Porcine computational modeling to investigate developmental dysplasia of the hip.

While it is well-established that early detection and initiation of treatment of developmental dysplasia of the hip (DDH) is crucial to successful clinical outcomes, research on the mechanics of the hip joint during healthy and pathological hip development in infants is limited. Quantification of mechanical behavior in both the healthy and dysplastic developing joints may provide insight into the causes of DDH and facilitate innovation in treatment options. In this study, subject-specific three-dimensional finite element models of two pigs were developed: one healthy pig and one pig with induced dysplasia in the right hindlimb. The objectives of this study were: (1) to characterize mechanical behavior in the acetabular articular cartilage during a normal walking cycle by analyzing six metrics: contact pressure, contact area, strain energy density, von Mises stress, principal stress, and principal strain; and (2) to quantify the effect on joint mechanics of three anatomic abnormalities previously identified as related to DDH: variation in acetabular coverage, morphological changes in the femoral head, and changes in the articular cartilage. All metrics, except the contact area, were elevated in the dysplastic joint. Morphological changes in the femoral head were determined to be the most significant factors in elevating contact pressure in the articular cartilage, while the effects of acetabular coverage and changes in the articular cartilage were less significant. The quantification of the pathomechanics of DDH in this study can help identify key mechanical factors that restore normal hip development and can lead to mechanics-driven treatment options.

Age-dependent changes in collagen crosslinks reduce the mechanical toughness of human meniscus.

The mechanical resilience of the knee meniscus is provided by a group of structural proteins in the extracellular matrix. Aging can alter the quantity and molecular structure of these proteins making the meniscus more susceptible to debilitating tears. In this study, we determined the effect of aging on the quantity of structural proteins and collagen crosslinks in human lateral meniscus, and examined whether the quantity of these molecules was predictive of tensile toughness (area under the stress-strain curve). Two age groups were tested: a young group under 40 and an older group over 65 years old. Using mass spectrometry, we quantified the abundance of proteins and collagen crosslinks in meniscal tissue that was adjacent to the dumbbell-shaped specimens used to measure uniaxial tensile toughness parallel or perpendicular to the circumferential fiber orientation. We found that the enzymatic collagen crosslink deoxypyridinoline had a significant positive correlation with toughness, and reductions in the quantity of this crosslink with aging were associated with a loss of toughness in the ground substance and fibers. The non-enzymatic collagen crosslink carboxymethyl-lysine increased in quantity with aging, and these increases corresponded to reductions in ground substance toughness. For the collagenous (Types I, II, IV, VI, VIII) and non-collagenous structural proteins (elastin, decorin, biglycan, prolargin) analyzed in this study, only the quantity of collagen VIII was predictive of toughness. This study provides valuable insights on the structure-function relationships of the human meniscus, and how aging causes structural adaptations that weaken the tissue's mechanical integrity.

Increased deformations are dispensable for cell mechanoresponse in engineered bone analogs mimicking aging bone marrow.

Aged individuals and astronauts experience bone loss despite rigorous physical activity. Bone mechanoresponse is in-part regulated by mesenchymal stem cells (MSCs) that respond to mechanical stimuli. Direct delivery of low intensity vibration (LIV) recovers MSC proliferation in senescence and simulated microgravity models, indicating that age-related reductions in mechanical signal delivery within bone marrow may contribute to declining bone mechanoresponse. To answer this question, we developed a 3D bone marrow analog that controls trabecular geometry, marrow mechanics and external stimuli. Validated finite element (FE) models were developed to quantify strain environment within hydrogels during LIV. Bone marrow analogs with gyroid-based trabeculae of bone volume fractions (BV/TV) corresponding to adult (25%) and aged (13%) mice were printed using polylactic acid (PLA). MSCs encapsulated in migration-permissive hydrogels within printed trabeculae showed robust cell populations on both PLA surface and hydrogel within a week. Following 14 days of LIV treatment (1g, 100 Hz, 1 hour/day), type-I collagen and F-actin were quantified for the cells in the hydrogel fraction. While LIV increased all measured outcomes, FE models predicted higher von Mises strains for the 13% BV/TV groups (0.2%) when compared to the 25% BV/TV group (0.1%). Despite increased strains, collagen-I and F-actin measures remained lower in the 13% BV/TV groups when compared to 25% BV/TV counterparts, indicating that cell response to LIV does not depend on hydrogel strains and that bone volume fraction (i.e. available bone surface) directly affects cell behavior in the hydrogel phase independent of the external stimuli. Overall, bone marrow analogs offer a robust and repeatable platform to study bone mechanobiology.

