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Repair of an intercalated long bone defect with a synthetic biodegradable bone-inducing implant
Yoneda, M., H. Terai, et al. (2005), Biomaterials 26(25): 5145-52.
Abstract: Recombinant human bone morphogenetic protein (rhBMP)-2 in a block copolymer composed of poly-D,L-lactic acid with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) as a carrier and porous beta-tricalcium phosphate (beta-TCP) blocks were used to generate a new fully absorbable osteogenic biomaterial. The bone regenerability of the rhBMP-2/PLA-DX-PEG/beta-TCP composite was studied in a critical-sized rabbit bone defect model. In an initial study, a composite of PLA-DX-PEG (250 mg) and beta-TCP (300 mg) loaded with or without rhBMP2 (50 microg) was implanted into a 1.5 cm intercalated bone defect created in a rabbit femur. Defects were assessed by biweekly radiography until 8 weeks postoperatively. The bony union of the defect was recognized only in the BMP-loaded group. To obtain further data on biomechanical and remodeling properties, another BMP-loaded composites group was made and observed up to 24 weeks. All defects were completely repaired without residual traces of implants. Anatomical and mechanical properties of the repaired bone examined by histology, 3-dimensional CT (3D-CT) and mechanical testing were essentially equivalent to the nonoperated-on femur at 24 weeks. These experimental results indicate that fully absorbable rhBMP-2/PLA-DX-PEG/beta-TCP is a promising composite having osteogenicity efficient enough for repairing large bone defects.

Repair of bone tissue affected by osteoporosis with hydroxyapatite-poly-L-lactide (HAp-PLLA) with and without blood plasma
Ajdukovic, Z., S. Najman, et al. (2005), J Biomater Appl 20(2): 179-90.
Abstract: The aim of this study is to examine the reparatory ability of the synthetic biomaterial hydroxyapatite-poly-L-lactide (HAp-PLLA), the replacement of alveolar ridge, and rehabilitation of bone defects caused by osteoporosis, in an experimental group of animals. The experiments are performed on syngeneic Sprague Dawley rats. Osteoporosis is induced by glucocorticoids in rats during a 12-week period. After this, the experimental group of animals is divided into five subgroups. An artificial defect is made in the alveolar bone on the left side of the mandible. In one group of animals, the defect is left to heal by itself, while in other groups, pure HAp-PLLA or one mixed with plasma is implanted. The best results are achieved by the implantation of the HAp-PLLA composite biomaterial mixed with autologous plasma. Formation of a new mandibular bone is seen, growing intensely, leading to rapid osteogenesis.

Repair of bony defect with combination biomaterials
Velich, N., Z. Nemeth, et al. (2004), J Craniofac Surg 15(1): 11-5.
Abstract: BACKGROUND: Numerous possibilities are available for the reconstruction of facial bone defects. The materials used to fill such defects must satisfy various requirements. One of the most important is that they must undergo transformation into autologous bone tissue in the process of remodeling. AIM: A report is given of the long-term results of augmentations of large bone defects performed with different bone-substitute materials in two patients. PATIENTS AND METHODS: In one case, augmentation was carried out with beta-tricalcium phosphate after the removal of a fibromyxoma. In the second case, three large cystic lesions in the mandible of a patient with Gorlin-Goltz syndrome were filled with beta-tricalcium phosphate, with a mixture of beta-tricalcium phosphate and platelet concentrate, or with hydroxyapatite of algal origin. The process of ossification was checked at 6-month intervals by means of clinical, radiologic (orthopantomograms and two-dimensional and three-dimensional computer tomograms), and histologic methods. RESULTS: At 1 year after the intervention, the site of the augmentation was in all cases occupied by hard tissue of good quality. With the given imaging procedures, it was difficult to distinguish between the original bone and the region filled with bone-substitute material. The three-dimensional computer tomogram images indicated that the contours and quality of the new bone corresponded with the physiologic and anatomical conditions. The histologic examinations show the remodeling of the bone-substitute materials. DISCUSSION: The bone-substitute materials applied in these cases fully satisfied the demands of transformation into bone (remodeling). The speed of remodeling seemed to be the fastest when the mixture of beta-tricalcium phosphate and platelet concentrate was used.

