The Woodruff School

SUMMARY

Each year, there are 12 million skeletal fractures in the United States alone, and about 5% of these injuries do not heal and are classified as non-unions. In the context of bone repair, controlled mechanical stimulation has been reported to accelerate healing, while excessive mechanical instability results in non-union. Given these findings, many researchers have sought controlled mechanical stimulation as a putative target to augment endogenous bone regeneration. The study of mechanobiology in vivo, however, has largely remained qualitative, since the temporal progression of local stresses and strains cannot be measured accurately. This technical limitation hinders the ability of researchers to elucidate the role of mechanical cues in bone repair and to employ mechanical stimulation as a therapeutic technique.

The main objectives of this work are to develop technical approaches to longitudinally monitor the mechanical environment during bone healing and to elucidate how mechanical cues contribute to the promotion or impairment of repair. Our overall hypothesis is that local mechanical cues regulate acute phases of bone regeneration, subsequently promoting robust healing or non-union. To test this hypothesis, we will engineer and deploy a novel wireless, implantable strain sensor platform to obtain direct, non-invasive, longitudinal measurements of the mechanical environment in pre-clinical models of fracture repair and non-union. We will use the measurements to quantify the progression of the tissue-level mechanical environment using in vivo image-based finite element models. Finally, we will characterize and compare the early stage biological environment produced in each model.

At the conclusion of the proposed experiments, we expect to have attained a deeper understanding of how specific mechanical cues regulate bone repair, and to have established a novel strain sensor platform to further investigate these processes in future studies. The knowledge gained by this thesis could be useful in the development of interventional strategies to stimulate bone repair via controlled mechanical loading or functional rehabilitation. In addition, the technological outcomes of this thesis could serve as foundational support for the expanded utilization of implantable sensor technologies, which is a promising research direction with broad implications toward enhanced disease characterization, therapeutic testing, and clinical monitoring.

SUBJECT:	Ph.D. Proposal Presentation

BY:	Brett Klosterhoff

TIME:	Tuesday, June 25, 2019, 1:00 p.m.

PLACE:	IBB Building, 1128

TITLE:	Mechanobiological Regulation of Acute Phase Bone Repair

COMMITTEE:	Dr. Robert Guldberg, Co-Chair (ME) Dr. Nick Willett, Co-Chair (BME) Dr. Edward Botchwey (BME) Dr. Keat Ghee Ong (BME) Dr. Scott Hollister (BME) Dr. Jeff Weiss (ME)

SUMMARY Each year, there are 12 million skeletal fractures in the United States alone, and about 5% of these injuries do not heal and are classified as non-unions. In the context of bone repair, controlled mechanical stimulation has been reported to accelerate healing, while excessive mechanical instability results in non-union. Given these findings, many researchers have sought controlled mechanical stimulation as a putative target to augment endogenous bone regeneration. The study of mechanobiology in vivo, however, has largely remained qualitative, since the temporal progression of local stresses and strains cannot be measured accurately. This technical limitation hinders the ability of researchers to elucidate the role of mechanical cues in bone repair and to employ mechanical stimulation as a therapeutic technique. The main objectives of this work are to develop technical approaches to longitudinally monitor the mechanical environment during bone healing and to elucidate how mechanical cues contribute to the promotion or impairment of repair. Our overall hypothesis is that local mechanical cues regulate acute phases of bone regeneration, subsequently promoting robust healing or non-union. To test this hypothesis, we will engineer and deploy a novel wireless, implantable strain sensor platform to obtain direct, non-invasive, longitudinal measurements of the mechanical environment in pre-clinical models of fracture repair and non-union. We will use the measurements to quantify the progression of the tissue-level mechanical environment using in vivo image-based finite element models. Finally, we will characterize and compare the early stage biological environment produced in each model. At the conclusion of the proposed experiments, we expect to have attained a deeper understanding of how specific mechanical cues regulate bone repair, and to have established a novel strain sensor platform to further investigate these processes in future studies. The knowledge gained by this thesis could be useful in the development of interventional strategies to stimulate bone repair via controlled mechanical loading or functional rehabilitation. In addition, the technological outcomes of this thesis could serve as foundational support for the expanded utilization of implantable sensor technologies, which is a promising research direction with broad implications toward enhanced disease characterization, therapeutic testing, and clinical monitoring.