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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. () ()

A biocompatible heterogeneous hydrogel of poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) showing an open porous structure, viscoelastic properties similar to the neural tissue and a large surface area available for cell interaction, was evaluated for its ability to promote tissue repair and axonal regeneration in the transected rat spinal cord. After implantation, the polymer hydrogel could correctly bridge the tissue defect, from a permissive interface with the host tissue to favour cell ingrowth, angiogenesis and axonal growth occurred within the microstructure of the network. Within 3 months the polymer implant was invaded by host derived tissue, glial cells, blood vessels and axons penetrated the hydrogel implant. Such polymer hydrogel matrices which show neuroinductive and neuroconductive properties have the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost of tissue.

Spinal cords of adult cats were transected and subsequently reconnected with the biocompatible porous poly (N-[2-hydroxypropyl] methacrylamide) hydrogel, NeuroGel. Tissue repair was examined at various time points from 6-21 months post reconstructive surgery. We examined two typical phenomena, astrogliosis and scar formation, in spines reconstructed with the gel and compared them to those from transected non-reconstructed spines. Confocal examination with double immunostaining for glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) showed that the interface formed between the hydrogel and the spine stumps did prevent scar formation and only a moderate gliosis was observed. The gel implant provided an adequate environment for growth of myelinated fibers and we saw angiogenesis within the gel. Electron microscopy showed that regenerating axons were myelinated by Schwann cells rather than oligodendrocytes. Moreover, the presence of the gel implant lead to a considerable reduction in damage to distal caudal portions of the spine as assessed by the presence of more intact myelinated fibers and a reduction of myelin degradation. Neurologic assessments of hindlimb movement at various times confirmed that spinal cord reconstruction was not only structural but also functional. We conclude that NeuroGel lead to functional recovery by providing a favorable substrate for regeneration of transected spinal cord, reducing glial scar formation and allowing angiogenesis.

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There is currently a lack of effective ways to achieve functional tissue repair of the chronically injured spinal cord. We investigated the potential of using NeuroGel, a biocompatible polymer hydrogel, to induce a reconstruction of the rat spinal cord after chronic compression-produced injury. NeuroGel was inserted 3 months after a severe injury into the post-traumatic lesion cavity. Rats were placed in an enriched environment and the functional deficits were measured using the BBB rating scale. A significant improvement in the mean BBB scores was observed. Rats without enriched environment and severely injured rats with an enriched environment alone showed no improvement; however, 7 months after reconstructive surgery using NeuroGel, a reparative neural tissue had formed within the polymer gel that included myelinated axons and dendro-dendritic contacts. NeuroGel implantation into a chronic spinal cord injury therefore resulted in tissue reconstruction and functional improvement, suggesting that such an approach may have therapeutic value in the repair of focal lesions in humans.

This study examined the ability of NeuroGel, a biocompatible porous poly [N-(2-hydroxypropyl) methacrylamide] hydrogel, to establish a permissive environment across a 3 mm gap in the cat spinal cord in order to promote tissue reconstitution and axonal regeneration across the lesion. Animals with NeuroGel implants were compared to transection-only controls and observed for 21 months. The hydrogel formed a stable bridge between the cord segments. Six months after reconstructive surgery, it was densely infiltrated by a reparative tissue composed of glial cells, capillary vessels and axonal fibres. Axonal labelling and double immunostaining for neurofilaments and myelin basic protein, showed that descending supraspinal axons of the ventral funiculus and afferent fibres of the dorsal column regenerated across the reconstructed lesion. Fifteen months after reconstructive surgery, axons had grown, at least, 12 mm into the distal cord tissue, and in the rostral cord there was labelling of neurons of the intermediate gray matter. Electron microscopy showed that after 9 months, most of the regenerating axons were myelinated, principally by Schwann cells. Newly formed neurons presumably from precursor cells of the ependyma and/or migrating neurons were observed within the reparative tissue after 21 months. Results indicate that functional deficit, as assessed by treadmill training, and morphological changes following double transection of the spinal cord can be modified by the implantation of NeuroGel. This technology offers the potential to promote the formation of a neural tissue equivalent via a reparative neohistogenesis process, that facilitates and supports regenerative growth of axons.