Biomedical subjects

Clark T Hung

Publications and source records attributed to Clark T Hung.

At least 19 recordsLinked to original sources

PubMed2006

A mixture theory analysis for passive transport in osmotic loading of cells.

The theory of mixtures is applied to the analysis of the passive response of cells to osmotic loading with neutrally charged solutes. The formulation, which is derived for multiple solute species, incorporates partition coefficients for the solutes in the cytoplasm relative to the external solution, and accounts for cell membrane tension. The mixture formulation provides an explicit dependence of the hydraulic conductivity of the cell membrane on the concentration of permeating solutes. The resulting equations are shown to reduce to the classical equations of Kedem and Katchalsky in the limit when the membrane tension is equal to zero and the solute partition coefficient in the cytoplasm is equal to unity. Numerical simulations demonstrate that the concentration-dependence of the hydraulic conductivity is not negligible; the volume response to osmotic loading is very sensitive to the partition coefficient of the solute in the cytoplasm, which controls the magnitude of cell volume recovery; and the volume response is sensitive to the magnitude of cell membrane tension. Deviations of the Boyle-van't Hoff response from a straight line under hypo-osmotic loading may be indicative of cell membrane tension.

Biological Transport↗

PubMed2006

Frictional response of bovine articular cartilage under creep loading following proteoglycan digestion with chondroitinase ABC.

The specific aim of this study was to investigate the effect of chondroitinase ABC treatment on the frictional response of bovine articular cartilage against glass, under creep loading. The hypothesis is that chondroitinase ABC treatment increases the friction coefficient of bovine articular cartilage under creep. Articular cartilage samples (n = 12) harvested from two bovine knee joints (1-3 months old) were divided into a control group (intact specimens) and a treated group (chondroitinase ABC digestion), and tested in unconfined compression with simultaneous continuous sliding (+/- 4 mm at 1 mm/s) under a constant applied stress of 0.5 MPa, for 2500 s. The time-dependent response of the friction coefficient was measured. With increasing duration of loading, treated samples exhibited a significantly higher friction coefficient than control samples as assessed by the equilibrium value (treated: micro(eq) = 0.19 +/- 0.02; control: micro(eq) = 0.12 +/- 0.03; p = 0.002), though the coefficient achieved immediately upon loading did not increase significantly (treated: micro(min) = 0.0053 +/- 0.0025; control: micro(min) = 0.037 +/- 0.0013; p = 0.19). Our results demonstrate that removal of the cartilage glycosaminoglycans using chondroitinase ABC significantly increases the overall time-dependent friction coefficient of articular cartilage. These findings strengthen the motivation for developing chondroprotective strategies by increasing cartilage chondroitin sulfate content in osteoarthritic joints.

Animals↗

PubMed2005

Spatial and temporal development of chondrocyte-seeded agarose constructs in free-swelling and dynamically loaded cultures.

Dynamic deformational loading has been shown to significantly increase the development of material properties of chondrocyte-seeded agarose hydrogels, however little is known about the spatial development of the material properties within these constructs. In this study, a technique that combines video microscopy and optimized digital image correlation, was applied to assess the spatial development of material properties in tissue-engineered cartilage constructs cultured in free-swelling and dynamically-loaded conditions (3h/day, 5 days/week, and maintained in free-swelling conditions when not being loaded) over a 6-week period. Although homogeneous at day 0, both free-swelling and dynamically loaded samples progressively developed stiffer outer edges and a softer central region. The distribution of GAGs and collagens were shown to mimic this profile. These results indicate that although dynamic loading augments the development of bulk properties in these samples, possibly by overcoming some of the diffusion limitation and nutrient transport issues, the overall profile of construct properties in the axial direction remains qualitatively the same as in free-swelling culture conditions. Poisson's ratio of these constructs increased over time in culture with increased fixed charged density contributed by the GAGs, but this increase was significantly less in dynamically loaded samples by day 42. Polarized light microscopy of Picrosirius Red labeled samples, at an angle perpendicular to the direction of loading, suggests that these differences in Poisson's ratio may be due to improved organization of collagen network in the dynamically loaded samples.

