An update–tissue engineered nerve grafts for the repair of peripheral nerve injuries

Abstract

Peripheral nerve injuries (PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts (ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts (TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems (DDS), co-administration of platelet-rich plasma (PRP), and pretreatment with chondroitinase ABC (Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix (ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia (DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair

“…Many grafts have been developed to facilitate nerve regeneration and sustain a pro-regenerative environment in the distal segment. 33,[41][42][43][44][45][46] However, there has been limited focus on the ability for a graft to influence the intrinsic regenerative capacity of the proximal neuron. To the best of our knowledge, this is the first study to investigate the effect of different peripheral nerve repair strategies on the proximal neuron health and regenerative capacity.…”

The Success and Failure of the Schwann Cell Response to Nerve Injury

“…Because of this, most human nerve injuries involve chronic denervation of the more distal parts of damaged nerves and of the target tissues such as muscle. This results in target atrophy, while neurons gradually die and surviving neurons may fail to sustain their capacity to regenerate axons during the extended period required for repair (Höke, 2006a; Sulaiman and Gordon, 2013; Patel et al, 2018).…”

Restoration of Neurological Function Following Peripheral Nerve Trauma

“…Veins are promising as conduits [167,168]. Clinically, empty vein conduits appear to have a 3-cm-long limit for their ability to induce axon regeneration [169].…”