Repair of experimental arteriotomy in rabbit aorta using a new resorbable elastin-fibrin biomaterial
Lefebvre, F., F. Drouillet, et al. (1989), J Biomed Mater Res 23(12): 1423-32.
Abstract: A new artificial connective matrix which results from two reactions of fibrinogen and fibronectin on elastin was used to obturate a slit made in the abdominal aorta of rabbit. The so-called Elastin-Fibrin biomaterial behaved as a scaffold through which all the different structures were restored to their former condition. At 3 months, the material had disappeared and no thrombus, no inflammation or reject had been detected.

Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds
Solchaga, L. A., J. S. Temenoff, et al. (2005), Osteoarthritis Cartilage 13(4): 297-309.
Abstract: OBJECTIVE: The natural repair of osteochondral defects can be enhanced with biocompatible, biodegradable materials that support the repair process. It is our hypothesis that hyaluronan-based scaffolds are superior to synthetic scaffolds because they provide biological cues. We tested this thesis by comparing two hyaluronan-based scaffolds [auto cross-linked polysaccharide polymer (ACP) and HYAFF-11] to polyester-based scaffolds [poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA)] with similar pore size, porosity and degradation times. DESIGN: Fifty-four rabbits received bilateral osteochondral defects. One defect received a hyaluronan-based scaffold and the contralateral defect received the corresponding polyester-based scaffold. Rabbits were euthanized 4, 12 and 20 weeks after surgery and the condyles dissected and processed for histology. RESULTS: Only ACP-treated defects presented bone at the base of the defect at 4 weeks. At 12 weeks, only defects treated with rapidly dissolving implants (ACP and PLGA) presented bone reconstitution consistently, while bone was present in only one third of those treated with slowly dissolving scaffolds (HYAFF-11 and PLLA). After 20 weeks, the articular surface of PLGA-treated defects presented fibrillation more frequently than in ACP-treated defects. The surface of defects treated with slowly dissolving scaffolds presented more cracks and fissures. CONCLUSIONS: The degradation rate of the scaffolds is critical for the repair process. Slowly dissolving scaffolds sustain thicker cartilage at the surface but, it frequently presents cracks and discontinuities. These scaffolds also delay bone formation at the base of the defects. Hyaluronan-based scaffolds appear to allow faster cell infiltration leading to faster tissue formation. The degradation of ACP leads to rapid bone formation while the slow degradation of HYAFF-11 prolongs the presence of cartilage and delays endochondral bone formation.

Repair of the immature and mature craniofacial skeleton with a carbonated calcium phosphate cement: assessment of biocompatibility, osteoconductivity, and remodeling capacity
Smartt, J. M., Jr., J. Karmacharya, et al. (2005), Plast Reconstr Surg 115(6): 1642-50.
Abstract: BACKGROUND: The apatite compounds used most commonly in craniofacial reconstruction are highly crystalline and biologically inert ceramics. Because their capacity to be replaced by native bone is limited, they have found little application in repair of the growing craniofacial skeleton. Carbonated calcium phosphate cements more closely resemble the mineral phase of bone, thereby offering enhanced bioresorption and osteoconductivity, but their fate in the immature and mature craniofacial skeleton has not been investigated. METHODS: The authors hypothesized that the capacity for cell-mediated remodeling of carbonated calcium phosphate cements is based on (1) their crystallographic and compositional similarity to the mineral phase of bone and (2) the osteogenic capacity of the host. Four noncritical-sized calvarial defects were created in six 3-week-old and six 16-week-old Yorkshire pigs. The defects were repaired with autologous bone, sintered carbonated calcium phosphate cement disks with a higher crystal order, or carbonated calcium phosphate cement (Norian CRS; Synthes Maxillofacial, West Chester, Pa.). The fourth defect was left empty as a control. Specimens were harvested at 30 and 90 days postoperatively. RESULTS: Empty defects healed with dense fibroconnective tissue in all groups. Autologous bone grafts underwent complete remodeling and replacement with woven bone at both time points. Sintered carbonated calcium phosphate disks demonstrated no bony ingrowth or remodeling. In immature animals, carbonated calcium phosphate cement implants were progressively replaced with woven bone through osteoclast-mediated resorption and osteoblast-mediated bone formation. Only minimal remodeling of the carbonated calcium phosphate cement implants was observed in skeletally mature animals. CONCLUSIONS: The results of these experiments suggest that the extent of remodeling of carbonated calcium phosphate cement is dependent on both the composition of the implant itself and the osteogenic capacity of the host and that carbonated calcium phosphate cement may be used successfully for inlay applications in the immature craniofacial skeleton.

