Bone Morphogenetic Protein-2 (BMP-2) is a growth factor in the TGF-β cytokine family, among other ubiquitous effects in development, it promotes bone mineralization by inducing osteoblast differentiation from precursor cells. This effect is the basis of its use as a therapeutic in procedures such as spinal fusion. However, because of its ubiquitous nature, side effects such as inflammation and swelling of surrounding tissues can be seen when the amount of BMP-2 implanted and released is not regulated. In the extracellular space, BMP-2 has numerous endogenous binding proteins. Among these is secreted phosphoprotein 24 (spp24). This protein can be modified in hopes of isolating the residues necessary to bind with BMP-2. This binding protein and its peptide derivatives can be used to modulate the release of BMP-2. Using a collagen sponge as a

delivery vehicle, the rate and pattern of release can be analyzed. Collagen sponges can serve as tissue engineering scaffolds that can host cell growth. An analysis of growth factor release from implantable collagen sponges cannot ignore the effect of ingrowth of osteoblast precursor cells. To study BMP-2 release modulation by spp24 with cellular response as an output, a perfusion bioreactor can be used. Perfusion bioreactors immerse a scaffold in growth media, delivering nutrients and gases permitting cell growth. In the bioreactor efflux, the release of BMP-2 from the sponge can be quantified. A BMP-2 scaffold-bioreactor system has the advantage of being sufficiently well-characterized in terms of parameters to the point where simulation is possible. Furthermore, the designed bioreactor can be fabricated to verify the predictions made by simulation. Finally, the BMP-2 SMAD pathway can be used to create a cellular model to predict the response generated by BMP-2 release.

In light of their escalating exposure to possible environmental toxicants, there are many biological systems that need to be evaluated in a resource and time efficient manner. Understanding how toxicants behave in relation to their physicochemical properties and within complex biological media is especially important toward developing a stronger scientific foundation of these systems so that adequate regulatory decisions may be made. While there are many emerging methods available for the detection and characterization of these chemicals, nanotechnology has presented itself as a promising alternative toward creating more efficient assays. In particular, metallic nanoparticles and thin films exhibit unique optical properties that allow for highly sensitive and multiplexed studies to be performed. These plasmonic materials often preclude the use of molecular tags and labels, enabling direct characterizations and enhancing the throughput of biomolecular studies. However, their lack of specificity toward certain targets and potential toxicity has thus far precluded their widespread use in toxicity testing.

The cell membrane, a natural signal transducer, represents one of the fundamental structures for biological recognition and communication. These interfaces principally function as a selective barrier to exogenous materials, including ions, signaling molecules, growth factors, and toxins; therefore, understanding interactions at membrane interfaces is a vital step in elucidating how biological responses are effected. Supported lipid bilayers, which may easily be tailored in composition and complexity, are ideal interfaces for coupling to plasmonic assays since they may be supported in close proximity to metallic nanoparticles and thin films, where measurements are most sensitive. This research will focus on the coupling of plasmonic materials and biomimetic interfaces to increase the sensitivity, efficiency, and throughput of conventional toxicity assays. The fabrication of new plasmonic materials for membrane-based assays is presented, as well as method developments in membrane array formation and opportunities for hyphenation with complementary analytical techniques.

Background: Medicare reimbursement to hospitals for spinal fusion surgery is provided as a fixed payment for each admission based on Diagnosis Related Group (DRG). This system is predicated on the assumption that patients can be grouped into relatively homogenous units of resource use such that a single payment will adequately cover the costs of inpatient hospitalization for most patients within a given DRG. However, a previous study in total joint arthroplasty (TJA) showed that variation within DRGs can lead to differences between hospital costs and Medicare reimbursement, resulting in predictable financial losses to hospitals and hindering access to care for some patients. No study to our knowledge has investigated cost variation within current spinal fusion DRGs.

Aims: The aims of this thesis are to investigate cost variation within spinal fusion DRGs to determine whether variation within these groups meets an acceptable standard and to propose alternative spinal fusion DRGs, defined according to surgical invasiveness, that attempt to decrease the cost variation within current spinal fusion DRGs.

Methods: Direct hospital costs were obtained from the 2011 Nationwide Inpatient Sample (NIS) using cost-to-charge ratios. Our primary outcome was the coefficient of variation (CV), defined as the ratio of the standard deviation (SD) to the mean (CV=SD/mean x 100), for all hospital costs within a given DRG. CVs for spinal fusion DRGs (453-460) were compared to an established benchmark of TJA “DRG 209” (aggregate of DRGs [466-470]) to determine if cost variation within current spinal fusion DRGs is, in fact, “acceptable.” We then modified a previously validated measure of surgical invasiveness and used it to re-categorize patients into new spinal fusion DRGs. Finally, we calculated the CV for these new DRGs to determine if this re-categorization resulted in a decrease in cost variation relative to existing spinal fusion DRGs.

Results: CV for costs within spinal fusion DRGs ranged from 44.16 for DRG 460 (spinal fusion except cervical w/o CC/MCC) to 52.6 for DRG 456 (spinal fusion except cervical w spinal curvature/malignancy/infection or 9+ fusion levels with MCC). The benchmark group, DRG 209, was found to have a CV of 38.2. The CVs for costs within spinal fusion DRGs were all significantly higher than the benchmark group (p < 0.0001). Re-categorizing patients into new DRGs according to surgical invasiveness resulted in a decrease in CV for costs within most groups.

Discussion: Our findings demonstrate that cost variation within current spinal fusion DRGs is unacceptably high. As in TJA, this variation may be leading to differences between costs and reimbursement that places undue financial burden on some hospitals and potentially compromises access to care for some patients. Re-categorizing patients into new DRGs according to surgical invasiveness results in decreased cost variation and may offer an alternative strategy for defining spinal fusion payment groups that ensures more equitable hospital reimbursement and improved patient access to care.