Balance Assessment Using a Smartwatch Inertial Measurement Unit with Principal Component Analysis for Anatomical Calibration.

Balance assessment, or posturography, tracks and prevents health complications for a variety of groups with balance impairment, including the elderly population and patients with traumatic brain injury. Wearables can revolutionize state-of-the-art posturography methods, which have recently shifted focus to clinical validation of strictly positioned inertial measurement units (IMUs) as replacements for force-plate systems. Yet, modern anatomical calibration (i.e., sensor-to-segment alignment) methods have not been utilized in inertial-based posturography studies. Functional calibration methods can replace the need for strict placement of inertial measurement units, which may be tedious or confusing for certain users. In this study, balance-related metrics from a smartwatch IMU were tested against a strictly placed IMU after using a functional calibration method. The smartwatch and strictly placed IMUs were strongly correlated in clinically relevant posturography scores (r = 0.861-0.970, p < 0.001). Additionally, the smartwatch was able to detect significant variance (p < 0.001) between pose-type scores from the mediolateral (ML) acceleration data and anterior-posterior (AP) rotation data. With this calibration method, a large problem with inertial-based posturography has been addressed, and wearable, "at-home" balance-assessment technology is within possibility.

Inverse dynamics analysis of youth pitching arm kinetics using body composition imaging.

This study's objectives were to: (1) assess whether dual energy X-ray absorptiometry (DXA)-mass inverse dynamics (ID) alters predictions of youth pitching arm kinetics and (2) investigate correlations between kinetics and body composition. Eighteen 10- to 11-year-olds pitched 10 fastballs. DXA scans were conducted to obtain participant-specific upper arm, forearm, and hand masses. Pitching arm segment masses and kinetics calculated with scaled and DXA masses were compared with paired t-tests and correlations were investigated with linear regression. Hand (p < 0.001) and upper arm (p < 0.001) DXA masses were greater, while forearm (p < 0.001) DXA masses were lesser, than their scaled masses. Shoulder compressive force (p < 0.001), internal rotation torque (p < 0.001), and horizontal adduction torque (p = 0.002) increased when using DXA masses. Shoulder compressive force correlated with body mass (p < 0.001) and body mass index (BMI; p = 0.002) and elbow varus torque correlated with body mass (p < 0.05). The main conclusions were that (1) using participant-specific mass ratios leads to different predictions of injury-related pitching arm kinetics and, thus, may improve our understanding of injury risk factors; and (2) pitching arm kinetics were correlated with body composition measures and a relatively high total body mass and/or BMI may increase shoulder and/or elbow injury risk.

Baseball Pitching Arm Three-Dimensional Inertial Parameter Calculations From Body Composition Imaging and a Novel Overweight Measure for Youth Pitching Arm Kinetics.

Many baseball pitching studies have used inverse dynamics to assess throwing arm kinetics as high and repetitive kinetics are thought to be linked to pitching injuries. However, prior studies have not used participant-specific body segment inertial parameters (BSIPs), which are thought to improve analysis of high-acceleration motions and overweight participants. This study's objectives were to (1) calculate participant-specific BSIPs using dual energy X-ray absorptiometry (DXA) measures, (2) compare inverse dynamic calculations of kinetics determined by DXA-calculated BSIPs (full DXA-driven inverse dynamics) against kinetics using the standard inverse dynamics approach with scaled BSIPs (scaled inverse dynamics), and (3) examine associations between full DXA-driven kinetics and overweight indices: body mass index (BMI) and segment mass index (SMI). Eighteen participants (10-11 years old) threw 10 fastballs that were recorded for motion analysis. DXA scans were used to calculate participant-specific BSIPs (mass, center of mass, radii of gyration) for each pitching arm segment (upper arm, forearm, hand), BMI, and SMI. The hypotheses were addressed with t-tests and linear regression analyses. The major results were that (1) DXA-calculated BSIPs differed from scaled BSIPs for each pitching arm segment; (2) calculations for shoulder, but not elbow, kinetics differed between the full DXA-driven and scaled inverse dynamics analyses; and (3) full DXA-driven inverse dynamics calculations for shoulder kinetics were more often associated with SMI than BMI. Results suggest that using participant-specific BSIPs and pitching arm, SMIs may improve evidence-based injury prevention guidelines for youth pitchers.

