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.

Evaluation of novel injectable hydrogels for nucleus pulposus replacement.

Branched copolymers composed of poly(N-isopropylacrylamide) (PNIPAAm) and poly(ethylene glycol) (PEG) are being investigated as an in situ forming replacement for the nucleus pulposus of the intervertebral disc. A family of copolymers was synthesized by varying the molecular weight of the PEG blocks and molar ratio of NIPAAm monomer units to PEG branches. Gel swelling, dissolution, and compressive mechanical properties were characterized over 90 days and stress relaxation behavior over 30 days immersion in vitro. It was found that the NIPAAm to PEG molar ratio did not affect the equilibrium swelling and compressive mechanical properties. However, gel elasticity exhibited a dependency on both the PEG block molecular weight and content. The equilibrium gel water content increased and compressive modulus decreased with increasing PEG block size. While all of the branched copolymers showed significant increases in stress relaxation time constant compared to the homopolymer (p < 0.05), the high PEG content PNIPAAm-PEG (4600 and 8000 g/mol) exhibited the maximum elasticity. Because of its high water content, requisite stiffness and high elastic response, PNIPAAm-PEG (4600 g/mol) will be further evaluated as a candidate material for nucleus pulposus replacement.