Influence of cross-linked hyaluronic acid hydrogels on neurite outgrowth and recovery from spinal cord injury.
OBJECTIVE
Therapies that use bioactive materials as replacement extracellular matrices may hold the potential to mitigate the inhibition of regeneration observed after central nervous system trauma. Hyaluronic acid (HA), a nonsulfated glycosaminoglycan ubiquitous in all tissues, was investigated as a potential neural tissue engineering matrix.


METHODS
Chick dorsal root ganglia were cultured in 3D hydrogel matrices composed of cross-linked thiol-modified HA or fibrin. Samples were cultured and images were acquired at 48-, 60-, and 192-hour time points. Images of all samples were analyzed at 48 hours of incubation to quantify the extent of neurite growth. Cultures in crosslinked thiolated HA exhibited more than a 50% increase in neurite length compared with fibrin samples. Furthermore, cross-linked thiolated HA supported neurites for the entire duration of the culture period, whereas fibrin cultures exhibited collapsed and degenerating extensions beyond 60 hours. Two concentrations of the thiolated HA (0.5 and 1%) were then placed at the site of a complete thoracic spinal cord transection in rats. The ability of the polymer to promote regeneration was tested using motor evoked potentials, retrograde axonal labeling, and behavioral assessments. There were no differences in any of the parameters between rats treated with the polymer and controls.


CONCLUSIONS
The use of a cross-linked HA scaffold promoted robust neurite outgrowth. Although there was no benefit from the polymer in a rodent spinal cord injury model, the findings in this study represent an early step in the development of semisynthetic extracellular matrice scaffolds for the treatment of neuronal injury.
Horn
Eric M
EM
Harrington Department of Bioengineering, Arizona State University, Tempe, USA.
Beaumont
Michael
M
Shu
Xiao Zheng
XZ
Harvey
Adrian
A
Prestwich
Glenn D
GD
Horn
Kris M
KM
Gibson
Alan R
AR
Preul
Mark C
MC
Panitch
Alyssa
A
D000818:Animals; D002642:Chick Embryo; D003432:Cross-Linking Reagents; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology; D008297:Male; D016501:Neurites / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods
D003432:Cross-Linking Reagents; D020100:Hydrogels; D013438:Sulfhydryl Compounds; D005337:Fibrin; D006820:Hyaluronic Acid