Knee Angles After Crosstalk Correction With Principal Component Analysis in Gait and Cycling.

Principal component analysis (PCA) has been used as a post-hoc method for reducing knee crosstalk errors during gait analysis. PCA minimizes correlations between flexion-extension (FE), abduction-adduction (AA), and internal-external rotation (IE) angles. However, previous studies have not considered PCA for exercises involving knee flexion angles that are greater than those typically experienced during gait. Thus, the goal of this study was to investigate using PCA to correct for crosstalk during one exercise (i.e., cycling) that involves relatively high flexion angles. Fifteen participants were tested in gait and cycling using a motion analysis system. Uncorrected FE, AA and IE angles were compared to those calculated with PCA performed on (1) all angles (FE-AA-IE PCA correction) and (2) only FE-AA angles (FE-AA PCA correction). Significant differences existed between uncorrected and FE-AA-IE PCA corrected AA and IE angles for both exercises, between uncorrected and FE-AA PCA corrected AA angles for both exercises, and between FE-AA-IE and FE-AA PCA corrected IE angles for cycling. Correlations existed before PCA correction and were eliminated following PCA correction with the exception that FE-IE correlations remained following FE-AA PCA correction. Since the two PCA analyses differed only in their IE angle predictions for the high flexion exercise (cycling), IE angle results were compared to previous studies. Using FE-AA PCA correction may be the preferred protocol for cycling as it appeared to retain physiological IE angle correlations at high flexion angles. However, there exists a critical need for studies aimed at obtaining more accurate IE angles in such exercises.

Knee joint biomechanics in transtibial amputees in gait, cycling, and elliptical training.

Transtibial amputees may experience decreased quality of life due to increased risk of knee joint osteoarthritis (OA). No prior studies have compared knee joint biomechanics for the same group of transtibial amputees in gait, cycling, and elliptical training. Thus, the goal of this study was to identify preferred exercises for transtibial amputees in the context of reducing risk of knee OA. The hypotheses were: 1) knee biomechanics would differ due to participant status (amputee, control), exercise, and leg type (intact, residual) and 2) gait kinematic parameters would differ due to participant status and leg type. Ten unilateral transtibial amputee and ten control participants performed exercises while kinematic and kinetic data were collected. Two-factor repeated measures analysis of variance with post-hoc Tukey tests and non-parametric equivalents were performed to determine significance. Maximum knee compressive force, extension torque, and abduction torque were lowest in cycling and highest in gait regardless of participant type. Amputee maximum knee extension torque was higher in the intact vs. residual knee in gait. Amputee maximum knee flexion angle was higher in the residual vs. intact knee in gait and elliptical. Gait midstance knee flexion angle timing was asymmetrical for amputees and knee angle was lower in the amputee residual vs. control non-dominant knees. The results suggest that cycling, and likely other non-weight bearing exercises, may be preferred exercises for amputees due to significant reductions in biomechanical asymmetries and joint loads.

Effects of Game Pitch Count and Body Mass Index on Pitching Biomechanics in 9- to 10-Year-Old Baseball Athletes.

