Articular cartilage provides an almost frictionless surface for the articulating ends of the bone. Cartilage functions to lubricate and transmit compressive forces resulting from joint loading and impact. If the cartilage is damaged, through traumatic injury or disease, it lacks the ability of self-repairing as the tissue lacks vascular system. If the injuries to articular cartilage are left untreated, they may progress to Osteoarthritis. Osteoarthritis, a degenerative disease, is one of the leading disabilities in the United States. Tissue engineering has the potential to regenerate healthy hyaline cartilage, which can alleviate pain and restore the functions of normal tissue. This study explores the production of engineered cartilage on top of composite calcium phosphate scaffold. The current research is related to a biphasic approach to cartilage tissue engineering — in which one layer supports to form subchondral bone (osteogenesis) and another supports cartilage formation (chondrogenesis). Chondrocyte and bone marrow-derived stem cell attachment to chitosan will be investigated for producing a bilayered construct for osteochondral repair. The main objectives of my research include the following: attachment and proliferation of human mesenchymal stem cells on chitosan calcium phosphate scaffolds, techniques to create a biphasic construct, the effect of coating chitosan calcium phosphate scaffolds with type I collagen and determining the ideal bead size for making chitosan calcium phosphate scaffolds.

Precise sexing–97% to 99% accuracy–of adult chest plates is possible when highly predictive costal cartilage ossification patterns are combined with four simple metric determinations. More than 1100 chest plate roentgenograms were evaluated for ossification pattern, fourth rib width, corpus width, sternal length and sternal area in an adult decedent population. An elementary, empirically obtained algorithm using the patternings and measurements, along with simple derivations (sternal length and area indices) was developed and then applied in chest plate sexing. This technique is not only easy, rapid and inexpensive, but it also results in a permanent and easily stored record.

This paper presents a biotribological study on cartilage wear and friction, using a system of cartilage-on-stainless steel. This study is a part of the ongoing biotribology research by Dr. Furey at the Virginia Polytechnic Institute and State University. Two loads (65 N and 20 N) and three lubricants (saline reference, reference + hyaluronic acid, and bovine synovial fluid) were tested and evaluated using several analysis techniques. These techniques included wear analysis by hydroxyproline measurement, scanning electron microscopy (SEM), histologic sectioning and staining, numerical analysis of friction and specimen displacement data, and Fourier transform infrared (FTIR) analysis. Biochemical wear analysis showed that, under high load, the saline reference generated the most wear, hyaluronic acid produced less wear, and bovine synovial fluid produced the least. Wear was sensitive to load with all three lubricants, but was not significantly affected by the lubricant under low load. SEM photographs and histologic sections showed evidence of plowing and surface delamination, as well as another wear mechanism that produced wear markings perpendicular to the direction of sliding. Opaque films remained on the polished stainless steel disks after saline and hyaluronic acid tests, but not after synovial fluid tests. FTIR analysis of these films, as well as fresh and worn cartilage, showed that the cartilage experienced chemical changes during sliding. / Master of Science

During ambulation, lower-extremity joint angles and net moments influence knee joint load. It is unclear which mechanical variables most strongly correlate with acute articular cartilage (AC) catabolism in response to ambulation. Purpose: To determine which mechanical variables are most strongly correlated to acute AC catabolism, and to test the acute effect of ambulation speed on AC catabolism, while controlling for load frequency. Methods: 18 able-bodied subjects (9 male, 9 female; age = 23 ± 2 y; mass = 68.3 ± 9.6 kg; height = 1.70 ± 0.08 m) completed three separate ambulation sessions: slow (preferred walking speed), medium (+50% of walking speed), and fast (+100% of walking speed). For each session, subjects completed 4000 steps on an instrumented treadmill while ten high-speed cameras recorded synchronized video data. Various, discrete, three-dimensional joint kinematic and kinetic variables were averaged across 20 total stance phases (5 stance phases at 1000, 2000, 3000, and 4000 steps). Blood samples were collected pre-, post-, 30-min post-, and 60-min post-ambulation. Serum cartilage oligomeric matrix protein (COMP) concentration was determined using an enzyme-linked immunosorbent assay. A stepwise multiple linear regression analysis was used to evaluate the relationships between serum COMP change and lower-extremity joint angles and moments. A mixed model ANCOVA was used to evaluate serum COMP concentration between sessions across time. Results: Peak ankle inversion, knee extension, knee abduction, hip flexion, hip extension, and hip abduction moment, and knee flexion angle at impact, explained 61.4% of the total variance in serum COMP change (p < 0.001), due to ambulation. COMP concentration increased 28%, 18%, and 5% immediately after ambulation for the running, jogging, and walking sessions, respectively. All sessions were significantly different immediately post-ambulation (p < 0.01). Conclusion: Certain lower-extremity joint mechanics are associated with acute AC catabolism, due to ambulation. Several key mechanical variables (e.g., peak knee extension, knee abduction, and hip abduction moments) explain much regarding the variance in serum COMP increase. These lower-extremity variables can be used to predict acute AC catabolism, allowing researchers and clinicians to better predict and/or understand AC catabolism. Additionally, when load frequency is controlled, increased ambulation speed acutely results in increased AC catabolism. Ambulation speed does not, however, influence serum COMP elevation duration. Joint mechanics and load frequency appear to be responsible for the magnitude of COMP increase, while duration of COMP elevation post-ambulation is dictated by load frequency.

