Biomaterial-Based Schwann Cell Transplantation and Schwann Cell-Derived Biomaterials for Nerve Regeneration

Abstract

Schwann cells (SCs) dominate the regenerative behaviors after peripheral nerve injury by supporting axonal regrowth and remyelination. Previous reports also demonstrated that the existence of SCs is beneficial for nerve regeneration after traumatic injuries in central nervous system. Therefore, the transplantation of SCs/SC-like cells serves as a feasible cell therapy to reconstruct the microenvironment and promote nerve functional recovery for both peripheral and central nerve injury repair. However, direct cell transplantation often leads to low efficacy, due to injection induced cell damage and rapid loss in the circulatory system. In recent years, biomaterials have received great attention as functional carriers for effective cell transplantation. To better mimic the extracellular matrix (ECM), many biodegradable materials have been engineered with compositional and/or topological cues to maintain the biological properties of the SCs/SCs-like cells. In addition, ECM components or factors secreted by SCs also actively contribute to nerve regeneration. Such cell-free transplantation approaches may provide great promise in clinical translation. In this review, we first present the current bio-scaffolds engineered for SC transplantation and their achievement in animal models and clinical applications. To this end, we focus on the physical and biological properties of different biomaterials and highlight how these properties affect the biological behaviors of the SCs/SC-like cells. Second, the SC-derived biomaterials are also reviewed and discussed. Finally, the relationship between SCs and functional biomaterials is summarized, and the trends of their future development are predicted toward clinical applications.

Multimodular Bio-Inspired Organized Structures Guiding Long-Distance Axonal Regeneration

“…Biohybrid approaches for neural tissue engineering seem to have better results in terms of functional recovery in comparison with purely material-based constructs [ 40 ]. SC have demonstrated to enhance axonal growth in vitro [ 41 ] and to regenerate nerves in combination with implants [ 35 , 42 ], and even in the CNS they proved to support the recovery of spinal cord function [ 43 ]. The regeneration of tract-like axon structures demands bridging sometimes long distances directing axon growth in an ordered way.…”

Clinical Trials Targeting Secondary Damage after Traumatic Spinal Cord Injury

“…In general, biomaterials have been demonstrated to increase cell survival during [ 199 , 359 ] and after [ 200 , 360 ] injection into the spinal cord, which correlated with improved functional outcomes [ 361 , 362 , 363 ]. Furthermore, biomaterial scaffolds have been developed that can better maintain cell phenotypes of adhered cells, including MSCs [ 364 ], SCs [ 365 ], and NS/PCs [ 366 ]. Such promising preclinical results have led researchers to initiate clinical trials investigating the safety and efficacy of biomaterial-mediated cell transplantation after SCI.…”

“…Autologous nerve grafts, often derived from the peripheral sural nerve, represent another scaffold with potential to enhance the therapeutic effects of cell transplants after SCI. While not yet approved for clinical use, therapeutic strategies based on providing SCs or SC-laden autologous nerve grafts have been largely effective at treating PNS injuries [ 365 , 367 ]. In a study with a small number of patients with chronic SCI, safety and modest functional improvements were reported with transplantation of autologous sural nerve grafts and OECs [ 228 ] or BM-MSCs [ 368 ].…”

Development and In Vitro Differentiation of Schwann Cells

“…Often, these materials can be further micropatterned and/or functionalized. A detailed overview of the biomaterials used and how their properties affect Schwann cell biology has been provided in recent reviews [ 359 , 360 , 361 ].…”