Biomedical subjects

X Edward Guo

Publications and source records attributed to X Edward Guo.

At least 19 recordsLinked to original sources

PubMed2007

The generalized triphasic correspondence principle for simultaneous determination of the mechanical properties and proteoglycan content of articular cartilage by indentation.

The triphasic mixture theory has been used to describe the mechanical and physicochemical behaviors of articular cartilage under some specialized loading conditions. However, the mathematical complexities of this theory have limited its applications for theoretical analyses of experimental studies and models for predicting cartilage and other biological tissues' deformational behaviors. A generalized correspondence principle has been established in the present study, and this principle shows that the equilibrium deformational behavior of a charged-hydrated material under loading is identical to that of an elastic medium without charge. A set of explicit formulas has been derived to correlate the mechanical properties of an equivalent material with the intrinsic elastic moduli, fixed charge density and free-ion concentration within the cartilage tissue. The validity of these formulas is independent of the deformation state of the elastic solid matrix under an infinitesimal strain. Therefore they can be employed for any loading conditions, such as confined or unconfined compression, tension, and indentation tests, etc. In the current study, the fixed charge density of bovine cartilage is determined from the indentation creep data using this generalized correspondence principle. The proteoglycan content results were then compared with those from biochemical assay, yielding a linear regression slope of 1.034. Additionally a correspondence principle within a framework of cubic symmetry and a bilinear response in tension-compression (the conewise linear elasticity model) has also been developed to demonstrate the potential application of current methodology for inhomogeneous, anisotropic and nonlinear situations.

Animals↗

PubMed2006

Spatially varying material properties of the rat caudal intervertebral disc.

STUDY DESIGN: The use of a microscopy based material testing technique to assess the local material properties of rat caudal intervertebral discs under uniaxial compression. OBJECTIVES: To better understand the cell environment of rat caudal intervertebral discs during mechanical loading and elucidate better the role of the nucleus pulposus to the overall disc material properties. SUMMARY OF BACKGROUND DATA: Rat tail models of disc degeneration have been widely used for their similarity with the degeneration phenomena in human beings. Degenerative patterns in the disc are often inhomogeneous, however, only average material properties of rodent discs have been studied. Knowledge of the spatially varying properties within the disc is necessary to understand the disc cell milieu during tissue loading. METHODS: Rat caudal motion segments were tested intact, sectioned, and with alterations of nucleus pulposus using microscopy based techniques. Local displacements and strains were obtained using digital image correlation. Strains and load measurements were used to get the average apparent Young's modulus, peak stress, local Young's modulus, and local Poisson's ratio. RESULTS: There was no difference observed in the average apparent Young's modulus among experimental groups. Peak stresses decreased significantly when the nucleus pulposus was replaced with extremely fluid-like materials. The axial displacement field showed 3 distinct linear distributions in samples which were sectioned. The center region in all groups had significantly smaller axial strain and showed a higher local Young's modulus. CONCLUSIONS: The average equilibrium Young's modulus may be dependent on short-range ultrastructural organization. Spatially varying material properties within the intervertebral disc may be caused by orientation of fiber bundles in the different regions of the anulus fibrosus. The fiber bundles are better able to resist compressive loads when oriented parallel rather than perpendicular to the loading direction. At equilibrium, the anulus fibrosus also appears to have a shielding effect independent of the material filling up the nucleus pulposus space.

Animals↗

PubMed2006

Localization and distribution of cartilage oligomeric matrix protein in the rat intervertebral disc.