The global objective of this research was to identify the proteins secreted by stem cells in response to mechanical stress. Since it has been shown in previous studies that conditioned medium from compressed chick limb bud cells cultured in alginate can initiate chondrogenesis in non-compressed cells, it was hypothesized that the conditioned medium contains valuable growth/differentiation factors. Due to cartilage?s limited capacity for repair, factors that stimulate stem-cell mediated regeneration are highly sought. To discern these proteins, conditioned medium was collected from cyclically compressed stage 23/24 chick limb buds suspended in alginate. The proteins were extracted, separated by 2-D gel electrophoresis, and evaluated by mass spectroscopy. While a few regulators of chondrogenesis were observed, such as FGF receptor, actin, and IP3 receptor, many potential peptides were not found in the database. However, this study showed that ascertaining proteins produced by chondrocytes in response to mechanical stimulation should be pursued.

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Tribology is the science of interacting surfaces in relative motion. It is specifically concerned with the friction, wear and lubrication of these surfaces. Although tribology has conventionally been associated with the surface interaction of mechanical systems, concepts of tribology have also been important in the study of biological systems. Biotribology is one of the newest fields to emerge in the discipline of tribology. It can be described as the study of friction, wear and lubrication of biological systems, mainly synovial joints such as the human hip and knee. Osteoarthritis (OA) is partially characterized by the loss of articular cartilage from the contacting surface of the articulating bones in synovial joints. Although it has been studied extensively, the exact pathways and pathogenesis of OA have yet to be determined. Several factors have been cited as possible contributors to the condition. These factors can primarily be grouped into two categories of mechanical or biochemical abnormalities. Research in biotribology enables the examination of both the mechanical and biochemical factors involved in joint lubrication and OA. This research has focussed on the mechanisms of normal joint lubrication, as well as the possible connections between biotribology and osteoarthritis. Particular emphasis is placed on the effects of biochemical changes and environment on cartilage wear and damage. Studies were carried out using a test device developed to study the tribological properties of articular cartilage, in vitro. A cartilage-on-cartilage test configuration was used with bovine articular cartilage and a cartilage-on-stainless steel configuration used with lapine articular cartilage. Articulating surfaces were put in sliding contact under a normal load. Natural and biochemically modified environments were created to simulate possible normal and pathologic in vivo conditions. Wear and friction of the articular cartilage were measured and related to biochemical environments which are suspected in clinical cases of OA. Quantitative measurement of cartilage wear was achieved through hydroxyproline assay of the post-test lubricants. Surface and subsurface damage were also examined through the use of scanning electron microscopy and histological staining techniques. The results of four separate studies demonstrated that: (1) exposure of bovine cartilage to collagenase-3, an enzyme suspected in the cartilage degeneration seen in OA, significantly increased cartilage wear (p = 0.001); (2) lapine cartilage with surgically induced OA exhibited higher coefficients of friction, but no significant increase in wear over normal cartilage from the same animal; (3) the addition of white blood cell lysate, comparable to what would be seen in mild joint inflammation, to synovial fluid significantly increased cartilage wear over normal synovial fluid (p = 0.002); (4) the removal of "boundary lubricating" surface-active phospholipids (SAPLs) from normal synovial fluid had no significant effect on cartilage wear. These results demonstrate that biochemical changes in the cartilage, as well as the synovial fluid, can lead to increased wear of and damage to the articular cartilage surface. How these changes may occur in living systems remains to be determined. The use of the tribological test device developed and various analytical techniques has made it possible to quantitatively evaluate the effects of biochemical changes and environment on the wear and damage of articular cartilage. These studies have demonstrated that research in biotribology has the potential to make significant contributions to the current knowledge not only of normal joint lubrication but of joint pathology as well. / Ph. D.

