Evaluation of novel injectable hydrogels for nucleus pulposus replacement

Abstract

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.

Scaffolding in tissue engineering: general approaches and tissue-specific considerations

“…Further enhancement in the swelling and mechanical stability of the scaffolds for nucleus or annulus replacement such as crosslinking without compromising cell viability [45] should be encouraged as these physical properties favor the restoration and maintenance of disc height. Evaluation of the mechanical properties of injectable polymers such as hyaluronic acid gel [28] and polyethylene glycol [115] against different engineering parameters should also be encouraged as replacing the mechanical function is equally important as replacing the cellular function in matrix secretion in this stage of degeneration.…”

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

“…Exciting possibilities also exist for the use of replacement total IVDs using biocompatible and biomechanically competent PLGA and PLA scaffolds seeded with AF and NP cells [88,89]. Novel injectable hydrogels which can be seeded with a number of cell types have also been developed for NP replacement strategies [111,145].…”

Tissue engineering and the intervertebral disc: the challenges

“…Spinal fusion, a commonly performed surgical procedure (200,000 spinal fusions in 2002 in the US [16]), is not an optimal treatment as it is not always successful [53] and can result in limited flexibility, in addition to possibly inducing degenerative changes in adjacent vertebrae [48,70,79]. In an attempt to preserve motion, other approaches have been developed [89] such as partial or total disc replacement [53,87,103,107,119,126]. As there are numerous clinical contraindications to artificial disc implant surgery and as the complications can be catastrophic, the confirmation of the utility of this approach awaits long term outcome data.…”