Modeling fatigue failure in soft tissue using a visco-hyperelastic model with discontinuous damage.

Soft tissue is susceptible to injury from single high-magnitude static loads and from repetitive low-magnitude fatigue loads. While many constitutive formulations have been developed and validated to model static failure in soft tissue, a modeling framework is not well-established for fatigue failure. Here we determined the feasibility of using a visco-hyperelastic damage model with discontinuous damage (strain energy-based damage criterion) to simulate low- and high-cycle fatigue failure in soft fibrous tissue. Cyclic creep data from six uniaxial tensile fatigue experiments of human medial meniscus were used to calibrate the specimen-specific material parameters. The model was able to successfully simulate all three characteristic stages of cyclic creep, and predict the number of cycles until tissue rupture. Mathematically, damage propagated under constant cyclic stress due to time-dependent viscoelastic increases in tensile stretch that in turn increased strain energy. Our results implicate solid viscoelasticity as a fundamental regulator of fatigue failure in soft tissue, where tissue with slow stress relaxation times will be more resistant to fatigue injury. In a validation study, the visco-hyperelastic damage model was able to simulate characteristic stress-strain curves of pull to failure experiments (static failure) when using material parameters curve fit to the fatigue experiments. For the first time, we've shown that a visco-hyperelastic discontinuous damage framework can model cyclic creep and predict material rupture in soft tissue, and may enable the reliable simulation of both fatigue and static failure behavior from a single constitutive formulation.

Bridge Plate Fixation of Distal Femur Fractures: Defining Deficient Radiographic Callus Formation and Its Associations.

OBJECTIVE: To determine whether deficient early callus formation can be defined objectively based on the association with an eventual nonunion and specific patient, injury, and treatment factors. METHODS: Final healing outcomes were documented for 160 distal femur fractures treated with locked bridge plate fixation. Radiographic callus was measured on postoperative radiographs until union or nonunion had been declared by the treating surgeon. Deficient callus was defined at 6 and 12 weeks based on associations with eventual nonunion through receiver-operator characteristic analysis. A previously described computational model estimated fracture site motion based on the construct used. Univariable and multivariable analyses then examined the association of patient, injury, and treatment factors with deficient callus formation. RESULTS: There were 26 nonunions. The medial callus area at 6 weeks <24.8 mm 2 was associated with nonunion (12 of 39, 30.8%) versus (12 of 109, 11.0%), P = 0.010. This association strengthened at 12 weeks with medial callus area <44.2 mm 2 more closely associated with nonunion (13 of 28, 46.4%) versus (11 of 120, 9.2%), P <0.001. Multivariable logistic regression analysis found limited initial longitudinal motion (OR 2.713 (1.12-6.60), P = 0.028)) and Charlson Comorbidity Index (1.362 (1.11-1.67), P = 0.003) were independently associated with deficient callus at 12 weeks. Open fracture, mechanism of injury, smoking, diabetes, plate material, bridge span, and shear were not significantly associated with deficient callus. CONCLUSION: Deficient callus at 6 and 12 weeks is associated with eventual nonunion, and such assessments may aid future research into distal femur fracture healing. Deficient callus formation was independently associated with limited initial longitudinal fracture site motion derived through computational modeling of the surgical construct but not more routinely discussed parameters such as plate material and bridge span. Given this, improved methods of in vivo assessment of fracture site motion are necessary to further our ability to optimize the mechanical environment for healing. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Finite element modeling of meniscal tears using continuum damage mechanics and digital image correlation.

