Neural tissue formation within porous hydrogels implanted in brain and spinal cord lesions: ultrastructural, immunohistochemical, and diffusion studies.
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. () ()
Woerly
S
S
Organogel Canada Ltée, Québec City, QC, Canada.
Petrov
P
P
Syková
E
E
Roitbak
T
T
Simonová
Z
Z
Harvey
A R
AR
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D001672:Biocompatible Materials; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D003712:Dendrites / Q000648:ultrastructure; D004058:Diffusion; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000293:injuries / Q000648:ultrastructure; D020100:Hydrogels / Q000737:chemistry; D008854:Microscopy, Electron; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D009457:Neuroglia / Q000648:ultrastructure; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D014945:Wound Healing / Q000187:drug effects*
D001672:Biocompatible Materials; D020100:Hydrogels; D011109:Polymethacrylic Acids; C011533:Duxon