Effects of mechanical loading on cortical defect repair using a novel mechanobiological model of bone healing

Chao Liu, Robert Carrera, Vittoria Flamini, Lena Kenny, Pamela Cabahug-Zuckerman, Benson M. George, Daniel Hunter, Bo Liu, Gurpreet Singh, Philipp Leucht, Kenneth A. Mann, Jill A. Helms, Alesha Castillo

Research output: Contribution to journalArticle

Abstract

Mechanical loading is an important aspect of post-surgical fracture care. The timing of load application relative to the injury event may differentially regulate repair depending on the stage of healing. Here, we used a novel mechanobiological model of cortical defect repair that offers several advantages including its technical simplicity and spatially confined repair program, making effects of both physical and biological interventions more easily assessed. Using this model, we showed that daily loading (5 N peak load, 2 Hz, 60 cycles, 4 consecutive days) during hematoma consolidation and inflammation disrupted the injury site and activated cartilage formation on the periosteal surface adjacent to the defect. We also showed that daily loading during the matrix deposition phase enhanced both bone and cartilage formation at the defect site, while loading during the remodeling phase resulted in an enlarged woven bone regenerate. All loading regimens resulted in abundant cellular proliferation throughout the regenerate and fibrous tissue formation directly above the defect demonstrating that all phases of cortical defect healing are sensitive to physical stimulation. 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) was an order of magnitude larger than strain values on the proximal and distal borders (~ 50–100 με). It is concluded that loading during the early stages of repair may impede stabilization of the injury site important for early bone matrix deposition, whereas loading while matrix deposition and remodeling are ongoing may enhance stabilization through the formation of additional cartilage and bone.

Original languageEnglish (US)
Pages (from-to)145-155
Number of pages11
JournalBone
Volume108
DOIs
StatePublished - Mar 1 2018

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Keywords

  • Bone repair
  • Cortical defect
  • Mechanical loading
  • Mechanobiology
  • Mouse tibia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Liu, C., Carrera, R., Flamini, V., Kenny, L., Cabahug-Zuckerman, P., George, B. M., Hunter, D., Liu, B., Singh, G., Leucht, P., Mann, K. A., Helms, J. A., & Castillo, A. (2018). Effects of mechanical loading on cortical defect repair using a novel mechanobiological model of bone healing. Bone, 108, 145-155. https://doi.org/10.1016/j.bone.2017.12.027