Meniscal tears are a common, painful, and debilitating knee injury with limited treatment options. Computational models that predict meniscal tears may help advance injury prevention and repair, but first these models must be validated using experimental data. Here we simulated meniscal tears with finite element analysis using continuum damage mechanics (CDM) in a transversely isotropic hyperelastic material. Finite element models were built to recreate the coupon geometry and loading conditions of forty uniaxial tensile experiments of human meniscus that were pulled to failure either parallel or perpendicular to the preferred fiber orientation. Two damage criteria were evaluated for all experiments: von Mises stress and maximum normal Lagrange strain. After we successfully fit all models to experimental force-displacement curves (grip-to-grip), we compared model predicted strains in the tear region at ultimate tensile strength to the strains measured experimentally with digital image correlation (DIC). In general, the damage models underpredicted the strains measured in the tear region, but models using von Mises stress damage criterion had better overall predictions and more accurately simulated experimental tear patterns. For the first time, this study has used DIC to expose strengths and weaknesses of using CDM to model failure behavior in soft fibrous tissue.

Guidelines for Accurate Multi-Temporal Model Registration of 3D Scanned Objects.

Changes in object morphology can be quantified using 3D optical scanning to generate 3D models of an object at different time points. This process requires registration techniques that align target and reference 3D models using mapping functions based on common object features that are unaltered over time. The goal of this study was to determine guidelines when selecting these localized features to ensure robust and accurate 3D model registration. For this study, an object of interest (tibia bone replica) was 3D scanned at multiple time points, and the acquired 3D models were aligned using a simple cubic registration block attached to the object. The size of the registration block and the number of planar block surfaces selected to calculate the mapping functions used for 3D model registration were varied. Registration error was then calculated as the average linear surface variation between the target and reference tibial plateau surfaces. We obtained very low target registration errors when selecting block features with an area equivalent to at least 4% of the scanning field of view. Additionally, we found that at least two orthogonal surfaces should be selected to minimize registration error. Therefore, when registering 3D models to measure multi-temporal morphological change (e.g., mechanical wear), we recommend selecting multiplanar features that account for at least 4% of the scanning field of view. For the first time, this study has provided guidelines for selecting localized object features that can provide accurate 3D model registration for 3D scanned objects.

Dots-on-Plots: A Web Application to Analyze Stress-Strain Curves From Tensile Tests of Soft Tissue.

The calculation of tensile mechanical properties from stress-strain curves is a fundamental step in characterizing material behavior, yet no standardized method exists to perform these calculations for soft tissue. To address this deficiency, we developed a free web application called Dots-on-Plots2 that fully automates the calculation of tensile mechanical properties from stress-strain curves. The analyzed mechanical properties include the strength, strain, and energy at four points of interest (transition, yield, ultimate, and rupture), and the linear modulus. Users of Dots-on-Plots can upload multiple files, view and download results, and adjust threshold settings. This study determined a threshold setting that minimized error when calculating the transition point, where the stress-strain curve "transitions" from a nonlinear "toe" region to a linear region. Using the optimal threshold (2% stress deviation from a linear region fit), Dots-on-Plots calculated the transition strains from twenty tensile experiments of human meniscus to be 0.049 ± 0.007, which nearly matched the known transition strain values of 0.050 ± 0.006 (determined using finite element parameter optimization). The sensitivity of the calculated transition strain to the shape of various stress-strain curves was analyzed using sets of model-generated synthetic data. This free web application offers a convenient and reliable tool to systematically enhance the speed, transparency, and consistency of mechanical analysis across biomedical research groups.

In vitro method to quantify and visualize mechanical wear in human meniscus subjected to joint loading.

