Medical implants are commonly known to instigate inflammatory cascade due to adverse immune reaction to foreign bodies. This might cause pain, inflammation, infection, and even implant rejection, directly affecting the quality of life of the patient. Meloxicam is a widely used selective cyclooxygenase-2 inhibitor for reducing inflammation in orthopedic patients. However, meloxicam causes gastric ulcers, which is primarily due to inhibition of cyclooxygenase-1 in the gastrointestinal tract. In addition, the recommended dosing frequency of meloxicam is multiple times a day to maintain effective plasma concentration. 316 L stainless steel has been extensively used in orthopedic implants due to its biocompatibility, resistance to corrosion, and excellent mechanical strength. Moreover, conventional manufacturing of metal implants has various limitations, such as the production of standard shapes and therefore lack the customization. However, 3D printing can provide flexibility to obtain different shapes and allows “on-demand” fabrication of patient-specific implants in a clinical environment. Therefore, multilayered biomedical surface coatings composed of meloxicam/PLGA on 3D printed stainless steel (316 L) implant was developed as it could sustain the release for a prolonged period and enhance patient compliance. A thorough examination of the safety and efficacy of biomedical coatings at the in vitro level is of paramount importance for its faster introduction to clinical trials. The surface morphology of 3D printed implants revealed a smooth, uniform, and homogenous surface without any macroscopic defects. All the coated implants showed a decrease in the surface roughness (Ra) compared to the uncoated specimens. The cumulative amount of drug release was found to be linearly proportional to the percentage of incorporated drug. Higher drug-loaded implants (20%) showed rapid release of meloxicam compared to 10% and 15% drug loaded implants. However, significant changes in the drug release profile were observed as a result of changing the thickness of the polymer. The implants with 1.5x and 2x coating thickness considerably extended the drug release for more than 30 days, confirming the capability of this approach to achieve a long and sustained drug release for effective anti-inflammatory activity. Since our objective was to not only measure but also to understand the behavior of drug release, several known models were utilized to describe the release profile. The model that was able to best-fit the majority of the data with high statistical significance was Higuchi model with R2 of 0.992. In vitro tests using human osteosarcoma (U2OS) cells revealed that substantially more osteosarcoma cells were attached to meloxicam coated stainless steel implants than to uncoated implants within first few hours of contact. This increase in cell adhesion on meloxicam coated samples may be due to the possible smoother surface with mean Ra of 44.5 µm. The cell proliferation of meloxicam coated implants was greater than the control ones and the percentage of live cells were about the same at 24h and 48h for both coated and control samples. Therefore, coating of meloxicam/PLGA on 3D printed stainless steel implants could possibly sustain the drug release, reduce the adverse drug reactions and promote tissue regeneration in orthopedic patients.
Upon completion, participants will be able to understand the significance of localized and sustained delivery of an anti-inflammatory drug from the implant surface to prevent implant rejections
Upon completion, participants will be able to describe the potential advantages of 3D printed metal implants compared to conventional manufacturing techniques
Upon completion, participants will be able to understand the significance of biomedical coatings for promoting osteointegration, fixation, and stability of orthopedic implants
Upon completion, participants will be able to understand various characterization methods ranging from chemical, biological as well as functional testing of medical devices for determining the safety and efficacy of biomedical coatings