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Current Research of Dr. Ryan Roeder

Contrast Agents for Micro-Computed Tomography of Microdamage in Bone

Current Funding: U.S. Army Medical and Materiel Command, Peer Reviewed Medical Research Program
Graduate Students: Ryan D. Ross, Travis L. Turnbull, Matthew J. Meagher, Lisa Cole
Collaborators: Glen L. Niebur (Notre Dame)

Microdamage accumulates in bone tissue due to repetitive mechanical loading.  Accumulation of microdamage in bone tissue can lead to increased fracture susceptibility, including stress fractures in active individuals (e.g., military recruits) and fragility fractures in the elderly.  The total cost of stress fractures is estimated to exceed $10M/year in medical expenses and lost duty for the U.S. Army.  Current methods for detecting microdamage use thin histological sections which are inherently invasive, destructive, tedious and two-dimensional.  Non-invasive, three-dimensional detection of microdamage would enable scientific study of the role of microdamage in bone fragility and clinical (in vivo) assessment of microdamage accumulation.

Therefore, the objective of this project is to investigate the detection of microdamage in bone by contrast-enhanced micro-computed tomography using (1) precipitated barium sulfate for non-destructive, 3-D detection, and (2) functionalized gold nanoparticles for targeted delivery and non-invasive (in vivo) detection.  Whether through improved understanding of the etiology of stress and osteoporotic fractures, or the development of improved clinical methods to diagnose fracture risk, this work is aimed at improving bone health in military personnel and civilians, ranging from new recruits and athletes to retired veterans and the elderly.

Z. Zhang, R.D. Ross and R.K. Roeder, “Preparation of functionalized gold nanoparticles as a targeted X-ray contrast agent for damaged bone tissue,” Nanoscale, 2 [4] 582-586 (2010). doi:10.1039/b9nr00317g

H. Leng, X. Wang, G.L. Niebur and R.K. Roeder, “Micro-Computed Tomography of Fatigue Microdamage in Cortical Bone Using a Barium Sulfate Contrast Agent,” J. Mech. Behav. Biomed. Mater., 1 [1] 68-75 (2008). doi:10.1016/j.jmbbm.2007.06.002


Hydroxyapatite Whisker Reinforced Polymer Biocomposites and Scaffolds

Current Funding: U.S. Army Medical Research and Materiel Command
Graduate Students: Robert J. Kane, Timothy L. Conrad, Christina H. Merrill
Undergraduates: Tess FitzpatrickCollaborators: Stephen Smith, M.D. (North Central Neurosurgery, South Bend, IN), Diane Wagner (Notre Dame), Glen L. Niebur (Notre Dame)

In order to meet the challenges of the next century, new synthetic biomaterials must be developed that are able to interact synergistically with natural tissues and biological processes.  The extracellular matrix of bone tissue is a collagen matrix reinforced with elongated apatite mineral crystals which exhibit preferred orientation along directions of principal stress.  Hydroxyapatite (HA) is the closest synthetic equivalent to human bone mineral, and is biocompatible and bioactive in vivo.  Despite hundreds of studies over the last thirty years, very few HA reinforced polymers have been able to mimic the mechanical properties of bone tissue at comparable levels of porosity and/or reinforcement.  A major reason for this is that the integrity of the HA/polymer interface is typically limited to mechanical interlock.  The use of elongated single crystal HA whiskers has resulted in significantly improved static and fatigue properties compared to conventional equiaxed powders. Therefore, the overall objective of this project is to investigate processing-structure-property relationships in HA whisker reinforced polymer biocomposites and scaffolds.

Polyaryletherketones (PAEK) have many attractive characteristics for orthopaedic and spinal implants, including radiolucency and mechanical properties similar to bone tissue. However, current PAEK implants are dense and bioinert, which limits osteointegration and implant stability.  Therefore, novel porous and bioactive HA whisker reinforced PAEK biocomposites have been investigated.  The HA volume fraction and/or porosity have been tailored to mimic human bone tissue.  The mechanical properties of dense and porous HA whisker reinforced PAEK were similar to those of human cortical bone and vertebral trabecular bone, respectively.  The ability to manufacture PAEK implants with tailored levels and placement of bioactive reinforcements and porosity opens new opportunities for implant design, which may translate into new treatment options for improved implant fixation, including interbody spinal fusion.

Collagen scaffolds are attractive for tissue engineering due to similarity to the composition of native bone tissue, including the ability to be resorbed and remodeled, but typically exhibited poor mechanical properties.  HA whisker reinforcement and novel processing methods have been investigated and show to result in significantly improved mechanical properties.  The biocompatibility and bioactivity of HA whisker reinforced PEEK and collagen scaffolds are being investigated using in vitro cell culture and by intramuscular implantation in rats.  Finally, both scaffolds are also being investigated in conjunction with bone morphogenetic proteins (BMPs) and/or adipose-derived adult stem cells in a rat tibial osteotomy fracture healing model.

