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Mechanical characterization of biomaterials
Sanders, J. E. and S. G. Zachariah (1997), Ann N Y Acad Sci 831: 232-43.
Abstract: Experimental testing and computational modeling are two useful tools for mechanical characterization of biomaterials, providing insight into material stresses and strains and the possibility of mechanical failure and fatigue. Another interesting issue to consider, however, is tissue response to mechanical stress and strain and incorporation of that knowledge into design to create materials that form mechanically effective tissue-material interfaces in vivo. Experimental testing, computational modeling, and tissue response to stress and strain are discussed in the context of enhancing biomaterial design.

Mechanical evaluation and design of a multilayered collagenous repair biomaterial
Gloeckner, D. C., M. S. Sacks, et al. (2000), J Biomed Mater Res 52(2): 365-73.
Abstract: One method of fabricating implantable biomaterials is to utilize biologically derived, chemically modified tissues to form constructs that are both biocompatible and remodelable. Rigorous mechanical characterization is a necessary component in material evaluation to ensure that the constructs will withstand in vivo loading. In this study we performed an in-depth biaxial mechanical and quantitative structural analysis of GraftPatch (GP), a biomaterial constructed by assembling chemically treated layers of porcine small intestinal submucosa (SIS). The mechanical behavior of GP was compared to both native SIS and to glutaraldehyde-treated bovine pericardium (GLBP) as a reference biomaterial. Under biaxial loading, GP was found to be stiffer than native SIS and mechanically anisotropic, with the preferred fiber direction demonstrating greater stiffness. Quantitative structural analysis using small-angle light scattering indicated a uniform fiber structure similar to GLBP and SIS. To enable test-protocol-independent quantitative comparisons, the biaxial mechanical data were fit to an orthotropic constitutive model, which indicated a similar degree of mechanical anisotropy between the three groups. We also demonstrate how the constitutive model can be used to design layered biocomposite materials that can undergo large deformations.

Mechanical model for critical strain in mineralizing biological tissues: application to bone formation in biomaterials
Harrigan, T. P. and J. D. Reuben (1997), Biomaterials 18(12): 877-83.
Abstract: A simple theoretical model for the role of strain energy density in the initial mineralization of soft tissues is presented and used to derive a limit of the allowable strain in tissue engineered biomaterials. The model incorporates the mechanical energy in calcified tissue due to time-varying loads into the more commonly used energetic arguments for mineralization. By using the Voight (equal-strain) and Reuss (equal-stress) composite material models to relate the volumetric density of calcified tissue to overall material modules, two models were developed to assess the effect of an imposed overall material strain on mineralization. A rate equation based on strain energy was used to model the kinetics of mineralization, and the stability of the rate equation was assessed, leading to a limit on overall material strain based on the specific energy for mineralization of soft tissues. The result depended on the stiffness of the material in series with the mineralizing tissue. Taking the stiffness of the material in series with the tissue as infinite lead to a prediction of critical strain for mineralization in the calcifying biological tissue which was the same on the Reuss and Voight models. The interaction of this theoretical model with biological factors and some clinical implications of the model are discussed.

Mechanical optimization of an arteriovenous malformation embolization material: a predictive model analysis
Birdno, M. and B. Vernon (2005), Ann Biomed Eng 33(2): 191-201.
Abstract: Arteriovenous malformations (AVMs) pose a constant danger of hemorrhages, seizures, and headaches to patients; they also disrupt oxygen-rich blood flow entering capillaries of the brain. We have utilized a linear model to mechanically characterize and optimize a water-borne, reverse emulsion, self-reactive, in situ cross-linking material, which we propose clinical use as an embolization material. The material is formed by cross-linking various acrylate and thiol multifunctional precursors with NaOH supplemented PBS. We compared theoretical elastic modulus values to modulus values observed during compression testing to determine the cross-linking efficiency of the material. Empirically determined elastic moduli for various material compositions ranged from 0.76 to 2.26 MPa, with corresponding cross-link efficiencies averaging 55+/-4%. We predict a reduction in theoretical circumferential stress exerted on AVM vasculature from 4933 to 10.9 Pa after embolization with the optimal material configuration. Theoretical risk of AVM rupture, as defined by Hademenos et al., was reduced below 1.0% for extreme variations of vessel modulus, thickness, and blood pressure after embolization with the optimized material. We will be using this material configuration to embolize swine rete mirabile AVM models and further assess the clinical viability of this potential embolization material.

