Xinfeng Shi

In vivo biocompatibility of ultra-short single-walled carbon nanotube/biodegradable polymer nanocomposites for bone tissue engineering

Scaffolds play a pivotal role in the tissue engineering paradigm by providing temporary structural support, guiding cells to grow, assisting the transport of essential nutrients and waste products, and facilitating the formation of functional tissues and organs. Single-walled carbon nanotubes (SWNTs), especially ultra-short SWNTs (US-tubes), have proven useful for reinforcing synthetic polymeric scaffold materials. In this article, we report on the in vivo biocompatibility of US-tube reinforced porous biodegradable scaffolds in a rabbit model. US-tube nanocomposite scaffolds and control polymer scaffolds were implanted in rabbit femoral condyles and in subcutaneous pockets. The hard and soft tissue response was analyzed with micro-computed tomography (micro CT), histology, and histomorphometry at 4 and 12 weeks after implantation. The porous US-tube nanocomposite scaffolds exhibited favorable hard and soft tissue responses at both time points. At 12 weeks, a three-fold greater bone tissue ingrowth was seen in defects containing US-tube nanocomposite scaffolds compared to control polymer scaffolds. Additionally, the 12 week samples showed reduced inflammatory cell density and increased connective tissue organization. No significant quantitative difference in polymer degradation was observed among the various groups; qualitative differences between the two time points were consistent with expected degradation due to the progression of time. Although no conclusions can be drawn from the present study concerning the osteoinductivity of US-tube nanocomposite scaffolds, the results suggest that the presence of US-tubes may render nanocomposite scaffolds bioactive assisting osteogenesis.

Injectable in situ cross-linkable nanocomposites of biodegradable polymers and carbon nanostructures for bone tissue engineering.

This study investigates the effects of nanostructure size and surface area on the rheological properties of un-cross-linked poly(propylene fumarate) (PPF) nanocomposites and the mechanical properties of cross-linked nanocomposites as a function of the nanostructure loading. Three model carbon nanostructures were examined, C60 fullerenes, ultra-short single-walled carbon nanotubes (US-tubes) and single-walled carbon nanotubes (SWNTs). Rheological measurements showed that C60 and US-tube un-cross-linked nanocomposites exhibited viscous-like characteristics with the complex viscosity independent of frequency for nanostructure concentrations up to 1 wt%. Compressive and flexural mechanical testing demonstrated significant mechanical reinforcement of US-tube and SWNT nanocomposites as compared to cross-linked polymer alone, with an up to twofold increase in the mechanical properties. Scanning electron microscopy examination of the fracture surface of cross-linked US-tube nanocomposite revealed lack of aggregation of US-tubes. Although sol fraction studies did not provide any evidence of additional cross-linking, due to the presence of US-tubes in the nanocomposites, transmission electron microscopy studies suggested the crystallization of PPF on the surface of US-tubes which can contribute to the mechanical reinforcement of the US-tube nanocomposites. These results demonstrate that the rheological properties of un-cross-linked nanocomposites depend mainly on the carbon nanostructure size, whereas the mechanical properties of the cross-linked nanocomposites are dependent on the carbon nanostructure surface area. The data also suggest that US-tube nanocomposites are suitable for further consideration as injectable scaffolds for bone tissue engineering applications.

Magnetic resonance imaging studies on gadonanotube-reinforced biodegradable polymer nanocomposites

We report about the in vitro cytotoxicity and MRI studies of Gd(3+)ions-doped ultra-short single-walled carbon nanotube (gadonanotubes), gadonanotubes- reinforced poly(lactic-co-glycolic acid) (PLGA) polymer nanocomposites and in vivo small animal MRI studies using the gadonanotubes. These studies were performed to explore the suitability of gadonanotubes-reinforced PLGA polymer nanocomposite as a model scaffold for noninvasive magnetic resonance imaging (MRI) to evaluate nanotube release during the degradation process of the scaffold and their biodistribution upon release from the polymer matrix in vivo. The gadonanotubes at 1-100 ppm and the gadonanotubes/PLGA nanocomposites (2 wt % gadonanotubes) did not show any cytotoxicity in vitro as demonstrated using the LIVE/DEAD viability assay. For the first time, r(2) relaxivity measurements were obtained for the superparamagnetic gadonanotubes. In vitro 7T MRI of the superparamagnetic gadonanotubes ([Gd] = 0.15 mM) suspended in a biocompatible 1% Pluronic F127 solution, gave a r(2) value of 578 mM(-1) s(-1). Upon subcutaneous injection of the gadonanotubes suspension into the dorsal region of rats, the high r(2) value translated into excellent and prolonged negative contrast enhancement of in vivo T(2)weighted proton MRI images. The in vitro characterization of the nanocomposite discs and their degradation process by MRI, showed strong influence of the gadonanotube on water proton relaxations. These results indicate that the gadonanotubes/PLGA nanocomposites are suitable for further in vivo studies to track by MRI the biodegradation release and biodistribution of gadonanotubes.