G.L. Converse, T.L. Conrad, C.H. Merrill and R.K. Roeder, “Hydroxyapatite whisker reinforced polyetherketoneketone bone ingrowth scaffolds,” Acta Biomaterialia, 6 [3] 856-863 (2010). doi:10.1016/j.actbio.2009.08.004

R.K. Roeder, S.M. Smith, T.L. Conrad, N.J. Yanchak, C.H. Merrill and G.L. Converse, “Porous and Bioactive PEEK Implants for Interbody Spinal Fusion,” Adv. Mater. Process., 167 [10] 46-48 (2009). doi:10.1361/amp16710p37

G.L. Converse, T.L. Conrad and R.K. Roeder, “Mechanical properties of hydroxyapatite whisker reinforced polyetherketoneketone composite scaffolds,” J. Mech. Behav. Biomed. Mater., 2 [6] 627-635 (2009). doi:10.1016/j.jmbbm.2009.07.002


Micro-Computed Tomography of Dentinal Cracks

Graduate Students: Travis L. Turnbull
Collaborators: Jamie J. Kruzic (Oregon State), Jack L. Ferracane and Thomas J. Hilton (Oregon Health and Science University)

Cracked teeth are commonly observed in dental practice and are potentially symptomatic.  Current methods for the diagnosis of cracks that may compromise teeth are all based on optical assessment, which suffers from an inherent inability to assess the severity of cracks, particularly sub-surface dentinal cracks.  Therefore, the objective of this project is to investigate non-destructive, three-dimensional detection of dentinal cracks in teeth using contrast-enhanced micro-computed tomography. 

M.D. Landrigan, J.C. Flatley, T.L. Turnbull, J.J. Kruzic, J.L. Ferracane, T.J. Hilton and R.K. Roeder, “Detection of dentinal cracks using contrast-enhanced micro-computed tomography,” J. Mech. Behav. Biomed. Mater., 3 [2] 223-227 (2010). doi:10.1016/j.jmbbm.2009.10.003


Structural and Mechanical Anisotropy in Human Cortical Bone Tissue

Graduate Students: Justin M. Deuerling
Undergraduates: David Rudy

Bone tissue consists of directional structural features across several unique hierarchical scales, ranging from nano-scale crystals and molecules to the macroscopic shape.  The foundational structural unit across the hierarchical scales is a two phase arrangement of anisometric bone mineral (apatite) preferentially oriented in a collagen matrix.  Despite a growing database of measurements for the mechanical anisotropy of cortical bone, few efforts have been made to quantitatively measure influential structural features, e.g., the preferred orientation of bone mineral, and virtually no efforts have been made to correlate the anisotropy to structural measurements.  Furthermore, the mechanical anisotropy in cortical bone is known to vary with anatomic location.  Therefore, the overall objectives of this work are to (1) characterize and quantitatively correlate anatomic variation in the mechanical anisotropy of human cortical bone with measurements of relevant structural features and (2) use this data to develop new micromechanical models which account for non-uniformity and anisotropy within hierarchical scaling.

Anatomic variation in the elastic anisotropy and inhomogeneity of human cortical bone tissue was investigated using ultrasonic wave propagation.  The human femoral diaphysis was shown to exhibit statistically significant anatomic variation in the elastic anisotropy and inhomogeneity, which may have important implications for whole bone numerical models and mechanobiology.  A specimen-specific multi-scale model was developed to predict the anisotropic elastic constants of human cortical bone tissue based upon seven relevant structural parameters across multiple length scales.  A sensitivity analysis indicated that the apatite crystal volume fraction and orientation distribution function (ODF) were the most influential structural parameters affecting model predictions of the magnitude and anisotropy, respectively, of elastic constants.  Model predictions generated using an experimentally measured apatite crystal ODF compared favorably with the experimental measurements for both the longitudinal and transverse elastic constants, as well as the anisotropy ratio.  In contrast, model predictions generated using common assumptions of perfectly aligned and randomly oriented apatite crystals did not accurately predict the measured elastic constants and anisotropy. 

J.M. Deuerling, W. Yue, A.A. Espinoza Orías and R.K. Roeder, “Specimen-specific multiscale model for the anisotropic elastic constants of human cortical bone,” J. Biomechanics, 42 [13] 2061-2067 (2009). doi:10.1016/j.jbiomech.2009.06.002

A.A. Espinoza Orías, J.M. Deuerling, M.D. Landrigan, J.E. Renaud and R.K. Roeder, “Anatomic variation in the elastic anisotropy of cortical bone tissue in the human femur,” J. Mech. Behav. Biomed. Mater., 2 [3] 255-263 (2009). doi:10.1016/j.jmbbm.2008.08.005