Novel bilayer coating on gentamicin-loaded titanium nanotube for orthopedic implants applications

• Published in: International journal of pharmaceutics Vol. 636; p. 122764
• Main Authors: Shaygani, Hossein, Seifi, Saeed, Shamloo, Amir, Golizadeh, Mortaza, Rahnamaee, Seyed Yahya, Alishiri, Mojgan, Ebrahimi, Sina
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-04-2023
• Subjects: Alginates; Anti-Bacterial Agents - chemistry; Antibiotic controlled release; Biopolymer coating; Chitosan - chemistry; Coated Materials, Biocompatible - chemistry; Drug Implants; Gentamicins; Layer-by-layer assembly (LbL); Molecular dynamics; Nanotubes - chemistry; Orthopedic infections; Surface Properties; Titania nanotube; Titanium - chemistry; Molecular dynamics; Layer-by-layer assembly (LbL); Titania nanotube; Biopolymer coating; Orthopedic infections; Antibiotic controlled release
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.122764

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Fabricating a multifunctional orthopedic implant which prevents post-surgery infection is highly desirable in advanced materials applications. However, designing an antimicrobial implant, which simultaneously promotes a sustained drug release and satisfactory cell proliferation, remains a challenge. The current study presents a drug-loaded surface-modified titanium nanotube (TNT) implant with different surface chemistry which was developed to investigate the effect of surface coating on drug release, antimicrobial activity, and cell proliferation. Accordingly, sodium alginate and chitosan were coated on the surface of TNT implants with different coating orders through layer-by-layer assembly. The coatings' swelling ratio and degradation rate were around 613% and 75%, respectively. The drug release results showed that surface-coatings prolonged the releasing profile for about 4 weeks. Chitosan coated TNTs demonstrated greater inhibition zone at 16.33mm compared with the other samples where no inhibition zone was observed. However, chitosan and alginate coated TNTs exhibited smaller inhibition zones at 48.56mm and 43.28mm, respectively, compared to bare TNT, which can be attributed to the coatings preventing the antibiotic burst release. Higher viability of cultured osteoblast cells was observed for chitosan-coated TNT as the top layer compared to the bare TNT at 12.18%, indicating improved bioactivity of TNT implants when the chitosan has the most contact with cells. Coupled with the cell viability assay, molecular dynamics (MD) simulations were carried out by placing collagen and fibronectin near the considered substrates. In agreement with cell viability results, MD simulations also indicated that chitosan had the highest adsorption energy approximately 60Kcal/mol. In summary, the proposed bilayer chitosan-coated drug-loaded TNT implant with chitosan and sodium alginate coating as the top and the bottom layers, respectively, can be a potential candidate for orthopedic applications in the light of its bacterial biofilm prevention, better osteoconductivity, and providing an adequate drug release profile.