STUDY DESIGN: Whole rat intervertebral disc (IVD), as well as the anulus fibrosus (AF) and the nucleus pulposus (NP) were studied using immunoblot, immunohistochemistry, and reverse-transcription followed by polymerase chain reaction (RT-PCR) methods to investigate the expression and distribution of cartilage oligomeric matrix protein (COMP). OBJECTIVES: To investigate the expression and distribution patterns of COMP in normal IVD. SUMMARY OF BACKGROUND DATA: COMP is an extracellular matrix protein abundantly expressed in articular and growth plate cartilage, as well as bone, ligament, tendon, and synovium. The potential importance of COMP to the spine has been underscored by its mutations that lead to skeletal dysplasia with characteristic platyspondyly. However, the expression and distribution of COMP in spine and IVD has not been illustrated before. METHODS: The presence of COMP protein was investigated by immunoblotting using a COMP antibody F8 on protein extractions from whole IVD and AF or NP. To compare the expression levels of COMP between lumbar and tail IVDs, and between AF and NP of the IVD, wet weight of the tissues were used for normalization. To show that COMP can be made by IVD cells in situ, RT-PCR was used to investigate the COMP mRNA message. The distribution patterns of COMP in IVD were investigated using immunohistochemistry studies with COMP antibody F8. RESULTS: COMP is expressed at both the protein and mRNA levels in both the AF and NP of both the lumbar spine and tail IVD. Immunohistochemistry studies show that COMP is found in the extracellular matrix of the IVD, exhibiting lamellar distribution pattern in the AF region. When normalized to wet weight, COMP is found to be expressed at higher levels in the lumbar than the tail IVD, and within the IVD, greater in the AF than the NP region. CONCLUSIONS: Our results demonstrate the expression of COMP in both the AF and NP of the IVD. COMP is a component of the extracellular matrix of AF and NP, with a lamellar distribution pattern in the AF. Our data suggest that COMP may play a role in the normal structure of IVD.

Animals↗

PubMed2006

Prediction of cortical bone elastic constants by a two-level micromechanical model using a generalized self-consistent method.

A two-level micromechanical model of cortical bone based on a generalized self-consistent method was developed to take into consideration the transversely isotropic elasticity of many microstructural features in cortical bone, including Haversian canals, resorption cavities, and osteonal and interstitial lamellae. In the first level, a single osteon was modeled as a two-phase composite such that Haversian canals were represented by elongated pores while the surrounding osteonal lamellae were considered as matrix. In the second level, osteons and resorption cavities were modeled as multiple inclusions while interstitial lamellae were regarded as matrix. The predictions of cortical bone elasticity from this two-level micromechanical model were mostly in agreement with experimental data for the dependence of transversely isotropic elasticity of human femoral cortical bone on porosity. However, variation in cortical bone elastic constants was greater in experimental data than in model predictions. This could be attributed to variations in the elastic properties of microstructural features in cortical bone. The present micromechanical model of cortical bone will be useful in understanding the contribution of cortical bone porosity to femoral neck fractures.

Adult↗

PubMed2006

Quantification of the roles of trabecular microarchitecture and trabecular type in determining the elastic modulus of human trabecular bone.

UNLABELLED: The roles of microarchitecture and types of trabeculae in determining elastic modulus of trabecular bone have been studied in microCT images of 29 trabecular bone samples by comparing their Young's moduli calculated by finite element analysis (FEA) with different trabecular type-specific reconstructions. The results suggest that trabecular plates play an essential role in determining elastic properties of trabecular bone. INTRODUCTION: Osteoporosis is an age-related disease characterized by low bone mass and architectural deterioration. Other than bone volume fraction (BV/TV), microarchitecture of bone is also believed to be important in governing mechanical properties of trabecular bone. We quantitatively examined the role of microarchitecture and relative contribution of trabecular types of individual trabecula in determining the elastic property of trabecular bone. MATERIALS AND METHODS: Twenty-nine human cadaveric trabecular bone samples were scanned at 21-mum resolution using a microCT system. Digital topological analysis (DTA) consisting of skeletonization and classification was combined with a trabecular type-specific reconstruction technique to extract the skeleton and identify topological type of trabeculae of the original trabecular bone image. Four different microCT-based finite element (FE) models were constructed for each specimen: (1) original full voxel; (2) skeletal voxel; (3) rod-reconstructed, preserving rod volume and plate skeleton; and (4) plate-reconstructed, preserving plate volume and rod skeleton. For each model, the elastic moduli were calculated under compression along each of three image-coordinate axis directions. Plate and rod tissue fractions directly measured from DTA-based topological classification were correlated with the elastic moduli computed from full voxel model. RESULTS: The elastic moduli of skeleton models were significantly correlated with those of full voxel models along all three coordinate axes (r(2) = 0.38 approximately 0.53). The rod-reconstructed model contained 21.3% of original bone mass and restored 1.5% of elastic moduli, whereas the plate-reconstructed model contained 90.3% of bone mass and restored 53.2% of elastic moduli. Plate tissue fraction showed a significantly positive correlation (r(2) = 0.49) with elastic modulus by a power law, whereas rod tissue fraction showed a significantly negative correlation (r(2) = 0.42). CONCLUSIONS: These results quantitatively show that the microarchitecture alone affects elastic moduli of trabecular bone and trabecular plates make a far greater contribution than rods to the bone's elastic behavior.

