Author Identifier
Zhiwei Zhong: https://orcid.org/0000-0002-8190-5797
Date of Award
2025
Document Type
Thesis - ECU Access Only
Publisher
Edith Cowan University
Degree Name
Doctor of Philosophy
School
School of Medical and Health Sciences
First Supervisor
Elin Gray
Second Supervisor
Simon Laws
Third Supervisor
Yimin Xu
Abstract
Traumatic brain injury (TBI) is a neurological condition resulting from an insult to the brain by an external force, and it is associated with high mortality and disability. Its diagnosis and treatment consume significant medical resources and result in a significant burden on the family and society. Currently, there is a lack of effective nerve injury repair therapies for patients with TBI. Stem cells possess the characteristics of proliferation and differentiation, which can enhance the local microenvironment and contribute to the repair of nerve injuries. Exosomes derived from stem cells can serve as paracrine factors and mediate the biological effects of stem cells. Transplantation therapy using exosomes (also referred to as exosome transplantation) can help avoid immune rejection, teratogenicity, and other adverse reactions associated with the direct transplantation of stem cells. However, exosome transplantation is not without its challenges, including difficulties in obtaining exosomes and a low utilisation rate during the transplantation process.
As discussed in the review in Chapter 1, the application of three-dimensional (3D) bioprinting technology not only stimulates the maintenance of stem cell characteristics but also enhances the efficiency of stem cell culture and increases exosome production. Furthermore, exosome carriers, such as biocompatible hydrogels, facilitate the localized release and concentration maintenance of exosomes. Combining these two approaches can effectively address the challenges associated with exosome transplantation. In this study, we explored the efficacy of integrating stem cell-derived exosomes produced through 3D printing with hydrogels to promote neural repair after TBI.
In Chapter 2, we isolated bone marrow mesenchymal stem cells (BM-MSCs) from rat bone marrow using an adherent culture method. Subsequently, these BM-MSCs were induced to differentiate into neural stem cells (NSCs). Exosomes were extracted from both MSCs and NSCs and administered to Sprague-Dawley (SD) rats with TBI. Postoperative neurological recovery was assessed using the modified neurological severity score (mNSS). Additionally, immunohistochemistry was employed to evaluate neuronal regeneration at the injury site, as well as the presence of astrocytes, microglia, and angiogenesis. The results demonstrated that exosome treatment significantly enhanced neurological recovery in TBI rats, with NSC-derived exosomes exhibiting superior efficacy in promoting neuronal regeneration, reducing inflammation, and stimulating angiogenesis.
In Chapter 3, we utilised 3D coaxial bioprinting to encapsulate high concentrations of NSCs within hollow fibres for culture. Exosomes were extracted from both two-dimensional (2D) and 3D-cultured NSCs and administered to SD rats with TBI. Our findings revealed that 3D coaxial bioprinting significantly increased the exosome yield per unit volume of supernatant. Furthermore, exosomes derived from 3D-cultured NSCs effectively promoted neural repair, reduced inflammation, and enhanced angiogenesis at the injury site, demonstrating comparable therapeutic efficacy to those obtained from 2D-NSC cultures.
In Chapter 4, 3D NSC-derived exosomes were encapsulated within chitosan-polyethylene glycol-aldehyde hyaluronic acid (Chi-PEG-AHA) hydrogels and inoculated to the injured area of SD rats one day post-surgery to evaluate their therapeutic effects on TBI. The results demonstrated that the Chi-PEG-AHA hydrogel, in combination with 3D NSC-derived exosomes, significantly enhanced neural repair, attenuated gliosis, reduced the inflammatory response, and promoted angiogenesis at the injury site.
Overall, the results of the studies conducted in this thesis successfully demonstrate significant effects on neural repair, highlighting the potential of this innovative approach to promoting recovery following TBI.
DOI
10.25958/c2w7-hm81
Access Note
Access to this thesis is embargoed until 7th August 2030
Recommended Citation
Zhong, Z. (2025). Efficacy of exosome derived from 3D printing stem cell combines with hydrogel to promote neural repair after traumatic brain injury. Edith Cowan University. https://doi.org/10.25958/c2w7-hm81