Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor | Department of Biomedical Engineering | en_US |
| dc.contributor.advisor | Zhao, Xin (BME) | en_US |
| dc.creator | Mei, Quanjing | - |
| dc.identifier.uri | https://theses.lib.polyu.edu.hk/handle/200/14086 | - |
| dc.language | English | en_US |
| dc.publisher | Hong Kong Polytechnic University | en_US |
| dc.rights | All rights reserved | en_US |
| dc.title | Biomimetic GelMA-based hydrogels for 3D neural tissue engineering | en_US |
| dcterms.abstract | The nervous system is a complex, multi-layered tissue system. The lack of access to live human brain tissue and the inherent limitations of animal research make it difficult to study the functions of the nervous system and the diseases affecting it. It is possible to construct neural tissue mimics (NTMs) in vitro. However, these experiments are typically conducted on two-dimensional (2D) substrates and cannot accurately represent the three-dimensional (3D) microstructure of neural tissues. To address this issue, biomimetic gelatin-methacryloyl (GeIMA) hydrogels with highly desired biological and physical characteristics similar to the extracellular matrix (ECM) in nature have been developed to investigate neural development, neurogenesis, and electrophysiology in a 3D environment. | en_US |
| dcterms.abstract | In the first part of this study, by varying the polymer compositions of GeIMA and long-chain polyethylene glycol diacrylate (PEGDA), biomimetic hydrogels with tensile and compressive moduli of approximately 10 and 0.8 kPa, respectively, were created to simulate the mechanical environment of neural tissues. In vitro findings indicated that the GeIMA-PEGDA hydrogels were biocompatible to sustain stem cell growth, proliferation, differentiation, and neurite extension. Also, stretching significantly increased neurite extension, axon elongation, and directionally oriented neurites along the direction of stretching. In addition, immunofluorescence staining, and relative gene expression revealed that stretching could facilitate the upregulation of neuronal differentiation-related proteins and genes, such as glial fibrillary acidic protein (GFAP) and neuron-specific class III beta-tubulin (Tuj-1). In conclusion, the unique mechanical properties of GelMA-PEGDA could not only promote neuronal differentiation toward a particular lineage, but stretching is an intriguing strategy for boosting the efficiency of neural stem cell (NSC) therapies. | en_US |
| dcterms.abstract | In the second part of the study, poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) was incorporated as an additive improving the conductive properties of GelMA-PEGDA hydrogels. In contrast to non-conductive hydrogel, the conductive hydrogel itself could promote neuronal development. With electrical stimulation (ES), the conductive hydrogel could further induce stem cell differentiation with increased neuronal extension and relative gene expression. Meanwhile, stretching could also induce neuronal differentiation and directional alignment of axon extension, consistent with the previous part. The co-stimulation of mechanical stretching and electrical stimulation had synergetic effects on neuronal development, namely promoted neurite outgrowth, increased filopodia density and neurite branching, upregulated relative expression of neuronal differentiation genes, and higher electrical activity of encapsulated neuronal cells. This study enriched the knowledge about the directed differentiation of NSC within 3D microenvironment through physical cues, offering theoretical basis for the effectiveness and feasibility of NSC therapy. | en_US |
| dcterms.abstract | To further fabricate 3D NTMs with customisable sizes, forms, and functionalities, in this chapter, a novel host-guest hydrogel bio-ink based on GelMA and hyaluronic acid was developed for bioprinting. The rheological results indicated that host-guest hydrogel had excellent shear-thinning and fast self-healing properties, which endowed hydrogels with outstanding printability to be produced and maintained in diverse structures. Meanwhile, the host-guest interaction could protect cells from high shear force during printing, and cells maintained high viability and proliferation after printing. In addition to mimicking the neural structure, host-guest interaction mimicked the dynamic ECM environment that regulated cell behaviours (cell morphology, spreading, and migration) and function of the neural system (electroactivity and signal transmission), forming a united neural network. With good cell viability and electroactivity, we believe that the NTMs developed using host-guest hydrogels hold great promise in replicating the structure and function of different neural tissues, allowing researchers to investigate the underlying mechanisms of neural communication and information processing, as well as the mechanisms of nerve damage and repair to develop potential treatments for neural regeneration. | en_US |
| dcterms.abstract | Overall, a range of biomimetic GelMA hydrogels were developed for studying neural development, neurogenesis, and electrophysiology. These hydrogels had high biocompatibility for neural cell encapsulation and provided a 3D matrix, which would be more effective in recapitulating neural tissues compared to 2D counterparts. We then fabricated NTMs through bioprinting to mimic the intricate structure of the nervous system. The 3D-printed NTMs had controlled structure and high electrophysiological activity to form interconnected 3D neural networks. Overall, these studies help achieve the following: (1) enrich the existing literature on the directed differentiation of NSC in a 3D microenvironment induced by physical stimuli; (2) offer a foundation for the efficacy and practicability of NSC treatment; (3) improve translational applicability and present a better model for studying neural regeneration. | en_US |
| dcterms.extent | xv, 209 pages : color illustrations | en_US |
| dcterms.isPartOf | PolyU Electronic Theses | en_US |
| dcterms.issued | 2023 | en_US |
| dcterms.educationalLevel | Ph.D. | en_US |
| dcterms.educationalLevel | All Doctorate | en_US |
| dcterms.accessRights | open access | en_US |
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