BACKGROUND: Pitching while fatigued and body composition may increase the injury risk in youth and adult pitchers. However, the relationships between game pitch count, biomechanics, and body composition have not been reported for a study group restricted to 9- to 10-year-old athletes. HYPOTHESIS: During a simulated game with 9- to 10-year-old athletes, (1) participants will experience biomechanical signs of fatigue, and (2) shoulder and elbow kinetics will correlate with body mass index (BMI). STUDY DESIGN: Descriptive laboratory study. METHODS: Thirteen 9- to 10-year-old youth baseball players pitched a simulated game (75 pitches). Range of motion and muscular output tests were conducted before and after the simulated game to quantify fatigue. Kinematic parameters at foot contact, maximum external rotation, and maximum internal rotation velocity (MIRV), as well as maximum shoulder and elbow kinetics between foot contact and MIRV were compared at pitches 1-5, 34-38, and 71-75. Multivariate analyses of variance were used to test the first hypothesis, and linear regressions were used to test the second hypothesis. RESULTS: MIRV increased from pitches 1-5 to 71-75 (P = .007), and head flexion at MIRV decreased from pitches 1-5 to 34-38 (P = .022). Maximum shoulder horizontal adduction, external rotation, and internal rotation torques increased from pitches 34-38 to 71-75 (P = .031, .023, and .021, respectively). Shoulder compression force increased from pitches 1-5 to 71-75 (P = .011). Correlations of joint torque/force with BMI were found at every pitch period: for example, shoulder internal rotation (R2 = 0.93, P < .001) and elbow varus (R2 = 0.57, P = .003) torques at pitches 1-5. CONCLUSION: Several results differed from those of previous studies with adult pitchers: (1) pitch speed remained steady, (2) shoulder MIRV increased, and (3) shoulder kinetics increased during a simulated game. The strong correlations between joint kinetics and BMI reinforce previous findings that select body composition measures may be correlated with pitching arm joint kinetics for youth baseball pitchers. CLINICAL RELEVANCE: The results improve our understanding of pitching biomechanics for 9- to 10-year-old baseball pitchers and may be used in future studies to improve evidence-based injury prevention guidelines.

3-dimensional metrics of proximal femoral shape deformities in Legg-Calvé-Perthes disease and slipped capital femoral epiphysis.

Legg-Calvé-Perthes disease (LCPD) and slipped capital femoral epiphysis (SCFE) are two common pediatric hip disorders that affect the 3-dimensional shape and function of the proximal femur. This study applied the principles of continuum mechanics to statistical shape modeling (SSM) and determined 3-D metrics for the evaluation of shape deformations in normal growth, LCPD, and SCFE. CT scans were obtained from 32 patients with asymptomatic, LCPD, and SCFE hips ((0.5-0.9 mm)2 in-plane resolution, 0.63 mm slice thickness). SSM was performed on segmented proximal femoral surfaces, and shape deformations were described by surface displacement, strain, and growth plate angle metrics. Asymptomatic normal femurs underwent coordinated, growth-associated surface displacements and anisotropic strains that were site-specific and highest at the greater trochanter. After size- and age-based shape adjustment, LCPD femurs exhibited large displacements and surface strains in the femoral head and neck, with associated changes in femoral head growth plate angles. Mild SCFE femurs had contracted femoral neck surfaces, and surface displacements in all regions tended to increase with severity of slip. The results of this paper provide new 3-D metrics for characterizing the shape and biomechanics of the proximal femur. Statement of Clinical Significance: Quantitative 3-D metrics of shape may be useful for understanding and monitoring disease progression, identifying target regions for shape modulation therapies, and objectively evaluating the success of such therapies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1526-1535, 2018.

An Equilibrium Constitutive Model of Anisotropic Cartilage Damage to Elucidate Mechanisms of Damage Initiation and Progression.

Traumatic injuries and gradual wear-and-tear of articular cartilage (AC) that can lead to osteoarthritis (OA) have been hypothesized to result from tissue damage to AC. In this study, a previous equilibrium constitutive model of AC was extended to a constitutive damage articular cartilage (CDAC) model. In particular, anisotropic collagen (COL) fibril damage and isotropic glycosaminoglycan (GAG) damage were considered in a 3D formulation. In the CDAC model, time-dependent effects, such as viscoelasticity and poroelasticity, were neglected, and thus all results represent the equilibrium response after all time-dependent effects have dissipated. The resulting CDAC model was implemented in two different finite-element models. The first simulated uniaxial tensile loading to failure, while the second simulated spherical indentation with a rigid indenter displaced into a bilayer AC sample. Uniaxial tension to failure simulations were performed for three COL fibril Lagrangian failure strain (i.e., the maximum elastic COL fibril strain) values of 15%, 30%, and 45%, while spherical indentation simulations were performed with a COL fibril Lagrangian failure strain of 15%. GAG damage parameters were held constant for all simulations. Our results indicated that the equilibrium postyield tensile response of AC and the macroscopic tissue failure strain are highly dependent on COL fibril Lagrangian failure strain. The uniaxial tensile response consisted of an initial nonlinear ramp region due to the recruitment of intact fibrils followed by a rapid decrease in tissue stress at initial COL fibril failure, as a result of COL fibril damage which continued until ultimate tissue failure. In the spherical indentation simulation, damage to both the COL fibril and GAG constituents was located only in the superficial zone (SZ) and near the articular surface with tissue thickening following unloading. Spherical indentation simulation results are in agreement with published experimental observations. Our results indicate that the proposed CDAC model is capable of simulating both initial small magnitude damage as well as complete failure of AC tissue. The results of this study may help to elucidate the mechanisms of AC tissue damage, which initiate and propagate OA.

