, developed, and utilized a novel 'cytodetachment' methodology to quantify the force required to displace attached cells. We allowed bovine articular chondrocytes to attach and spread on a substratum of either fibronectin, bovine serum albumin, or standard microscope glass. The cytodetacher was then employed to displace the cells from the substratum. Our results demonstrate that a significantly greater force is required to detach cells from fibronectin versus the two other substrata, suggesting that a cell's actin cytoskeleton and perhaps focal adhesions contribute significantly to its mechanical adhesiveness. The cytodetacher allows us to directly measure the force required for cell detachment from a substratum and to indirectly determine the ability of different substrata to support cell adhesion.

Actins↗
PubMed1999

Isolation and characterization of polyethylene wear debris associated with osteolysis following total shoulder arthroplasty.

We evaluated the interface membranes surrounding three total shoulder prostheses that had been removed because of progressive aseptic loosening associated with osteolysis. The mean time between the uncomplicated initial arthroplasty and the revision procedure was twelve years (10.5, 10.5, and 16.0 years). Membranes from around both the humeral and the glenoid component were obtained from all three shoulders and were studied histologically to determine the biological response involved in the development of aseptic loosening. For the purpose of comparison, periprosthetic tissue was also obtained from the sites of four failed total hip prostheses that were associated with osteolysis. Polyethylene particles were retrieved with an enzymatic digestion technique that involved the use of papain. Raman vibrational spectroscopy verified that the particles were ultra-high molecular weight polyethylene. The particles were isolated from the tissue, and a computerized image-analysis system characterized 582 of them in terms of size and morphology. Each particle was defined with the use of six shape descriptors: equivalent circle diameter, roundness, form factor, aspect ratio, elongation, and outline fractal dimension. The particles from the hips had a mean equivalent circle diameter (and standard error of the mean) of 0.62 +/- 0.03 micrometer, were predominantly globular in shape, and had low mean values for aspect ratio (1.46 +/- 0.02) and elongation (1.85 +/- 0.03) and relatively high values for roundness (0.74 +/- 0.01) and form factor (0.87 +/- 0.01). In contrast, the particles from the shoulders had a mean equivalent circle diameter of 1.04 +/- 0.03 micrometers. In addition, they had relatively high values for aspect ratio (2.36 +/- 0.07) and elongation (4.96 +/- 0.23) and correspondingly low values for roundness (0.54 +/- 0.01) and form factor (0.67 +/- 0.01), indicating that they were more fibrillar in shape. The particles from the shoulders and those from the hips were significantly different (p < 0.0001) with respect to all of the descriptors except outline fractal dimension. The particles from the shoulders, in general, were larger and more fibrillar than the particles from the hips.

Aged↗
PubMed1999

The effect of ultra-high molecular weight polyethylene wear debris on MG63 osteosarcoma cells in vitro.

BACKGROUND: Focal osteolysis due to ultra-high molecular weight polyethylene wear debris involves effects on both bone resorption and bone formation. METHODS: The response of MG63 osteoblast-like osteosarcoma cells to ultra-high molecular weight polyethylene wear debris isolated by enzymatic digestion of granulomatous tissue obtained from the sites of failed total hip arthroplasties was examined. Scanning electron microscopy, particle-size analysis, and Fourier transform infrared spectroscopy were used to characterize the number, morphology, size distribution, and chemical composition of the particles. Cell response was assessed by adding particles at varying dilutions to confluent cultures and measuring changes in cell proliferation (number of cells and [3H]-thymidine incorporation), osteoblast function (alkaline-phosphatase-specific activity and osteocalcin production), matrix production (collagen production and proteoglycan sulfation), and local cytokine production (prostaglandin-E2 production). RESULTS: The mean size of the particles was 0.60 micrometer, and 95 percent of the particles had a size of less than 1.5 micrometers. The number of particles per gram of tissue ranged from 1.39 to 3.38x10(9). Three of the four batches of particles were endotoxin-free. Exposure of the cells to particles of wear debris significantly increased the number of cells (p<0.05) and the [3H]-thymidine incorporation (p<0.05) in a dose-dependent manner. In contrast, the addition of particles decreased alkaline-phosphatase-specific activity and osteocalcin production. Collagen production and proteoglycan sulfation were also decreased, while prostaglandin-E2 synthesis was increased by the addition of particles. CONCLUSIONS: Ultra-high molecular weight polyethylene particles isolated from human tissue stimulated osteoblast proliferation and prostaglandin-E2 production and inhibited cell differentiation and matrix production. These results indicate that particles of wear debris inhibit cell functions associated with bone formation and that osteoblasts may produce factors in response to wear debris that influence neighboring cells, such as osteoclasts and macrophages. CLINICAL RELEVANCE: Particles of wear debris, especially ultra-high molecular weight polyethylene, have been implicated in the loosening of implants and the development of osteolysis. The present study shows that particles of ultra-high molecular weight polyethylene isolated from human tissue inhibit osteoblast functions associated with bone formation. In addition, particles of wear debris induced osteoblasts to secrete factors capable of influencing neighboring cells, such as osteoclasts and macrophages. These results suggest that osteoblasts may play a role in the cascade of events leading to granuloma formation, osteolysis, and failure of orthopaedic implants.

