Synthetic hydrogel guidance channels facilitate regeneration of adult rat brainstem motor axons after complete spinal cord transection

Synthetic guidance channels or tubes have been shown to promote axonal regeneration within the spinal cord from brainstem motor nuclei with the inclusion of agents such as matrices, cells, or growth factors to the tube. We examined the biocompatibility and regenerative capacity of synthetic hydrogel tubular devices that were composed of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA). Two PHEMA-MMA channels, having a mean elastic modulus of either 177 or 311 kPa were implanted into T8-transected spinal cords of adult Sprague Dawley rats. The cord stumps were inserted into the channels and fibrin glue was applied to the cord-channel interface. An expanded polytetrafluoroethylene (ePTFE) membrane was used for duraplasty. Controls underwent cord transection alone. Gross and microscopic examination of the spinal cords showed continuity of tissue within the synthetic guidance channels between the cord stumps at 4 and 8 weeks. There was a trend towards an increased area and width of bridging neural tissue in the 311-kPa guidance channels compared to the 177-kPa channels. Neurofilament stained axons were visualized within the bridging tissue, and serotonergic axons were found to enter the 311-kPa channel. Retrograde axonal tracing revealed regeneration of axons from reticular, vestibular, and raphe brainstem motor nuclei. For both channels, there was minimal scarring at the channel-cord interface, and less scarring at the channel-dura interface compared to that observed next to the ePTFE. The present study is the first to show that axons from brainstem motor nuclei regenerated in unfilled synthetic hydrogel guidance channels after complete spinal cord transection

Growth factor enhancement of peripheral nerve regeneration through a novel synthetic hydrogel tube

Object. The authors’ long-term goal is repair of peripheral nerve injuries by using synthetic nerve guidance devices that improve both regeneration and functional outcome relative to an autograft. They report the in vitro processing and in vivo application of synthetic hydrogel tubes that are filled with collagen gel impregnated with growth factors.Methods. Poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (PHEMA-MMA) porous 12-mm-long tubes with an inner diameter of 1.3 mm and an outer diameter of 1.8 mm were used to repair surgically created 10-mm gaps in the rat sciatic nerve. The inner lumen of the tubes was filled with collagen matrix alone or matrix supplemented with either neurotropin-3 at 1 g/ml, brain-derived neurotrophic factor at 1 g/ml, or acidic fibroblast growth factor (FGF-1) at 1 or 10 g/ml. Nerve regeneration through the growth factor–enhanced tubes was assessed at 8 weeks after repair by histomorphometric analysis at the midgraft level and in the nerve distal to the tube repair. The tubes were biostable and biocompatible, and supported nerve regeneration in more than 90% of cases. Nerve regeneration was improved in tubes in which growth factors were added, compared with empty tubes and those containing collagen gel alone (negative controls). Tubes filled with 10 g/ml of FGF-1 dispersed in collagen demonstrated regeneration comparable to autografts (positive controls) and showed significantly better regeneration than the other groups.Conclusions. The PHEMA-MMA tubes augmented with FGF-1 in their lumens appear to be a promising alternative to autografts for repair of nerve injuries. Studies are in progress to assess the long-term biocompatibility of these implants and to enhance regeneration further

Characterization of neural stem cells on electrospun poly(epsilon-caprolactone) submicron scaffolds: evaluating their potential in neural tissue engineering

Development of biomaterials with specific characteristics to influence cell behaviour has played an important role in exploiting strategies to promote nerve regeneration. The effect of three-dimensional (3D) non-woven electrospun poly(ε-caprolactone) (P

Biomaterials for Brain Tissue Engineering

Neurological disorders such as traumatic brain injuries or stroke result in neuronal loss and disruption of the brain parenchyma. Current treatment strategies are limited in that they can only mitigate the degeneration process or alleviate the symptoms but do not reverse the condition. In contrast, regenerative cell-based therapies offer long-term hope for many patients. Bioactive scaffolds are likely to reinforce the success of cell replacement therapies by providing a microenvironment that facilitates the survival, proliferation, differentiation, and connectivity of transplanted and/or endogenous cells. This Review outlines various biomaterials (including hydrogels, self-assembling peptides, and electrospun nanofibres) that have been investigated for the repair of brain tissue, and discusses strategies for the immobilization of biomolecules. An overview of the potential clinical applications of such scaffolds in neurodegenerative diseases is also provided

Tissue engineered alternatives to nerve transplantation for repair of peripheral nervous system injuries

To date the best regenerative strategies to repair peripheral nerve injuries (PNI) have used peripheral nerve grafts.[1] However, this strategy is inherently flawed, requiring that a second injury be created to harvest the tissue for the primary injury repair. A better strategy would be to prepare a synthetic graft that mimics the properties of a peripheral nerve graft. Non-nerve biologic tissue and synthetic biodegradable material as bridges for neural repair have been utilized for over a century (reviewed by Doolabh et al [2]). Although offering considerable promise, artificial conduits have had only limited success, possibly due to their simple design and the lack of multiple stimuli of regeneration. In developing a bioengineered nerve graft, we have been systematically investigating a number of strategies to optimize nerve regeneration through tubular devices. We report our initial results with the use of bioengineered nerve grafts for repair of PNI in a rat model