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Background
I received my Bachelor's degree in anthropology from the University of Texas at Austin and my Ph.D. in biological anthropology from the State University of New York at Stony Brook (advisor: Brigitte Demes).
I am interested in many aspects of orthopaedics/bone biology research. In recent years, I have driven or collaborated on projects in osteoporosis, bone tissue engineering, osteoclast biology, methods in mCT imaging (structure and density analyses), and functional morphology. This broad research experience has informed my primary interests in bone fragility/quality and bone metabolism. I use an integrative approach to test current models/hypotheses about bone fragility/quality and bone metabolism, designing research projects that can elucidate mechanistic and evolutionary explanations.
I am currently working on several research projects described below.
Bone metabolism - Role of micro-damage in remodeling, development of a hummingbird model
My primary goal right now is to establish a new avian model for biomedical research to better understand bone remodeling. Avian models, like the Trochilidae (hummingbirds), offer a unique opportunity to better understand remodeling in a cyclic loading model. All structural support materials wear with use and time. The unique thing about our skeleton is that the wear damage we accumulate in the form of micro-cracks over time typically gets repaired via the process of remodeling. Hummingbirds engage in hovering flight, a locomotor mode that requires incredibly high frequency wing loading (but most likely lower absolute loads). They are dependent on hovering flight for eating and to change locations (they do not walk). To put all this in context, a medium-sized hummingbird species will perform one million full wing strokes in approximately seven hours of flight. In truth, they will hit this mark in around two weeks. It is estimated that your garden variety terrestrial mammal or adult human will achieve a million loading cycles in a couple years or more. At present, it is unclear how much, if any, microdamage accumulates in the hummingbird wing and how this contrasts with the hind limb, which is not dynamically loaded. The hummingbird offers an ideal natural experiment through which we can learn more about these issues as well as topics such as cartilage biology in a cyclic loading model. I am currently working with my colleague and friend, Dr. Patrick O'Connor, to collect pilot data on the macro-, micro-, and ultra-structure of trochilid cortical bone.
Osteoporosis - Efficacy of a novel anabolic treatment in the fight against bone loss
Activin is a member of the TGF-b superfamily of proteins. Members of this superfamily, TGF-b and BMP-2 for example, are known players in bone biology. Recent in-vitro work indicates that inhibition of the activin pathway on osteoblasts promotes bone deposition. We know that inhibtion of this pathway in mice increases bone mass and rescues an OVX phenotype (Pearsall et al. 2008, PNAS). We are now assessing the efficacy of this novel drug treatment in a large animal model, the Cynomolgus monkey (Macaca fascicularis). This animal model is ideal because Cynos and humans share similar hormone cycles and intracortically remodel bone (unlike rodents). Our early results indicate that activin-inhibition treatment significantly increases lumbar vertebral body trabecular BV/TV, compressive bone strength (Fajardo et al., 2007, ASBMR), and, unlike PTH, does not co-stimulate bone resorption (Lotinun et al., 2008, ASBMR).
Bone imaging
My primary interest in this area is mCT (Fajardo et al., 2001 AJPA; Fajardo et al., 2002 AJPA) but I am generally interested in different modalities used to assess bone quality. In a recently published study, colleagues and I reported that beam-hardening and object size introduce significant error into mCT-based measurements of bone tissue mineral density (Fajardo et al., 2008, Bone). Complicating efforts to correct these artifacts is that the direction of the accuracy error is dependent on the interaction of several factors including object true density, object size, object shape/structure (e.g. solid, metaphyseal-like, or porous), and the beam-hardening correction algorithm applied. Furthermore, recent work published by my lab mates, Ara Nazarian and Brian Snyder, highlights how scan settings affect mCT-based bone tissue mineral density measurements as well (Nazarian et al., 2008, Bone). Overall, these studies strongly suggest that research investigating the accuracy of μCT-based measurement of bone tissue density continue since this imaging tool is broadly used in pre-clinical trials that are the foundation for advancing experiments on therapeutic agents to larger pre-clinical models and eventually human trials.
Body size scaling in bone mechanics
I am interested in how evolution to larger body size and its associated mechanical demands impact bone structure, especially in metaphyseal-like regions, and cellular level (bone remodeling) processes within phylogenetic groups and across clades of mammals/vertebrates. My own preliminary data indicate a puzzling (but not unique) pattern in which primate bone fails to adapt in the femur and vertebra appropriately to increased forces generated by body mass. I would like to explore this area further within Primates and other mammalian models, investigating empirically and computationally the comparative mechanical behavior of these bones.
