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

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.

Osteoconductive and Osteoinductive Surface Modifications of Biomaterials for Bone Regeneration: A Concise Review

“…Interestingly, the coating also inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation of macrophages, leading to reduced osteoclastogenesis on the coated biomaterial and improved osseointegration of PLGA/aspirin coating at the implantation site. In turn, Ding et al [80] developed plasma-sprayed HA-coated polyethylene terephthalate (PET) ligaments with a simvastatin-chitosan coating, which significantly enhanced osteogenic differentiation of MC3T3-E1 cells by increasing the level of expression of osteogenic-related genes, including Col I, BMP-2, OC, and bALP. Developed coating had also the ability to improve osseointegration of the implant with bone tissue in vivo in a rat model.…”

Chemical Modification Strategy to Improve Biological Activity of Carbon Fiber-Reinforced Poly(ether ether ketone) Implants

“…Moreover, the synergistic effect of CPN and SIM could further improve the bioactivity, angiogenic activity, and osseointegration properties of CFRPEEK. There have been multiple papers using CS/SIM to improve bone regeneration of implant materials, the methods including spin coating, impregnation, electrospinning, electrophoretic deposition, spin-assisted layer-by-layer technique, etc. − In contrast, this study cleverly adsorbent and immobilized hydrophobic SIM through the special pore structure and carboxyl groups of CP-COOH surfaces, then prevented the rapid diffusion of SIM through covalently grafting CPN biocoating. Compared with other methods, from a design perspective, this study fully utilized the morphology and groups on the material surface.…”

Effect of chitosan/inorganic nanomaterial scaffolds on bone regeneration and related influencing factors in animal models: A systematic review

“…Chitosan has been proven to be biocompatible, biodegradable, and antibacterial with no osteoinductivity ( Lee et al, 2020 ; Mahmoud et al, 2020 ) but has a certain extent of synergistic effect with the existence of other osteogenic factors ( Mathews et al, 2011 ). Ding et al (2019b) co-cultured polyethylene terephthalate (PET)/HA membranes, which have different compositions, with mouse pre-osteoblasts and detected the expression of osteogenesis-related genes. They found that compared with the PET/HA membranes, the expression of collagen-1 (COL-1), alkaline phosphatase (ALP), and osteocalcin (OCN) was upregulated in the CS/PET/HA groups, indicating that the addition of chitosan prompted proliferation or osteogenic differentiation of cells.…”