Title:A New Paradigm in Spinal Cord Injury Therapy: from Cell-free
Treatment to Engineering Modifications
Volume: 23
Issue: 5
Author(s): Bo Qin, Xi-min Hu, Yan-xia Huang, Rong-hua Yang*Kun Xiong*
Affiliation:
- Department of Burn and Plastic Surgery, Guangzhou First
People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China
- Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha,
410013, China
- Hunan Key Laboratory of Ophthalmology, Changsha, 410008, China
- Key Laboratory of Emergency
and Trauma, Ministry of Education, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199,
China
Keywords:
Extracellular vesicles, engineering, spinal cord injury, drug loading, biomaterials, sustained delivery.
Abstract: Spinal cord injury (SCI) is an intractable and poorly prognostic neurological disease, and
current treatments are still unable to cure it completely and avoid sequelae. Extracellular vesicles
(EVs), as important carriers of intercellular communication and pharmacological effects, are considered
to be the most promising candidates for SCI therapy because of their low toxicity and immunogenicity,
their ability to encapsulate endogenous bioactive molecules (e.g., proteins, lipids, and nucleic
acids), and their ability to cross the blood-brain/cerebrospinal barriers. However, poor targeting, low
retention rate, and limited therapeutic efficacy of natural EVs have bottlenecked EVs-based SCI therapy.
A new paradigm for SCI treatment will be provided by engineering modified EVs. Furthermore,
our limited understanding of the role of EVs in SCI pathology hinders the rational design of novel EVbased
therapeutic approaches. In this study, we review the pathophysiology after SCI, especially the
multicellular EVs-mediated crosstalk; briefly describe the shift from cellular to cell-free therapies for
SCI treatment; discuss and analyze the issues related to the route and dose of EVs administration;
summarize and present the common strategies for EVs drug loading in the treatment of SCI and point
out the shortcomings of these drug loading methods; finally, we analyze and highlight the feasibility
and advantages of bio-scaffold-encapsulated EVs for SCI treatment, providing scalable insights into
cell-free therapy for SCI.