Immune-cell-mediated tissue engineering strategies for peripheral nerve injury and regeneration.

During the process of peripheral nerve repair, there are many complex pathological and physiological changes, including multi-cellular responses and various signaling molecules, and all these events establish a dynamic microenvironment for axon repair, regeneration, and target tissue/organ reinnervation. The immune system plays an indispensable role in the process of nerve repair and function recovery. An effective immune response not only involves innate-immune and adaptive-immune cells but also consists of chemokines and cytokines released by these immune cells. The elucidation of the orchestrated interplay of immune cells with nerve regeneration and functional restoration is meaningful for the exploration of therapeutic strategies. This review mainly enumerates the general immune cell response to peripheral nerve injury and focuses on their contributions to functional recovery. The tissue engineering-mediated strategies to regulate macrophages and T cells through physical and biochemical factors combined with scaffolds are discussed. The dynamic immune responses during peripheral nerve repair and immune-cell-mediated tissue engineering methods are presented, which provide a new insight and inspiration for immunomodulatory therapies in peripheral nerve regeneration.

IKVAV functionalized oriented PCL/Fe3O4 scaffolds for magnetically modulating DRG growth behavior.

The re-bridging of the deficient nerve is the main problem to be solved after the functional impairment of the peripheral nerve. In this study, a directionally aligned polycaprolactone/triiron tetraoxide (PCL/Fe3O4) fiber scaffolds were firstly prepared by electrospinning technique, and further then grafted with IKVAV peptide for regulating DRG growth and axon extension in peripheral nerve regeneration. The results showed that oriented aligned magnetic PCL/Fe3O4 composite scaffolds were successfully prepared by electrospinning technique and possessed good mechanical properties and magnetic responsiveness. The PCL/Fe3O4 scaffolds containing different Fe3O4 concentrations were free of cytotoxicity, indicating the good biocompatibility and low cytotoxicity of the scaffolds. The IKVAV-functionalized PCL/Fe3O4 scaffolds were able to guide and promote the directional extension of axons, the application of external magnetic field and the grafting of IKVAV peptides significantly further promoted the growth of DRGs and axons. The ELISA test results showed that the AP-10 F group scaffolds promoted the secretion of nerve growth factor (NGF) from DRG under a static magnetic field (SMF), thus promoting the growth and extension of axons. Importantly, the IKVAV-functionalized PCL/Fe3O4 scaffolds could significantly up-regulate the expression of Cntn2, PCNA, Sox10 and Isca1 genes related to adhesion, proliferation and magnetic receptor function under the stimulation of SMF. Therefore, IKVAV-functionalized PCL/Fe3O4 composite oriented scaffolds have potential applications in neural tissue engineering.