Work-related musculoskeletal disorders (WMSDs) continue to present a substantial personal and economic burden. Biomarkers, in providing objective measures of physiological changes, may offer advantages over current tools for WMSD risk assessment. Existing work has identified biomarkers of cartilage and muscle damage, and demonstrated responsiveness to various forms of physical activity and biomechanical loading. Here, three studies were complete to further assess the occupational relevance/utility of three selected biomarkers: Cartilage Oligomeric Matrix Protein (COMP), Interleukin-6 (IL6), and Creatine Kinase (CK). First, the effects of age, obesity, gender, and diurnal variation was investigated. Significant effects of time, age, and gender were evident, as well as some interactive effects, for COMP and CK, but not IL6. Second, biomarker levels were compared between individuals in occupations having relatively high and low WMSD risk. IL6 levels were greater in the high-risk group, while COMP levels demonstrated an oscillatory pattern, and CK levels did not vary between groups. Third, physical demands were imposed on the lumbar spine during a repetitive flexion/extension task, under conditions with different loading and frequency. IL6 levels varied significantly over time and between added load levels, while CK levels varied over time and was influenced by load and frequency. These studies demonstrate important features of biomarkers; that personal confounding factors need to be considered, that select biomarkers may be sensitive to occupational risk factor exposure, and particularly to task parameters in lifting activities involving the lower back. Further, these studies reveal important information concerning the relevance of the selected biomarkers, favorable time points for biomarker collection, and approximate biomarker levels expected between occupations and exposure to common risk factors. These results support the use of biomarkers in occupational settings for assessing exposure and WMSD risk imposed by common risk factors. Sensitivity to exposure levels is an important precursor to risk prediction, however prospective work is needed to verify predictive validity. / Ph. D.

Osteoarthritis is the most prevalent musculoskeletal disease in humans, severely reducing the standard of living of millions of people. Osteoarthritis is characterized by degeneration and loss of articular cartilage which leads to pain, and loss of joint motility and function. Individuals suffering from severe osteoarthritis are commonly treated with full knee replacements. The procedure does eliminate the problem of degrading cartilage tissue; however, it does not fully restore function and its lifetime can be limited. To overcome the disadvantages of current treatments, tissue engineering has become a focus of research to regenerate cartilage. Tissue engineering attempts to repair or replace damaged tissue with cells, biomaterials, and/or molecular signals. Biodegradable scaffolds serve as a temporary replacement for the tissue until it has regenerated. Two types of scaffolds that have been used in tissue engineering are electrospun scaffolds and hydrogels. We have proposed and fabricated a scaffold for cartilage tissue engineering that incorporates an electrospun cylinder and a thermosetting hydrogel in order to provide improved properties compared to either individual material. Electrospun cylinders were created by sintering electrospun mats that include salt pores. The addition of salt pores decreased the mechanical properties of the electrospun materials while also improving the capability of cells to infiltrate into the scaffold. The sintering process involved the connecting of one electrospun mat to an adjacent one. Specifically, poly(d,l-lactide) was capable of sintering to an adjacent electrospun mat when exposed to either heat (near the glass transition temperature) or tetrahydrofuran vapor. The sintering process did not deteriorate the structure or function of the electrospun material. Sintering allowed the creation of unique structures of electrospun material that previously could not be produced. A thermosetting hydrogel was added to the scaffold to replicate the function of proteoglycans present in articular cartilage. A composite scaffold of electrospun polymer and hydrogel showed improved mechanical properties and better integration of the scaffold in vivo compared to an electrospun scaffold with no hydrogel. In conclusion, the composite electrospun and hydrogel scaffold could become an excellent tissue engineering scaffold to treat patients suffering from osteoarthritis. / Ph. D.