Integrating qPLM and biomechanical test data with an anisotropic fiber distribution model and predictions of TGF-ß1 and IGF-1 regulation of articular cartilage fiber modulus.

A continuum mixture model with distinct collagen (COL) and glycosaminoglycan elastic constituents was developed for the solid matrix of immature bovine articular cartilage. A continuous COL fiber volume fraction distribution function and a true COL fiber elastic modulus ([Formula: see text] were used. Quantitative polarized light microscopy (qPLM) methods were developed to account for the relatively high cell density of immature articular cartilage and used with a novel algorithm that constructs a 3D distribution function from 2D qPLM data. For specimens untreated and cultured in vitro, most model parameters were specified from qPLM analysis and biochemical assay results; consequently, [Formula: see text] was predicted using an optimization to measured mechanical properties in uniaxial tension and unconfined compression. Analysis of qPLM data revealed a highly anisotropic fiber distribution, with principal fiber orientation parallel to the surface layer. For untreated samples, predicted [Formula: see text] values were 175 and 422 MPa for superficial (S) and middle (M) zone layers, respectively. TGF-[Formula: see text]1 treatment was predicted to increase and decrease [Formula: see text] values for the S and M layers to 281 and 309 MPa, respectively. IGF-1 treatment was predicted to decrease [Formula: see text] values for the S and M layers to 22 and 26 MPa, respectively. A novel finding was that distinct native depth-dependent fiber modulus properties were modulated to nearly homogeneous values by TGF-[Formula: see text]1 and IGF-1 treatments, with modulated values strongly dependent on treatment.

In vitro articular cartilage growth with sequential application of IGF-1 and TGF-ß1 enhances volumetric growth and maintains compressive properties.

In vitro cultures with insulin-like growth factor-1 (IGF-1) and transforming growth factor-ß1 (TGF-ß1) have previously been shown to differentially modulate the growth of immature bovine articular cartilage. IGF-1 stimulates expansive growth yet decreases compressive moduli and increases compressive Poisson's ratios, whereas TGF-ß1 maintains tissue size, increases compressive moduli, and decreases compressive Poisson's ratios. The current study's hypothesis was that sequential application of IGF-1 and TGF-ß1 during in vitro culture produces geometric and compressive mechanical properties that lie between extreme values produced when using either growth factor alone. Immature bovine articular cartilage specimens were harvested and either untreated (D0, i.e., day zero) or cultured in vitro for either 6 days with IGF-1 (D6 IGF), 12 days with IGF-1 (D12 IGF), or 6 days with IGF-1 followed by 6 days with TGF-ß1 (D12 SEQ, i.e., sequential). Following treatment, all specimens were tested for geometric, biochemical, and compressive mechanical properties. Relative to D0, D12 SEQ treatment enhanced volumetric growth, but to a lower value than that for D12 IGF. Furthermore, D12 SEQ treatment maintained compressive moduli and Poisson's ratios at values higher and lower, respectively, than those for D12 IGF. Considering the previously described effects of 12 days of treatment with TGF-ß1 alone, D12 SEQ induced both growth and mechanical property changes between those produced with either IGF-1 or TGF-ß1 alone. The results suggest that it may be possible to vary the durations of select growth factors, including IGF-1 and TGF-ß1, to more precisely modulate the geometric, biochemical, and mechanical properties of immature cartilage graft tissue in clinical repair strategies.

Contribution of proteoglycan osmotic swelling pressure to the compressive properties of articular cartilage.