Repeated rapid shear-responsiveness of peptide hydrogels with tunable shear modulus
Ramachandran, S., Y. Tseng, et al. (2005), Biomacromolecules 6(3): 1316-21.
Abstract: A pair of mutually attractive but self-repulsive decapeptides, with alternating charged/neutral amino acid sequence patterns, was found to co-assemble into a viscoelastic material upon mixing at a low total peptide concentration of 0.25 wt %. Circular dichroism spectroscopy of individual decapeptide solutions revealed their random coil conformation. Transmission electron microscopy images showed the nanofibrillar network structure of the hydrogel. Dynamic rheological characterization revealed its high elasticity and shear-thinning nature. Furthermore, the co-assembled hydrogel was capable of rapid recoveries from repeated shear-induced breakdowns, a property desirable for designing injectable biomaterials for controlled drug delivery and tissue engineering applications. A systematic variation of the neutral amino acids in the sequence revealed some of the design principles for this class of biomaterials. First, viscoelastic properties of the hydrogels can be tuned through adjusting the hydrophobicity of the neutral amino acids. Second, the beta-sheet propensity of the neutral amino acid residue in the peptides is critical for hydrogelation.

Repetitive subcutaneous implantation of different types of (biodegradable) biomaterials alters the foreign body reaction
van Luyn, M. J., J. A. Plantinga, et al. (2001), Biomaterials 22(11): 1385-91.
Abstract: In the present study two biodegradable materials (cross-linked collagens) and two non-biodegradable materials (polyurethane and silicone) were applied in a repetitive subcutaneous implantation model in rats. In contrast to the first challenge, the second challenge with the same type of material, but at a different subcutaneous site of the same animal, induced an increase of macrophages and giant cells inside the biodegradable materials. Additionally, only after the second challenge clusters and accumulations of plasma cells were present in the surrounding tissue of each type of material. In the same areas an increase of MHC II expression was measured by immunocytochemistry. Differences in the numbers of macrophages and T cells were not observed around the explants. Undifferentiated B cells or NK cells were not present at any time point. The results indicate that alterations observed after the second challenge did not depend on biodegradation of the materials. Significance of these findings should be considered in view of increased and repetitive use of the same type of biomaterial (possibly for different application sites) for implantation in patients.

Replamineform porous biomaterials for hard tissue implant applications
White, E. W., J. N. Weber, et al. (1975), J Biomed Mater Res 9(4): 23-7.
Abstract: By means of the newly developed Replamineform process, the unique pore microstructures found in the skeletal calcium carbonate of certain reef corals can be replicated or reproduced with high precision in a wide variety of materials suitable for hard tissue implant and prosthetic applications. The advantages of fabricating porous biomaterials with this method include closely controlled size of both the pore diameters and the diameters of the pore interconnections, and virtually complete interconnection of the uniformly spaced pores. These properties are of great importance in implant devices, because tissue ingrowth, the stimulation of new bone formation, the suppression of undesirable scar tissue, the inhibition of adverse body responses, and firm biological fixation of the implanted material all depend upon the nature of the pore-microstructure configuration. Replamineform preparation of Al2O3, TiO2, hydroxyapatite, silver, Co-Cr-Mo alloys, and polymers is described in detail, and the characterization procedures used to determine the physical and structural properties of their materials are discussed. A few of the routinely measured characteristics include (1) quantitative computerized SEM image analysis for determining the volume, size and shape distributions of the macro and microporosity and the grain size measurement of the solid; (2) nondestructive x-radiography of specimens to reveal any internal defects; (3) mechanical strength measurements of randomly selected specimens. Experimental results up to now clearly demonstrate the superiority of microstructures imparted to metals, ceramics, and polymers with the Replamineform process.

