Engineered implantable nanotechnology sensor and electrically-controlled release of antibiotic and anti-inflammatory drugs using polypyrrole films electrodeposited on titanium for orthopedic implants.

摘要

The development of electrochemical sensors and responsive drug delivery systems are current challenges in the field of orthopedics. Micro and nanotechnology enable the development of dynamic systems that integrate an external signal in response to a biological environment within a living system. This research included the development and examination of: (i) multiwalled carbon nanotubes (MWCNTs) grown out of anodized nanotubular titanium (MWCNT-Ti) to sense bone growth, biofilm formation, or scar tissue growth next to an implant in situ, and (ii) a biodegradable and electroactive conductive polymer (polypyrrole, PPy) to deliver antibiotic (penicillin/streptomycin) and anti-inflammatory (dexamethasone) drugs through the application of voltage to increase implant efficacy based on information from (i). Importantly, MWCNT-Ti enhanced the redox reaction of ferri/ferrocyanide and of the proteins synthesized by osteoblasts (bone-forming cells) remaining cytocompatible with osteoblasts and even enhancing osteoblast differentiation (alkaline phosphatase activity and calcium deposition) after 21 days of culture in vitro when compared to anodized nanotubular Ti and commercially pure Ti. Penicillin/streptomycin (P/S) and dexamethasone (Dex) were embedded simultaneously during the electrodeposition of PPy films on such materials. The PPy doped drugs enhanced osteoblast adhesion and proliferation, in vitro, whereas they inhibited fibroblast (fibrous-tissue forming cells) adhesion and proliferation when compared to conventional Ti. Both drugs (P/S and Dex) were released at about 80% of their initial concentration into PBS buffer after applying 5 cycles of cyclic voltammetry (CV) from -1 V to 1 V with scan rate of 100 mV/s. The bioactivity of P/S and Dex was confirmed by analyzing bacteria (Staphylococcus epidermidis ) and macrophages (inflammatory and immune-response cells) functions in vitro, before and after electrically-triggered release. After 5 CV cycles, the P/S releases decreased the number of Staphylococcus epidermidis after 1 and 12 hours, while the Dex releases decreased the macrophage adhesion after 8 and 13 hours. Results showed that MWCNTs and conductive PPy were cytocompatibility with osteoblasts, and that these conducting bio-nanomaterials can be integrated with electronic devices for the development of an implantable closed-loop sensing and therapeutic system for orthopedic applications.