http://hdl.handle.net/1721.1/7628 2013-05-24T13:41:59Z http://hdl.handle.net/1721.1/76172 Developing osteoarthritis treatments through cartilage tissue engineering and molecular imaging Casasnovas Ortega, Nicole Tissue engineering can be applied to develop therapeutic techniques for osteoarthritis, a degenerative disease caused by the progressive deterioration of cartilage in joints. An inherent goal in developing cartilage-replacement treatments is ensuring that tissue-engineered constructs possess the same properties as native cartilage tissue. Biochemical assays and imaging techniques can be used to study some of the main components of cartilage and assess the value of potential therapies. Agarose and self-assembling peptides have been used to make hydrogels for in vitro culture of bovine bone marrow stromal cells (BMSCs) which can differentiate into chondrocytes, undergo chondrogenesis, and produce cartilage tissue. So far, differences in cell morphology that characterize chondrogenesis had been observed in peptide hydrogels like KLD and RAD but not in the 2.0% agarose hydrogels typically used for culture. A tissue engineering study was conducted to determine if a suitable environment for cell proliferation and differentiation could be obtained using different agarose compositions. BMSCs were cultured in 0.5%, 1.0%, and 2.0% agarose hydrogels for 21 days following TGF-p1 supplementation. Results indicate that the 0.5% agarose hydrogels are clearly inferior scaffolds when compared to the 1.0% and 2.0% agarose hydrogels, which are generally comparable. Since agarose gels appear to be suboptimal in promoting chondrogenesis, self-assembling peptides should be used in future studies. In addition to the biochemical assays traditionally used in cartilage tissue engineering studies, atomic force microscopy (AFM) can be used to image aggrecan, one of the main components of cartilage. Imaging studies were carried out using fetal bovine epiphyseal aggrecan to optimize previous extraction and sample preparation procedures, as well as an AFM imaging protocol, for samples containing aggrecan. Experiments were conducted with 10, 25, and 50 ptg/mL aggrecan solutions to find the minimum concentration needed to create aggrecan monolayers on APTES-mica that would yield acceptable AFM images (25 [mu]g/mL). AFM instrument and software parameters were optimized to find the working range of the integral and proportional gains (0.2 - 0.4 and 0.6 - 0.8, respectively) and to increase the resolution, showing fields at the 800 nm level. Finally, an image processing protocol relevant to these molecules was established. Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2012.; Cataloged from PDF version of thesis. Page 104 blank.; Includes bibliographical references. 2012-01-01T00:00:00Z http://hdl.handle.net/1721.1/76111 Cervical mucus prorperties stratifv risk for preterm birth Yao, Grace Preterm birth impacts 15 million babies every year, leading to morbidity, mortality, significant health care costs, and lifelong consequences. The causes of preterm birth are unknown, resulting in ineffective treatment, but it is correlated with ascension of vaginal bacteria through the cervix, which is normally protected by a dense mucus plug during pregnancy. This mucus plug, consisting of a tight meshwork of glycoproteins called mucins, should prevent pathogens from accessing the sterile uterine environment. Cervical mucus from women at high risk and low risk for preterm birth was collected and compared. The aim of this study was to discover differences that will lead to clues about why preterm birth occurs, and ultimately what can be done about it in terms of prevention and intervention. Using rheological techniques and a translocation assay, we found that cervical mucus from women at high risk is more translucent and more elastic under both elongational and shear stress, than cervical mucus in normal pregnancies. These properties more closely resemble mucus during ovulation, when spermatozoa can most easily penetrate the barrier, than mucus in normal pregnancy. Furthermore, high risk mucus is more permeable to beads of comparable size to viruses, suggesting the barrier is weakened and foreign particles may harmfully traverse it to cause intrauterine infection. The techniques in this paper have not been previously used to study cervical mucus in the context of preterm labor, but their results may have important implications. If these mucus properties in women indeed permit increased bacterial infection through the cervix, then they can be used to stratify patients, allowing for more personalized prenatal care to lower the rate of preterm birth. Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2012.; Cataloged from PDF version of thesis.; Includes bibliographical references (p. 46-52). 2012-01-01T00:00:00Z http://hdl.handle.net/1721.1/76110 EMG control of prosthetic ankle plantar flexion Wang, Jing, M. Eng. Massachusetts Institute of Technology Similar to biological human ankle, today's commercially available powered ankle-foot prostheses can vary impedance and deliver net positive ankle work. These commercially available prostheses are intrinsically controlled. Users cannot intuitively change ankle controller's behavior to perform movements that are not part of the repetitive walking gait cycle. For example, when transition from level ground walking to descending stairs, user cannot intuitively initiate or control the amount of ankle angle deflexion for a more normative stair descent gait pattern. This paper presents a hybrid controller that adds myoelectric control functionality to an existing intrinsic controller. The system employs input from both mechanical sensors on the ankle as well as myoelectric signals from gastrocnemius muscle of the user. This control scheme lets the user to modulate the gain of command ankle torque upon push off during level ground walking and stair ascent. It also allows the user to interrupt level ground walking control cycle and initiate ankle plantar flexion during stair descent. As a preliminary study, ankle characteristics such as ankle angle and torque were measured and compared to biological ankle characteristics. Results show that the proposed hybrid controller can maintain existing controller's biomimetic characteristics. In addition, it can also recognize to a qualitative extent the intended command torque for ankle push off and user's desire to switch between control modalities for different terrains. The study shows that it is possible and desirable to use neural signals as control signals for prosthetic leg controllers. Keyword: Myoelectric control, powered prosthesis, proportional torque control Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2011.; Cataloged from PDF version of thesis.; Includes bibliographical references (p. 59-60). 2011-01-01T00:00:00Z http://hdl.handle.net/1721.1/73350 Design and synthesis of inhibitors of dTDP-D-glucose 4,6-dehydrate (Rm1B), and enzyme required for dTDP-L-rhamnose production in M. tuberculosis Kadaba, Neena Sujata, 1981- Thesis (S.M. in Molecular and Systems Toxicology)--Massachusetts Institute of Technology, Biological Engineering Division, 2003.; Vita.; Includes bibliographical references (leaves 60-62). 2003-01-01T00:00:00Z