Biocompatible polymer coatings for implants in the peripheral nervous system : in vivo study of polymer-coated microbeads in the rat sciatic model
Background: Implants in the peripheral nervous system (PNS) can potentially restore sensory feedback, improve motor control and alleviate phantom-limb pain in upper-limb amputees. However, nervous system implants have poor long-term function and biocompatibility when implanted into the body due to foreign body reaction. Dendrimer (DND) and Poly-D-Lysine (PDL) are two synthetic polymers with properties that could improve the performance of these interfaces. In my masters’ research, my objective is to determine whether these synthetic polymers could promote the formation of presynaptic elements on artificial surfaces in vivo making intraneural implants more biocompatible and long-lasting. Methods: In the coated microsphere in vivo experiment, a nerve crush injury model in the rat was used for the study. PDL-coated, DND-coated and uncoated beads were injected into the rat sciatic nerve at the crush site and 5 mm distal to the crush site. The nerves were then harvested after 4, 6 and 8 weeks and stained for neurofilament and synaptophysin. Synaptophysin puncta were then counted on the bead surface for each group. Additionally, in a proof-of-concept experiment, two uncoated electrodes were implanted into the rat sciatic nerve. Nerve recordings were then performed every week, and the threshold nerve potential in the sciatic nerve was measured by only varying the pulse duration of the stimulation. Results: The coated microsphere in vivo experiment demonstrated that DND-coated microspheres had a significantly higher number of synaptophysin puncta around their surface from 4 to 8 weeks compared to uncoated beads. At 4 weeks, the DND condition also showed a significantly higher number of synaptophysin puncta around its microbeads vs. the PDL condition for the distal site. In the uncoated electrode in vivo experiment, the results showed that the two implants could stimulate and record threshold nerve potentials in the rat sciatic nerve for one week and two weeks respectively before being non-functional. Conclusion: Our study showed for the first time that DND has a stable synapse-promoting property that is superior to PDL in vivo and that our electrode design can be used to assess the long-term signal stability of peripheral nerve implants.
Lysine Synthetic Polymers Foreign Body Reaction Microspheres Synaptophysin Nerve Crush Amputees Peripheral Nervous Injuries Intraneural Electrodes