Mechanical properties and early clinical experience with xenograft biomaterials
McMaster, W. C. (1986), Bull Hosp Jt Dis Orthop Inst 46(2): 174-84.
Abstract: Evaluation of new materials for ligament and tendon reconstruction has opened up a new area of orthopaedic research. This report outlines the mechanical properties, animal evaluations, and early clinical results from tests of a xenograft biomaterial of bovine source treated with a gluteraldehyde-based process. A clinical trial under FDA guidelines is currently underway.

Mechanical properties and osteoconductivity of porous bioactive titanium
Takemoto, M., S. Fujibayashi, et al. (2005), Biomaterials 26(30): 6014-23.
Abstract: Porous bioactive titanium implants (porosity of 40%) were produced by a plasma-spray method and subsequent chemical and thermal treatments of immersion in a 5M aqueous NaOH solution at 60 degrees C for 24 h, immersion in distilled water at 40 degrees C for 48 h, and heating to 600 degrees C for 1 h. Compression strength and bending strength were 280 MPa (0.2% offset yield strength 85.2 MPa) and 101 MPa, respectively. For in vivo analysis, bioactive and nontreated porous titanium cylinders were implanted into 6mm diameter holes in rabbit femoral condyles. The percentage of bone-implant contact (affinity index) of the bioactive implants (BGs) was significantly larger than for the nontreated implants (CGs) at all postimplantation times (13.5 versus 10.5, 16.7 versus 12.7, 17.7 versus 10.2, 19.1 versus 7.8 at 2, 4, 8 and 16 weeks, respectively). The percentage of bone area ingrowth showed a significant increase with the BGs, whereas with the CGs it appeared to decrease after 4 weeks (10.7 versus 9.9, 12.3 versus 13.1, 15.2 versus 9.8, 20.6 versus 8.7 at 2, 4, 8 and 16 weeks, respectively). These results suggest that porous bioactive titanium has sufficient mechanical properties and biocompatibility for clinical use under load-bearing conditions.

Mechanical properties and remodeling of hybrid cardiac constructs made from heart cells, fibrin, and biodegradable, elastomeric knitted fabric
Boublik, J., H. Park, et al. (2005), Tissue Eng 11(7-8): 1122-32.
Abstract: Hybrid cardiac constructs with mechanical properties suitable for in vitro loading studies and in vivo implantation were constructed from neonatal rat heart cells, fibrin (Fn), and biodegradable knitted fabric (Knit). Initial (2-h) constructs were compared with native heart tissue, studied in vitro with respect to mechanical function (stiffness, ultimate tensile strength [UTS], failure strain epsilon(f), strain energy density E) and compositional remodeling (collagen, DNA), and implanted in vivo. For 2-h constructs, stiffness was determined mainly by the Fn and was half as high as that of native heart, whereas UTS, epsilon(f), and E were determined by the Knit and were, respectively, 8-, 7-, and 30-fold higher than native heart. Over 1 week of static in vitro culture, cell-mediated, serum-dependent remodeling was demonstrated by a 5-fold increase in construct collagen content and maintenance of stiffness not observed in cell-free constructs. Cyclic stretch further increased construct collagen content in a manner dependent on loading regimen. The presence of cardiac cells in cultured constructs was demonstrated by immunohistochemistry (troponin I) and Western blot (connexin 43). However, in vitro culture reduced Knit mechanical properties, decreasing UTS, epsilon(f), and E of both constructs and cell-free constructs and motivating in vivo study of the 2-h constructs. Constructs implanted subcutaneously in nude rats for 3 weeks exhibited the continued presence of cardiomyocytes and blood vessel ingrowth by immunostaining for troponin I, connexin 43, and CD-31. Together, the data showed that hybrid cardiac constructs initially exhibited supraphysiologic UTS, epsilon(f), and E, and remodeled in response to serum and stretch in vitro and in an ectopic in vivo model.

