Injectable Cell-Biopolymer Gels for Neural Tissue Repair

Abstract

Injury to the brain, spinal cord, the retina, and other central nervous system (CNS) tissues triggers a cascade of biochemical events that can lead to debilitating and largely irreversible consequences. Damage to the CNS results in an environment that is normally unfavorable for axonal regeneration thus preventing the repair and reestablishment of functional neural connections. An effective treatment requires a strategy that combines replacement of damaged cells, delivery of growth promoting factors, and removal or deactivation of inhibitory agents. Research reported here has been focused on development of injectable biopolymer gels to act as a favorable environment for cells that can affect neural repair. Such gels are designed to bridge the lesion site and fill the cystic cavity (e.g. for spinal cord injury) and provide a favorable terrain for regrowth of axons by delivering cells and neurotrophic factors to the site of injury. Carboxymethyl-cellulose-alginate (CMC-ALG) gels and hyaluronate-alginate (HA-ALG) gels have been prepared with varying compositions and degrees of ionic crosslinking for use as injectable cell matrices. Homogeneous, in situ-forming gels were synthesized by the gradual release of Ca ions via the reaction of calcium carbonate and glucono-delta-lactone. Gelation times were evaluated at room and physiologic temperatures and rheological properties were determined in a Paar-Physica UDS 200 rheometer with cone-and-plate geometry. The effects of composition, calcium ion concentration, and temperature on gelation time and rheology were determined. These gels, containing viable microglial, stem, or Schwann cells, are now of interest for neural repair by injection of cell-gel preparations at the site of CNS tissue damage.