Battlefield traumatic long bone injuries are often accompanied with infections and the loss of natural periosteal tissue, an essential source of progenitor cells and signaling molecules for triggering effective fracture repair and graft healing. Consequently, bone graft-mediated repair of such injuries often suffers from a significant failure rate. The proposed off-the-shelf pseudo-periosteum (PP), in the form of nanocrystalline HA (nHA)-mineralized cellulose nanofiber mesh, is designed to locally deliver protein therapeutics, antibiotics, and progenitor cells around the surface of structural allografts, thereby reconstituting a desired biochemical/cellular microenvironment, promoting graft healing. This strategy can benefit injured soldiers by reducing the risk for infections and amputation, and by improving the overall success rate of bone graft-mediated long bone repair.

Compared to conventional poly(lactic-co-glycolic acid)-based growth factor delivery platforms, the PP designed here has higher affinity for recombinant protein therapeutics. Consequently, lower effective loading doses of recombinant proteins can be accomplished with the PP, enabling cost reduction and the minimization of systemic side effects associated with diffused proteins. In addition, this user-friendly composite PP mesh can be wrapped around any type of bone graft (autografts, allografts, and synthetic grafts) or press-fit into any osseous void, thus beneficial to a broad spectrum of orthopedic surgical procedures. Finally, the PP can be loaded with various combinations of protein therapeutics and antibiotics to achieve optimal clinical outcome based on individual patient's needs.

The efficacy of the PP-based therapeutic strategy will be examined using a rat femoral segmental defect model in a three-year timeframe. In the proposed rodent model, the natural periosteal tissue surrounding the critical-sized defect will be circumferentially removed to emulate the challenging scenario of battlefield traumatic long bone injuries. If validated, this new therapeutic strategy can have profound impact on limb salvage among injured soldiers.