Publications
Fajardo RJ, Pearsall S, Pearsall AE, Manoharan RK, Roberts B, Grinberg A, Davies M, Monnell T, Ucran J, Barazza M, Kelly C, Khanzode D, Underwood K, Kumar R, Bouxsein ML. In Prep. Treatment with Soluble Receptor for Activin Increases Bone Mass and Structure in the Axial and Appendicular Skeleton of Female Cynomolgus Macaques (Macaca fascicularis). Will be submitted to Bone
Fajardo RJ, Cory E, Patel ND, Nazarian A, Laib A, Manoharan RK, Schmitz JE, De Silva JM, MacLatchy LM, Snyder BD, and Bouxsein ML. In Press. Specimen size and porosity can introduce error into μCT-based tissue mineral density measurements. Bone.
Fajardo RJ, Hernandez E, O’Connor PM. 2007. Axial postcranial skeletal pneumaticity: a quantitative microCT assessment of vertebral structure in birds. J Anat 211:138-147
Fajardo RJ, Müller R, Ketcham RA, and Colbert M. 2007. Nonhuman anthropoid primate femoral neck trabecular architecture and its relationship to locomotor mode. Anat Rec, Adv Integr Anat Evol Biol: 290:422-436
Marolt D, Augst A, Freed LE, Vepari C, Fajardo R, Patel N, Gray M, Farley M, Kaplan D, and Vunjak-Novakovic G. 2006. Bone and cartilage tissue constructs grown using human bone marrow stromal cells, silk scaffolds and rotating bioreactors. Biomaterials 27:6138-6149.
Karageorgiou V, Tomkins M, Fajardo R, Meinel L, Snyder B, Wade K, Chen J, Vunjak-Novakovic G, and Kaplan DL. 2006. Porous silk fibroin 3-D scaffolds for delivery of bone morphogenetic protein-2 in vitro and in vivo. J Biomed Mater Res Pt A 78A:324-334.
Meinel L, Betz O, Fajardo R, Hofmann S, Nazarian A, Cory E, Hilbe M, McCool J, Langer R, Vunjak-Novakovic G, Merkle HP, Rechenberg B, Kaplan DL, and Kirker-Head C. 2006. Silk based biomaterials to heal critical sized femur defects. Bone 39:922-931.
Meinel L, Hofmann S, Betz O, Fajardo R, Merkle HP, Langer R, Evans CH, Vunjak-Novakovic G, and Kaplan DL. 2006. Osteogenesis by human mesenchymal stem cells cultured on silk biomaterials: Comparison of adenovirus mediated gene transfer and protein delivery of BMP-2. Biomaterials 27:4993-5002.
Bouxsein ML and Fajardo RJ. 2005. Significance of cancellous bone in the femoral neck. Letter to the Editor. The Lancet 366: 1523-1524.
Meinel L, Fajardo R, Hofmann S, Langer R, Chen J, Snyder B, Vunjak-Novakovic G, and Kaplan D. 2005. Silk-implants for the healing of critical size bone defects. Bone 37: 688-698.
Meinel L, Karageorgiou V, Hofmann S, Fajardo R, Snyder B, Li CM, Zichner L, Langer R, Vunjak-Novakovic G, and Kaplan DL. 2004. Engineering bone-like tissue in vitro using human bone marrow stem cells and silk scaffolds. J. Biomed. Mater. Res. Part A 71A:25-34.
Meinel L, Karageorgiou V, Fajardo R, Snyder B, Patil VS, Zichner L, Kaplan D, Langer R, and Vunjak-Novakovic, G. 2004. Bone tissue engineering using human mesenchymal stem cells: Effects of scaffold material and medium flow. Ann Biomed Eng 32:112-122.
Fajardo RJ, Ryan TM, and Kappelman J. 2002. Assessing the accuracy of high-resolution x-ray computed tomography of primate trabecular bone by comparisons with histological sections. Am J Phys Anthropol 118: 1-10
Fajardo RJ, and Müller R. 2001. Three-dimensional analysis of nonhuman primate trabecular architecture using micro-computed tomography. Am J Phys Anthropol 115:327-336
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