PT  - JOURNAL ARTICLE
AU  - Chao Liu
AU  - Robert Carrera
AU  - Vittoria Flamini
AU  - Lena Kenny
AU  - Pamela Cabahug-Zuckerman
AU  - George Benson
AU  - Daniel Hunter
AU  - Bo Liu
AU  - Gurpreet Singh
AU  - Philipp Leucht
AU  - Kenneth A. Mann
AU  - Jill A. Helms
AU  - Alesha B. Castillo
TI  - Effects of mechanical loading on cortical defect repair using a novel mechanobiological model of bone healing
AID  - 10.1101/190819
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 190819
4099  - http://biorxiv.org/content/early/2017/09/19/190819.short
4100  - http://biorxiv.org/content/early/2017/09/19/190819.full
AB  - Mechanical loading is an important aspect of post-surgical care. The timing of load application relative to the injury event is thought to differentially regulate repair depending on the stage of healing. Here, we show using a novel mechanobiological model of cortical defect repair that daily loading (5 N peak load, 2 Hz, 60 cycles, 4 consecutive days) during hematoma consolidation and inflammation disrupts the injury site and activates cartilage formation on the periosteal surface adjacent to the defect. We also show that daily loading during the matrix deposition phase enhances both bone and cartilage formation at the defect site, while loading during the remodeling phase results in an enlarged woven bone regenerate. All loading regimens resulted in abundant cellular proliferation within the regenerate and at the periosteal surface and fibrous tissue formation directly above the defect. Stress was concentrated at the edges of the defect during exogenous loading, and finite element (FE)-modeled longitudinal strain (εzz) values along the anterior and posterior borders of the defect (~2200 με) were an order of magnitude larger than strain values on the proximal and distal borders (~50-100 με). These findings demonstrate that all phases of cortical defect healing are sensitive to physical stimulation. In addition, the proposed novel mechanobiological model offers several advantages including its technical simplicity and its well-characterized and spatially confined repair program, making effects of physical and biological interventions more easily assessed.