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Biomedical subjects

D R Carter

Publications and source records attributed to D R Carter.

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

Mechanically modulated cartilage growth may regulate joint surface morphogenesis.

The development of normal joints depends on mechanical function in utero. Experimental studies have shown that the normal surface topography of diarthrodial joints fails to form in paralyzed embryos. We implemented a mathematical model for joint morphogenesis that explores the hypothesis that the stress distribution created in a functional joint may modulate the growth of the cartilage anlagen and lead to the development of congruent articular surfaces. We simulated the morphogenesis of a human finger joint (proximal interphalangeal joint) between days 55 and 70 of fetal life. A baseline biological growth rate was defined to account for the intrinsic biological influences on the growth of the articulating ends of the anlagen. We assumed this rate to be proportional to the chondrocyte density in the growing tissue. Cyclic hydrostatic stress caused by joint motion was assumed to modulate the baseline biological growth, with compression slowing it and tension accelerating it. Changes in the overall shape of the joint resulted from spatial differences in growth rates throughout the developing chondroepiphyses. When only baseline biological growth was included, the two epiphyses increased in size but retained convex incongruent joint surfaces. The inclusion of mechanobiological-based growth modulation in the chondroepiphyses led to one convex joint surface, which articulated with a locally concave surface. The articular surfaces became more congruent, and the anlagen exhibited an asymmetric sagittal profile similar to that observed in adult phalangeal bones. These results are consistent with the hypothesis that mechanobiological influences associated with normal function play an important role in the regulation of joint morphogenesis.

Biomechanical Phenomena↗
PubMed1999

Computer model of endochondral growth and ossification in long bones: biological and mechanobiological influences.

Endochondral growth and ossification, the processes by which cartilage increases in size and is replaced by bone, are affected by biological factors such as intrinsic genetic makeup and systemic chemical agents. In addition, these processes are affected by epigenetic mechanical factors: they may be accelerated in regions of intermittent high shear stress and decelerated in regions of intermittent high hydrostatic pressure. Previous models of bone development have not incorporated both biological and mechanobiological influences on endochondral growth and ossification. We have implemented a finite element analysis to model a developing bone rudiment from 8 weeks of gestational development to approximately 2 years after birth. As a function of time, we calculated a maturity index that reflects the progression of a region of cartilage through the endochondral ossification sequence of proliferation, hypertrophy, mineralization, and replacement by bone. We calculated a specific growth rate for each region of cartilage and estimated overall longitudinal growth of the rudiment. Regions of cartilage replaced by bone were remodeled. The results from the maturity index can be compared with distributions of proliferative, hypertrophic, and mineralized cartilage seen on histology at various stages in development. The results of the simulation predicted prenatal and postnatal developmental events, including formation of a secondary ossific nucleus, a layer of articular cartilage, and a growth plate. Our results demonstrate the necessity to include biological and mechanobiological influences when endochondral growth and ossification are considered.

Animals↗
PubMed1999

DXA-derived section modulus and bone mineral content predict long-bone torsional strength.

Previous studies have used dual energy x-ray absorptiometry (DXA) scans to calculate the section modulus (Z) of adolescent and adult human femurs. The DXA-derived values of Z were assumed to be proportional to bone strength in bending and torsion. In this study we used dog (n 5), pig (n 4), and human (n 13) femurs covering a linear bone mineral content (BMCL) range of 0.91-6.1 g/cm. Using DXA scans, ex vivo torsional strength tests, and torsional finite element models, we assessed the validity of using the DXA-derived Z value as an indicator of strength. The correlation between BMCL and strength was r2 = 0.87 and the correlation between Z and strength was r2 = 0.86. Based on finite element results, the dog and pig section moduli were adjusted to be comparable to the human data based on cross-sectional shape and bone tissue shear strength differences. With these adjustments, the correlation between adjusted section modulus and measured strength did not improve (r2 = 0.87). These data indicate that DXA-derived section modulus can be used to predict strength over a wide range of bone sizes. However, a clear advantage of using DXA-derived section modulus rather than BMCL could not be found.

