Improved osteogenic activity and inhibited bacterial biofilm formation on andrographolide-loaded titania nanotubes

Eryou Feng; Kaiwei Shen; Feitai Lin; Wentao Lin; Tao Zhang; Yiyuan Zhang; Fengfei Lin; Yun Yang; Changjian Lin

doi:10.21037/atm-20-4901

Improved osteogenic activity and inhibited bacterial biofilm formation on andrographolide-loaded titania nanotubes

Ann Transl Med. 2020 Aug;8(16):987. doi: 10.21037/atm-20-4901.

Authors

Eryou Feng¹, Kaiwei Shen¹, Feitai Lin¹, Wentao Lin¹, Tao Zhang¹, Yiyuan Zhang¹, Fengfei Lin², Yun Yang³, Changjian Lin⁴

Affiliations

¹ Department of Arthrosis Surgery, Fuzhou Second Hospital Affiliated to Xiamen University, Teaching Hospital of Fujian Medical University, Fuzhou, China.
² Department of Orthopaedics, Fuzhou Second Hospital Affiliated to Xiamen University, Teaching Hospital of Fujian Medical University, Fuzhou, China.
³ Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials Research, College of Physical Science and Technology, Xiamen University, Xiamen, China.
⁴ State Key Laboratory of Physical Chemistry of Solid Surfaces, and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.

Abstract

Background: Delivery of local drugs with a titania nanotube is an attractive approach to combat implant-related infection. Our earlier study has confirmed that nanotubes loaded with gentamicin could significantly improve the antibacterial ability. On this basis, the used andrographolide in this paper has a high antibacterial activity, which cannot only avoid the evolution of antibiotic-resistant bacteria but also has simultaneously excellent biocompatibility with osteogenic cells.

Methods: Two mg of andrographolide was loaded into titania nanotubes, which were fabricated into different diameters (50 and 100 nm) and 200 nm length by the method of lyophilization and vacuum drying. We chose a standard strain, Staphylococcus epidermidis (American Type Culture Collection 35984), and two clinical isolates, S. aureus 376 and S. epidermidis 389 to research the bacterial adhesion at 6, 12 and 24 hours and biofilm formation at 48, and 72 hours on the andrographolide-loaded nanotubes (NT-A) using the diffusion plate method. Smooth titanium (smooth Ti) and nanotubes with no drug loading (NT) were also inclusive and analyzed. Furthermore, the Sprague-Dawley (SD) rats mesenchymal stem cells were used to assess the influence of nanotubular topographies on the osteogenic differentiation of mesenchymal stem cells.

Results: Our results showed that NT-A could inhibit bacterial adhesion and biofilm formation on implant surfaces. NT-A and NT, especially those with 100 nm diameters, were found to significantly promoted cell attachment, proliferation, diffusion, and osteogenic differentiation when compared with smooth Ti, while the same diameter in NT-A and NT did not differ.

Conclusions: Titania nanotube modification and andrographolide loading can significantly improve the antibacterial ability and osteogenic activity of orthopedic implants. Nanotubes-based local delivery could be a promising strategy for combating implant-associated infection.

Keywords: Andrographolide; bacteria adhesion; biofilm formation; implant-associated infection; titania nanotubes.