Natural Medicinal Drug Delivery from 3D Printed Scaffold and Surface Modified TI6AL4v Implants for Chemoprevention, Osteogenesis and Anti-inflammation for Bone Tissue Engineering Application
The objective of this research is to understand the role of natural medicinal compounds (NMCs) in bone tissue engineering application by modifying their release kinetics from the porous 3DP scaffold, evaluating their in vitro osteoblast (hFOB) proliferating and osteosarcoma (MG-63) preventing efficacy, and investigating their effect on osteogenesis, anti-inflammation and wound healing in rat distal femur model.Curcumin, although exhibit excellent antioxidant, anti-inflammatory, anticancer and osteogenic activities, suffers from extremely poor bioavailability. To enhance its bioavailability and to provide higher release, poly-(I? -caprolactone) (PCL), poly-ethylene-glycol (PEG) and poly-lactide-co-glycolide (PLGA) is used as the polymeric system to enable the continuous release of curcumin from the hydroxyapatite matrix for 22 days. The presence of curcumin in interconnected 3DP TCP scaffolds results in enhanced bone formation after 6 weeks in rat distal femur model. Complete mineralized bone formation increases from 29.6% to 44.9% in curcumin-coated scaffolds compared to control. In a follow-up study, we have further improved the bioavailability of curcumin by encapsulating it in a liposome, followed by the incorporation onto 3DP TCP scaffolds with designed porosity. Interestingly, liposomal curcumin released from the 3DP scaffold shows significant cytotoxicity towards MG-63 cells, while it promoted hFOB cell viability and proliferation. Presence of genistein, a soy-isoflavone shows a 90% reduction in vitro MG-63 cell viability and proliferation after 11 days, while, daidzein, another primary isoflavone, promotes in vitro hFOB cellular activities in both static and dynamic cell culture. In vitro H&E staining confirms controlled co-delivery of soy-isoflavones from the 3DP scaffold significantly reduces inflammatory cell recruitment at the surgery site after 24 hours of implantation in a rat distal femur model.Another more stable form of calcium phosphate, hydroxyapatite (HA) is utilized as a coating on metallic orthopedic implants for load-bearing applications. Coated implants are loaded with curcumin and vitamin K2, which enhances in vitro hFOB cell activities, while lowers in vitro MG-63 cell proliferation after 3, 7 and 11 days. Modified Masson Goldner staining of the tissue-implant section shows an improved contact between tissue and implant in dual drug-loaded HA-coated Ti implants compared to control implants in in vitro rat distal femur model