Absorptiometry, Photon↗
PubMed1998

A model for loading-dependent growth, development, and adaptation of tendons and ligaments.

The geometric and material properties of tendons and ligaments change during growth and development. While some of the changes occur in the absence of mechanical loading, normal development requires the mechanical stimulus provided by normal physical activity. We have developed an analytical framework for quantitatively describing changes in uniaxial tendon and ligament properties throughout ontogeny. In our approach, cross-sectional area, modulus, and strength undergo baseline levels of development due to inherent time-dependent biological influences. The properties also change in response to mechanobiological influences by adapting to maintain a constant daily strain stimulus under changing load conditions. We have implemented a computer algorithm based on these concepts and obtained results consistent with experimental observations of normal tendon and ligament growth and development reported by other investigators. Additional results suggest that these concepts can also explain tendon and ligament adaptation to increased or decreased loading experienced during development.

Adaptation, Physiological↗
PubMed1998

An energy dissipation-based model for damage stimulated bone adaptation.

Based on experimental observations, several researchers have proposed a role for damage processes in stimulating an adaptive response in bone. In the current study we propose a model for bone adaptation based on cyclic energy dissipation as a measure of bone damage creation. By reanalyzing the fatigue data of Pattin et al. (1996), we derive a uniaxial form of the damage based formulation applicable to cortical regions experiencing primarily longitudinal stresses. Because of the experimentally observed difference between damage formation under tension and compression (Pattin et al., 1996), this formulation naturally predicts a difference in the adaptive response to tensile and compressive loading. This feature distinguishes the new formulation from existing strain energy based adaptation theories which treat tensile and compressive strains identically. Thus, developmental adaptation in response to unequal generation of damage provides one possible explanation for the experimentally observed difference between peak tensile and compressive bone surface strains.

Adaptation, Physiological↗
PubMed1998

Mechanobiology of skeletal regeneration.

Skeletal regeneration is accomplished by a cascade of biologic processes that may include differentiation of pluripotential tissue, endochondral ossification, and bone remodeling. It has been shown that all these processes are influenced strongly by the local tissue mechanical loading history. This article reviews some of the mechanobiologic principles that are thought to guide the differentiation of mesenchymal tissue into bone, cartilage, or fibrous tissue during the initial phase of regeneration. Cyclic motion and the associated shear stresses cause cell proliferation and the production of a large callus in the early phases of fracture healing. For intermittently imposed loading in the regenerating tissue: (1) direct intramembranous bone formation is permitted in areas of low stress and strain; (2) low to moderate magnitudes of tensile strain and hydrostatic tensile stress may stimulate intramembranous ossification; (3) poor vascularity can promote chondrogenesis in an otherwise osteogenic environment; (4) hydrostatic compressive stress is a stimulus for chondrogenesis; (5) high tensile strain is a stimulus for the net production of fibrous tissue; and (6) tensile strain with a superimposed hydrostatic compressive stress will stimulate the development of fibrocartilage. Finite element models are used to show that the patterns of tissue differentiation observed in fracture healing and distraction osteogenesis can be predicted from these fundamental mechanobiologic concepts. In areas of cartilage formation, subsequent endochondral ossification normally will proceed, but it can be inhibited by intermittent hydrostatic compressive stress and accelerated by octahedral shear stress (or strain). Later, bone remodeling at these sites can be expected to follow the same mechanobiologic adaptation rules as normal bone.

Adaptation, Physiological↗
PubMed1998

A microstructural model for the tensile constitutive and failure behavior of soft skeletal connective tissues.