Aged↗

PubMed2005

Osteoblast elastic modulus measured by atomic force microscopy is substrate dependent.

The actin and microtubule cytoskeleton have been found to contribute to the elastic modulus of cells, which may be modulated by adhesion to extracellular matrix (ECM) proteins and subsequent alterations in the cytoskeleton. In this study, the apparent elastic modulus (Eapp) of osteoblast-like MC3T3-E1 cells adhered to fibronectin (FN), vitronectin (VN), type I collagen (COLI), fetal bovine serum (FBS), or poly-l-lysine (PLL), and bare glass were determined using an atomic force microscope (AFM). The E(app) of osteoblasts adhered to ECM proteins (FN, VN, COLI, and FBS) that bind cells via integrins were higher compared to cells on glass and PLL, which adhere cells through nonspecific binding. Also, osteoblasts adhered to FN, VN, COLI, and FBS had F-actin stress fiber formation, while osteoblasts on glass and PLL showed few F-actin fibers. Disruption of the actin cytoskeleton decreased E(app) of osteoblasts plated on FN to the level of osteoblasts plated on glass, while microtubule disruption had no significant effect. This suggests that the elevated modulus of osteoblasts adhered to FN was due to remodeling of the actin cytoskeleton upon adhesion to ECM proteins. Modulation of cell stiffness upon adhesion to various substrates may influence mechanosignal transduction in osteoblasts.

Actins↗

PubMed2005

Immune response and effect of adenovirus-mediated human BMP-2 gene transfer on the repair of segmental tibial bone defects in goats.

BACKGROUND: Tissue-engineered bone may be used for filling bone defects. There are, however, no reports on this technique used in large animals. METHODS: We evaluated the effectiveness of, and immune response in repairing diaphyseal bone defects by gene transfer using bone morphogenetic proteins (BMPs). We used adenovirus-mediated human BMP-2 (Adv-hBMP-2) gene-transduced bone marrow stromal cells (BMSCs) to repair 2.1-cm segmental tibial bone defects in goats (group I, n = 7). An Adv-ssgal-transduced BMSC group (group II, n = 5), a non-transduced BMSC group (group III, n = 5), and an untreated group (group IV, n = 2) were used as controls. Self-secreted extracellular matrix was used as cellular carrier. RESULTS: Radiographic and histomorphometric examination demonstrated more callus in the bone defects of group I compared to other groups. Week 24 after implantation, the defect healing rates of groups I, II, III, and IV were 6/7, 1/5, 2/5, and 0/2, respectively. The maximum compressive strength of new tissue in the bone defects of group I was higher than those of groups II and III. Temporary cellular and persistent humoral immune responses against adenovirus were detected after hBMP-2 gene transfer. INTERPRETATION: We found that Adv-hBMP-2 genetransduced BMSCs had superior osteoinductivity in the repair of tibial bone defects in goats, but it could cause temporary cellular and persistent humoral immune responses against adenovirus.

Adenoviridae↗

PubMed2005

An application of nanoindentation technique to measure bone tissue Lamellae properties.

Measuring the microscopic mechanical properties of bone tissue is important in support of understanding the etiology and pathogenesis of many bone diseases. Knowledge about these properties provides a context for estimating the local mechanical environment of bone related cells thait coordinate the adaptation to loads experienced at the whole organ level. The objective of this study was to determine the effects of experimental testing parameters on nanoindentation measures of lamellar-level bone mechanical properties. Specifically, we examined the effect of specimen preparation condition, indentation depth, repetitive loading, time delay, and displacement rate. The nanoindentation experiments produced measures of lamellar elastic moduli for human cortical bone (average value of 17.7 +/- 4.0 GPa for osteons and 19.3 +/- 4.7 GPa for interstitial bone tissue). In addition, the hardness measurements produced results consistent with data in the literature (average 0.52 +/- 0.15 GPa for osteons and 0.59 +/- 0.20 GPa for interstitial bone tissue). Consistent modulus values can be obtained from a 500-nm-deep indent. The results also indicated that the moduli and hardnesses of the dry specimens are significantly greater (22.6% and 56.9%, respectively) than those of the wet and wet and embedded specimens. The latter two groups were not different. The moduli obtained at a 5-nm/s loading rate were significantly lower than the values at the 10- and 20-nm/s loading rates while the 10- and 20-nm/s rates were not significantly different. The hardness measurements showed similar rate-dependent results. The preliminary results indicated that interstitial bone tissue has significantly higher modulus and hardness than osteonal bone tissue. In addition, a significant correlation between hardness and elastic modulus was observed.

