Electronic Theses and Dissertations

Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

Committee Chair

John Williams

Committee Member

Omar Skalli

Committee Member

Amy Curry

Committee Member

Aaryani Sajja

Abstract

The growth plate of a long bone is an organ comprised of a thin layer of hyaline cartilage sandwiched between epiphyseal and metaphyseal bone and surrounded by fibrous tissues. The cartilage tissue can be divided into three histological zones reflecting the activities of the chondrocytes from the epiphysis toward the metaphysis: a reserve, proliferative and hypertrophic zone. Longitudinal growth occurs by a process of endochondral ossification in which cartilage in the hypertrophic zone at the metaphyseal border is calcified and then replaced by bone while new cartilage is produced in the proliferative zone. Application of mechanical loading modulates the chondrocyte activity in the proliferative and hypertrophic zones. As growth continues the growth plate develops into a three-dimensional interlocking interface of hills and valleys, termed mammillary processes, and a layer of compact subchondral bone arises at the border of the reserve zone and epiphysis. The undulations on the metaphyseal side of the growth plate are formed by endochondral ossification. The mechanism by which the undulations between the reserve zone and subchondral epiphysis form has not been elucidated. Recent discoveries of stem-like cells in the reserve zone suggest that reserve zone cells may also modulate growth under mechanical loading. To explore this possible function the present work examined the histology and chemistry of the interface between the reserve zone and epiphyseal bone in a pig model. Elastic and poroelastic multiscale finite element models of the growth plate were developed to investigate the depth-dependent biomechanical microenvironment of reserve zone chondrocytes, particularly cells close to the subchondral bone and proliferative zone. The histological, chemical and computational results suggest that reserve zone chondrocytes near the epiphysis participate in a slower second endochondral ossification front that develops the subchondral bone plate forming undulations that match those on the metaphyseal side. Computational results indicate that dynamic loading engenders fluid shear stresses around reserve zone cells that may signal dividing cells to orient and align in columns. The depth-dependent micro-mechanical environment of the reserve zone cell is highly sensitive to the permeability of the subchondral bone plate and to the rate of loading.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

Notes

embargoed

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