We propose a microstructural model for the uniaxial tensile constitutive and failure behavior of soft skeletal connective tissues. The model characterizes the tissues as two-phase composites consisting of collagen fibers embedded in ground substance. Nonlinear toe region behavior in the stress versus strain curve results from the straightening of crimped fibers and from fiber reorientation. Subsequent linear behavior results from fiber stretching affected by fiber volume fraction, collagen type, crosslink density, and fiber orientation. Finally, the tissue fails when fibers successively rupture at their ultimate tensile strain. We apply the model to tendon, meniscus, and articular cartilage. The model provides a consistent approach to modeling the tensile behavior of a wide range of soft skeletal connective tissues.

Animals↗
PubMed1997

Correspondence between theoretical models and dual energy x-ray absorptiometry measurements of femoral cross-sectional growth during adolescence.

We have developed an analytical model of long bone cross-sectional ontogeny in which appositional growth of the diaphysis is primarily driven by mechanical stimuli associated with increasing body mass during growth and development. In this study, our goal was to compare theoretical predictions of femoral diaphyseal structure from this model with measurements of femoral bone mineral and geometry by dual energy x-ray absorptiometry. Measurements of mid-diaphyseal femoral geometry and structure were made previously in 101 Caucasian adolescents and young adults 9-26 years of age. The data on measured bone mineral content and calculated section modulus were compared with the results of our analytical model of cross-sectional development of the human femur over the same age range. Both bone mineral content and section modulus showed good correspondence with experimental measurements when the relationships with age and body mass were examined. Strong linear relationships were evident for both parameters when examined as a function of body mass.

Absorptiometry, Photon↗
PubMed1997

Adaptive bone remodeling incorporating simultaneous density and anisotropy considerations.

Over 100 years ago, Wolff hypothesized that cancellous bone altered both its apparent density and trabecular orientation in response to mechanical loads. A mathematical counterpart of this principle is derived by adding a remodeling rule for the rate-of-change of the full anisotropic stiffness tensor (all 21 independent terms) to the density rate-of-change rule adapted from an existing isotropic theory. As a result, anisotropy and density patterns develop such that the local stiffness tensor is optimal for the given series of applied loadings. The method does not rely on additional morphological measures of trabecular orientation. Furthermore, assumptions of material symmetry are not required, and any observed regions of orthotropy, transverse isotropy, or isotropy are a result entirely of the functional adaptation of the bone and not the consequence of a modeling assumption. This approach has been implemented with the finite element method and applied to a two-dimensional model of the proximal femur with encouraging results.

Anisotropy↗
PubMed1997

The DSM-IV Outline for Cultural Formulation: a critical demonstration with American Indian children.

OBJECTIVE: The publication of DSM-IV is notable for the improved coverage of cultural issues in the diagnosis of mental disorders. In particular, Appendix I of DSM-IV includes an "Outline for Cultural Formulation" (Outline) which assists the clinician in evaluating the impact of an individual's cultural context on diagnosis and treatment. However, the capacity of the Outline to facilitate the development of comprehensive cultural formulations for children and adolescents has not been established. In this article the use of the Outline with American Indian children is reviewed critically. METHOD: Based on the Outline, cultural case formulations for four American Indian children were developed and their comprehensiveness was assessed. RESULTS: Applied to the case material, the Outline provided a clear template for the development of cultural formulations. Nonetheless, several gaps in the material required by the Outline were identified, particularly in the areas concerning cultural identity and cultural elements of the therapeutic relationship. CONCLUSIONS: Clinicians working with children should recognize the strengths as well as the limitations of the Outline and expand their cultural descriptions accordingly. Several additions to the text of the Outline that will facilitate the development of comprehensive cultural formulations specific to children and adolescents are proposed.

Case Management↗
PubMed1996

Determinants of femoral geometry and structure during adolescent growth.

