Megan Oest, PhD

RESEARCH ABSTRACT

Cellular Mechanisms Mediating Therapeutic Radiation Damage to Bone: A common complication following focal radiation therapy for soft tissue sarcoma is late-onset insufficiency fracture of the bone. While radiation-induced morphological changes to the bone have been documented, these changes alone do not explain the increased risk for fragility fracture. Using a mouse model of focal hindlimb irradiation, we have documented an early, transient increase in osteoclast numbers followed by persistent loss of osteoclasts long-term, and extensive modifications to the bone matrix post-irradiation. These alterations in osteoclast number correlate temporally with loss of trabecular bone. Persistence of poor quality bone matrix post-irradiation highlights the importance of retaining functional osteoclast and osteoclast progenitor cell populations long-term. We are characterizing this radiation-induced progenitor cell damage and osteoclast dysfunction, and investigating potential preventative pharmacologic interventions. (Funding: Baldwin Foundation)

Biochemical and Mechanical Alterations to Bone Following Radiotherapy: Radiation-induced bone fragility is best explained using a model that assumes embrittlement of bone's material properties following radiation. We hypothesize that this embrittlement may occur through biochemical alterations to the organic matrix and alterations to mineral crystallinity. Using Raman spectroscopy, mechanical testing, and assessment of advanced glycation end product accumulation, we are exploring time and location-dependent biochemical alterations to bone following radiation therapy. (Funding: NIH/NIAMS, PI: Timothy Damron, Co-Is: Kenneth Mann, David Kohn & Michael Morris at UMichigan)

Novel Biomaterials for Stabilization and Repair of Critically Sized Bone Defects: We are investigating the use of novel shape-memory polymer scaffolds and electrospun shape-memory polymer sleeves as methods of rapidly stabilizing bone defects, reconstructing comminuted fractures, and delivering antimicrobial and osteoinductive agents to facilitate autologous repair long-term. We have completed preliminary testing of this technology in a mouse femoral defect model, and are scaling up to larger animal models for eventual human application. (Funding: Nappi Family Awards, co-PI: James Henderson, Syracuse University)

Publications:

1.    Oest ME, Mann KA, Zimmerman ND, Damron TA. (2016) PTH(1-34) transiently protects against radiation-induced bone damage. Calcified Tissue International epub ahead of print.

2.    Baker RM, Tseng L-F, Iannolo MT, Oest ME, Henderson JH. (2016) Self-deploying shape memory polymer scaffolds for grafting and stabilizing complex bone defects: a mouse femoral segmental defect study. Biomaterials 76:388-398.

3.    Oest ME, Franken V, Kuchera T, Strauss J, Damron TA. (2015) Long-term loss of osteoclasts and unopposed cortical mineral apposition following limited field irradiation. Journal of Orthopaedic Research 33(3): 334-342.

4.    Oest ME, Damron TA. (2014) Focal therapeutic irradiation induces an early transient increase in bone glycation. Radiation Research 181(4):439-43.

5.    Oest ME, Miller MA, Howard KI, Mann KA. (2014) A novel in vitro loading system to produce supraphysiologic fluid shear stress. Journal of Biomechanics 47(2):518-525.

6.    Gong B, Oest ME, Mann KA, Damron TA, Morris MD. (2013) Raman Spectroscopy Demonstrates Prolonged Alteration of Bone Chemical Composition Following Extremity Localized Irradiation. Bone 57(1):252-258.

7.    Keenawinna L, Oest ME, Mann KA, Spadaro JA, Damron TA. (2013) Zoledronic Acid Prevents Loss of Trabecular Bone Following Focal Irradiation in Mice. Journal of Radiation Research 180(1):89-99.

8.    Wojtowitcz AM, Shekaran A, Oest ME, Dupont KM, Templeman KL, Hutmacher DW, Guldberg RE, Garcia AJ. (2010) Coating of biomaterial scaffolds with the collagen-mimetic peptide GFOGER for bone defect repair. Biomaterials, 31(9): 2574-2582.

9.    Liang C, Oest ME, Jones JC, Prater MR. (2009) Gestational high saturated fat diet alters C57BL/6 mouse perinatal skeletal formation. Birth Defects Research Part B Developmental and Reproductive Toxicology, 86(5):377-384.

10.Liang C, Oest ME, Prater MR. (2009) Intrauterine exposure to high saturated fat diet elevates risk of adult-onset chronic diseases in C57Bl/6 mice. Birth Defects Research Part B Developmental and Reproductive Toxicology, 86(5):362-369.

11.Oest ME, Jones JC, Hatfield C, Prater MR. (2008) Micro-CT evaluation of murine fetal skeletal development yields greater morphometric precision over traditional clear-staining methods. Birth Defects Research Part B Developmental and Reproductive Toxicology 83(6):582-589.

12.Guldberg RE, Duvall CL, Peister A, Oest ME, Lin AS, Palmer AW, Levenston ME. (2008) 3D imaging of tissue integration with porous biomaterials. Biomaterials 29 (28):3757-3761.

13.Guldberg RE, Oest ME, Dupont K, Peister A, Deutsch E, Kolambkar Y, Mooney D. (2007) Biologic augmentation of polymer scaffolds for bone repair. Journal of Musculoskeletal and Neuronal Interactions 7(4):333-334.

14.Duty AO, Oest ME, Guldberg RE. (2007) Cyclic mechanical compression in vivo increases mineralization of cell-seeded polymeric orthopaedic tissue constructs. Journal of Biomechanical Engineering 129(4):531-539.

15.Oest ME, Dupont KM, Kong, HJ, Mooney, DJ, Guldberg RE. (2007) Quantitative assessment of scaffold and growth factor-mediated repair of critically sized bone defects. Journal of Orthopaedic Research 25(7):941-950.

16.Rai B, Oest ME, Dupont KM, Ho KH, Teoh SH, Guldberg RE. (2007) Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate scaffolds for segmental bone defect repair. Journal of Biomedical Materials Research A 81(4):888-899.

17.Guldberg RE, Oest ME, Lin AS, Ito H, Chao X, Gromov K, Goater JJ, Koefoed M, Schwarz EM, O'Keefe RJ, Zhang X. (2004) Functional integration of tissue-engineered bone constructs. Journal of Musculoskeletal and Neuronal Interactions 4(4):399-400.

18.   Guldberg RE, Ballock RT, Boyan BD, Duvall CL, Lin AS, Nagaraja S, Oest ME, Phillips J, Porter BD, Robertson G, Taylor WR. (2003) Analyzing bone, blood vessels, and biomaterials with microcomputed tomography. IEEE Engineering in Medicine and Biology 22(5):77-83.

19.   Bower CK, Parker JE, Higgins AZ, Oest ME, Wilson JT, Valentine BA, Bothwell MK, McGuire J. (2002) Protein antimicrobial barriers to bacterial adhesion: in vitro and in vivo evaluation of nisin-treated implantable materials. Colloids and Surfaces B: Biointerfaces 25(1):81-90.

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