Funded Projects - 2014

The global market for microelectronic medical implants, accessories and supplies was worth an estimated $15.4 billion in 2010. This market is expected to grow to $24.8 billion in 2016. While pacemakers and defibrillators are in a mature market, rapid growth is underway with neuro-stimulators and implantable drug pumps. Electronic implants are limited by battery life, power consumption and size of the overall devices.

In research funded by a Coulter seed grant, the principal investigators found that the size of implantable antennas could be significantly reduced and antenna efficiency could be significantly improved by the use of high dielectric constant materials that match the high dielectric constant of body tissues. This finding opens the door to development of implantable devices that are smaller, that consume less power, and that are more comfortable for patients. Smaller devices will also expand the pool of patients eligible to receive implantable electronic devices.

In the next step toward commercialization, the principal investigators will work to modify the current dielectric materials to obtain biocompatibility and incorporate them into a new telemetry design.

The World Health Organization (WHO) estimates that in 2013 Mycobacterium tuberculosis (TB) represented more than half of the $2 billion medical diagnostic market. Additionally, WHO states that there are 8.6 million cases of TB diagnosed each year, while 1.3 million people die of TB each year. The current gold standard for TB testing is either chest radiography or plate culture, which is then followed by drug sensitivity screening. Chest radiography is available in many developing nations, but is not practical in resource-limited settings. The more popular technique in developing nations is plate culture, which often takes weeks before results are known.

A rapid, low cost TB test that can be performed in low resource settings is a global health priority. The principal investigators have recently developed an inexpensive soft lithographic process for producing nano-ordered plasmonic gratings with extraordinary electromagnetic field enhancements that are ideally suited for detection of TB infection in low resource settings. These novel nano-gratings can be used to perform antigen-antibody assays such as interferon gamma (IFNγ) test for TB infection using common fluorescence detection technology and are potentially adaptable to multiplexing and drug resistance screening.

This new diagnostic platform technology has broad clinical applications in both high and low resource settings.

The global market for molecular imagining and diagnostics is robust with industry wide estimates reaching $8.1 billion by 2017. Additionally, the total North American breast tumor imaging market is worth $925 million with 1.3 million patients diagnosed with breast cancer in 2013. More importantly, 450,000 patients die annually due to breast cancer. Many of these deaths are from recurrent breast cancer (RBC). Current breast cancer imaging agents are limited by their inability to detect small tumors and/or their high incidence of false positives. A sensitive and specific imaging technique that can detect breast cancer recurrence and metastasis in time to establish curative therapy is urgently needed.

The principal investigators have developed a receptor-targeted nanoconjugate-Scan (RTN-Scan) that addresses the sensitivity and specificity limitations of the FDA approved SPECT imaging agent Miraluma and PET imaging with F-18, FDG. RTN-Scan is a multifunctional nanoconstruct comprised of a gold nanoparticle chelated with a PET emitting gallium isotope and a Gastrin releasing peptide (GRP). GRP receptors are overexpressed in 71% of patients with primary and metastatic breast cancer. Attachment of a therapeutic radionuclide to the nanoconjugate to selectively irradiate the tumor would potentially create a theranostic platform for the diagnosis, staging, and treatment of breast cancer.

Cartilage loss leading to osteoarthritis (OA) is common, affecting an estimated 27 million Americans age 25 and above. The direct medical costs of OA are estimated at $28.6 billion per year. Osteochondral allografts (OCA) are often used to treat issues arising from OA but their use is limited by their short shelf life (~30 days). Once OA becomes severe a total joint replacement becomes necessary to prevent debilitating pain. The availability of an effective early treatment of OA could reduce the need for joint replacement and allow patients to maintain active lives.

In a joint project between the University of Missouri and Columbia University, the principal investigators are developing an off the shelf, single-surgery cartilage restoration product that will allow high-function outcomes in younger, active patients. ECHON is a bi-layered construct of engineered cartilage integrated with an underlying porous substrate cultured under defined conditions so as to promote development of functional properties that are similar to native OCA. This bio-hybrid graft is a venture into regenerative medicine that is potentially suitable for repair of both focal cartilage defects and entire articular surfaces. The team has successfully translated their patented graft fabrication technology from a bovine model to canine preclinical models of regenerative cartilage surgery.

As the next step toward human clinical use, the researchers will now prepare ECHON constructs using human chondrocytes and assess their in vivo performance in an established animal model.

Currently, osteochondral allografts (OCA) are used to treat defects in joints resulting from osteochondritis dissecans injury, trauma and osteoarthritis. This encompasses a significant and increasing number of affected patients estimated to be 600,000 to 900,000 per year in the US. In their current form, OCAs are circular cross-section grafts that are easy to create but lack optimal shapes to effectively repair non-circular defects, particularly large ones.

Current standard of care uses these circular grafts in a 'snowman' pattern that consists of overlapping multiple grafts. The associated problems include technical difficulty, poor use of donor tissue, non-anatomical reconstruction and compromised graft stability. The principal investigators are working on a system that makes it possible to repair large OCD defects with a single allograft. The system will be comprised of cutting guides in clinically relevant sizes, a reaming tool to create the socket and a cutting system to create the anatomical graft.

The anatomical OCA system will preserve native tissue better than existing repair instrumentation resulting in faster healing times, improved graft stability and better patient outcomes.