Mechanical properties of bacterial cellulose and interactions with smooth muscle cells
Backdahl, H., G. Helenius, et al. (2006), Biomaterials 27(9): 2141-9.
Abstract: Tissue engineered blood vessels (TEBV) represent an attractive approach for overcoming reconstructive problems associated with vascular diseases by providing small calibre vascular grafts. The aim of this study has been to evaluate a novel biomaterial, bacterial cellulose (BC), as a potential scaffold for TEBV. The morphology of the BC pellicle grown in static culture was investigated with SEM. Mechanical properties of BC were measured in Krebs solution and compared with the properties of porcine carotid arteries and ePTFE grafts. Attachment, proliferation and ingrowth of human smooth muscle cells (SMC) on the BC were analysed in vitro. The BC pellicle had an asymmetric structure composed of a fine network of nanofibrils similar to a collagen network. The shape of the stress-strain response of BC is reminiscent of the stress-strain response of the carotid artery, most probably due to the similarity in architecture of the nanofibrill networks. SMC adhered to and proliferated on the BC pellicle; an ingrowth of up to 40mum was seen after 2 weeks of culture. BC exhibit attractive properties for use in future TEBV.

Mechanical properties of implantable biomaterials
Meaney, D. F. (1995), Clin Podiatr Med Surg 12(3): 363-84.
Abstract: This chapter was intended to review many of the terms used to describe the behavior of biomaterials including linear elastic, plastic, and viscoelastic behavior. Common testing methods for evaluating the behavior of biomaterials were also reviewed. Uniaxial loading, perhaps the most common testing procedure, can characterize both time-independent (i.e., linear elastic and plastic) and time-dependent (viscoelastic) materials with a controlled loading condition. Bending tests, because of their ease, are also popular and can describe linear elastic and plastic behavior fairly well. Vibratory methods to measure viscoelastic behavior, on the other hand, are less popular but are essential if the expected loading condition of the biomaterial will be fairly rapid. Taken together, these tests form the foundation for understanding the applicability of a specific material for use as an implant, and can be used to predict not only the failure thresholds for the implant but also the expected remodeling response of the bone once the implant has been placed in situ. For this reason, characterizing the mechanical properties of implant materials has been and will continue to be an important step in implant design.

Mechanical properties of laser cut poly(L-lactide) micro-specimens: implications for stent design, manufacture, and sterilization
Grabow, N., M. Schlun, et al. (2005), J Biomech Eng 127(1): 25-31.
Abstract: BACKGROUND: The development of endoluminal stents from polymeric materials requires an understanding of the basic mechanical properties of the polymer and the effects of manufacturing and sterilization on those properties. METHODS: Pure poly(L-lactide) (PLLA) and PLLA containing varying amounts of triethylcitrate (TEC) as a plasticizer (5-10-15%) were studied. The specimens were solution-cast and CO2 laser-cut. Specimen dimensions were adapted to the strut size of polymeric vascular stents. The properties of the PLLA micro-specimens were assessed before and after sterilization (EtO cold gas, H2O2-plasma, beta- and gamma-irradiation). Tensile tests, and creep and recovery tests were carried out at 37 degrees C. Additionally the thermal and thermo-mechanical characteristics were investigated using dynamic-mechanical analysis (DMA) and differential scanning calorimetry (DSC). RESULTS: The results showed the dramatic influence of the plasticizer content and sterilization procedure on the mechanical properties of the material. Laser cutting had a lesser effect. Hence the effects of processing and sterilization must not be overlooked in the material selection and design phases of the development process leading to clinical use. Altogether, the results of these studies provide a clearer understanding of the complex interaction between the laser machining process and terminal sterilization on the primary mechanical properties of PLLA and PLLA plasticized with TEC.