The mechanical wear and tear of soft connective tissue from repetitive joint loading is a primary factor in degenerative joint disease, and therefore methods are needed to accurately characterize wear in joint structures. Here, we evaluate the accuracy of using a structured light 3D optical scanning system and modeling software to quantify and visualize volume loss in whole human meniscus subjected to in vitro joint loading. Using 3D printed meniscus replicas with known wear volumes, we determined that this novel imaging method has a mean accuracy of approximately 13 mm3, corresponding to a mean error of less than 7% when measuring meniscal volumetric changes of 0.2 cm3 (size of a pea). The imaging method was then applied to measure the in vitro wear of whole human menisci at four time points when a single cadaveric knee was subjected to one million cycles of controlled joint loading. The medial and lateral menisci reached steady state volumetric reductions of 0.72 cm3 and 0.34 cm3 per million cycles, respectively. Colorimetric maps of linear wear depth revealed high wear and deformation in the posterior regions of both the medial and lateral menisci. For the first time, this study has developed a method to accurately characterize volume loss in whole meniscus subjected to in vitro joint loading. This 3D scanning method offers researchers a new investigative tool to study mechanical wear and joint degeneration in meniscus, and other soft connective tissues.

Tensile fatigue strength and endurance limit of human meniscus.

The knee menisci are prone to mechanical fatigue injury from the cyclic tensile stresses that are generated during daily joint loading. Here we characterize the tensile fatigue behavior of human medial meniscus and investigate the effect of aging on fatigue strength. Test specimens were excised from the medial meniscus of young (under 40 years) and older (over 65 years) fresh-frozen cadaver knees. Cyclic uniaxial tensile loads were applied parallel to the primary circumferential fibers at 70%, 50%, 40%, or 30% of the predicted ultimate tensile strength (UTS) until failure occurred or one million cycles was reached. Equations for fatigue strength (S-N curve) and the probability of fatigue failure (unreliability curves) were created from the measured number of cycles to failure. The mean number of cycles to failure at 70%, 50%, 40%, and 30% of UTS were estimated to be approximately 500, 40000, 340000, and 3 million cycles, respectively. The endurance limit, defined as the tensile stress that can be safely applied for the average lifetime of use (250 million cycles), was estimated to be 10% of UTS (∼1.0 MPa). When cyclic tensile stresses exceeded 30% of UTS (∼3.0 MPa), the probability of fatigue failure rapidly increased. While older menisci were generally weaker and more susceptible to fatigue failures at high-magnitude tensile stresses, both young and older age groups had similar fatigue resistance at low-magnitude tensile stresses. In addition, we found that fatigue failures occurred after the dynamic modulus decreased during cyclic loading by approximately 20%. This experimental study has quantified fundamental fatigue properties that are essential to properly predict and prevent injury in meniscus and other soft fibrous tissues.

Applying ASTM Standards to Tensile Tests of Musculoskeletal Soft Tissue: Methods to Reduce Grip Failures and Promote Reproducibility.

Tensile testing is an essential experiment to assess the mechanical integrity of musculoskeletal soft tissues, yet standard test methods have not been developed to ensure the quality and reproducibility of these experiments. The ASTM International standards organization has created tensile test standards for common industry materials that specify geometric dimensions of test specimens (coupons) that promote valid failures within the gage section (midsubstance), away from the grips. This study examined whether ASTM test standards for plastics, elastomers, and fiber-reinforced composites are suitable for tensile testing of bovine meniscus along the circumferential fiber direction. We found that dumbbell (DB) shaped coupons based on ASTM standards for elastomers and plastics had an 80% and 60% rate of midsubstance failures, respectively. The rate of midsubstance failures dropped to 20% when using straight (ST) coupons based on ASTM standards for fiber-reinforced composites. The mechanical properties of dumbbell shaped coupons were also significantly greater than straight coupons. Finite element models of the test coupons revealed stress distributions that supported our experimental findings. In addition, we found that a commercial deli-slicer was able to slice meniscus to uniform layer thicknesses that were within ASTM dimensional tolerances. This study provides methods, recommendations, and insights that can advance the standardization of tensile testing in meniscus and other soft fibrous tissues.

Effect of age on the failure properties of human meniscus: High-speed strain mapping of tissue tears.