Aged↗

PubMed2005

The effect of matrix tension-compression nonlinearity and fixed negative charges on chondrocyte responses in cartilage.

Thorough analyses of the mechano-electrochemical interaction between articular cartilage matrix and the chondrocytes are crucial to understanding of the signal transduction mechanisms that modulate the cell metabolic activities and biosynthesis. Attempts have been made to model the chondrocytes embedded in the collagen-proteoglycan extracellular matrix to determine the distribution of local stress-strain field, fluid pressure and the time-dependent deformation of the cell. To date, these models still have not taken into account a remarkable characteristic of the cartilage extracellular matrix given rise from organization of the collagen fiber architecture, now known as the tension-compression nonlinearity (TCN) of the tissue, as well as the effect of negative charges attached to the proteoglycan molecules, and the cell cytoskeleton that interacts with mobile ions in the interstitial fluid to create osmotic and electro-kinetic events in and around the cells. In this study, we proposed a triphasic, multi-scale, finite element model incorporating the Conewise Linear Elasticity that can describe the various known coupled mechanical, electrical and chemical events, while at the same time representing the TCN of the extracellular matrix. The model was employed to perform a detailed analysis of the chondrocytes' deformational and volume responses, and to quantitatively describe the mechano-electrochemical environment of these cells. Such a model describes contributions of the known detailed micro-structural and composition of articular cartilage. Expectedly, results from model simulations showed substantial effects of the matrix TCN on the cell deformational and volume change response. A low compressive Poisson's ratio of the cartilage matrix exhibiting TCN resulted in dramatic recoiling behavior of the tissue under unconfined compression and induced significant volume change in the cell. The fixed charge density of the chondrocyte and the pericellular matrix were also found to play an important role in both the time-dependent and equilibrium deformation of the cell. The pericellular matrix tended to create a uniform osmolarity around the cell and overall amplified the cell volume change. It is concluded that the proposed model can be a useful tool that allows detailed analysis of the mechano-electrochemical interactions between the chondrocytes and its surrounding extracellular matrix, which leads to more quantitative insights in the cell mechano-transduction.

Animals↗

PubMed2005

Interfacial strength of cement lines in human cortical bone.

In human cortical bone, cement lines (or reversal lines) separate osteons from the interstitial bone tissue, which consists of remnants of primary lamellar bone or fragments of remodeled osteons. There have been experimental evidences of the cement line involvement in the failure process of bone such as fatigue and damage. However, there are almost no experimental data on interfacial properties of cement lines in human cortical bone. The objective of this study is to design and assemble a precision and computer controlled osteon pushout microtesting system, and to experimentally determine the interfacial strength of cement lines in human cortical bone by performing osteon pushout tests. Thirty specimens were prepared from humeral diaphyses of four human subjects. Twenty specimens were tested under the condition of a small hole in the supporting plate, in which the cement line debonding occurred. The cement line interfacial strength ranged from 5.38 MPa to 10.85 MPa with an average of 7.31 +/- 1.73 MPa. On the other hand, ten specimens were tested under the condition of a large hole in the supporting plate, in which the shear failure inside osteons was observed. The specimens tested under the condition of the large hole resulted in an average shear strength of 73.71 +/- 15.06 MPa, ranging from 45.97 MPa to 93.74 MPa. Therefore, our results suggest that the cement line interface between osteon and interstitial bone tissue is weaker than that between bone tissue lamellae.

Biomechanical Phenomena↗

PubMed2004

Osteocyte viability and regulation of osteoblast function in a 3D trabecular bone explant under dynamic hydrostatic pressure.