Animals↗

PubMed2005

Direct measurement of osmotic pressure of glycosaminoglycan solutions by membrane osmometry at room temperature.

Articular cartilage is a hydrated soft tissue composed of negatively charged proteoglycans fixed within a collagen matrix. This charge gradient causes the tissue to imbibe water and swell, creating a net osmotic pressure that enhances the tissue's ability to bear load. In this study we designed and utilized an apparatus for directly measuring the osmotic pressure of chondroitin sulfate, the primary glycosaminoglycan found in articular cartilage, in solution with varying bathing ionic strength (0.015 M, 0.15 M, 0.5 M, 1 M, and 2 M NaCl) at room temperature. The osmotic pressure (pi) was found to increase nonlinearly with increasing chondroitin sulfate concentration and decreasing NaCl ionic bath environment. Above 1 M NaCl, pi changes negligibly with further increases in salt concentration, suggesting that Donnan osmotic pressure is negligible above this threshold, and the resulting pressure is attributed to configurational entropy. Results of the current study were also used to estimate the contribution of osmotic pressure to the stiffness of cartilage based on theoretical and experimental considerations. Our findings indicate that the osmotic pressure resulting from configurational entropy is much smaller in cartilage (based on an earlier study on bovine articular cartilage) than in free solution. The rate of change of osmotic pressure with compressive strain is found to contribute approximately one-third of the compressive modulus (H(A)(eff)) of cartilage (Pi approximately H(A)(eff)/3), with the balance contributed by the intrinsic structural modulus of the solid matrix (i.e., H(A) approximately 2H(A)(eff)/3). A strong dependence of this intrinsic modulus on salt concentration was found; therefore, it appears that proteoglycans contribute structurally to the magnitude of H(A), in a manner independent of osmotic pressure.

Animals↗

PubMed2005

Shear stress alters the expression of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) in Schwann cells.

Schwann cells within a peripheral nerve respond robustly after an axonal injury. Recent results have revealed that Schwann cells undergo concurrent proliferation and apoptosis after a chronic nerve injury that is independent of axonal pathology. Although the exact nature of the stimulus that produces this Schwann cell response remains unknown, we postulated that this response may be triggered directly by mechanical stimuli. Thus, we sought to determine how pure Schwann cells responded to a sustained shear stress in the form of laminar fluid flow by evaluating for proliferation, expression of S-100, myelin-associated glycoprotein (MAG), and myelin basic protein (MBP). Immunohistochemistry demonstrated that the Schwann cells were positive for S-100, MAG, and MBP in greater than 99% of the experimental cells. Stimulated cells also revealed an increased rate of proliferation by as much as 100% (p<.001). The mRNA expression of MAG and MBP was down-regulated by 21% (p<.035) and 18% (p<.015), respectively, in experimental cells from RT-PCR assays. Furthermore, Western blot showed a down-regulation in MAG and MBP protein expression by 29% (p<.035) and 35% (p<.02), respectively. This study provides novel information regarding Schwann cell direct response to this physical stimulus that is not secondary to an axonal injury.

Animals↗

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

Effects of enzymatic degradation on the frictional response of articular cartilage in stress relaxation.

