Juyi Li1 Clement Marmorat1 Yeshayahu Talmon1 Raphael Davis1 Miriam Rafailovich1

1, Stony Brook University, Stony Brook, New York, United States

The role of synovial fluids is to enable frictionless motion of joints and provide shock absorbance within the spinal cord for the central nervous system. Injury, disease, and even aging can degrade the structure and mechanical response of the fluid. Here we report on engineering a substitute for the nucleus pulposus, the viscous fluid within the spinal cord discs. Herniation of lumbar discs is a painful condition, which often requires surgical intervention, where the nucleus pulposus is removed and the disc space is fused. Recently hydrogels have been proposed as possible replacements. Yet, despite a great deal of effort, several major challenges must be overcome; The materials are tough and yet injectable and extremely flexible, biocompatible and yet non-adhesive and resistive to enzymatic degradation. Consequently a variety of chemically cross linked synthetic gels or viscous natural hydrogels have not been successful. Here we report on the use of Pluronic physical gels, which we have successfully bioprinted, injected, and shown to prevent scarring and degradation in-vivo in dog trials. The results were very surprising since, despite their tremendous mechanical flexibility, these tri-block copolymers are very sensitive to fluid volume changes. We demonstrate, using SEM microscopy on gel cryo-sections, together with in-situ x-ray analysis, that in addition to the standard parameters defining the equilibrium state, the stability of physical gels is dependent on the dynamical aspects of the fluid medium. Using a specially constructed flow chamber, we show that for a Pluronic F127 physical gel, the degradation process can be greatly reduced under high fluid flow rate tangential to the gel surface. Since the physical gel is formed by an ordered crystal of micelles, stabilized by entanglements within their coronas, a simple model is proposed where swelling can occur only when the flow rate is less that the reptation time. Otherwise, rather than dissociating into individual micelles, the micelle gel responds collectively to the surface shear forces as an elastic solid, which deforms in a direction perpendicular to the flow in order to minimize stress. This aspect of the Pluronic triblock copolymer system greatly extends their application from an injectable drug delivery carrier to a structural component which is at once injectable, and yet able to sustain deformation and resist dissolution in physical fluids.

[1] Bhatnagar, Divya, Miriam Rafailovich, and Raphael Davis. "Methods Useful in Optimizing the Treatment of Neuropathies and Targeting Tissues with Cosmetic Botulinum Injections." U.S. Patent Application No. 13/463,766.