Replantation of 45 avulsed permanent teeth: a 1-year follow-up study
Chappuis, V. and T. von Arx (2005), Dent Traumatol 21(5): 289-96.
Abstract: Thirty-four patients with 45 avulsed and replanted permanent teeth were followed for 1 year. All teeth were soaked in tetracycline before replantation. In addition, enamel matrix derivative was used in teeth with dry storage times exceeding 30 min. Splinting was carried out with a non-rigid titanium splint and was limited to 7-10 days. Within that period, root canal treatment was begun in all teeth with a closed apex, whereas teeth with an open apex and ideal post-traumatic storage were not instrumented. All patients were given tetracycline systematically for 10 days. The survival rate of replanted avulsed permanent teeth was 95.6% at the 1-year follow-up. In 82.2%, root canal treatment was performed. Pulp survival was never observed, but three teeth had pulp canal obliteration. Normal periodontal healing was observed in 57.7% of teeth; 42.3% of teeth showed external root resorption (28.9% replacement resorption, 6.7% infection-related resorption, 6.7% surface resorption). The occurrence of replacement resorption correlated with the period of extraoral dry storage. Compared with other clinical studies on avulsed and replanted teeth, the present study reports a higher percentage of periodontal healing. The favorable treatment outcome may be associated with a strict protocol to enforce endodontic treatment, the use of topical and systemic tetracycline, and the relatively high number of ideally stored teeth following avulsion. In contrast, the present study has a follow-up period limited to 1 year.

Replantation of permanent incisors in children using Emdogain
Barrett, E. J., D. J. Kenny, et al. (2005), Dent Traumatol 21(5): 269-75.
Abstract: The aim of this study was to determine whether application of an enamel matrix protein derivative, Emdogain (Biora AB Malmo, Sweden) to the root surface of avulsed permanent incisors would improve postreplantation outcomes in a pediatric population. Between June 1999 and May 2002, 25 avulsed permanent maxillary incisors (22 centrals and three laterals) were treated with Emdogain and followed for up to 32 months, mean duration 20.6 months (range: 6.9-32.5 months). Mean patient age at the time of treatment was 12.0 years (range: 7.7-17.6 years) and mean extra-alveolar duration was 185 min (range: 100-300 min). At the end of their follow-up each of the replanted incisors demonstrated radiographic evidence of replacement root resorption and clinical evidence of ankylosis. None of the replanted teeth were affected by inflammatory root resorption and there was no evidence of infection. When compared with the control samples from Barrett and Kenny (Endod Dent Traumatol 1997;15:269-72.) and Andersson et al. (Endod Dent Traumatol 1989;5:38-47.) this sample treated with the Emdogain protocol demonstrated significantly less root resorption than either of the control samples (anova, P < 0.0001). Although the Emdogain protocol did not produce periodontal regeneration, it did eliminate inflammatory resorption and infection and led to significantly less root resorption compared with the two historical controls.

Reply to letter regarding interpretation of results of ACTIVE Study
Sluzewski, M. and W. J. van Rooij (2005), AJNR Am J Neuroradiol 26(9): 2436-7.

Residence-time dependent changes in fibrinogen adsorbed to polymeric biomaterials
Balasubramanian, V., N. K. Grusin, et al. (1999), J Biomed Mater Res 44(3): 253-60.
Abstract: It has generally been accepted that biomaterials adsorbing the least amount of the plasma protein fibrinogen following exposure to blood will support less platelet adhesion and therefore exhibit less thrombogenicity. Several studies suggest, however, that the conformation or orientation of immobilized fibrinogen rather than the total amount adsorbed plays an important role in determining the blood compatibility of biomaterials. The purpose of this study was to investigate time-dependent functional changes in fibrinogen adsorbed to polytetrafluoroethylene (PTFE), polyethylene (PE), and silicone rubber (SR). Fibrinogen was adsorbed to these materials for 1 min and then allowed to 'reside" on the surfaces for up to 2 h prior to assessing its biological activity. Changes in fibrinogen reactivity were determined by measuring the adhesion of 51Cr-labeled platelets, the binding of a monoclonal antibody (mAb) directed against an important functional region of the fibrinogen molecule (the gamma-chain dodecapeptide sequence 400-411), and the ability of blood plasma to displace previously adsorbed fibrinogen. Platelet adhesion differed among the polymeric materials studied, and PTFE and PE samples exhibited a small decrease in adhesion with increasing fibrinogen residence time. Platelet adhesion to SR was the least among all materials studied and showed no variation with residence time. When using PTFE and SR as substrates, mAb recognition of adsorbed fibrinogen did not change with residence time whereas that on PE decreased slightly. The mAb binding was least to fibrinogen adsorbed to SR, which is in agreement with the platelet adhesion results. Finally, the ability of plasma to displace previously adsorbed fibrinogen decreased dramatically with increasing residence time on all materials. These in vitro studies support the hypothesis that fibrinogen undergoes biologically significant conformational changes upon adsorption to polymeric biomaterials, a phenomenon that may contribute to the hemocompatibility of the materials following implantation in the body.