Our goal was to understand developmental determinants of femoral structure during growth and sexual maturation by relating femoral measurements to gender and developmental factors (age, pubertal stage, height, and body mass). The bone mineral content of the femur was measured by dual energy x-ray absorptiometry in 101 healthy Caucasian adolescents and young adults, 9-26 years of age. After some simplifying assumptions had been made, cross-sectional geometric properties of the femoral midshaft were estimated. Two geometry-based structural indicators, the section modulus and whole bone strength index, were calculated to assess the structural characteristics of the femur. Femoral strength, as described by these structural indicators, increased dramatically from childhood through young adulthood. Regressions were performed between these femoral measurements and the developmental factors. Our data show that of age, pubertal stage, body mass, and height, body mass is the strongest predictor of femoral cross-sectional properties, and the correlation of body mass with femoral cross-sectional structure is independent of gender. A model including all four developmental factors and gender did not substantially increase the accuracy of predictions compared with the model with body mass alone. In light of previous research, we hypothesize that body mass is an indicator of in vivo loading and that this in vivo loading influences the cross-sectional growth of the long bones.

Absorptiometry, Photon↗
PubMed1996

In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure.

This study tested the effects of hydrostatic pressure (10 MPa) on adult articular chondrocyte mRNA and extracellular matrix synthesis in vitro. High density primary cultures of bovine chondrocytes were exposed to hydrostatic pressure applied intermittently at 1 Hz or constantly for 4 hours in serum-free medium or in medium containing 1% fetal bovine serum. mRNAs for aggrecan, types I and II collagen, and beta-actin were analyzed by Northern blots and quantified by slot blots. Proteoglycan synthesis was quantified by 35SO4 uptake into cetylpyridinium chloride-precipitable glycosaminoglycans, and cell-associated aggrecan and type-II collagen were detected by immunohistochemical techniques. In serum-free medium, intermittent pressure increased aggrecan mRNA signal by 14% and constant pressure decreased type-II collagen mRNA signal by 16% (p < 0.05). In the presence of 1% fetal bovine serum, intermittent pressure increased aggrecan and type-II collagen mRNA signals by 31% (p < 0.01) and 36% (p < 0.001), respectively, whereas constant pressure had no effect on either mRNA. Intermittent and constant pressure stimulated glycosaminoglycan synthesis 65% (p < 0.001) and 32% (p < 0.05), respectively. Immunohistochemical detection of cell-associated aggrecan and type-II collagen was increased in response to both intermittent and constant pressure. These data support the hypothesis that physiologic hydrostatic pressure directly influences the extracellular matrix metabolism of articular chondrocytes.

Aggrecans↗
PubMed1996

Cyclic mechanical property degradation during fatigue loading of cortical bone.

Fatigue damage accumulation has been demonstrated in living bone and postulated as a stimulus to the bone modeling and remodeling response. Mechanical property degradation is one manifestation of fatigue damage accumulation. This study examines changes in secant modulus and cyclic energy dissipation behavior during axial load-controlled fatigue loading of cortical bone specimens. The findings suggest that secant modulus degradation and cyclic energy dissipation are greatly increased at loading levels above critical damage strain thresholds of 2500 and 4000 mu epsilon in tensile and compressive fatigue, respectively. Tensile and compressive fatigue loading also caused different forms of modulus degradation at loading levels above these thresholds. Bone behaves as a linear viscoelastic material below these thresholds, even after prior property degradation at higher loading levels. Cyclic energy dissipation was proportional to the 2.1 power of the applied effective strain range for all loadings below 2500 mu epsilon. Above 2500 mu epsilon, tensile fatigue loading caused cyclic energy dissipation proportional to the 5.8 power of the applied effective strain range. Compressive fatigue loading dissipated cyclic energy proportional to the 4.9 power of applied effective strain range over 4000 mu epsilon. Lifetime energy dissipation over all fatigue tests to fracture at a single loading level was well fitted by the same power law in the number of cycles to failure raised to the 0.6 power. Loading levels of 2500 mu epsilon in tension and 4000 mu epsilon in compression are within the ranges observed in living animals, and thus these phenomena may play a role in initiating the remodeling response in live bone tissue.