The negatively charged proteoglycans (PG) provide compressive resistance to articular cartilage by means of their fixed charge density (FCD) and high osmotic pressure (π(PG)), and the collagen network (CN) provides the restraining forces to counterbalance π(PG). Our objectives in this work were to: 1), account for collagen intrafibrillar water when transforming biochemical measurements into a FCD-π(PG) relationship; 2), compute π(PG) and CN contributions to the compressive behavior of full-thickness cartilage during bovine growth (fetal, calf, and adult) and human adult aging (young and old); and 3), predict the effect of depth from the articular surface on π(PG) in human aging. Extrafibrillar FCD (FCD(EF)) and π(PG) increased with bovine growth due to an increase in CN concentration, whereas PG concentration was steady. This maturation-related increase was amplified by compression. With normal human aging, FCD(EF) and π(PG) decreased. The π(PG)-values were close to equilibrium stress (σ(EQ)) in all bovine and young human cartilage, but were only approximately half of σ(EQ) in old human cartilage. Depth-related variations in the strain, FCD(EF), π(PG), and CN stress profiles in human cartilage suggested a functional deterioration of the superficial layer with aging. These results suggest the utility of the FCD-π(PG) relationship for elucidating the contribution of matrix macromolecules to the biomechanical properties of cartilage.

Modeling the collagen fibril network of biological tissues as a nonlinearly elastic material using a continuous volume fraction distribution function.

Despite distinct mechanical functions, biological soft tissues have a common microstructure in which a ground matrix is reinforced by a collagen fibril network. The microstructural properties of the collagen network contribute to continuum mechanical tissue properties that are strongly anisotropic with tensile-compressive asymmetry. In this study, a novel approach based on a continuous distribution of collagen fibril volume fractions is developed to model fibril reinforced soft tissues as a nonlinearly elastic and anisotropic material. Compared with other approaches that use a normalized number of fibrils for the definition of the distribution function, this representation is based on a distribution parameter (i.e. volume fraction) that is commonly measured experimentally while also incorporating pre-stress of the collagen fibril network in a tissue natural configuration. After motivating the form of the collagen strain energy function, examples are provided for two volume fraction distribution functions. Consequently, collagen second-Piola Kirchhoff stress and elasticity tensors are derived, first in general form and then specifically for a model that may be used for immature bovine articular cartilage. It is shown that the proposed strain energy is a convex function of the deformation gradient tensor and, thus, is suitable for the formation of a polyconvex tissue strain energy function.

Differential regulation of immature articular cartilage compressive moduli and Poisson's ratios by in vitro stimulation with IGF-1 and TGF-beta1.

Mechanisms of articular cartilage growth and maturation have been elucidated by studying composition-function dynamics during in vivo development and in vitro culture with stimuli such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-beta1). This study tested the hypothesis that IGF-1 and TGF-beta1 regulate immature cartilage compressive moduli and Poisson's ratios in a manner consistent with known effects on tensile properties. Bovine calf articular cartilage from superficial-articular (S) and middle-growth (M) regions were analyzed fresh or following culture in medium with IGF-1 or TGF-beta1. Mechanical properties in confined (CC) and unconfined (UCC) compression, cartilage matrix composition, and explant size were assessed. Culture with IGF-1 resulted in softening in CC and UCC, increased Poisson's ratios, substantially increased tissue volume, and accumulation of glycosaminoglycan (GAG) and collagen (COL). Culture with TGF-beta1 promoted maturational changes in the S layer, including stiffening in CC and UCC and increased concentrations of GAG, COL, and pyridinoline crosslinks (PYR), but little growth. Culture of M layer explants with TGF-beta1 was nearly homeostatic. Across treatment groups, compressive moduli in CC and UCC were positively related to GAG, COL, and PYR concentrations, while Poisson's ratios were negatively related to concentrations of these matrix components. Thus, IGF-1 and TGF-beta1 differentially regulate the compressive mechanical properties and size of immature articular cartilage in vitro. Prescribing tissue growth, maturation, or homeostasis by controlling the in vitro biochemical environment with such growth factors may have applications in cartilage repair and tissue engineering.

A nonlinear constituent based viscoelastic model for articular cartilage and analysis of tissue remodeling due to altered glycosaminoglycan-collagen interactions.

