Advances in Biomimetic Nerve Guidance Conduits for Peripheral Nerve Regeneration

Abstract

Injuries to the peripheral nervous system are a common clinical issue, causing dysfunctions of the motor and sensory systems. Surgical interventions such as nerve autografting are necessary to repair damaged nerves. Even with autografting, i.e., the gold standard, malfunctioning and mismatches between the injured and donor nerves often lead to unwanted failure. Thus, there is an urgent need for a new intervention in clinical practice to achieve full functional recovery. Nerve guidance conduits (NGCs), providing physicochemical cues to guide neural regeneration, have great potential for the clinical regeneration of peripheral nerves. Typically, NGCs are tubular structures with various configurations to create a microenvironment that induces the oriented and accelerated growth of axons and promotes neuron cell migration and tissue maturation within the injured tissue. Once the native neural environment is better understood, ideal NGCs should maximally recapitulate those key physiological attributes for better neural regeneration. Indeed, NGC design has evolved from solely physical guidance to biochemical stimulation. NGC fabrication requires fundamental considerations of distinct nerve structures, the associated extracellular compositions (extracellular matrices, growth factors, and cytokines), cellular components, and advanced fabrication technologies that can mimic the structure and morphology of native extracellular matrices. Thus, this review mainly summarizes the recent advances in the state-of-the-art NGCs in terms of biomaterial innovations, structural design, and advanced fabrication technologies and provides an in-depth discussion of cellular responses (adhesion, spreading, and alignment) to such biomimetic cues for neural regeneration and repair.

An Adaptable Drug Delivery System Facilitates Peripheral Nerve Repair by Remodeling the Microenvironment

“…In general, the diameter of axons can fall within the range of 4–16 μm, with fascicles potentially containing only a few to several hundred axons. The thickness of the epineurium varies from 1 to 100 μm, depending on the specific nerve and its location, making it exceedingly challenging to determine optimal channel size that accurately mimics the fascicle anatomy . It has been noticed that the relatively large pore diameter of fillers seemed more favorable to encouraging functional regeneration.…”

“…The thickness of the epineurium varies from 1 to 100 μm, depending on the specific nerve and its location, making it exceedingly challenging to determine optimal channel size that accurately mimics the fascicle anatomy. 72 It has been noticed that the relatively large pore diameter of fillers seemed more favorable to encouraging functional regeneration. Axons growing longitudinally in alginate hydrogels exhibited a higher density when the scaffold pore size was increased, with the greatest axon density observed at the range of 71−86 μm.…”

Multichannel Conduits with Fascicular Complementation: Significance in Long Segmental Peripheral Nerve Injury

“…The incorporation of fascicular architecture to the nerve conduits provides a confined environment and accelerates the nerve regeneration process. 9 Thus, the exact size matching of fascicles at the injured site is crucial for successful functional re-establishment. Yan et al observed promising functional restoration and end-organ innervation during autologous nerve transplantation with exact fascicular matching on rat models of a 15 mm sciatic nerve defect.…”

“…The number of fascicles increases at the level of branching, and their magnitude becomes thinner as they reach the joints. The incorporation of fascicular architecture to the nerve conduits provides a confined environment and accelerates the nerve regeneration process . Thus, the exact size matching of fascicles at the injured site is crucial for successful functional re-establishment.…”

Conductive and alignment-optimized porous fiber conduits with electrical stimulation for peripheral nerve regeneration

“…The NGC effectively isolates the regenerated nerve axon from surrounding scar tissue, therefore preventing compression of the nerve by adjacent tissues [ 6 ]. Additionally, the NGC plays a crucial role in accurately directing nascent neural tissue towards its intended target organ [ 7 ].…”