Residual stress in hydroxyapatite coating: nonlinear analysis and high-energy synchrotron measurements
Fogarassy, P., B. Cofino, et al. (2005), IEEE Trans Biomed Eng 52(7): 1161-6.
Abstract: The thermal deposition of hydroxyapatite (HA) on titanium alloy substrate (Ti-6A1-4V) leads to a structure that has very good osseointegration properties. However, clinical failures have been occasionally reported at the interface between substrate and coating. Lifetime is the main parameter in such prostheses; therefore, in order to improve their quality, it is necessary to evaluate the level of stresses near the interface. The high-energy synchrotron radiation combines the advantages of a bulk analysis and reduced volume of the gauge. The objective of our study was to calculate the residual stress using a nonlinear finite-element model and to measure residual stress level near the interface, in the hydroxyapatite coating and in titanium alloy substrate with a nondestructive and high-resolution experiment. The high-energy synchrotron radiation of the BM16 beam-line at ESRF (Grenoble-France) was used with a resolution of down to 10 micrometers. The experimental measurements validate the results found by means of nonlinear finite-element analysis of the plasma spraying induced stress.

Resistance to sliding with 3 types of elastomeric modules
Griffiths, H. S., M. Sherriff, et al. (2005), Am J Orthod Dentofacial Orthop 127(6): 670-5; quiz 754.
Abstract: INTRODUCTION: Super Slick (TP Orthodontics, LaPorte, Ind), a polymeric-coated ligature, has recently been introduced to the orthodontic market. The manufacturer claims it will significantly reduce friction. The purposes of this study were to determine whether Super Slick modules show lower friction than round and rectangular modules and to put the frictional forces into perspective with a self-ligating bracket. METHODS: Maxillary premolar, stainless steel, self-ligating, and monocrystalline brackets with.022-in slots were used with straight lengths of.018-in and.019 x.025-in stainless steel wires. Buccal segment models were set up with 1 molar band and 2 premolar brackets for each test group: self-ligating brackets with the slide closed, self-ligating brackets with the slide open, and monocrystalline brackets. The latter 2 groups were tested with all 3 types of elastomeric module. Each setup was tested both under dry conditions and after soaking in a water bath for 1 hour. RESULTS: The self-ligating brackets demonstrated virtually zero friction with each combination of wire and environmental condition. When the different bracket and elastomeric module combinations were compared, significant differences were observed. In all but 2 combinations, round modules provided the least resistance to sliding and rectangular modules the greatest, with Super Slick modules in between the 2. The self-ligating bracket provided the least resistance to sliding of all the bracket/ligation combinations and almost entirely eliminated friction under the conditions of this experiment. CONCLUSIONS: Super Slick modules demonstrated greater resistance to sliding than conventional round modules, but not rectangular. Self-ligating brackets provided the least resistance to sliding of all bracket/ligation combinations and were the only method that almost entirely eliminated friction. The.018-in and.019 x.025-in wires exhibited similar friction in the dry state, but, when wet, the.018-in wire produced less friction. Ceramic brackets demonstrated greater resistance to sliding than stainless steel brackets. Lubrication reduced the friction with.018-in wires and increased it for.019 x.025-in wires.

Resolving the challenges of producing small-bore tubing
Eriksson, J. (2005), Med Device Technol 16(4): 14-7.
Abstract: Experience shows that sufficient time and resources must be allocated to writing a specification. It is essential to be clear about the intended use of the tubing. Once the preliminary specification has been compiled, trial and error is often a necessary part of the process of making a successful product. Finally, all polymers are affected by the environment and their previous history.

Resorbability of bone substitute biomaterials by human osteoclasts
Schilling, A. F., W. Linhart, et al. (2004), Biomaterials 25(18): 3963-72.
Abstract: Third generation biomaterials are being designed with the aim that once implanted they will help the body to heal itself. One desirable characteristic of these materials in bone is their ability to be remodeled, i.e. that osteoclasts resorb the material and it is subsequently replaced by newly formed bone through osteoblastic activity. So far the only way to test this biological property of bone substitutes are animal experiments with all their limitations like ethics, costs and limited transferability to man. The present study was designed, to develop a human in vitro assay, allowing to generate human osteoclasts directly on the biomaterial. The assay was validated using calcium phosphate cement and PMMA as biomaterials. Quantification was performed by raster electron microscopy and computer assisted image analysis. Dentin was used as internal standard. Our assay shows iso-bone resorbability of calcium phosphate cement in comparison to unresorbable PMMA cement. Both current clinical orthopedic practice and future skeletal engineering may profit from the availability and use of a test system for the assessment of resorption quality. The assay presented here allows to address this question of resorbability and to select the best materials for the use as bone substitutes in specific patients.