The knee meniscus is a soft fibrous tissue with a high incidence of injury in older populations. The objective of this study was to determine the effect of age on the failure behavior of human knee meniscus when applying uniaxial tensile loads parallel or perpendicular to the primary circumferential fiber orientation. Two age groups were tested: under 40 and over 65 years old. We paired high-speed video with digital image correlation to quantify for the first time the planar strains occurring in the tear region at precise time points, including at ultimate tensile stress, when the tissue begins losing load-bearing capacity. On average, older meniscus specimens loaded parallel to the fiber axis had approximately one-third less ultimate tensile strain and absorbed 60% less energy to failure within the tear region than younger specimens (p < 0.05). Older specimens also had significantly reduced strength and material toughness when loaded perpendicular to the fibers (p < 0.05). These age-related changes indicate a loss of collagen fiber extensibility and weakening of the non-fibrous matrix with age. In addition, we found that when loaded perpendicular to the circumferential fibers, tears propagated near the planes of maximum tensile stress and strain. Whereas when loaded parallel to the circumferential fibers, tears propagated oblique to the loading axis, closer to the planes of maximum shear stress and strain. Our experimental results can assist the selection of valid failure criteria for meniscus, and provide insight into the effect of age on the failure mechanisms of soft fibrous tissue.

Print-A-Punch: A 3D printed device to cut dumbbell-shaped specimens from soft tissue for tensile testing.

The failure behavior and mechanical properties of soft tissue can be characterized by conducting uniaxial tensile tests on small sectioned specimens, called test coupons. An ideal coupon geometry for tensile testing is a dumbbell shape (dog-bone), yet the cost and time required to fabricate custom steel punches to cut dumbbell-shaped coupons has hindered their universal application in biomechanics research. In this study, we developed an economical and reliable cutting device that can extract dumbbell-shaped coupons from soft biological tissue. The novel device, called Print-A-Punch, uses three-dimensional (3D) printed components in combination with standard fasteners and replaceable flexible razors. We identified design factors that influence the dimensional accuracy and symmetry of elastomer coupons extracted using this cutting device, and demonstrated its use on bovine meniscus. Advantages of this 3D printed device include a fast fabrication time, low material cost, good accuracy, replaceable blades, and an ability to scale coupon dimensions for specific tissues and experiments. By reducing the cost and time to cut accurate dumbbell-shaped coupons, this technology can facilitate the broad adoption of standard test methods that improve the quality and reproducibility of tensile tests in soft biological tissue. Researchers can freely download a set of STL files from this study to build their own Print-A-Punch device (https://boisestate.edu/coen-ntm/technology/print-a-punch).

Center of Biomedical Research Excellence in Matrix Biology: Building Research Infrastructure, Supporting Young Researchers, and Fostering Collaboration.

The Center of Biomedical Research Excellence in Matrix Biology strives to improve our understanding of extracellular matrix at molecular, cellular, tissue, and organismal levels to generate new knowledge about pathophysiology, normal development, and regenerative medicine. The primary goals of the Center are to i) support junior investigators, ii) enhance the productivity of established scientists, iii) facilitate collaboration between both junior and established researchers, and iv) build biomedical research infrastructure that will support research relevant to cell-matrix interactions in disease progression, tissue repair and regeneration, and v) provide access to instrumentation and technical support. A Pilot Project program provides funding to investigators who propose applying their expertise to matrix biology questions. Support from the National Institute of General Medical Sciences at the National Institutes of Health that established the Center of Biomedical Research Excellence in Matrix Biology has significantly enhanced the infrastructure and the capabilities of researchers at Boise State University, leading to new approaches that address disease diagnosis, prevention, and treatment. New multidisciplinary collaborations have been formed with investigators who may not have previously considered how their biomedical research programs addressed fundamental and applied questions involving the extracellular matrix. Collaborations with the broader matrix biology community are encouraged.

Development of Photoactive g-C3N4/Poly(vinyl alcohol) Composite Hydrogel Films with Antimicrobial and Antibiofilm Activity.

