Date of Graduation

Spring 2018

Document Type

Honors Research Project

Degree Name

Bachelor of Science

Major

Biology

Research Sponsor

Dr. Matthew Becker

First Reader

Dr. Brian Bagatto

Second Reader

Dr. Hazel Barton

Abstract

Orthopedic surgeries have continued to increase, but the material of choice remains constant: titanium. Titanium has become the benchmark implant material due to its durability and non-immunogenic properties. However, while high rates of success are correlated with joint replacement surgery, certain patients with predisposed diseases such as diabetes or arthritis may have increased complications.1 This can be due to lack of osseointegration due to decreased bone formation and mineralization,2 which will lead to increased rates of infection or aseptic loosening of the implant from the bone. 3 Current methods to alleviate these complications include invasive revisional surgeries, which can be emotionally taxing and dangerous towards the patient. Fortunately, new research has shown that bioactive peptides are able to modify titanium surfaces and mimic natural proteins to increase osseointegration.4 Previously, through solid phase peptide synthesis, a series of multivalent dendrons containing bioactive osteogenic growth peptide (OGP) domain and a titanium binding domain consisting of surface binding catechol groups were obtained. Dendrons containing 4 catechol units displayed increased binding strength to titanium oxide surfaces compared to the 2- and 1-unit analogs.5 Titanium oxide functionalized with this peptide molecule and seeded with mouse calverial derived stem cells (MC3T3) showed up-regulation of osteogenic markers bone sialoprotein (BSP) and osteocalcin (OCN) by 3-fold and 60-fold relative to controls after 21 days. Furthermore, there was a 3-fold increase in calcium deposition.6 These promising results suggest that these peptides may enhance bone regeneration in vivo. In this research, a study was performed in vivo to appraise this model and further apply it to other bioactive peptide mimics such as bone morphogenetic proteins (BMP) 2, 7, and 9. Surgical Grade 5 titanium (Ti6Al4V) pins were coated with the peptide molecules and implanted into Sprague Dawley Rat femurs. Biomechanical and histological analyses showed an increase in bone growth from a period of two to five weeks, which may indicate therapeutic benefits for these bioconjugates in diabetic animal models.

Comments

Research was conducted under Derek Luong, who is a graduate student in the Department of Polymer Science and Engineering. Surgeries were also conducted with Orthopaedic resident, Chad Broering.

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