Category: Formulation and Quality
Purpose: Bone implants are inevitable treatment options for complicated bone fracture surgery. There is an increasing interest in natural, semi-synthetic and synthetic polymeric biomaterials as three-dimensional (3D) polymeric scaffolds. Despite of exhibiting controllable degradation, good mechanical properties and precise modification tendency, synthetic polymeric scaffolds cannot be as bioactive as natural polymers. The main challenge in synthetic implants is the inadequate degree of biocompatibility. Natural polymers like gelatin, chondroitin sulfate, chitosan etc. seem to have an edge over synthetic polymers in term of biocompatibility and easy biodegradation. The installation of bone implants on the site of injury is bound to trigger immune cascade and inflammatory mediators which is alleviated with applications of natural polymers. The incorporation of such polymers on implants might provide ample opportunities to regulate the drug release without focusing on the complications of their residence at the site of action. In this work, 3D Printed 316L metal implants loaded with dexamethasone were produced through spray coating, in order to serve the purpose of avoiding inflammation that can occur after surgery. The applications of 3D printing allow custom modification of implants per requirement with alterations in shape, size and porosity to achieve the controlled release with optimized dose as per personalized treatment approach.
Methods: The metal implants specimens were prepared from 316L Stainless Steel using layer by layer approach of additive manufacturing in Renishaw AM 250 printer (Laser beam powder bed fusion system). The line roughness and surface porosity variables of the specimens were noted using Keyence microscopy technique (Keyence Digital Microscope VHX-6000). Dexamethasone (1 mg per implant) was deposited on surface by using airbrush spray coating followed by evaporation of the organic solvent. Gelatin and chondroitin sulfate aqueous solutions were prepared in various concentrations, coated simultaneously one after another and allowed to dry before addition of successive layers (1,2). The coacervate film is formed by electrostatic attraction between gelatin and chondroitin sulfate in the presence of crosslinking agent like glutaraldehyde (3). The final film over metal surface was characterized for its thickness by Keyence microscopy. The release of drug from the implant was carried out in vitro using PBS:Ethanol (9:1) release media over a period of 6 days to determine the drug elution profiles of implants. The whole media was replaced at each time point with fresh media and analyzed using UV-Spectrophotometric analysis. The steel implants after release studies were soaked in coacervate film digestion media (Acetonitrile-water containing collagenase/Calcium Chloride) overnight to detect the residual amount of drug present in the implant.
Results: The content uniformity of the drug loaded on implant was 87.34%±8.6 (n=9) (Table 1). This assures the reproducibility of coating method to provide uniformity of the polymer deposition and drug content deposition. The thickness of the top layer was observed to be 247.4µ±9.39 (n=9) using Keyence Microscope to ensure the homogeneous coating throughout the length of the surface (Figure 1). The initial burst release of 16%±0.9 (n=4) was observed in first two hours whereas 54.96%±2.31 of cumulative release was achieved in first 24 hours. The two successive batches showed similar release profile with almost all the drug released within 6 days (Figure 2).
Conclusion: Through this study, we were successful to optimize the drug loading of dexamethasone and polymer coating parameters on the rough surface of 3D printed 316L Stainless Steel implants. Sustained release of dexamethasone was achieved for a week period and the release profile was reproducible in successively coated batches with comparable surface roughness. These promising in vitro results have created an urge of in vivo investigation of such 3D printed implants and their application in large animals such as horses.
Manjusha Annaji– Student, Auburn University, Auburn, Alabama
Jayachandra Babu Ramapuram– Professor, Auburn University, Harrison School of Pharmacy, Department of Drug Discovery and Development, Auburn, Alabama
Robert Arnold– Auburn, Alabama
Amal Kaddoumi– Auburn, Alabama
Nima Shamsaei– Auburn, Alabama
Masoud Samani– Auburn, Alabama
Kayla Corriveau– Auburn, Alabama