Free-standing, composite hydrogels containing the visible-light responsive metal-free semiconductor graphitic carbon nitride (g-C3N4) as an integral component have been fabricated by direct casting techniques. At 0.67% g-C3N4 loading, intermolecular interactions between the semiconductor particles and the PVA polymer chains enhance both the mechanical and photophysical properties of the resulting hydrogels. In contrast, much higher g-C3N4 loadings of 3.3 or 6.7% g-C3N4 resulted in growth of the average semiconductor particle size and reduction in interactions between the incorporated photocatalyst and the PVA chains. The increased dimensions of the g-C3N4 semiconductor particles had the effect of compromising the mechanical properties of the composite system and reducing the lifetime of photogenerated charge carriers. However, the close proximity of g-C3N4 particles that is realized at increased semiconductor loading densities improves the absorption cross section of the material, resulting in an overall improvement in the photocatalytic activity of the material. Application of visible radiation caused all of the composite hydrogels to generate hydrogen peroxide (H2O2) at catalytic rates of 0.9-2.5 µM/min, while H2O2 decomposition rates remained similar across the different preparations. In studies to examine antimicrobial performance, irradiation of 6.7% g-C3N4/PVA hydrogel samples with visible radiation (400 ≤ λ ≤ 800 nm) generated sufficient H2O2 to significantly reduce both the viable planktonic cell population and biofilm formation in cultures of Pseudomonas aeruginosa.

Prechondrogenic ATDC5 Cell Attachment and Differentiation on Graphene Foam; Modulation by Surface Functionalization with Fibronectin.

Graphene foam holds promise for tissue engineering applications. In this study, graphene foam was used as a three-dimension scaffold to evaluate cell attachment, cell morphology, and molecular markers of early differentiation. The aim of this study was to determine if cell attachment and elaboration of an extracellular matrix would be modulated by functionalization of graphene foam with fibronectin, an extracellular matrix protein that cells adhere well to, prior to the establishment of three-dimensional cell culture. The molecular dynamic simulation demonstrated that the fibronectin-graphene interaction was stabilized predominantly through interaction between the graphene and arginine side chains of the protein. Quasi-static and dynamic mechanical testing indicated that fibronectin functionalization of graphene altered the mechanical properties of graphene foam. The elastic strength of the scaffold increased due to fibronectin, but the viscoelastic mechanical behavior remained unchanged. An additive effect was observed in the mechanical stiffness when the graphene foam was both coated with fibronectin and cultured with cells for 28 days. Cytoskeletal organization assessed by fluorescence microscopy demonstrated a fibronectin-dependent reorganization of the actin cytoskeleton and an increase in actin stress fibers. Gene expression assessed by quantitative real-time polymerase chain reaction of 9 genes encoding cell attachment proteins (Cd44, Ctnna1, Ctnnb1, Itga3, Itga5, Itgav, Itgb1, Ncam1, Sgce), 16 genes encoding extracellular matrix proteins (Col1a1, Col2a1, Col3a1, Col5a1, Col6a1, Ecm1, Emilin1, Fn1, Hapln1, Lamb3, Postn, Sparc, Spp1, Thbs1, Thbs2, Tnc), and 9 genes encoding modulators of remodeling (Adamts1, Adamts2, Ctgf, Mmp14, Mmp2, Tgfbi, Timp1, Timp2, Timp3) indicated that graphene foam provided a microenvironment conducive to expression of genes that are important in early chondrogenesis. Functionalization of graphene foam with fibronectin modified the cellular response to graphene foam, demonstrated by decreases in relative gene expression levels. These findings illustrate the combinatorial factors of microscale materials properties and nanoscale molecular features to consider in the design of three-dimensional graphene scaffolds for tissue engineering applications.

A Hand-Held Device to Apply Instrument-Assisted Soft Tissue Mobilization at Targeted Compression Forces and Stroke Frequencies.

