Negative pressure therapy stimulates healing of critical-size calvarial defects in rabbits

Negative pressure therapy (NPT) is the controlled application of subatmospheric pressure to wounds. It has been shown to stimulate healing across a broad spectrum of soft-tissue wounds, at least in part from the application of mechanical stress on cells and tissues in the wound environment. This study tests the hypothesis that application of NPT to cranial critical-size defects (CSD) in skeletally mature rabbits leads to osseous healing. NPT was delivered 1, 4, 6 or 10 days over CSD-containing calcium phosphate scaffolds placed in contact with intact dura. At 12 weeks after defect creation, NPT groups exhibited significantly greater defect bridging and bone within the scaffolds (P<0.01). Increasing duration of NPT did not result in a greater amount of bone within the scaffolds, but did increase the amount of bone distributed in the upper half of the scaffolds. Appearance of tissue within defects immediately following the removal of NPT at day 6 suggests alternating regions of dural compression and distention indicative of cell stretching. Dura and adjacent tissue were composed of multiple cell layers that extended up into the scaffolds, lining struts and populating pore spaces. An extracellular matrix densely populated with cells and capillaries, as well as larger vessels, infiltrated pores of NPT-treated scaffolds, while scattered spindle-shaped cells and sparse stroma are present within pores of control scaffolds. This rabbit model data suggest that NPT activates within mature dura a natural healing cascade that results in osseous tissue formation without the addition of exogenous factors or progenitor cells.