Resorbable materials and composites. New concepts in orthopedic biomaterials
Parsons, J. R. (1985), Orthopedics 8(7): 907-15.
Abstract: For the last several decades, research in orthopedic biomaterials has remained focused on homogeneous plastics and metals. Initial research resulted in rapid improvements and a number of standardized materials emerged. With time, development of these materials has become a slower, more deliberate process. Recently, however, investigators have sought to broaden the scope of orthopedic biomaterials research. New materials systems are now under consideration. These systems include natural and synthetic resorbable polymerics and resorbable ceramics. A variety of composite materials are under primary investigation or in clinical trials. Our emerging understanding of these new materials is rapidly leading to new surgical applications not possible with conventional metals and plastics.

Response of bone and cartilage cells to biomaterials in vivo and in vitro
Boyan, B. D., Z. Schwartz, et al. (1993), J Oral Implantol 19(2): 116-22; discussion 136-7.
Abstract: In vivo and in vitro models have been developed to study the bone/material interface. The in vivo model exploits the osteogenesis that accompanies marrow ablation of the rat tibia and uses morphological and biochemical changes in extracellular organelles, called matrix vesicles, as markers of the healing process. Matrix vesicles, which are associated with primary bone formation and calcification, are produced by osteoblasts and are sensitive to cellular and environmental regulation. In bone adjacent to bone-bonding implants, matrix vesicle number increases, as does its alkaline phosphatase activity. In bone adjacent to nonbonding materials, matrix vesicle activity is inhibited. The materials exert systemic effects which can also be studied by use of matrix vesicles. Cell models are needed in order for the specificity of the cellular response to the material to be understood. By the use of culture plates sputter-coated with implant materials, the response of cells can be studied under controlled conditions. Comparison of the response of costochondral chondrocytes at two stages of endochondral development demonstrates that the effects of various materials are surface- and cell-maturation-dependent. Cells cultured on Ti exhibited increased alkaline-phosphatase-specific activity, whereas those cultured on Al2O3 have decreased enzyme activity.

Response of heterograft heart valve biomaterials to moderate cyclic loading
Sun, W., M. Sacks, et al. (2004), J Biomed Mater Res A 69(4): 658-69.
Abstract: We have recently demonstrated that noncalcific tissue damage can lead to significant collagen degradation in clinically explanted bioprosthetic heart valves (BHVs). In the present study we quantified the early response of glutaraldehyde treated bovine pericardium (GLBP) to cyclic tensile loading to begin to elucidate the mechanisms of noncalcific tissue degeneration in BHV biomaterials. GLBP specimens were cycled at 30 Hz to a maximum uniaxial strain of 16% (corresponding to approximately 1-MPa peak stress), with the loading direction parallel to the preferred collagen fiber (PD) direction. After 30 x 10(6) cycles, specimens were subjected to biaxial mechanical testing, then cycled until 65 x 10(6) cycles. The results indicated a permanent change in the unloaded tissue dimensions of +7.1% strain in the PD direction and -7.7% strain in the cross fiber direction (XD) after 65 x 10(6) cycles and an increase of the collagen crimp period from 40.6 to 45.2 microm by 65 x 10(6) cycles (p = 0.05). Fourier transform IR spectroscopy analysis indicated that cyclic fatigue of GLBP leads to both collagen conformational changes and early denaturation. Furthermore, no significant changes in areal strain were found under 1-MPa equibiaxial stress, indicating that cyclic loading changed the collagen fiber orientation but not the overall tissue compliance. These observations suggest that while deterioration of collagen begins immediately, fiber straightening and reorientation dominates the changes in the mechanical behavior up to 65 x 10(6) cycles. The present study underscores the complexity of the response of biologically derived biomaterials to cyclic mechanical loading. Improved understanding of these phenomena can potentially guide the development of novel chemical treatment methods that seek to improve BHV durability by minimizing these degenerative processes.


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