A constituent based nonlinear viscoelastic (VE) model was modified from a previous study (Vena, et al., 2006, "A Constituent-Based Model for the Nonlinear Viscoelastic Behavior of Ligaments," J. Biomech. Eng., 128, pp. 449-457) to incorporate a glycosaminoglycan (GAG)-collagen (COL) stress balance using compressible elastic stress constitutive equations specific to articular cartilage (AC). For uniaxial loading of a mixture of quasilinear VE constituents, time constant and relaxation ratio equations are derived to highlight how a mixture of constituents with distinct quasilinear VE properties is one mechanism that produces a nonlinear VE tissue. Uniaxial tension experiments were performed with newborn bovine AC specimens before and after approximately 55% and approximately 85% GAG depletion treatment with guanidine. Experimental tissue VE parameters were calculated directly from stress relaxation data, while intrinsic COL VE parameters were calculated by curve fitting the data with the nonlinear VE model with intrinsic GAG viscoelasticity neglected. Select tissue and intrinsic COL VE parameters were significantly different from control and experimental groups and correlated with GAG content, suggesting that GAG-COL interactions exist to modulate tissue and COL mechanical properties. Comparison of the results from this and other studies that subjected more mature AC tissue to GAG depletion treatment suggests that the GAGs interact with the COL network in a manner that may be beneficial for rapid volumetric expansion during developmental growth while protecting cells from excessive matrix strains. Furthermore, the underlying GAG-COL interactions appear to diminish as the tissue matures, indicating a distinctive remodeling response during developmental growth.

Simulating the growth of articular cartilage explants in a permeation bioreactor to aid in experimental protocol design.

Recently a cartilage growth finite element model (CGFEM) was developed to solve nonhomogeneous and time-dependent growth boundary-value problems (Davol et al., 2008, "A Nonlinear Finite Element Model of Cartilage Growth," Biomech. Model. Mechanobiol., 7, pp. 295-307). The CGFEM allows distinct stress constitutive equations and growth laws for the major components of the solid matrix, collagens and proteoglycans. The objective of the current work was to simulate in vitro growth of articular cartilage explants in a steady-state permeation bioreactor in order to obtain results that aid experimental design. The steady-state permeation protocol induces different types of mechanical stimuli. When the specimen is initially homogeneous, it directly induces homogeneous permeation velocities and indirectly induces nonhomogeneous solid matrix shear stresses; consequently, the steady-state permeation protocol is a good candidate for exploring two competing hypotheses for the growth laws. The analysis protocols were implemented through the alternating interaction of the two CGFEM components: poroelastic finite element analysis (FEA) using ABAQUS and a finite element growth routine using MATLAB. The CGFEM simulated 12 days of growth for immature bovine articular cartilage explants subjected to two competing hypotheses for the growth laws: one that is triggered by permeation velocity and the other by maximum shear stress. The results provide predictions for geometric, biomechanical, and biochemical parameters of grown tissue specimens that may be experimentally measured and, consequently, suggest key biomechanical measures to analyze as pilot experiments are performed. The combined approach of CGFEM analysis and pilot experiments may lead to the refinement of actual experimental protocols and a better understanding of in vitro growth of articular cartilage.

A cartilage growth mixture model with collagen remodeling: validation protocols.

A cartilage growth mixture (CGM) model is proposed to address limitations of a model used in a previous study. New stress constitutive equations for the solid matrix are derived and collagen (COL) remodeling is incorporated into the CGM model by allowing the intrinsic COL material constants to evolve during growth. An analytical validation protocol based on experimental data from a recent in vitro growth study is developed. Available data included measurements of tissue volume, biochemical composition, and tensile modulus for bovine calf articular cartilage (AC) explants harvested at three depths and incubated for 13 days in 20% fetal borine serum (FBS) and 20% FBS+beta-aminopropionitrile. The proposed CGM model can match tissue biochemical content and volume exactly while predicting theoretical values of tensile moduli that do not significantly differ from experimental values. Also, theoretical values of a scalar COL remodeling factor are positively correlated with COL cross-link content, and mass growth functions are positively correlated with cell density. The results suggest that the CGM model may help us to guide in vitro growth protocols for AC tissue via the a priori prediction of geometric and biomechanical properties.