It was recently shown experimentally that the friction coefficient of articular cartilage correlates with the interstitial fluid pressurization, supporting the hypothesis that interstitial water pressurization plays a fundamental role in the frictional response by supporting most of the load during the early time response. A recent study showed that enzymatic treatment with chondroitinase ABC causes a decrease in the maximum fluid load support of bovine articular cartilage in unconfined compression. The hypothesis of this study is that treatment with chondroitinase ABC will increase the friction coefficient of articular cartilage in stress relaxation. Articular cartilage samples (n = 34) harvested from the femoral condyles of five bovine knee joints (1-3 months old) were tested in unconfined compression with simultaneous continuous sliding (+/-1.5 mm at 1 mm/s) under stress relaxation. Results showed a significantly higher minimum friction coefficient in specimens treated with 0.1 micro/ml of chondroitinase ABC for 24 h (micro(min) = 0.082+/-0.024) compared to control specimens (micro(min) = 0.047+/-0.014). Treated samples also exhibited higher equilibrium friction coefficient (micro(eq) = 0.232+/-0.049) than control samples (micro(eq) = 0.184+/-0.036), which suggest that the frictional response is greatly influenced by the degree of tissue degradation. The fluid load support was predicted from theory, and the maximum value (as a percentage of the total applied load) was lower in treated specimens (77+/-12%) than in control specimens (85+/-6%). Based on earlier findings, the increase in the ratio micro(min)/micro(eq) may be attributed to the decrease in fluid load support.

Animals↗

PubMed2005

A layered agarose approach to fabricate depth-dependent inhomogeneity in chondrocyte-seeded constructs.

Inspired by the depth-dependent inhomogeneity of articular cartilage, it was hypothesized that a novel layered agarose technique, using a 2% (wt/vol) top and a 3% (wt/vol) bottom layer, would create an inhomogenous tissue construct with distinct material properties in conjoined regions. The biochemical and mechanical development of these constructs was observed alongside uniform 2% and 3% constructs. Initially, uniform 3% agarose disks had the highest bulk Young's modulus (E(Y) approximately 28 kPa) of all groups. After 28 days of culture in 20% FBS-containing media, however, uniform 2% chondrocyte-seeded constructs achieved the highest Young's modulus compared to bilayered and 3% agarose disks. Though all three groups contained similar GAG content ( approximately 1.5% ww), uniform 2% agarose disks on day 28 possessed the highest collagen content ( approximately 1% ww). Unlike in either homogeneous construct type, microscopic analysis of axial strain fields in bilayered constructs in response to applied static compression revealed two mechanically disparate regions on day 0: a softer 2% layer and a stiffer 3% layer. With time in culture, this inhomogeneity became less distinct, as indicated by increased continuity in both the local displacement field and local E(Y), and depended on the level of FBS supplementation of the feed media, with lower FBS concentrations (10%) more closely maintaining the original distinction of material properties. These results shed positive light on a layered agarose technique for the production of inhomogeneous bilayered chondrocyte-seeded agarose constructs with applications for investigations of chondrocyte mechanotransduction and for possible use in the tissue engineering of inhomogeneous articular cartilage constructs.

Animals↗

PubMed2005

Patellofemoral joint biomechanics and tissue engineering.

Recent advances in the study of patellofemoral joint biomechanics have provided promising diagnosis and treatment modalities for patellofemoral joint disorders, such as quantitative assessment of cartilage lesions from noninvasive imaging, computer simulations of surgical procedures for optimizing surgical parameters and potentially predicting outcomes, and cartilage tissue engineering for the treatment of advanced degenerative joint disease. These technologies are still in development and their clinical potentials remain an ongoing topic of investigation. We review some of our progress in addressing these issues, and the important role of cartilage mechanics and lubrication in understanding the challenges regarding patellofemoral surgery and cartilage tissue engineering.

Biomechanical Phenomena↗

PubMed2004

Dynamic osmotic loading of chondrocytes using a novel microfluidic device.