Instrument-assisted soft tissue mobilization (IASTM) is a manual therapy technique that is commonly used to treat dysfunctions in ligaments and other musculoskeletal tissues. The objective of this study was to develop a simple hand-held device that helps users accurately apply targeted compressive forces and stroke frequencies during IASTM treatments. This portable device uses a force sensor, tablet computer, and custom software to guide the application of user-specified loading parameters. To measure performance, the device was used to apply a combination of targeted forces and stroke frequencies to foam blocks and silicone pads. Three operators using the device applied targeted forces between 0.3 and 125 N with less than 10% error and applied targeted stroke frequencies between 0.25 and 1.0 Hz with less than 3% error. The mean error in applying targeted forces increased significantly at compressive forces less than 0.2 N and greater than 125 N. For experimental validation, the device was used to apply a series of IASTM treatments over three-weeks to rodents with a ligament injury, and the targeted compressive force and stroke frequency were repeatedly applied with an average error less than 5%. This validated device can be used to investigate the effect of IASTM loading parameters on tissue healing in animal and human studies, and therefore can support the optimization and adoption of IASTM protocols that improve patient outcomes.

Mechanical Properties of Graphene Foam and Graphene Foam - Tissue Composites.

Graphene foam (GF), a 3-dimensional derivative of graphene, has received much attention recently for applications in tissue engineering due to its unique mechanical, electrical, and thermal properties. Although GF is an appealing material for cartilage tissue engineering, the mechanical properties of GF - tissue composites under dynamic compressive loads have not yet been reported. The objective of this study was to measure the elastic and viscoelastic properties of GF and GF-tissue composites under unconfined compression when quasi-static and dynamic loads are applied at strain magnitudes below 20%. The mechanical tests demonstrate a 46% increase in the elastic modulus and a 29% increase in the equilibrium modulus after 28-days of cell culture as compared to GF soaked in tissue culture medium for 24h. There was no significant difference in the amount of stress relaxation, however, the phase shift demonstrated a significant increase between pure GF and GF that had been soaked in tissue culture medium for 24h. Furthermore, we have shown that ATDC5 chondrocyte progenitor cells are viable on graphene foam and have identified the cellular contribution to the mechanical strength and viscoelastic properties of GF - tissue composites, with important implications for cartilage tissue engineering.

Quantifying wear depth in hip prostheses using a 3D optical scanner.

The visualization of wear depth in hip prostheses can assist the evaluation of new bearing materials and implant designs. The goal of this study was to develop an accurate, fast, and economical methodology to generate colorimetric maps of wear depth in hip implants using a structured light 3D optical scanning system. The accuracy and precision of this novel technique were determined using reference blocks with known wear depths. This technique was then used to measure the in vitro wear of a hip resurfacing device for canines that incorporates a highly cross-linked polyethylene liner. The 3D optical scanner had an average accuracy of 2.1 µm and an average precision of 1.4 µm, which corresponded to errors less than 10% when measuring wear depths of 20 µm or greater. The scanner was able to repeatedly generate 3D colorimetric maps of wear depth in highly cross-linked polyethylene liners in 20 min or less. These colorimetric maps identified localized regions with 3-fold greater wear than the average wear depth, and revealed liners with asymmetric wear patterns. For the first time, this study has validated the use of 3D optical scanning to quantify in vitro surface wear in a hip replacement device.

Extracellular Matrix Expression and Production in Fibroblast-Collagen Gels: Towards an In Vitro Model for Ligament Wound Healing.

Ligament wound healing involves the proliferation of a dense and disorganized fibrous matrix that slowly remodels into scar tissue at the injury site. This remodeling process does not fully restore the highly aligned collagen network that exists in native tissue, and consequently repaired ligament has decreased strength and durability. In order to identify treatments that stimulate collagen alignment and strengthen ligament repair, there is a need to develop in vitro models to study fibroblast activation during ligament wound healing. The objective of this study was to measure gene expression and matrix protein accumulation in fibroblast-collagen gels that were subjected to different static stress conditions (stress-free, biaxial stress, and uniaxial stress) for three time points (1, 2 or 3 weeks). By comparing our in vitro results to prior in vivo studies, we found that stress-free gels had time-dependent changes in gene expression (col3a1, TnC) corresponding to early scar formation, and biaxial stress gels had protein levels (collagen type III, decorin) corresponding to early scar formation. This is the first study to conduct a targeted evaluation of ligament healing biomarkers in fibroblast-collagen gels, and the results suggest that biomimetic in-vitro models of early scar formation should be initially cultured under biaxial stress conditions.