Articular cartilage tensile integrity: modulation by matrix depletion is maturation-dependent.

Articular cartilage function depends on the molecular composition and structure of its extracellular matrix (ECM). The collagen network (CN) provides cartilage with tensile integrity, but must also remodel during growth. Such remodeling may depend on matrix molecules interacting with the CN to modulate the tensile behavior of cartilage. The objective of this study was to determine the effects of increasingly selective matrix depletion on tensile properties of immature and mature articular cartilage, and thereby establish a framework for identifying molecules involved in CN remodeling. Depletion of immature cartilage with guanidine, chondroitinase ABC, chondroitinase AC, and Streptomyces hyaluronidase markedly increased tensile integrity, while the integrity of mature cartilage remained unaltered after depletion with guanidine. The enhanced tensile integrity after matrix depletion suggests that certain ECM components of immature matrix serve to inhibit CN interactions and may act as modulators of physiological alterations of cartilage geometry and tensile properties during growth/maturation.

Bioengineering cartilage growth, maturation, and form.

Cartilage of articular joints grows and matures to achieve characteristic sizes, forms, and functional properties. Through these processes, the tissue not only serves as a template for bone growth but also yields mature articular cartilage providing joints with a low-friction, wear-resistant bearing material. The study of cartilage growth and maturation is a focus of both cartilage biologists and bioengineers with one goal of trying to create biologic tissue substitutes for the repair of damaged joints. Experimental approaches both in vivo and in vitro are being used to better understand the mechanisms and regulation of growth and maturation processes. This knowledge may facilitate the controlled manipulation of cartilage size, shape, and maturity to meet the criteria needed for successful clinical applications. Mathematical models are also useful tools for quantitatively describing the dynamically changing composition, structure and function of cartilage during growth and maturation and may aid the development of tissue engineering solutions. Recent advances in methods of cartilage formation and culture which control the size, shape, and maturity of these tissues are numerous and provide contrast to the physiologic development of cartilage.

A nonlinear finite element model of cartilage growth.

The long range objective of this work is to develop a cartilage growth finite element model (CGFEM), based on the theories of growing mixtures that has the capability to depict the evolution of the anisotropic and inhomogeneous mechanical properties, residual stresses, and nonhomogeneities that are attained by native adult cartilage. The CGFEM developed here simulates isotropic in vitro growth of cartilage with and without mechanical stimulation. To accomplish this analysis a commercial finite element code (ABAQUS) is combined with an external program (MATLAB) to solve an incremental equilibrium boundary value problem representing one increment of growth. This procedure is repeated for as many increments as needed to simulate the desired growth protocol. A case study is presented utilizing a growth law dependent on the magnitude of the diffusive fluid velocity to simulate an in vitro dynamic confined compression loading protocol run for 2 weeks. The results include changes in tissue size and shape, nonhomogeneities that develop in the tissue, as well as the variation that occurs in the tissue constitutive behavior from growth.

Regulation of immature cartilage growth by IGF-I, TGF-beta1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network.

Cartilage growth may involve alterations in the balance between the swelling tendency of proteoglycans and the restraining function of the collagen network. Growth factors, including IGF-I, TGF-beta1, BMP-7, and PDGF-AB, regulate chondrocyte metabolism and, consequently, may regulate cartilage growth. Immature bovine articular cartilage explants from the superficial and middle zones were incubated for 13 days in basal medium or medium supplemented with serum, IGF-I, TGF-beta1, BMP-7, or PDGF-AB. Variations in tissue size, accumulation of proteoglycan and collagen, and tensile properties were assessed. The inclusion of serum, IGF-I, or BMP-7 resulted in expansive tissue growth, stimulation of proteoglycan deposition but not of collagen, and a diminution of tensile integrity. The regulation of cartilage metabolism by TGF-beta1 resulted in tissue homeostasis, with maintenance of size, composition, and function. Incubation in basal medium or with PDGF-AB resulted in small volumetric and compositional changes, but a marked decrease in tensile integrity. These results demonstrate that the phenotype of cartilage growth, and the associated balance between proteoglycan content and integrity of the collagen network, is regulated differentially by certain growth factors.