Many cells exhibit disparate responses to a mechanical stimulus depending on whether it is applied dynamically or statically. In this context, few studies have examined how cells respond to dynamic changes of the extracellular osmolality. In this study, we hypothesized that the cell size change response of cultured articular chondrocytes would be dependent on the frequency of applied osmotic loading. To test this hypothesis, we developed a novel microfluidic device, to apply hydrostatic pressure-driven dynamic osmotic loading by applying composition modulated flow, adapted from Tang and co-workers. This microfluidic device was used to study osmotic loads of +/-180 mOsm at a frequency up to 0.1 Hz with a constant minimal fluid-shear stress, and permit real-time monitoring of cell responses. Bovine articular chondrocytes were observed to exhibit increasing changes in cell volume with decreasing osmotic loading frequency. When the cell volume response was modeled by an exponential function, chondrocytes exhibited significantly different volume change responses to dynamic osmotic loading at 0.0125 Hz and static osmotic loading applied for a period of four minutes (Delta = +/-180 mOsm relative to the isotonic 360 mOsm). The intracellular calcium response at 0.0125 Hz was also monitored and compared with the response to static loading. Coupled with phenomenological or constitutive models, this novel approach could yield new information regarding cell material properties in response to dynamic loading that may contribute new insights into mechanisms of cellular homeostasis and mechanotransduction.

Animals↗

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

Roles of microtubules, cell polarity and adhesion in electric-field-mediated motility of 3T3 fibroblasts.

Direct-current electric fields mediate motility (galvanotaxis) of many cell types. In 3T3 fibroblasts, electric fields increased the proportion, speed and cathodal directionality of motile cells. Analogous to fibroblasts' spontaneous migration, we initially hypothesized that reorientation of microtubule components modulates galvanotaxis. However, cells with intact microtubules did not reorient them in the field and cells without microtubules still migrated, albeit slowly, thus disproving the hypothesis. We next proposed that, in monolayers wounded and placed in an electric field, reorientation of microtubule organizing centers and stable, detyrosinated microtubules towards the wound edge is necessary and/or sufficient for migration. This hypothesis was negated because field exposure mediated migration of unoriented, cathode-facing cells and curtailed migration of oriented, anode-facing cells. This led us to propose that ablating microtubule detyrosination would not affect galvanotaxis. Surprisingly, preventing microtubule detyrosination increased motility speed, suggesting that detyrosination inhibits galvanotaxis. Microtubules might enhance adhesion/de-adhesion remodeling during galvanotaxis; thus, electric fields might more effectively mediate motility of cells poorly or dynamically attached to substrata. Consistent with this hypothesis, incompletely spread cells migrated more rapidly than fully spread cells. Also, overexpression of PAK4, a Cdc42-activated kinase that decreases adhesion, enhanced galvanotaxis speed, whereas its lack decreased speed. Thus, electric fields mediate fibroblast migration via participation of microtubules and adhesive components, but their participation differs from that during spontaneous motility.

Animals↗

PubMed2004

Anisotropic strain-dependent material properties of bovine articular cartilage in the transitional range from tension to compression.

Articular cartilage exhibits complex mechanical properties such as anisotropy, inhomogeneity and tension-compression nonlinearity. This study proposes and demonstrates that the application of compressive loading in the presence of osmotic swelling can be used to acquire a spectrum of incremental cartilage moduli (EYi) and Poisson's ratios (upsilon ij) from tension to compression. Furthermore, the anisotropy of the tissue can be characterized in both tension and compression by conducting these experiments along three mutually perpendicular loading directions: parallel to split-line (1-direction), perpendicular to split-line (2-direction) and along the depth direction (3-direction, perpendicular to articular surface), accounting for tissue inhomogeneity between the surface and deep layers in the latter direction. Tensile moduli were found to be strain-dependent while compressive moduli were nearly constant. The peak tensile (+) Young's moduli in 0.15M NaCl were E+Y1=3.1+/-2.3, E+Y2=1.3+/-0.3, E+Y3(Surface)=0.65+/-0.29 and E+Y3(Deep)=2.1+/-1.2 MPa. The corresponding compressive (-) Young's moduli were E-Y1=0.23+/-0.07, E-Y2=0.22+/-0.07, E-Y3(Surface)=0.18+/-0.07 and E-Y3(Deep)=0.35+/-0.11 MPa. Peak tensile Poisson's ratios were upsilon+12=0.22+/-0.06, upsilon+21=0.13+/-0.07, upsilon+31(Surface)=0.10+/-0.03 and upsilon+31(Deep)=0.20+/-0.05 while compressive Poisson's ratios were upsilon-12=0.027+/-0.012, upsilon-21=0.017+/-0.07, upsilon-31(Surface)=0.034+/-0.009 and upsilon-31(Deep)=0.065+/-0.024. Similar measurements were also performed at 0.015 M and 2 M NaCl, showing strong variations with ionic strength. Results indicate that (a) a smooth transition occurs in the stress-strain and modulus-strain responses between the tensile and compressive regimes, and (b) cartilage exhibits orthotropic symmetry within the framework of tension-compression nonlinearity. The strain-softening behavior of cartilage (the initial decrease in EYi with increasing compressive strain) can be interpreted in the context of osmotic swelling and tension-compression nonlinearity.

