Neural Tissue Formation Within Porous Hydrogels Implanted in Brain and
Spinal Cord Lesions: Ultrastructural, Immunohistochemical, and Diffusion
Studies.
Woerly S, Petrov P, Sykova E, Roitbak T, Simonova Z, Harvey AR
Organogel Canada Ltee, Quebec City, QC, Canada.
A biocompatible heterogeneous hydrogel of poly [N-(2-hydroxypropyl)
methacrylamide] (PHPMA), was evaluated for its ability to promote tissue
repair and enhance axonal regrowth across lesion cavities in the brain
and spinal cord in adult and juvenile (P17-P21) rats. Incorporation of
PHPMA hydrogels into surrounding host tissue was examined at the ultrastructural
level and using immunohistochemical techniques. In addition, and in parallel
to these studies, diffusion parameters (volume fraction and tortuosity
of the gel network) of the PHPMA hydrogels were evaluated pre- to postimplantation
using an in vivo real-time iontophoretic method. The polymer hydrogels
were able to bridge tissue defects created in the brain or spinal cord,
and supported cellular ingrowth, angiogenesis, and axonogenesis within
the structure of the polymer network. As a result, a reparative tissue
grew within the porous structure of the gel, composed of glial cells, blood
vessels, axons and dendrites, and extracellular biological matrices, such
as laminin and/or collagen. Consistent with matrix deposition and tissue
formation within the porous structure of the PHPMA hydrogels, there were
measurable changes in the diffusion characteristics of the polymers. Extracellular
space volume decreased and tortuosity increased within implanted hydrogels,
attaining values similar to that seen in developing neural tissue. PHPMA
polymer hydrogel matrices thus show neuroinductive and neuroconductive
properties. They have the potential to repair tissue defects in the central
nervous system by replacing lost tissue and by promoting the formation
of a histotypic tissue matrix that facilitates and supports regenerative
axonal growth.