Background: Preliminary data from research co-funded by the Department of Defense (Biris/Principal Investigator [PI]; Anderson/Co-PI) across 68 goat models showed that our patent-protected, multi-component, biocompatible scaffolds enhance bone healing with no infection, inflammation, or rejection.

Hypothesis: Our breakthrough technology could provide viable treatment for complex bone injuries specific to battlefield conditions. To develop a final product for Food and Drug Administration review, we propose new research efforts to characterize the time-dependent large-size accelerated bone formation induced by our scaffold.

Specific Aims: The following aims are proposed: (1) Prove the long-term (1-year) biocompatibility and structural/functional restoration of regenerated bone using our scaffolds. (2) Determine the ability to regenerate long segmental defects (up to 10 cm). (3) Develop injectable, thermo-responsive and chemically cross-linkable composite scaffold systems for rapid bone formation.

Study Design: Work is expected to be performed concurrently on multiple aspects of the technology. For the construction of tissue-regeneration scaffolds, we will use our patented, three-dimensional, layer-by-layer deposition approach that will enable us to control of size, shape, and structure of the scaffold. Critical and subtotal bone defects will be created and the scaffolding systems implanted in rats/goats (Aim 1), goats (Aim 2), and rats (Aim 3) in orthopedic surgical conditions. Tissues will be collected for a thorough study of any adverse effects and bone formation kinetics.

Relevance: Experienced wounded Warfighters could return to service sooner, extending the Army's investment in their training and greatly improving their life quality. The potential beneficiary population also includes victims of automotive accidents and sports injuries.