Mechanical properties of the bone-porous biomaterial interface: elastic behavior
Moyle, D. D., J. J. Klawitter, et al. (1973), J Biomed Mater Res 7(3): 363-82.

Mechanical resistance of a new biomaterial, ostrich pericardium, and a new method of joining tissues combining suturing and a biological adhesive
Garcia Paez, J. M., A. Carrera Sanmartin, et al. (2005), J Biomed Mater Res B Appl Biomater 72(1): 9-16.
Abstract: We studied the mechanical behavior in response to tensile stress of samples of ostrich pericardium bonded with a cyanoacrylate glue or sewn with a rectangular, overlapping suture that was subsequently sealed with the same bioadhesive. Seventy-two trials were performed in three series of 24 samples each: series AG, glued with an overlap of 1 cm2; series ASG, sewn with a rectangular, overlapping suture and sealed; and series AC, control samples that were left intact. The mean stress at rupture in series AG (glued) was 0.1 MPa, much lower than the working stress of a human valve leaflet, which is approximately 0.25 MPa. In the control series, this stress was 26.28 MPa. At rupture in series ASG (sutured/glued), the suture material was being subjected to a stress of 64.91 MPa, thus confirming the existence of an interaction between the suture and the shear stress exerted by the suture on the samples of pericardium. In series ASG, the mean value for the resistance to rupture when measured in machine kg was 8.83 kg, lower than but similar to that recorded in the control series AC (10.26 kg). The percentages of reversible deformation, or elongation, once the samples were torn were similar in series AC (19.15%) and ASG (21.93%). This phenomenon can only be explained by the damage to the collagen fibers in the area around the rupture, while other more distant regions work at a lower load within the elastic limit. We conclude that cyanocrylate adhesives alone are not suitable as bonding materials in cardiac bioprostheses. The results with the rectangular, overlapping suture, when subsequently sealed with an adhesive, can be considered good because, although this approach does not impede shear stress, it does maintain an excellent degree of resistance to rupture of the samples thus joined. We stress the need to take into account the concentration of the load in the design of bioprostheses.

Mechanical signalling: lessons from the past that control the future
Williams, D. (2005), Med Device Technol 16(2): 9-10.
Abstract: Relative movement between an implanted material and tissues can play a decisive role in generating the host response. As with other components of the biocompatibility of devices, it is essential to control the mechanical signalling associated with this movement if we are to optimise this response.

Mechanics of soft-solid-liquid-crystal interfaces
Rey, A. D. (2005), Phys Rev E Stat Nonlin Soft Matter Phys 72(1 Pt 1): 011706.
Abstract: The interfacial mechanics of soft elastic solids and nematic liquid crystals is presented. The theory can be applied to interfaces involving gels, elastomers, biomaterials, and thermotropic nematic liquid crystals. A model of anisotropic elastic interfaces is formulated and used to derive two fundamental capillary quantities: (i) interfacial torques on the nematic orientation, and (ii) capillary pressure. The couplings between soft-solid deformation and liquid-crystal anisotropic interfacial tension is shown to lead to strain-induced anchoring transitions, and strain-induced morphological instabilities.

Mechanism of bone incorporation of beta-TCP bone substitute in open wedge tibial osteotomy in patients
Gaasbeek, R. D., H. G. Toonen, et al. (2005), Biomaterials 26(33): 6713-9.
Abstract: A histological study was performed of bone biopsies from 16 patients (17 biopsies) treated with open wedge high tibial osteotomies for medial knee osteoarthritis. The open wedge osteotomies were filled with a wedge of osteoconductive beta tricalcium phosphate (beta-TCP) ceramic bone replacement. At the time of removal of the fixation material, core biopsies of the area where the beta-TCP was located were taken at different follow-up periods (6-25 months). beta-TCP resorption, bone ingrowth and bone remodelling were studied. We hypothesized that the incorporation and remodelling process occurs similarly as in animals. Histology showed a good resorption of the beta-TCP with complete incorporation and remodelling into new bone. The different phases as described in animal studies were found. A correlation was found between histological findings and radiological assessment. In conclusion, beta-TCP appeared to be a bone replacement material with optimal biocompatibility, resorption characteristics and bone conduction properties for the clinical use.

