Load bearing regenerative repairs for the cartilaginous soft tissue of the intervertebral disc

Abstract

Cartilaginous load bearing soft tissues such as the nucleus pulposus in the intervertebral disc are affected by degenerative diseases and physical injury, which if not treated early can initiate a progressive decline in joint function and result in lower back pain. Early treatment options to repair the nucleus pulposus, regain immediate joint function, and aid in the regeneration of de novo tissue are necessary to restore the health and function of symptomatic joints. To satisfy the regenerative design criteria, a cellular hydrogel based approach was chosen and methods were examined to improve mechanical properties while maintaining an injectable and in situ formable scaffold. To improve the stiffness and fatigue resistance of the hydrogels, low molecular weight acrylated star-copolymers composed of D,L-lactide or trimethylene carbonate with caprolactone were mixed with an aqueous solution of methacrylated glycol chitosan to form a hydrogel-elastomer co-continuous morphology. After photo-cross-linking, the elastomer phase contributed the majority of the initial stiffness to the co-continuous scaffolds. Hydrolysis of the elastomer phase, controlled the decrease in the co-continuous scaffold modulus from fast (2 – 3 weeks) to slow (> 2 months) by changing D,L-lactide to trimethylene carbonate in the -caprolactone based elastomers. The slower degrading trimethylene carbonate based elastomer phase was able to maintain an approximate 1200 kPa equilibrium modulus in the co-continuous scaffolds during a 2 month in vitro static culture. Methacrylated prepolymers of glycol chitosan, hyaluronic acid, chondroitin sulfate and their blends were examined to improve the initial mechanical properties of the hydrogels and maintain the phenotype of the encapsulated chondrocytes during culture. A co-cross-linked mixture of methacrylated prepolymers, hyaluronic acid and chondroitin sulfate, had an initial equilibrium modulus of 260 kPa, which was maintained along with the highest number of the originally seeded cells (60 %) and cartilaginous matrix accumulation compared to the other hydrogels during a 1 month in vitro static culture. Overall, the development of the co-continuous hydrogel-elastomer morphology was able to produce an injectable cell encapsulating scaffold with an initial modulus greater than 1 MPa and demonstrated regenerative potential that would be suitable for the repair of cartilaginous load bearing soft tissues.