Animals↗

PubMed2004

The correspondence between equilibrium biphasic and triphasic material properties in mixture models of articular cartilage.

Mixture models have been successfully used to describe the response of articular cartilage to various loading conditions. Mow et al. (J. Biomech. Eng. 102 (1980) 73) formulated a biphasic mixture model of articular cartilage where the collagen-proteoglycan matrix is modeled as an intrinsically incompressible porous-permeable solid matrix, and the interstitial fluid is modeled as an incompressible fluid. Lai et al. (J. Biomech. Eng. 113 (1991) 245) proposed a triphasic model of articular cartilage as an extension of their biphasic theory, where negatively charged proteoglycans are modeled to be fixed to the solid matrix, and monovalent ions in the interstitial fluid are modeled as additional fluid phases. Since both models co-exist in the cartilage literature, it is useful to show how the measured properties of articular cartilage (the confined and unconfined compressive and tensile moduli, the compressive and tensile Poisson's ratios, and the shear modulus) relate to both theories. In this study, closed-form expressions are presented that relate biphasic and triphasic material properties in tension, compression and shear. These expressions are then compared to experimental findings in the literature to provide greater insight into the measured properties of articular cartilage as a function of bathing solutions salt concentrations and proteoglycan fixed-charge density.

Animals↗

PubMed2004

A paradigm for functional tissue engineering of articular cartilage via applied physiologic deformational loading.

Deformational loading represents a primary component of the chondrocyte physical environment in vivo. This review summarizes our experience with physiologic deformational loading of chondrocyte-seeded agarose hydrogels to promote development of cartilage constructs having mechanical properties matching that of the parent calf tissue, which has a Young's modulus E(Y) = 277 kPa and unconfined dynamic modulus at 1 Hz G* = 7 MPa. Over an 8-week culture period, cartilage-like properties have been achieved for 60 x 10(6) cells/ml seeding density agarose constructs, with E(Y) = 186 kPa, G* = 1.64 MPa. For these constructs, the GAG content reached 1.74% ww and collagen content 2.64% ww compared to 2.4% ww and 21.5% ww for the parent tissue, respectively. Issues regarding the deformational loading protocol, cell-seeding density, nutrient supply, growth factor addition, and construct mechanical characterization are discussed. In anticipation of cartilage repair studies, we also describe early efforts to engineer cylindrical and anatomically shaped bilayered constructs of agarose hydrogel and bone (i.e., osteochondral constructs). The presence of a bony substrate may facilitate integration upon implantation. These efforts will provide an underlying framework from which a functional tissue-engineering approach, as described by Butler and coworkers (2000), may be applied to general cell-scaffold systems adopted for cartilage tissue engineering.

Algorithms↗

PubMed2004

Cartilage interstitial fluid load support in unconfined compression following enzymatic digestion.