Adult↗
PubMed1999

Effects of diabetes mellitus on the biomechanical properties of human ankle cartilage.

Metabolic changes attributable to diabetes mellitus affect numerous organ systems in the body. For example, patients with diabetes have an increased number of musculoskeletal injuries and afflictions compared with patients without diabetes and experience more morbidity associated with injury and treatment. Although diabetes also may afflict articular cartilage, no studies have shown a conclusive link between diabetes and cartilage structural integrity. The objective of this study was to obtain and compare the intrinsic material properties of human ankle articular cartilage from patients with diabetes and those without diabetes. These biomechanical properties (aggregate modulus, Poisson's ratio, shear modulus, and permeability) were found to differ significantly between specimens from patients with diabetes and patients without diabetes. Specifically, cartilage from patients with diabetes was significantly softer and more permeable than cartilage from control subjects. For example, in the central portion of the talus, cartilage from patients with diabetes had a 38% smaller aggregate modulus, 37% smaller shear modulus, and 111% larger permeability than did tissue from patients without diabetes. These results provide evidence that joint pathologic processes in patients with diabetes may be associated with compromised structural integrity of articular cartilage.

Adolescent↗
PubMed1998

Orthopaedic applications for PLA-PGA biodegradable polymers.

Biodegradable polymers, especially those belonging to the family of polylactic acid (PLA) and polyglycolic acid (PGA), play an increasingly important role in orthopaedics. These polymers degrade by hydrolysis and enzymatic activity and have a range of mechanical and physical properties that can be engineered appropriately to suit a particular application. Their degradation characteristics depend on several parameters including their molecular structure, crystallinity, and copolymer ratio. These biomaterials are also rapidly gaining recognition in the fledging field of tissue engineering because they can be fashioned into porous scaffolds or carriers of cells, extracellular matrix components, and bioactive agents. Although their future appears to be bright, several questions regarding the biocompatibility of these materials linger and should be addressed before their wide-scale use. In the context of musculoskeletal tissue, this report provides a comprehensive review of properties and applications of biodegradable PLA/PGA polymers and their copolymers. Of special interest are orthopaedic applications, biocompatibility studies, and issues of sterilization and storage of these versatile biomaterials. Also discussed is the fact that terms such as PLA, PGA, or PLA-PGA do not denote one material, but rather a large family of materials that have a wide range of differing bioengineering properties and concomitant biological responses. An analysis of some misconceptions, problems, and potential solutions is also provided.

Absorbable Implants↗
PubMed1998

Changes in the fracture toughness of bone may not be reflected in its mineral density, porosity, and tensile properties.

Age-related changes in the skeleton often lead to an increase in the susceptibility of bone to fracture. Such changes most likely occur in the constituents of bone, namely, the mineral and organic phases, and in their spatial arrangement manifested as orientation and microstructure. In the past, however, bone loss or decline in bone mineral density has been considered to be the major contributing factor for the increased risk of bone fractures, and elastic modulus and ultimate strength have been commonly used to assess bone quality and strength. However, whether these properties provide sufficient information regarding the likelihood of bone to fracture remains debatable. Using a novel fracture toughness test, which measures the energy or stress intensity required to propagate a crack within a material, the objective of this study was to investigate if the mineral density and mechanical properties of bone can accurately predict bone fragility as measured by fracture toughness. Changes in fracture toughness (K(IC)), bone mineral density (BMD), elastic modulus (E), yield and ultimate strength (sigma y and sigma s), porosity (P0), and microhardness (Hv) of bone were examined as a function of age in a baboon model. With increasing age, the fracture toughness of bone decreased, and its microhardness increased. However, no significant changes were found in BMD, E, P0, sigma y, and sigma s as a function of age. In addition, simple regression analyses revealed no significant correlation between bone fracture toughness and the other parameters, except for microhardness of bone. The results of this study indicate that changes in bone fracture toughness may not be necessarily reflected in its mineral density, porosity, elastic modulus, yield strength, and ultimate strength.