Mechanism of complement activation during extracorporeal blood-biomaterial interaction: effects of heparin coated and uncoated surfaces
Kopp, R., K. Mottaghy, et al. (2002), Asaio J 48(6): 598-605.
Abstract: In vitro studies with miniaturized rotating circuits and heparinized human blood, as well as long-term extracorporeal membrane oxygenation with either heparin coated (HBS) or uncoated surfaces connected to adult sheep, were performed comparing the impact on complement activation in blood and on surfaces. Analysis of surface bound complement proteins revealed significantly reduced binding of activated C3 and C5b-9 to HBS in vitro, compared with uncoated surfaces, which was probably due to more HBS bound complement inhibitors (C1-Inhibitor, factor H) being present. This was reflected by significantly reduced activation of the alternative pathway (C3bBbP) and terminal complex (SC5b-9) by HBS but slightly increased levels of classic pathway complex (C1rs-C1-inhibitor). These results were confirmed during in vivo study by analysis of hemolytic complement function, activation specific C3 derived split products, and surface bound complement proteins. Increased binding of complement regulators to HBS appears to effectively reduce complement activation by biomaterials, leading to improved long-term biocompatibility.

Mechanism(s) of increased vascular cell adhesion on nanostructured poly(lactic-co-glycolic acid) films
Miller, D. C., K. M. Haberstroh, et al. (2005), J Biomed Mater Res A 73(4): 476-84.
Abstract: Studies have shown that poly(lactic-co-glycolic acid) (PLGA) films with nanometer surface features promote vascular endothelial and smooth muscle cell adhesion. The objective of this in vitro research was to begin to understand the mechanisms behind this observed increase in vascular cell adhesion. Results provided evidence that nanostructured PLGA adsorbed significantly more vitronectin and fibronectin from serum compared to conventional (or those not possessing nanometer surface features) PLGA. When separately preadsorbing both vitronectin and fibronectin, increased vascular smooth muscle and endothelial cell density was observed on nanostructured (compared to conventional) PLGA. Additionally, blocking of cell-binding epitopes of fibronectin and vitronectin significantly decreased vascular cell adhesion on nanostructured (compared to conventional) PLGA. For this reason, results of the present in vitro study demonstrated that cell adhesive proteins adsorbed in different quantities and altered bioactivity on nanostructured compared to conventional PLGA topographies, which (at least in part) may account for the documented increased vascular cell adhesion on nanostructured PLGA. In this manner, this study continues to provide evidence for the promise of nanostructured PLGA in vascular tissue engineering applications.

Mechanisms of biomaterial-induced superoxide release by neutrophils
Kaplan, S. S., R. E. Basford, et al. (1994), J Biomed Mater Res 28(3): 377-86.
Abstract: Biomaterial-centered infection is an important cause of the failure of prosthetic implants and organs. Because neutrophils mediate host defense against infection, the effect of biomaterials on neutrophil superoxide release and the mechanism of that effect were investigated using three materials commonly employed in surgical practice. The graft materials were expanded polytetrafluorethylene (PTFE), polyurethane and woven dacron. Polystyrene, a commonly used laboratory support vessel, was also studied. Both polystyrene and polyurethane were activating, but serum inhibitable, whereas PTFE was nonactivating, and woven dacron was not activating unless serum was present. The signaling mechanisms used by these materials demonstrated time and material dependency. Pertussis toxin inhibition of G protein-dependent activation had little or no effect on biomaterial induced activation, whereas FMLP-induced activation of the same biomaterial-associated cells was inhibited. Protein kinase C inhibition with staurosporine greatly inhibited polystyrene-induced activation, but had only a partial effect with polyurethane and even less effect with the activation associated with serum-treated woven dacron. These studies demonstrated that biomaterial contact-induced neutrophil activation differed from that described for cells in suspension, and showed that activation mechanisms on one material cannot be extrapolated to mechanisms on other materials.

