A drug eluting, osseointegrative phospholipid coating for orthopedic implants
Date
2011
Authors
Prawel, David A., author
James, Susan P., advisor
Popat, Ketul C., advisor
Kipper, Matt J., committee member
Ryan, Stewart D., committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Millions of implant surgeries are performed each year. Titanium is commonly used for implantable metallic devices, especially total hip and knee replacements. However, titanium implants are far from perfect. Although the absolute failure rate is not particularly high, the case-by-case direct and human cost of each device implant failure is tremendous. Cementless titanium implant devices, although preferred by surgeons, frequently fail due to loosening of the device, often as a result of poor integration of naturally forming bone with the metallic implant, and by infection. Phospholipids are naturally occurring substances that are shown to enhance integration of new bone with implants, and to help reduce inflammation, a common precursor to infection. In addition, numerous studies have shown phospholipids to be effective drug delivery agents. To date, dip and drip coating techniques for applying phospholipid coatings have been used on titanium. Both coating techniques are easy to perform, but result in coatings too thick and non-conformal for in vivo use. Electro-spraying (E-spray) is a method of atomizing a liquid by means of electrical forces. E-spraying provides the advantage of being able to create coatings with relatively high efficiencies because the electrical charge difference "carries" the liquid source material, which also provides good control of coating morphology, especially on rough and intricately shaped surfaces. Other advantages of this technique are low cost and easy setup. In our work, the E-spraying technique was successfully adapted to apply thin, conformal, consistent coatings of 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) to small, flat, commercially pure titanium plates. DOPS coatings were E-sprayed, then loaded with gentamicin sulfate (GS), a popular antibiotic used in treatment of osteomyelitis. An elution study was completed to assess drug delivery capabilities of the coatings. This work demonstrated that elution profile could be modified by changing E-spray parameters. Rat marrow stromal cells were harvested, and seeded onto the test coatings. Mesenchymal stem cells (MSCs) were selected from the general cell population, successfully cultured and differentiated into osteoblasts. Cytotoxicity of the coatings, along with cell viability, cell differentiation, biomineralization activity, cell morphology and early osseogenesis markers were evaluated at multiple time points in dual multi-week studies. DOPS coatings were found to be non-cytotoxic, and cell viability and biomineralization were higher on DOPS-coated surfaces and gentamicin-loaded coatings than on plain titanium samples. At the two week time point, excessive delamination of the coatings occurred in the cell growth environment. Research was undertaken to identify and test techniques to enhance coating retention. Surface chemistry was modified by passivation and pretreatment with calcium-chloride, and cholesterol was added to the DOPS E-spray. A repeated elution study demonstrated that elution profile could be modified as a result of changes in coating chemistry. An additional MSC cell study was completed to reconfirm the effects of enhanced coating chemistry on the cytotoxicity, cell viability and biomineralization. Cell morphology was re-evaluated at all time points via SEM imaging. Hydroxyapatite formation was confirmed. Preliminary osseogenesis biomarkers were also measured, showing deposition of osteocalcin and osteopontin, important protein precursors to normal bone growth, on enhanced coatings. This work demonstrates the viability of electro-sprayed DOPS coatings on titanium orthopedic implant material, and the enhanced osseogenic characteristics of these coatings. We also demonstrated that DOPS coatings can carry and release an antibiotic over time at clinically relevant dosages, and that this release profile can be engineered by modifications to E-spray process parameters, surface chemistry and E-sprayed material formulation.
Description
Rights Access
Subject
coatings
drug delivery
electrospray
implants
osseogenesis
phospholipid