Current Research Projects
Engineered Substrates for Stem Cell Derived Cardiomyocytes
The Crone Lab has developed micropatterning techniques to influence the maturation of immature cardiomyocytes (CMs) differentiated from stem cells. We have developed a technology platform that allows the production of a range of micropatterns on substrates of varying stiffness. In contrast to standard two-dimensional cultures of cardiomyocytes where cells form cell-cell junctions in all directions, we have shown that immature CM cells patterned in lanes repeatability form extremely polarized structures which produce synchronous contraction, increased nuclear alignment, and highly enhanced sarcomere organization. In recent research exploring the co-culture of CMs with cardiac fibroblasts, we have shown aligned extracellular matrix remodeling and enhanced cardiomyocyte functionality. This platform is highly adaptable and is relevant to fundamental cardiomyocyte research, drug discovery, and toxicity testing. This research is being conducted in collaboration with Prof. Tim Kamp’s research group and other co-investigators in the School of Medicine and Public Health.
Skeletal Muscle Constructs
While in vitro culture systems have limitations, they also have powerful advantages that enable controlled experimental investigation. Our culture platform has been adapted and optimized to study skeletal muscle where we have shown that progenitor cells remodeled their myofilament structure and formed elongated, multi-nucleated myotubes in response to topographical cues of the micropattern. Both micropattern width and substrate stiffness can be used to synergistically promote fusion and differentiation of stem cell derived myocytes that then exhibit spontaneous coordinated contractions. We also developed bundle-like myotubes using patient-derived induced pluripotent stem cell (iPSC) with Pompe disease which exhibited an enhanced disease phenotype with abnormal lysosome accumulations. Ongoing research with Prof. Masatoshi Suzuki in the School of Veterinary Medicine is investigating modelling of the muscle-tendon junction to study myotendinous junction development and repair.
Previous Research Projects
Biomaterials and Biomechanics
Biomedical devices such as stents and vascular grafts are often coated with various materials to prevent problems such as clotting around the device. Typically, the base material provides the mechanical properties desired while the coating provides biocompatibility. An alternative approach is to make the base material biocompatible. As an example, one of our research projects focused on the development of polyurethane based polymers that possess mechanical properties similar to the surrounding biological materials. Matching the mechanical properties of the device to the surrounding structures, especially the stiffness, results in better performance. We were able to produce two new medical device designs (coil-in-shell and gel-in-shell devices) for aneurism occlusion which were studied acutely in swine and long term in canines. Initial occlusion of sidewall aneurysms ranged from 71% to 100%, which was stable with no recurrence at 6 or 12 weeks. Beyond the highly successful in vitro studies, histological analysis conducted after 12 weeks showed that the polyurethane–hyaluronic acid copolymers promoted robust tissue healing at the aneurysm neck with no significant inflammatory response. This research has resulted in three patents in addition multiple publications and was done in collaboration with Prof. Kristyn Masters’ Group and neurological surgery co-investigators.
Shape Memory and Superelastic Behavior
Shape memory alloys are a unique class of materials that undergo a reversible phase transformation that allow the material to display dramatic, recoverable, stress-induced and temperature-induced deformations. Nickel titanium (NiTi) is one such shape memory alloy used in a range of industries for products such as biomedical devices and aerospace components. The most familiar uses of NiTi are arterial stents and dental arch wires used in orthodontic braces. The austenite-martensite phase transformation that occurs in shape memory alloys with changes in temperature or the applied stress is responsible for the unique thermomechanical properties of this material. My research has focused on developing a better fundamental understanding of these alloys through investigation of its macroscopic behavior and phase transformation mechanisms at the microscopic level. The most significant impact of my research in this area is the surface modification of NiTi shape memory alloys for improved wear and biocompatibility properties.
Nickel titanium (NiTi) is a particular shape memory alloy used in a wide variety of biomedical, aerospace, automotive and other applications. The most common use of NiTi that people are familiar with is the dental arch wire used in orthodontic braces. NiTi is also used to make high integrity couplings and connectors for defense, aerospace, and electronic applications where space savings and reliability are of key importance. See this education link for more background on shape memory alloys: MRSEC
Fracture of Shape Memory Alloys
The Crone Lab has addressed several key questions concerning the fracture behavior of NiTi and CuAlNi. NiTi is the shape memory alloy (SMA) most frequently used commercially. However, due to the cost of raw materials and difficulty of processing, applications using NiTi are limited due to cost. Another SMA that has drawn interest is CuAlNi given the low cost of raw materials and ease of processing. However, CuAlNi has not been used due to the tendancy of this alloy to fracture intergranuarlly at a low number of thermal or mechanical cycles. In order to understand the fracture mechanisms of shape memory alloys, experiments on notched polycrystalline and single crystal samples are currently being performed. These experiments have assisted in developing experimentally based models that delineate the mechanisms influencing fracture in NiTi and Cu-based shape memory alloys.
Nanostructured Shape Memory Alloys
Nanoscale materials have attracted strong interest because of the novel material properties that become possible when surface effects and grain boundary behavior play a larger role in the overall mechanical behavior of the material. Shape memory alloys also continue to be explored for more dramatic superelastic behavior. It has been shown that refinement to the microscale is correlated with enhancement of the properties in copper-based, iron-based alloys, and nickel-titanium shape memory alloys. Taking this a step further, my research has explored the properties that result from combining the effects of nanostructures and shape memory. At the onset of this research there were several open questions fundamental to the understanding of shape memory behavior, furthermore shape memory behavior in the nanometer regime had not yet been explored. Also, it was not known whether the transformation microstructures observed in single crystals and large grained materials would persist to nano-sized grains, or whether other transformation microstructures occur at these size scales. In our research we were able to create nanostructured shape memory alloys in bulk and particle form; explore the effect of grain constraint on the nucleation and propagation of phase transformation; investigate scaling effects on shape memory behavior; and improve fatigue life, workability, and superelastic behavior through grain refinement.
Composite Materials Containing Shape Memory Alloy Constituents
The Crone Lab has also investigated composite materials with shape memory alloy constituents. Composite materials are critical for many engineering applications because of the resultant properties that arise from the combination of dissimilar constituent materials. The ability to tailor material properties to meet specific high-performance needs makes composite materials very attractive for a wide range of technical applications. Introducing the properties of a shape memory alloy into a composite material creates opportunities for making multifunctional components and components capable of performing in ways that surpass the constituent materials. Some research has been done in this area but the creation of reliable materials is hampered by the disparity in the deformations that can be exhibited by a shape memory alloy compared to matrix materials such as metals and polymers.