Scope: Madhumathi Rao:State Matching: Kentucky Network for Innovation & Commercialization (#KYNETIC#) Yr 2

With population aging and increasing comorbidity, a growing number of patients develop metabolic bone diseases (MBD) such as osteoporosis and renal osteodystrophy from the associated effects on bone turnover and mineralization. Conditions such as kidney disease, organ transplant, bariatric surgery, cancer, HIV/AIDS, glucocorticoid use and other diseases, result in a significant increase in MBD. Over the past decade, therapeutic options for MBD have expanded rapidly, creating opportunities for targeted treatments. A bone biopsy is the current gold standard for diagnosing the specific type of MBD and facilitates the optimal use of bone-active agents in treatment. It provides information about the mineralized component of bone: turnover, mineralization and microarchitecture. In practice, bone biopsies are performed with trephines that were designed primarily to harvest bone marrow even though both tissues are processed very differently. Qualitative and quantitative histology for a bone biopsy is performed on un-decalcified sections cut from hard resin- or polymer- embedded blocks, preserving the cortical and trabecular microarchitecture. The modern trephines still use a manual technique, and often yield suboptimal bone tissue cores with inadequate preservation of microarchitecture. The manual biopsy technique requires significant training for the operator and is painful to the patient. Power drill modifications, while easier and less painful, yield small cores and produce damage artifacts and debris from an inappropriately designed cutting edge paired with a high- speed drill. These known problems with bone biopsy technology ultimately decrease provider and patient acceptance reducing the accuracy of diagnosis, underscoring the technology gap in meeting the need for appropriate tools. We have designed a dedicated power-driven bone biopsy trephine, compatible with clinical standard power drivers. The device has an optimized cutting edge and luminal design to retain a core suitable for analysis with preservation of cortical and trabecular microarchitecture. The design is currently protected by two provisional patent applications. In collaboration with our industry partner, we seek to translate this design into a working prototype that can be subjected to functional analysis over the first six months of funding. This period will also focus on formal regulatory assessment to identify testing requirements and formulate appropriate strategy. The following six months will refine the prototype using rigorous acceptance criteria and more intensive Feasibility Sample Testing with cadaveric bone samples at the University of Kentucky Bone Diagnostics Lab as our Go/NoGo decision gates. Subsequent product development and refinements will focus on bringing the product to a viable exit strategy over an estimated timeline of 6 to 12 months. Our team consists of a biomedical engineer, clinical experts including nephrologists, bone specialists, orthopedic surgeons, a bone scientist, and an industry partner. We are uniquely qualified to meet the challenges and needs of this project from design inception to clinical output.