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.

A series of F127–gelatin composite hydrogels with reverse thermo-responsive and tunable mechanical properties were developed.

N-Cadherin is a transmembrane glycoprotein that plays a crucial role in the condensation of mesenchymal cells by enhancing cell–cell interactions during the process of chondrogenesis. The biophysical and biochemical signals can incite enhanced cell–cell contact which ultimately determines the fate of stem cells. The role of cadherin mimetic peptides on the differentiation of mesenchymal stem cells is obscure and must be explored in greater detail. In this study, we designed and synthesized a series of bioactive peptide sequences that mimic the EC-1 domain of the cadherin peptide sequence His-Ala-Val (HAV) motif. These peptide hydrogelators can self-assemble into stable supramolecular nanofibrous hydrogels at physiological pH in the presence of Fmoc-diphenylalanine (2) with tunable mechanical stiffness. Human mesenchymal stem cells (3A6) were encapsulated in N-cadherin mimetic peptide hydrogels to evaluate their role in stem cell differentiation and chondrogenesis. The results suggested that these peptide hydrogels are nontoxic to 3A6 cells and promoted chondrogenesis. Interestingly, 3A6 cells exposed to Fmoc-GGHAVDI (1d) peptide solution showed an enhanced expression level of chondrogenic specific marker collagen-II (Col-II) in comparison with other peptide sequences. In contrast, when 3A6 cells were encapsulated in the hydrogel blend (2/1c), the peptide sequence with flanking amino acid serine exhibited greater material stiffness with enhanced glycosaminoglycan (GAG) distribution and high expression levels of chondrogenic specific markers for the cartilage-specific matrix. This suggests that substrate stiffness and peptide sequences can influence stem cell differentiation. The hydrogel with the HAV motif with greater substrate stiffness (2/1c) can promote the chondrogenic differentiation of human mesenchymal stem cells which can be a promising candidate for 3D cell culture and stem cell-based cartilage regeneration therapies.