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Bridging Mechanics & Biology to Understand the Periosteum's Role in Bone Regeneration: Towards a Parametric Approach to Engineering Replacement Periosteum

Moore, Shannon Rene
http://rave.ohiolink.edu/etdc/view?acc_num=case1370522085

Abstract Details

2013, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Bone tissue regeneration in critical sized defects presents a currently intractable challenge in orthopaedics. New approaches seek to harness or replicate the regenerative capacity of the periosteum, the tissue membrane bounding bone that provides a niche for mechanosensitive osteochondral progenitor cells. Yet periosteum's unique properties are not well understood across spatiotemporal scales or from a structure-function perspective. This thesis presents multiple length- (molecular, cellular, tissue) and time-scale (growth, aging, lifetime) approaches to elucidate periosteum’s structure-function relationships, while addressing key considerations for optimizing a clinically translatable periosteum substitute. Beginning at a tissue scale, a biomechanics model of a virtual human femur simulates the emergence of the linea aspera, a characteristic, anatomic ridge along the posterior aspect of the femur at puberty, predicting and quantifying life-long adaptation, while negating Pauwels' hypothesis that the linea aspera stiffens the femur in bending. This virtual case study of life-long functional adaptation demonstrates the utility of modern computational methods to test mechanobiological hypotheses relevant to evolution of form and function. Further, it suggests a role for the periosteum as a mediator of strong muscular attachments at the linea aspera. Thereafter, measurements of cadaveric periosteum from aged human femora provide unprecedented reference values for clinical translation. They also show a rather surprisingly weak relationship between periosteum's structural properties and prevailing mechanical environment, spawning new research questions regarding the mechanomodulatory processes by which this anisotropic, `smart’ material develops and is maintained. Then, building upon the clinical context, a critical sized defect model serves to assess bone regeneration following treatment with a novel surgical membrane designed to replicate periosteum's structural, barrier and cellular functions. High-resolution histomorphometry shows that incorporation of biological factors from autologous periosteum augments bone tissue generation, predominantly via an endochondral ossification pathway. Finally, a mechanistic, paired computational-analytical and multiscale model bridges periosteal mechanics and biology, predicting growth factor-regulated processes of tissue infilling in a simulated defect, and enabling parametric assessment to engineer next-generation periosteal replacements. As a whole, this work advances understanding of periosteal mechanobiology and underscores the need for follow-on studies to address current gaps in knowledge regarding mechanically mediated tissue generation, adaptation and repair.
Melissa Knothe Tate, PhD (Advisor)
161 p.
Biomechanics; Biomedical Engineering

Recommended Citations

Citations

  • Moore, S. R. (2013). Bridging Mechanics & Biology to Understand the Periosteum's Role in Bone Regeneration: Towards a Parametric Approach to Engineering Replacement Periosteum [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1370522085

    APA Style (7th edition)

  • Moore, Shannon. Bridging Mechanics & Biology to Understand the Periosteum's Role in Bone Regeneration: Towards a Parametric Approach to Engineering Replacement Periosteum. 2013. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1370522085.

    MLA Style (8th edition)

  • Moore, Shannon. "Bridging Mechanics & Biology to Understand the Periosteum's Role in Bone Regeneration: Towards a Parametric Approach to Engineering Replacement Periosteum." Doctoral dissertation, Case Western Reserve University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1370522085

    Chicago Manual of Style (17th edition)

case1370522085
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© 2013, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.