101
Views
7
CrossRef citations to date
0
Altmetric
Original Research

Encapsulation of a nanoporous simvastatin-chitosan composite to enhance osteointegration of hydroxyapatite-coated polyethylene terephthalate ligaments

, , , , &
Pages 4881-4893 | Published online: 04 Jul 2019
 

Abstract

Purpose

This study was designed to evaluate the in vitro and in vivo biocompatibility and osteointegration of plasma-sprayed hydroxyapatite (HA)-coated polyethylene terephthalate (PET) ligaments encapsulated with a simvastatin (SV)-chitosan (CS) composite.

Methods

This study compared the in vitro and in vivo bone responses to three different PET ligaments: SV/CS/PET-HA, CS/PET-HA and PET-HA. A field emission scanning electron microscope was used to characterize the morphology, and the in vitro SV release profile was analyzed. MC3T3 cells were cocultured with SV/CS/PET-HA, CS/PET-HA and PET-HA to test their biocompatibility using CCK-8 tests. Osteogenic differentiation was investigated by the expression of marker genes using qPCR. Osteointegration was performed by implanting the PET ligaments into the proximal tibia bone tunnels of male Sprague-Dawley rats for 3 weeks and 6 weeks. The bone-implant interface was evaluated by micro-computed tomography (micro-CT) and histological analysis.

Results

The characteristic nanoporous structures mainly formed on the surface of the plasma-sprayed HA particles in the SV/CS/PET-HA and CS/PET-HA groups. The SV release test showed that the sustained release of simvastatin lasted for 25 days in the SV/CS/PET-HA group. The in vitro studies demonstrated that the SV/CS/PET-HA ligaments induced osteogenic differentiation in the MC3T3 cells, with higher mRNA expression levels of collagen-1, bone morphogenetic protein-2, osteocalcin and alkaline phosphatase than those in the CS/PET-HA and PET-HA ligament groups. The in vivo tests showed that both micro-CT analysis (bone mineral density and bone volume per total volume) and histological analysis (bone implant contact and interface area) revealed significantly higher peri-implant bone formation and less interface area in the SV/CS/PET-HA group than in the other groups.

Conclusion

The SV-CS composite nanoporous structure was associated with the improved biocompatibility and osteogenic differentiation in vitro and enhanced osteointegration process in vivo of plasma-sprayed HA-coated PET ligaments.

Acknowledgments

This work was supported by National Key R&D Program of China (2016YFC1100300, 2017YFC0840100 and 2017YFC0840106), National Natural Science Foundation of China (No. 81572108 and No. 81772339), The Key Clinical Medicine Center of Shanghai (2017ZZ01006), Sanming Project of Medicine in Shenzhen (SZSM201612078), Shanghai Rising-Star Project (18QB1400500) and The Introduction Project of Clinical Medicine Expert Team for Suzhou (SZYJTD201714), Development Project of Shanghai Peak Disciplines-Integrative Medicine (20180101) and Shanghai Committee of Science and Technology (19441901600 and 19441902000).

Disclosure

The authors report no conflicts of interest in this work.