Interstitial fluid pressurization plays an important role in cartilage biomechanics and is believed to be a primary mechanism of load support in synovial joints. The objective of this study was to investigate the effects of enzymatic degradation on the interstitial fluid load support mechanism of articular cartilage in unconfined compression. Thirty-seven immature bovine cartilage plugs were tested in unconfined compression before and after enzymatic digestion. The peak fluid load support decreased significantly (p < 0.0001) from 84 +/- 10% to 53 +/- 19% and from 80 +/- 10% to 46 +/- 21% after 18-hours digestion with 1.0 u/mg-wet-weight and 0.7 u/mg-wet-weight of collagenase, respectively. Treatment with 0.1 u/ml of chondroitinase ABC for 24 hours also significantly reduced the peak fluid load support from 83 +/- 12% to 48 +/- 16% (p < 0.0001). The drop in interstitial fluid load support following enzymatic treatment is believed to result from a decrease in the ratio of tensile to compressive moduli of the solid matrix.

Animals↗

PubMed2004

Role of cell-associated matrix in the development of free-swelling and dynamically loaded chondrocyte-seeded agarose gels.

Chondrocytes embedded in agarose and subjected to dynamic deformational loading produce a functional matrix with time in culture, but there is usually a delay in the development of significant differences compared to free swelling. In this study, we hypothesized that the initial presence of a cell-associated matrix would expedite construct development in response to dynamic deformational loading. Seeded samples with enzymatically isolated chondrocytes and chondrons (the chondrocyte and its pericellular matrix) and examined the effects of seeding density and dynamic loading on the development of tissue properties. At 60 million/ml, dynamic loading significantly augmented the development of material properties in chondrocyte- and chondron-seeded constructs. Biochemical content and histological analysis indicated that the deposition of GAG, link protein and collagens are affected by the pre-existing cell-associated matrix of the chondron-seeded samples. The pericellular matrix associated with the chondrons did not expedite the development of material properties in response to deformational loading, disproving our hypothesis. The relative concentration and distribution of matrix proteins may play a major role in the disparate responses observed for the chondrocyte- and chondron-seeded cultures. In further support of these findings, culturing chondrocytes in agarose for two weeks prior to the application of deformational loading also did not exhibit expedited construct development.

Adaptation, Physiological↗

PubMed2004

Functional tissue engineering of chondral and osteochondral constructs.

Due to the prevalence of osteoarthritis (OA) and damage to articular cartilage, coupled with the poor intrinsic healing capacity of this avascular connective tissue, there is a great demand for an articular cartilage substitute. As the bearing material of diarthrodial joints, articular cartilage has remarkable functional properties that have been difficult to reproduce in tissue-engineered constructs. We have previously demonstrated that by using a functional tissue engineering approach that incorporates mechanical loading into the long-term culture environment, one can enhance the development of mechanical properties in chondrocyte-seeded agarose constructs. As these gel constructs begin to achieve material properties similar to that of the native tissue, however, new challenges arise, including integration of the construct with the underlying native bone. To address this issue, we have developed a technique for producing gel constructs integrated into an underlying bony substrate. These osteochondral constructs develop cartilage-like extracellular matrix and material properties over time in free swelling culture. In this study, as a preliminary to loading such osteochondral constructs, finite element modeling (FEM) was used to predict the spatial and temporal stress, strain, and fluid flow fields within constructs subjected to dynamic deformational loading. The results of these models suggest that while chondral ("gel alone") constructs see a largely homogenous field of mechanical signals, osteochondral ("gel bone") constructs see a largely inhomogeneous distribution of mechanical signals. Such inhomogeneity in the mechanical environment may aid in the development of inhomogeneity in the engineered osteochondral constructs. Together with experimental observations, we anticipate that such modeling efforts will provide direction for our efforts aimed at the optimization of applied physical forces for the functional tissue engineering of an osteochondral articular cartilage substitute.

Biocompatible Materials↗