UNLABELLED: A new trabecular bone explant model was used to examine osteocyte-osteoblast interactions under DHP loading. DHP loading enhanced osteocyte viability as well as osteoblast function measured by osteoid formation. However, live osteocytes were necessary for osteoblasts to form osteoids in response to DHP, which directly show osteoblast-osteocyte interactions in this in vitro culture. INTRODUCTION: A trabecular bone explant model was characterized and used to examine the effect of osteocyte and osteoblast interactions and dynamic hydrostatic pressure (DHP) loading on osteocyte viability and osteoblast function in long-term culture. MATERIALS AND METHODS: Trabecular bone cores obtained from metacarpals of calves were cleaned of bone marrow and trabecular surface cells and divided into six groups, (1) live cores + dynamic hydrostatic pressure (DHP), (2) live cores + sham, (3) live cores + osteoblast + DHP, (4) live cores + osteoblast + sham, (5) devitalized cores + osteoblast + DHP, and (6) devitalized cores + osteoblast + sham, with four culture durations (2, 8, 15, and 22 days; n = 4/group). Cores from groups 3-6 were seeded with osteoblasts, and cores from groups 5 and 6 were devitalized before seeding. Groups 1, 3, and 5 were subjected to daily DHP loading. Bone histomorphometry was performed to quantify osteocyte viability based on morphology and to assess osteoblast function based on osteoid surface per bone surface (Os/Bs). TUNEL staining was performed to evaluate the mode of osteocyte death under various conditions. RESULTS: A portion of osteocytes remained viable for the duration of culture. DHP loading significantly enhanced osteocyte viability up to day 8, whereas the presence of seeded osteoblasts significantly decreased osteocyte viability. Cores with live osteocytes showed higher Os/Bs compared with devitalized cores, which reached significant levels over a greater range of time-points when combined with DHP loading. DHP loading did not increase Os/Bs in the absence of live osteocytes. The percentage of apoptotic cells remained the same regardless of treatment or culture duration. CONCLUSION: Enhanced osteocyte viability with DHP suggests the necessity of mechanical stimulation for osteocyte survival in vitro. Furthermore, osteocytes play a critical role in the transmission of signals from DHP loading to modulate osteoblast function. This explant culture model may be used for mechanotransduction studies in long-term cultures.

Animals↗

PubMed2004

The dependence of transversely isotropic elasticity of human femoral cortical bone on porosity.

The objective of this study was to examine the dependence of the elastic properties of cortical bone as a transversely isotropic material on its porosity. The longitudinal Young's modulus, transverse Young's modulus, longitudinal shear modulus, transverse shear modulus, and longitudinal Poisson's ratio of cortical bone were determined from eighteen groups of longitudinal and transverse specimens using tensile and torsional tests on a servo-hydraulic material testing system. These cylindrical waisted specimens of cortical bone were harvested from the middle diaphysis of three pairs of human femora. The porosity of these specimens was assessed by means of histology. Our study demonstrated that the longitudinal Young's and shear moduli of human femoral cortical bone were significantly (p<0.01) negatively correlated with the porosity of cortical bone. Conversely, the elastic properties in the transverse direction did not have statistically significant correlations with the porosity of cortical bone. As a result, the transverse elastic properties of cortical bone were less sensitive to changes in porosity than those in the longitudinal direction. Additionally, the anisotropic ratios of cortical bone elasticity were found to be significantly (p<0.01) negatively correlated with its porosity, indicating that cortical bone tended to become more isotropic when its porosity increased. These results may help a number of researchers develop more accurate micromechanics models of cortical bone.

Adult↗

PubMed2004

Indentation determined mechanoelectrochemical properties and fixed charge density of articular cartilage.

As a nondestructive technique, the indentation test has been used, both in vitro and in vivo, to determine the in situ apparent mechanical properties of cartilage. In this study, a simple new algorithm was developed using the indentation creep test, combined with both biphasic and triphasic analyses to calculate simultaneously the apparent and intrinsic mechanical (aggregate modulus and Poisson's ratio) and an electrochemical properties, i.e., the fixed charge density (FCD) of the intact articular cartilage. The calculated FCD values were compared with those measured using the biochemical assay of the proteoglycan content in the tissue. It was found: (1) the FCDs obtained from this new indentation method (0.287 +/- 0.157 mEq/ml) were significantly correlated with the results from biochemical assay; (2) significantly positive linear relationships existed between the intrinsic and apparent mechanical moduli; (3) both the apparent and intrinsic mechanical properties correlated significantly with the proteoglycan content in the cartilage specimen. These results suggest two distinct interaction mechanisms between the collagen network and the proteoglycans in cartilage layer. The proteoglycans contribute to the mechanical properties of articular cartilage not only by the Donnan osmotic pressure induced by the fixed charges, but also by its bulk mass. Current study represents a first step toward developing a valid and effective method for the study of structure-function relationship in cartilage and possibly for future early stage OA detection in vivo.