Mechanisms of cholesterol-lowering effects of dietary insoluble fibres: relationships with intestinal and hepatic cholesterol parameters
van Bennekum, A. M., D. V. Nguyen, et al. (2005), Br J Nutr 94(3): 331-7.
Abstract: Fibres with a range of abilities to perturb cholesterol homeostasis were used to investigate how the serum cholesterol-lowering effects of insoluble dietary fibres are related to parameters of intestinal cholesterol absorption and hepatic cholesterol homeostasis in mice. Cholestyramine, chitosan and cellulose were used as examples of fibres with high, intermediate and low bile acid-binding capacities, respectively. The serum cholesterol levels in a control group of mice fed a high fat/high cholesterol (HFHC) diet for 3 weeks increased about 2-fold to 4.3 mm and inclusion of any of these fibres at 7.5 % of the diet prevented this increase from occurring. In addition, the amount of cholesterol accumulated in hepatic stores due to the HFHC diet was reduced by treatment with these fibres. The three kinds of fibres showed similar hypocholesterolaemic activity; however, cholesterol depletion of liver tissue was greatest with cholestyramine. The mechanisms underlying the cholesterol-lowering effect of cholestyramine were (1) decreased cholesterol (food) intake, (2) decreased cholesterol absorption efficiency, and (3) increased faecal bile acid and cholesterol excretion. The latter effects can be attributed to the high bile acid-binding capacity of cholestyramine. In contrast, incorporation of chitosan or cellulose in the diet reduced cholesterol (food) intake, but did not affect either intestinal cholesterol absorption or faecal sterol output. The present study provides strong evidence that above all satiation and satiety effects underlie the cholesterol-lowering properties of insoluble dietary fibres with moderate or low bile acid-binding capabilities.

Mechanisms of fibrinogen domains: biomaterial interactions
Tang, L. (1998), J Biomater Sci Polym Ed 9(12): 1257-66.
Abstract: Spontaneous adsorption of fibrinogen is critical to the pathogenesis of biomaterial-mediated inflammatory responses. However, the mechanism by which adsorbed fibrinogen affects phagocyte responses is still not clear. To investigate the molecular interaction between fibrinogen and biomaterials, fibrinogen fragments (D100 and E50) were generated and used in the present study. The results indicate that biomaterial: D100 interaction is essential to fibrinogen-mediated inflammatory responses, because biomaterials precoated with D100, but not E50, prompt strong inflammatory responses. Furthermore, the results from in vitro studies show that whole molecule fibrinogen and D100 exhibit very similar protein:surface interactions. Specifically: (1) both D100 and fibrinogen have high affinity for biomaterial surfaces; and (2) the retention rates of adsorbed D100 in both in vivo and in vitro environments are as high as that for adsorbed fibrinogen. On the other hand, E50 does bind to biomaterials but with low affinity because, once bound, it is not tightly adherent to the biomaterial surfaces. Taken together, the results suggest that the mechanism of fibrinogen-mediated inflammatory responses may involve the following three consecutive events: (1) after contact with blood or tissue fluid, the D domain tends to interact with biomaterial surfaces and is important in the tight binding of fibrinogen to implant surfaces; (2) the biomaterial surface then promotes conformational changes within the D domain, exposing P1 epitope (gamma 190-202, which interacts with phagocyte Mac-1 integrin); and (3) the engagement of Mac-1 integrin with P1 epitope then triggers subsequent phagocyte adherence and reactions.

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Last Modified: 8 February 2006