Development of injec table nanocomposite scaffolds of single -walled carbon nanotubes and biodegradable polymers for bone tissue engineering
Mikos, Antonios G.
Doctor of Philosophy
Nanocomposites based on single-walled carbon nanotubes (SWNTs) and poly(propylene fumarate) (PPF) were developed and characterized as injectable scaffold materials for bone tissue engineering. Similar to other synthetic biodegradable polymers, PPF lacks the mechanical properties required for regeneration of load-bearing bone tissue. SWNTs were applied as reinforcing agents because of their extremely high mechanical properties and aspect ratio. An effective load transfer from polymer matrix to SWNTs is needed for the mechanical reinforcement, which is challenged by the strong inter-tube aggregation of large SWNT bundles. Various methods including mechanical agitation, sonication, use of surfactants, and chemical functionalizations have been utilized to homogeneously disperse SWNTs in PPF. Characterized by melt-state rheology, mechanical testing, and electron microscopy, functionalized SWNTs (F-SWNTs) demonstrated excellent dispersion in PPF and a 2- to 3-fold increase in compressive and flexural mechanical properties with only 0.1 wt% loading concentration when compared to pure PPF. Another form of SWNTs, ultra-short SWNTs (US-tubes) with 20-80 nm length, demonstrated up to a 2-fold increase in mechanical properties over pure PPF and resulted in a less viscous nanocomposite for easier injection than uncut SWNTs. The in vitro cytocompatibility of these nanocomposites was evaluated based on cell response to their unreacted components, crosslinked networks, and degradation products. The results did not reveal any cytotoxicity for purified SWNTs, F-SWNTs, and US-tubes at 1-100 μg/mL concentrations. All three tested nanocomposites displayed nearly 100% cell viability and excellent cell attachment, indicating favorable cytocompatibility. Finally, scaffolds with porosity of 75-90 vol% were fabricated from nanocomposites of US-tubes and functionalized US-tubes using a thermal-crosslinking particulate-leaching technique. These highly porous scaffolds possessed nearly 100% interconnected pore structures. Mechanical properties of nanocomposite scaffolds were higher than or similar to those of PPF scaffolds for all the porosities examined. In vitro osteoconductivity of these nanocomposite scaffolds was supported by the excellent attachment and proliferation of bone marrow stromal cells. These results indicate the great potential of injectable SWNT/PPF nanocomposites as the basis for bone tissue engineering scaffolds.