Animals↗

PubMed2004

Geometric determinants to cement line debonding and osteonal lamellae failure in osteon pushout tests.

Cement lines are the boundaries between secondary osteons and the surrounding interstitial bone matrix in cortical bone. The interfacial properties of cement lines have been determined by osteon pushout tests. However, distinctively different material properties were obtained when osteon pushout tests were performed under different test geometries. In the present study, an axisymmetric two-dimensional finite element model was used to simulate an osteon pushout test using the test geometry of actual experiments. The results indicated that shear failure within the osteonal lamellae would occur when the osteon pushout test was performed under the condition of a thick specimen and large supporting hole. On the other hand, cement line debonding occurred when the osteon pushout test was performed using a thin specimen and small supporting hole. The finite element results were consistent with previous experiments of osteon pushout tests under different test geometries. Furthermore, the finite-element results suggest that a smoothly curved punch would most likely cause debonding at the cement line instead of osteonal lamellae.

Animals↗

PubMed2004

Fixed electrical charges and mobile ions affect the measurable mechano-electrochemical properties of charged-hydrated biological tissues: the articular cartilage paradigm.

The triphasic constitutive law [Lai, Hou and Mow (1991)] has been shown in some special 1D cases to successfully model the deformational and transport behaviors of charged-hydrated, porous-permeable, soft biological tissues, as typified by articular cartilage. Due to nonlinearities and other mathematical complexities of these equations, few problems for the deformation of such materials have ever been solved analytically. Using a perturbation procedure, we have linearized the triphasic equations with respect to a small imposed axial compressive strain, and obtained an equilibrium solution, as well as a short-time boundary layer solution for the mechano-electrochemical (MEC) fields for such a material under a 2D unconfined compression test. The present results show that the key physical parameter determining the deformational behaviors is the ratio of the perturbation of osmotic pressure to elastic stress, which leads to changes of the measurable elastic coefficients. From the short-time boundary layer solution, both the lateral expansion and the applied load are found to decrease with the square root of time. The predicted deformations, flow fields and stresses are consistent with the analysis of the short time and equilibrium biphasic (i.e., the solid matrix has no attached electric charges) [Armstrong, Lai and Mow (1984)]. These results provide a better understanding of the manner in which fixed electric charges and mobile ions within the tissue contribute to the observed material responses.

Biomechanical Phenomena↗

PubMed2003

Transgenic complementation of leptin receptor deficiency. II. Increased leptin receptor transgene dose effects on obesity/diabetes and fertility/lactation in lepr-db/db mice.

We have generated mice that are homozygous for a leptin receptor transgene that is expressed exclusively in neurons (NSE-LEPR-B). We had previously shown that this transgene in the hemizygous state is effective in ameliorating almost all aspects of leptin receptor deficiency. Now, we show that the transgene, in the homozygous state, almost fully corrects the excess adiposity of LEPR-deficient (db/db) mice. Body composition analyses indicate that the transgene is able to restrain the massive increase in adiposity observed in LEPR-deficient mice. Examination of hypothalamic agouti gene-related peptide and proopiomelanocortin mRNA shows normalization of these leptin-regulated transcripts. Interestingly, despite normalization of circulating leptin concentrations by the transgene in the fed state, transgenic db3J/db mice did not show fasting-induced reductions of circulating leptin. Increased adiposity of the transgenic db/db mice at 4 wk of age, immediately postweaning, suggests that the transgene is less effective in correcting the preferential fat deposition caused by LEPR deficiency. We noted that the morphology of brown adipose tissue is nearly normal, concordant with the cold tolerance conferred by the transgene. Aspects of the diabetes phenotype are also corrected: glucose and insulin concentrations are nearly normal, and islet hyperplasia is greatly diminished. The transgene also corrects the infertility of db/db females and confers the ability to lactate sufficiently to nurse normal-sized litters. Finally, the slightly increased adiposity and mild insulin resistance of transgenic db/db dams were not a contributory factor to the increased fat content of transgenic db/db male progeny.

