Anti‐Infective and Histogenic Bioscaffold for Bone Defect Repair

Abstract

The objective of this study was to develop a stable drug delivery platform that is biocompatible, biodegradable and would provide sustained combinatorial drug release for the control of bone infection while simultaneously supporting bone tissue regeneration. Chitosan has been widely used in tissue engineering and in a variety of biomedical applications due to its eco‐friendly and biodegradable properties and it possesses a physiochemistry similar to the extracellular matrix of bone. However, the application of chitosan has been limited by its inherent mechanical weakness. Halloysite nanotubes (HNTs) are a naturally‐occurring aluminosilicate clay with a hollow tubular structure. HNTs are widely used as a bulk filler to materially reinforce a variety of polymer materials from bone cement to rubber. They have also been shown to be a potent nanocontainer for the sustained release of varied bioactive factors. In this study, chitosan and HNTs and chitosan and HNTs, doped with gentamicin and BMP‐2, were combined in different wt./wt. ratios and cross‐linked with tripolyphosphate. The biodegradability, mechanical properties, and surface structure of the hybrid nanocomposites were tested. The ability of the nanocomposites to control bacterial growth while supporting bone tissue formation was also evaluated. Gentamicin was selected as a model drug to evaluate the drug release capability of the chitosan‐HNTs nanocomposites and with release, its effectiveness against E. coli was analyzed through growth inhibition studies. Results indicate that the addition of HNTs to the chitosan hydrogel significantly improved the gels’ mechanical properties, permitting an extended period of drug release, and without a negative affect on drug efficacy. The coatings were capable of inhibiting bacterial growth and osteoblasts cultured on the hydrogel surfaces showed enhanced growth and functionality. Our doped clay/chitosan nanocomposite may overcome the limitations of traditional anti‐bacterial hydrogels and its ability to support bone tissue formation may enable its use in bone defect repair results from osteomyelitis.Support or Funding InformationFunding for this project was provided by the Louisiana Governor's Biotechnology Initiative and Louisiana Board of Regents OPT‐IN program.