Exosome-Loaded Bioscaffolds for Spinal Cord Injuries: A Review

Abstract

Exosomes are naturally occurring cellular products released by various cell types in the body. Their composition is similar to that of human tissues, which reduces the risk of immune rejection. As critical mediators of intercellular communication, exosomes transmit signals and information that regulate the physiological states of surrounding tissues. Depending on their cellular origin and molecular content, exosomes can either promote nerve regeneration and functional recovery at the site of spinal cord injury (SCI) or exacerbate the local injury microenvironment. However, as a cellular product, the composition and function of exosomes are affected by the type and state of the cells from which they originate, and thus, there may be specificity problems in treatment, such as the possible instability of the therapeutic effect, et cetera. Moreover, exosomes need to be further optimized in terms of their delivery and release strategies in order to improve the duration and stability of the therapeutic effect. Thus, a single therapy approach is often insufficient to effectively support nerve repair following SCI. Numerous studies have demonstrated that encapsulating exosomes within biomaterial scaffolds enhances their delivery and retention at the injury site, thereby improving their viability. This paper reviews the latest research on stem cell-derived exosomes and biomaterials in the context of SCI. It further explores the combined application of exosomes and biomaterial scaffolds in SCI treatment, while also addressing the associated challenges and future prospects.

Keywords: biological material; exosomes; inflammatory reaction; neural repair; spinal cord injury; stem cells.

Figure 1

Exosomes derived from stem cells can be combined with hydrogels, nanospheres, 3D printed scaffolds, and graphene materials to treat spinal cord injuries, respectively. The image was produced by BioRender.com.

Figure 2

Therapeutic efficacy of exosomes from different MSCs in the treatment of SCI. MSCs can be obtained from bone marrow, dental pulp, umbilical cord, amniotic membrane, and adipose tissue. Exosomes derived from MSCs have anti-inflammatory and antiapoptotic effects and inhibit A1 astrocytes, promote axonal regeneration and macrophage polarization, and protect the blood–brain barrier. The image was produced by BioRender.com.

Figure 3

Gel-Exo facilitates recovery of complete SCI. (A) Gel-Exo SEM analysis. (B) Gel-Exo's representative stress–strain curve. (C) Postoperative weight changes. (D) BMS walking scores in the open field of mice with different treatments after SCI over the course of 8 weeks. ⁣^∗p  < 0.05 and ⁣^∗∗p  < 0.01 in comparison with SCI group. (E) Analysis of electrophysiology in mice under different treatments. (F) Amplitudes of MEPs: 3.23 ± 2.34, 3.52 ± 3.51, and 25.76 ± 5.65 μV for SCI, gel, and gel-Exo groups, respectively. ⁣^∗p  < 0.05 and ⁣^∗∗p  < 0.01, respectively, when compared with the SCI or Gel group. (G, H) Expression of major neuronal markers in injured spinal cord in each group. ⁣^∗p  < 0.05 and ⁣^∗∗p  < 0.01 when compared with SCI group or sham group. Adapted from He et al. [147 ]. Copyright 2022, Springer Nature.