Three-dimensional cellulose-hydroxyapatite nanocomposite enriched with dexamethasone loaded metal-organic framework: a local drug delivery system for bone tissue engineering

Abstract

Three-dimensional cellulose-hydroxyapatite nanocomposite integrated with dexamethasone loaded metal organic framework (HA/DMOF) has been synthesized as a local drug delivery system for bone tissue engineering. Initially, in situ dexamethasone encapsulated metal-organic frameworks (DMOFs) were developed and characterized. The synthesized DMOFs are 60-80nm in size with rhombohedral morphology. Results showed that nearly 16% dexamethasone (Dex) was loaded in DMOFs. These synthesized DMOF nanoparticles were efficiently integrated with carboxymethyl cellulose-hydroxyapatite nanocomposite for the development of three dimensional localized drug delivery system, namely, HA/DMOF. The synthesized HA/DMOF nanocomposite was structurally characterized using various techniques. The mechanical properties of HA/DMOFs were also measured by means of compression test. It was found that the compressive strength and compressive modulus of HA/DMOF nanocomposite are 16.31.57MPa and 0.54 +/- 0.073GPa respectively, which are in the range of cancellous bone. In-vitro release behaviour of Dex from both DMOFs and HA/DMOFs was examined in phosphate buffered solution. It was found that Dex molecules have been released very slowly from HA/DMOF nanocomposite compared to DMOF nanoparticles, and it was sustained for 4weeks. Cytocompatibility of HA/DMOF nanocomposite was evaluated against pre-osteoblast MC3T3 cells. It was found that the synthesized HA/DMOF nanocomposite is compatible to MC3T3 cells. Moreover, the ALP activity and extracellular mineralization capability of cells were enhanced when cultured with HA/DMOF nanocomposite. Results showed that the synthesized HA/DMOF nanocomposite is a promising material for possible therapeutic as well as load-bearing orthopedic applications.