Garland Fussell

Synthesis and recovery characteristics of branched and grafted PNIPAAm–PEG hydrogels for the development of an injectable load-bearing nucleus pulposus replacement

A family of injectable poly(N-isopropyl acrylamide) (PNIPAAm) copolymer hydrogels has been fabricated in order to tune mechanical properties to support load-bearing function and dimensional recovery for possible use as load-bearing medical devices, such as a nucleus pulposus replacement for the intervertebral disc. PNIPAAm-polyethylene glycol (PEG) copolymers were synthesized with varying hydrophilic PEG concentrations as grafted or branched structures to enhance dimensional recovery of the materials. Polymerizations were confirmed with attenuated total reflectance-Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy studies. Incorporation of PEG was effective in raising water content of pure PNIPAAm hydrogels (29.3% water for pure PNIPAAm vs. 47.7% for PEG branches and 39.5% for PEG grafts). PNIPAAm with 7% grafted as well as 7% branched PEG had significantly reduced compressive modulus compared to that of pure PNIPAAm. Initially recovered compressive strain was significantly increased for 7% PEG branches after pre-testing immersion in PBS for up to 33 days, while 7% PEG grafts decreased this value. Sample height recovery for pure PNIPAAm was limited to 31.6%, while PNIPAAm with 7% branches was increased to 71.3%. When mechanically tested samples were allowed to recover without load over 30 min, each composition was able to significantly recover height, indicating that the time to recovery is slower than the unloading rates typically used in testing. While the incorporation of hydrophilic PEG was expected to alter the mechanical behavior of the hydrogels, only the branched form was able to significantly enhance dimensional recovery.

The effect of protein-free versus protein-containing medium on the mechanical properties and uptake of ions of PVA/PVP hydrogels.

The effect of two simulated biological environments (protein-free and protein-containing) on ion uptake and physical properties of PVA/PVP hydrogels were explored in this work. It was found that over the immersion period in both media, wet mass of the hydrogels decreased and compressive moduli increased, likely due to increased polymer content with water loss as the hydrogels equilibrated with water. These changes were independent of polymer content and immersion medium. However, dry mass of the hydrogels increased dramatically when immersed in protein-free medium, changing only moderately in protein-containing medium. The increase in dry mass was attributed to ion uptake from immersion medium, as confirmed by EDXA. We postulate that differences between ion uptake in protein-free versus protein-containing medium is likely the result of serum proteins in the proteincontaining medium adsorbing to the surface, inhibiting transport of ions into the hydrogel.

Synthesis and characterization of injectable bioadhesive hydrogels for nucleus pulposus replacement and repair of the damaged intervertebral disc

Bioadhesive polymers are natural or synthetic materials that can be used for soft tissue repair. The aim of this investigation was to develop an injectable, bioadhesive hydrogel with the potential to serve as a synthetic replacement for the nucleus pulposus of the intervertebral disc or as an annulus closure material. Branched copolymers of poly(N-isopropylacrylamide) (PNIPAAm) and poly(ethylene glycol) (PEG) were blended with poly(ethylene imine) (PEI). This three component injectable system can form a precipitated gel at physiological temperature due to the phase transition of PNIPAAm. The injection of glutaraldehyde into the gel core will adhere the implant to the surrounding tissues. (1)H NMR results indicated the successful physical incorporation of PEI into the PNIPAAm-PEG network by blending. In addition, the covalent crosslinking between the amine functionalities on the PEI and the aldehyde functionalities on the glutaraldehyde was verified using FTIR difference spectroscopy. Mechanical characterization of these blends showed a significant increase (p < 0.05) in compressive modulus following glutaraldehyde injection. The in vitro bioadhesive force studies with porcine skin showed a significant increase (p < 0.05) in the mean maximum force of detachment for PNIPAAm-PEG/PEI gels when glutaraldehyde was injected into the gel core. The results of this study indicate that the reactivity between amines and aldehyde functionalities can be exploited to impart bioadhesive properties to PNIPAAm-PEG/PEI copolymers.