Aging↗
PubMed1998

New technique to extend the useful life of a biodegradable cartilage implant.

Biodegradable implants made of alpha-hydroxypolyesters, such as polylactic acid, polyglycolic acid, or their copolymers, undergo bulk degradation with a concomitant mass loss. Although biocompatibility or toxicity problems, which have occasionally been reported in response to these materials' in vivo behavior, have not been conclusively linked to rapid mass loss, we hypothesized that such implants should degrade and lose mass in a more uniform rate. To this end, we designed a new implant, intended to be used in articular cartilage repair, consisting of a blend of three copolymers of 50:50 poly(d,l)-lactide coglycolide with inherent viscosities of 0.23, 0.58, and 1.37 dL/g. The objective of the blend implant design was to achieve a slower rate of degradation and mass loss in comparison to a previous design, which used a single copolymer of inherent viscosity of 0.58 dL/g. The blend's in vitro degradation characteristics were obtained and compared to those of the control design in terms of mass, molecular weight, pH, mechanical properties, gross morphology, and porosity. Another objective of our study was to design and employ a novel test for assessing the permeability of porous scaffolds, using a custom apparatus under direct permeation conditions. Significant differences in the temporal behavior of the two groups were found. The blend implants maintained their overall structural integrity longer than control specimens (6 weeks versus 3 weeks). This was a surprising finding in light of the fact that losses in molecular weight were similar in the two groups. Extension of structural usefulness to 6 weeks, achieved by the method described in the study, can be expected to enhance the viability of this scaffold in an in vivo application such as cartilage repair. Thus, the blended copolymer implants may be more suitable in orthopedic applications, where a decreased degradation rate would be preferable.

Biocompatible Materials↗
PubMed1998

An interspecies comparison of bone fracture properties.

The purpose of this study was to investigate whether bone fracture properties change with species (humans, baboon, canine, bovine, and rabbit). A single-layer compact sandwich (SCS) specimen and fractography were employed to evaluate bone fracture properties. In conjunction with measurements of the density and volume fractions of the mineral and organic phases, bone microstructure were also investigated. The results of this study indicate that bone fracture properties vary considerably with species. These differences are most likely due to variations in microstructural and compositional properties of bone (mineral and collagen) between the species. Baboon bone exhibited most similar fracture, microstructural, and compositional properties compared to humans. However, significant differences were found in bone fracture properties between humans and the other three animal species. These differences were reflected either in bone microstructures or compositional properties. This interspecies comparison facilitates a better understanding of animal models and suitable use of the animal models in future bone fracture studies.

Adult↗
PubMed1997

Porous-coated titanium implant impregnated with a biodegradable protein delivery system.

Tissue ingrowth into porous-coated orthopedic and dental implants is commonly used as a means to achieve long-term fixation of these prostheses. However, the degree of tissue ingrowth is often inadequate and inconsistent. If the pores of these implants are impregnated with a controlled drug release system delivering relevant growth factors, then it might be possible to stimulate more tissue ingrowth. The present study introduces such a system based on biodegradable polymers and investigates its protein release profile and polymer degradation characteristics. Porous coated titanium implants were impregnated with a mixture of a 50%-50% polylactic acid-polyglycolic acid copolymer and a model protein, soybean trypsin inhibitor. Control implants contained only the polymer and no protein. The implants were subjected to hydrolytic degradation in phosphate buffered saline at 37 degrees C for periods of 3, 6, and 11 weeks. The protein release and the mass and molecular weight of the polymer were monitored. The results indicate that the protein is released in three distinct phases and the polymer loses almost all its mass and molecular weight by 11 weeks. There was a significant difference in the polymer degradation characteristics between the control and test implants, which might be the result of some complex polymer-protein interactions.