Adaptation, Physiological↗

PubMed2003

Anatomically shaped osteochondral constructs for articular cartilage repair.

Few successful treatment modalities exist for surface-wide, full-thickness lesions of articular cartilage. Functional tissue engineering offers a great potential for the clinical management of such lesions. Our long-term hypothesis is that anatomically shaped tissue constructs of entire articular layers can be engineered in vitro on a bony substrate, for subsequent implantation. To determine the feasibility, this study investigated the development of bilayered scaffolds of chondrocyte-seeded agarose on natural trabecular bone. In a series of three experiments, bovine chondrocytes were seeded in (1) cylindrical bilayered constructs of agarose and bovine trabecular bone, 0.53 cm2 in surface area and 3.2 mm thick, and were cultured for up to 6 weeks; (2) chondrocyte-seeded anatomically shaped agarose constructs reproducing the human patellar articular layer (area=11.7 cm2, mean thickness=3.4 mm), cultured for up to 6 weeks; and (3) chondrocyte-seeded anatomically shaped agarose constructs of the patella (same as above) integrated into a corresponding anatomically shaped trabecular bone substrate, cultured for up to 2 weeks. Articular layer geometry, previously acquired from human cadaver joints, was used in conjunction with computer-aided design and manufacturing technology to create these anatomically accurate molds. In all experiments, chondrocytes remained viable over the entire culture period, with the agarose maintaining its shape while remaining firmly attached to the underlying bony substrate (when present). With culture time, the constructs exhibited positive type II collagen staining as well as increased matrix elaboration (Safranin O staining for glycosaminoglycans) and material properties (Young's modulus and aggregate modulus). Despite the use of relatively large agarose constructs partially integrated with trabecular bone, no adverse diffusion limitation effects were observed. Anatomically shaped constructs on a bony substrate may represent a new paradigm in the design of a functional articular cartilage tissue replacement.

Animals↗

PubMed2003

Trabecular bone response to mechanical and parathyroid hormone stimulation: the role of mechanical microenvironment.

UNLABELLED: Bone response under combined mechanical and PTH stimuli is important in osteoporosis. A rat tail animal model with computer modeling was used to examine bone response to loading and PTH. PTH enhances and sustains increased bone formation rate, which directly correlates to mechanical microenvironment, suggesting beneficial effects of combined PTH treatment and exercise in preventing osteoporosis. INTRODUCTION: Using an in vivo rat tail vertebra model combined with a specimen-specific, high-resolution microcomputed tomography (microCT)-based finite element analysis (FEA) technique, trabecular bone response to combined dynamic compressive loading and parathyroid hormone (PTH) stimulation was characterized. MATERIALS AND METHODS: Two hundred twenty-four male Sprague-Dawley rats were randomly divided into seven treatment groups: (1) Control, (2) vehicle + 0N, (3) PTH + 0N, (4) vehicle + 50N, (5) PTH + 50N, (6) vehicle + 100N, and (7) PTH + 100N, with three treatment durations (1, 2, or 4 weeks). Rat PTH(1-34) was administered daily in the PTH-stimulated groups approximately 3 h before daily mechanical stimulation with 0, 50, or 100N dynamic compressive loading. microCT-based FEA was performed for each loaded vertebra after death. Bone histomorphometry was performed on trabecular bone with double fluorochrome labeling to assess bone formation. RESULTS: Daily mechanical loading or PTH administration significantly increased bone formation rate (BFR) compared with control or V + 0N with significant increases in both mineral apposition rate (MAR) and labeled bone surface (LS/BS). PTH, when combined with mechanical loading, enhanced BFR mainly through a significant increase in MAR after the first week and through a significant increase in LS/BS after 2 and 4 weeks. Synergistic effects in BFR were present when PTH was combined with mechanical loading, especially after 2 and 4 weeks, where the increase in BFR was sustained. However, when either PTH or mechanical loading was the only stimulus, the bone formation response diminished to the level of Control animals after 4 weeks. Furthermore, significant correlations were observed between the bone formation indices and trabecular bone tissue mechanical microenvironments at 1 and 2 weeks, with PTH administration enhancing and sustaining these correlations into 4 weeks. CONCLUSIONS: The synergistic effects of combined PTH and mechanical stimulation on trabecular bone formation rate suggest a potential benefit for combined PTH administration and exercise in the treatment of osteoporosis.

Animals↗