Abstract
Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome may be enhanced by bio-scaffolds specifically fabricated to provide the appropriate three-dimensional (3D) conduit, growth-permissive substrate, and trophic factor support required for cell survival and regeneration. In rodents, these scaffolds have been shown to promote axonal regrowth and restore limb motor function following experimental spinal cord or sciatic nerve injury. Combining the appropriate cell/exosome and scaffold type may thus achieve tissue repair and regeneration with safety and efficacy sufficient for routine clinical application. In this review, we describe the efficacies of bio-scaffolds composed of various natural polysaccharides (alginate, chitin, chitosan, and hyaluronic acid), protein polymers (gelatin, collagen, silk fibroin, fibrin, and keratin), and self-assembling peptides for repair of nerve injury. In addition, we review the capacities of these constructs for supporting in vitro cell-adhesion, mechano-transduction, proliferation, and differentiation as well as the in vivo properties critical for a successful clinical outcome, including controlled degradation and re-absorption. Finally, we describe recent advances in 3D bio-printing for nerve regeneration.
Highlights
The major focus of modern tissue engineering is repair and regeneration of the central nervous system (CNS) and peripheral nervous system (PNS) as these tissues have limited inherent regenerative potential in mammals [2], but numerous challenges remain before routine clinical application
Natural polymers used as structural components include various polysaccharides such as alginate, hyaluronic acid, chitin, and chitosan, and polymeric proteins such as gelatin, collagen, silk fibroin, fibrin, and keratin [29,30]
Many bio-scaffolds have been investigated for therapeutic efficacy using a wide array of nerve injury models
Summary
Tissue engineering combines findings from cell biology and material science to mimic the physical and chemical conditions of native tissue with the aim of functional restoration following injury [1]. Ideal scaffor 2D and 3D cell culture [4] and drug loading [5], and have demonstrated some value folds must possess the ability to replace damaged tissues with exogenous (transplanted) for tissue regeneration in various preclinical models [6,7]. For ability to replace damaged tissues with exogenous (transplanted) or endogenous cells of example, nerve damage is common following limb or head trauma and is frequently irrethe correct tissue architecture for functional restoration [8]. One major reason for this irreversibility is the absence of a is common following limb or head trauma and is frequently irreversible or difficult to growth-permissive environment following injury, so biocompatible scaffold materials are treat [9].
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