Biocompatible Materials↗
PubMed1997

Interfacial fracture toughness of tissue-biomaterial systems.

Tissue-biomaterial interfacial bonding strength plays a significant role in the success of the biomaterials used for load-bearing orthopedic prostheses. To assess the interfacial bonding strength, this study examined a fracture mechanics approach using a bilayer compact sandwich (BCS) specimen, in which a bilayer coupon comprising the interface between tissue and biomaterial was sandwiched between two holders. First, the theoretical basis for measuring interfacial fracture toughness using the BCS specimen was developed. Next, the effect of finite interlayer thickness on the measurements was addressed and a correction factor was determined using finite element analysis techniques. Accordingly, the theoretical solution was modified to account for the effect of the interlayer thickness. Finally, using a bone to bone-cement interface the BCS technique was empirically verified in terms of overall size, material combination, and interlayer thickness. It is expected that the BCS technique will provide an effective means for researchers to study and analyze tissue-biomaterial interfaces.

Biocompatible Materials↗
PubMed1997

Technique to control pH in vicinity of biodegrading PLA-PGA implants.

This in vitro study was performed to examine if the pH decrease in the vicinity of degrading polylactic acid (PLA) and polyglycolic acid (PGA) polymers can be offset by incorporation of basic salts within PLA-PGA implants. It has been suggested that such pH lowering results in adverse effects, which may be responsible for biocompatibility concerns raised recently about PLA and PGA polymers. The results indicated that all three salts investigated in this study were successful in controlling the decrease in pH due to the acidic degradation products of the copolymer. The pH of the test media for the control group fell to a value of 3.0 at 9 weeks. Implants containing calcium carbonate maintained the pH value between 7.4 and 6.3 throughout the degradation process. Implants with calcium hydroxyapatite and sodium bicarbonate controlled the pH values between 6.9 and 4.3 and 8.2 and 4.5, respectively. At 3 weeks, marked swelling of implants containing calcium carbonate or sodium bicarbonate was observed relative to the control implants. The molecular weight and mass changes in the implants did not show any significant differences at 9 weeks. Thus, results from this in vitro model show that a significant decrease in pH in the vicinity of PLA-PGA implants can be avoided by incorporating basic salts.

Biocompatible Materials↗
PubMed1996

Fracture toughness of bone using a compact sandwich specimen: effects of sampling sites and crack orientations.

The energy required to propagate a crack through bone can be estimated in terms of its fracture toughness, which is an intrinsic property and an important measure of the material's susceptibility to fracture. However, in the past detailed fracture toughness characterization of bone has been limited due to specimen size limitations. To address this issue the present study used a compact sandwich specimen and examined the variation in fracture toughness of bovine femoral bone as a function of testing sites and crack orientations. Two crack orientations, radial and circumferential, and three testing sites situated along the thickness of bone were investigated. The results indicated that there were statistically significant differences in fracture toughness between the testing sites for both radial and circumferencial cracks. Crack orientation also appeared to influence the fracture toughness at two of the test sites. The microstructure of bone and its fracture surface morphology were examined using microscopy and exhibited differences corresponding to the differences in fracture toughness, thus suggesting a correlation between microstructure and fracture toughness.

Animals↗
PubMed1996

Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers.

This is a review of salient studies of sterilization, toxicity, biocompatibility, clinical applications and current work in the field of orthopaedics, using implants made of polylactic acid (PLA), polyglycolic acid (PGA) and their copolymers. The intrinsic nature of these biomaterials renders them suitable for applications where temporally slow releases of bioactive agents in situ may be required. They are also desirable as fixation devices of bone, because they can virtually eliminate osteopenia associated with stress shielding or additional surgery. The majority of currently available sterilization techniques are not suitable for these thermoplastic materials and it may be desirable to develop new sterilization standards, which can account for the special character of PLA-PGA materials. Biocompatibility and toxicity studies suggest that, overall, PLA-PGA biomaterials may be suitable for orthopaedic applications, although certain problems, especially pertaining to reduction in cell proliferation, have been reported. Clinical applications are also promising, albeit not without problems usually associated with transient tissue inflammation. The future of these materials appears bright, especially in soft tissues. They may be used to address the exceedingly complex problem of osteochondral repair, but also as a means to enhance fixation and repair processes in tendons and ligaments.

Animals↗