Adolescent↗
PubMed1996

Mechanical factors in bone growth and development.

Mechanobiologic factors strongly influence skeletal ossification and regulate changes in bone geometry and apparent density during ontogeny. We have developed computer models that implement a simple mathematical rule relating cyclic tissue stresses to bone apposition and resorption. Beginning at the fetal stages of the femoral anlage, these models successfully predict the appositional bone growth and modeling observed in the development of the diaphyseal cross section. The same basic mechanobiologic rule can also predict the architectural construction of the proximal cancellous bone formed in regions of endochondral ossification. Geometry and density changes in adult diaphyseal and cancellous bone as a result of changes in physical activity can be simulated by invoking the same rule used during development. Future clinical and experimental work is needed to provide more quantitative data for mechanobiologic rules and elucidate the interactions between chemical and mechanical factors influencing bone biology.

Adaptation, Physiological↗
PubMed1996

Mechanical and geometric changes in the growing femora of BMP-5 deficient mice.

We examined the growth-related changes in femoral geometry and torsional strength in BMP-5 deficient short-ear mice over a 22-week time interval ("long-term" changes). Four groups of female mice (n = 6 per group) were examined: short-ear animals and their heterozygous control littermates at 4 and 26 weeks of age. In agreement with findings previously observed in a mixed-gender group of adult mice (26 weeks), the femora of short-ear animals were significantly smaller in length and cross section at both ages. The magnitudes of the differences between genotypes were comparable at each age, indicating that the overall rates of appositional and endochondral growth were similar for both genotypes over the 22-week period. In the adult animals, short-ear femora were 27 +/- 7% weaker in torsional strength due to their smaller cross-sectional geometry. However, bone strength in adult short-ear mice appeared to be adequate for animal size: No significant difference was detected in maximum femoral torque when normalized by body mass. In 4-week old animals, BMP-5 deficiency was associated with a 27 +/- 6% lower body mass, but the torsional strength of the femur was not significantly different from that of controls. Cross-sectional geometry was smaller in 4-week old short-ear mice, but the apparent bone material ultimate shear stress was elevated by 33 +/- 10%, thereby resulting in a whole bone torsional strength equivalent to that of the larger control mice. While the data suggest a higher material strength in the 4-week-old short-ear animals, no significant difference in the level of bone mineralization was detectable between genotypes at either age.

Analysis of Variance↗
PubMed1996

Different loads can produce similar bone density distributions.

Finite element models of a generic long bone and the proximal femur were used to identify important load characteristics and to determine whether small changes in load affect bone adaptation simulations. We also examined the effect of implants on the sensitivity of bone adaptation simulations to changes in loads. For each model, a primary load set was selected and incorporated in a bone adaptation simulation to generate a primary density distribution. A density-based load estimation method was used to determine a secondary set of loading conditions for each model. Each secondary load set was incorporated in a bone adaptation simulation and the resulting density distribution was compared to the corresponding primary density distribution. Nearly identical density distributions were produced for the natural generic long bone model (average nodal density difference 0.02 g/cm3). For the natural proximal femur model, the density distributions were very similar, but differences were apparent (average nodal density difference 0.07 g/cm3). The same primary and secondary load sets were used for bone adaptation simulations with implant models. For the proximal femur model, density distribution differences with the implant were very slightly less than those of the natural model. For the generic long bone model, the implant amplified differences between density distributions (average nodal density difference 0.14 g/cm3). Thus, variations in loading conditions may partially explain variations in long-term total joint outcome. The total equivalent stimulus load magnitudes for the two load sets for the generic long bone model were within 1%, and the stimulus-weighted average load directions were within 1 degree. The similarity of these parameters and the natural generic long bone density distributions indicate that the overall magnitude and average load direction are key factors affecting bone adaptation.

Adaptation, Physiological↗