Handcrafted multilayer PDMS microchannel scaffolds for peripheral nerve regeneration

Abstract

Injuries that result in the loss of limb functionality may be caused by the severing of the peripheral nerves within the affected limb. Several bioengineered peripheral nerve scaffolds have been developed in order to provide the physical support and topographical guidance necessary for the naturally disorganized axon outgrowth to reattach to distal nerve stumps as an alternative to other procedures, like nerve grafting. PDMS has been chosen for the base material of the scaffolds due to its biocompatibility, flexibility, transparency, and well-developed fabrication techniques. The process of observing the axon outgrowth across the nerve gaps with PDMS scaffolds has been challenging due to the limited number and fineness of longitudinal sections that can be extracted from harvested nerve tissue samples after implantation. To address this, multilayer microchannel scaffolds were developed with the object of providing more refined longitudinal observation of axon outgrowth by longitudinally 'sectioning' the device during fabrication, removing the need for much of the sample preparation process. This device was then implanted into the sciatic nerves of Lewis rats, and then harvested after two and four weeks to analyze the difference in nerve regeneration between two different time periods. The present layer by layer structure, which is separable after nerve regeneration and is treated as an individual layer during the histology process, provides the details of biological events during axonal regeneration. Confocal microscopic imaging showed the details of peripheral nerve regeneration including nerve branches and growth cones observable from within the microchannels of the multilayer PDMS microchannel scaffolds.

An Implantable Peripheral Nerve Recording and Stimulation System for Experiments on Freely Moving Animal Subjects

“…Neural interfacing systems in general, and particularly those at the periphery, have significantly benefited from recent advancements in technologies for safe communication pathways with the external world. The acquired data from efferent nerves and motor potential in the peripheral nervous system (PNS) is interpreted to provide meaningful behavior patterns, a variety of sensing feedbacks 1 – 3 , or to monitor restoration of motor and sensory functions in patients with spinal cord injuries 4 – 6 . The relatively new concept of “electroceuticals,” which suggests using electrical stimulation of peripheral nerves that control various organs, such as heart and lever, as a substitute for traditional drugs, to achieve a desired outcome, such as adjusting the blood pressure or glucose level, has generated new interest in interfacing with PNS 7 – 9 .…”

“…1b . The new system offers several advantages in the study of the sciatic nerve in terms of enabling long-term in vivo experiments without requiring the animal to carry batteries, lowering the risk of infections by eliminating the headstage transcutaneous connector, and eliminating the potential damage to the surrounding tissue by the long microwire bundle that was needed to connect the target peripheral nerves to the headstage, in addition to reducing the time and complexity of the surgical procedure 6 . The proposed system creates an enriched environment inside the standard homecage for inductively-powered peripheral nerve experiments without adding the burden of carrying large payloads by the freely behaving animal subjects, while eliminating long cables both inside and outside the animal body.…”

“…The proposed system creates an enriched environment inside the standard homecage for inductively-powered peripheral nerve experiments without adding the burden of carrying large payloads by the freely behaving animal subjects, while eliminating long cables both inside and outside the animal body.

Figure 1 Comparison between two configurations of an animal study involving peripheral nerve interface with sciatic nerve in rat model: ( a ) conventional battery-powered recording/stimulation headstages 6 , and ( b ) inductively-powered WINeRS-8 system in the wirelessly-powered EnerCage-HC2 arena.

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“… Comparison between two configurations of an animal study involving peripheral nerve interface with sciatic nerve in rat model: ( a ) conventional battery-powered recording/stimulation headstages 6 , and ( b ) inductively-powered WINeRS-8 system in the wirelessly-powered EnerCage-HC2 arena. …”

Handcrafted Microwire Regenerative Peripheral Nerve Interfaces with Wireless Neural Recording and Stimulation Capabilities

“…Previously, we developed 4-electrode and 8-electrode microwire regenerative peripheral nerve interfaces (µPNI) [21][22][23][24][25][26]. Here we report an advanced generation of the 16-electrode µPNI and even further advanced the µPNI with wireless communication capabilities.…”