Nano-reinforced hydro-filled 3D scaffold for neural tissue engineering
Date
2021
Authors
Mahumane, Gillian Dumsile
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Abstract
Traumatic brain injury (TBI) presents a serious challenge for modern medicine due to the poor
regenerative capabilities of the brain, complex pathophysiology, and lack of effective treatment for
TBI to date. Current approaches (pharmacological and non-pharmacological) are largely focused on
preventing further damage and rehabilitation instead of facilitating regeneration and tissue repair.
Although a decellularized brain tissue matrix would be the best choice for a neural tissue engineering
scaffold, the limitation brain tissue resource is a great obstacle for the practical application of this type
of scaffold (decellularized matrix). Tissue-engineered three-dimensional (3D) scaffolds have shown
various degrees of experimental success in augmenting cell survival, unfortunately, these biomaterial
scaffolds present with various limitations that lead to a lack of successful clinical translation. Hybrid
composite scaffolds hold promise for addressing some of the deficiencies of previous biomaterials
scaffolds for tissue engineering application. The objective of this work was to prepare a novel
neuromimetic three dimensional (3D) 3-in-1 scaffold system in the form of a nano-reinforced hydro filled cryogel scaffold for neural tissue application. The scaffold was fabricated via a stepwise process
whereby electrospun nanofibers where embedded in a polymer solution and crosslinker, incubation
at sub-zero temperature (-20°C) to produce a cryogel, followed by filling of the nano-reinforced
cryogel with a hydrogel. Fourier-transform infrared spectroscopy confirmed the presence of and
interaction between the composite polymer materials in the scaffold. The temperature related
observations from DSC and TGA analysis revealed the scaffolds thermal profile to be influenced by the
combination of its composites. The degradation temperature of the scaffold was well above the
physiological temperature of 37°C, indicative of stability and mechanical strength at ambient and
physiological temperatures for potential application as thermostable implants/delivery devices. The
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hybrid scaffold presented with an interconnected porous structure. A low mass loss of 36.5% was
observed after 28 days. This slow degradation is desired and supports the suitability for practical
application as an implant in the highly hydrated brain tissue environment. Mechanical characterization
using unconfined compression test, demonstrated the scaffold to be viscoelastic, possesses shape
memory properties, and a low compression modulus 525Pa. Effect on cell viability and proliferation
evaluated by MTT assay showed that the 3-in-1 scaffold was non-toxic to both PC12 and A172 cells
and therefore holds promising potential to support neural cell survival. Histological analysis revealed
that the novel 3-in-1 scaffold successfully filled the lesion site, maintained tissue-scaffold contact,
remained intact with the interconnected pores and was progressively infiltrated with cells and native
tissue material throughout the residence period in the brain. Based on the observed results, the
synthesized 3-in-1 scaffold properties suggest it has the potential to serve as an integrative and
supportive platform for neural tissue engineering application. A 3-in-1 neuromimetic scaffold system
is presented herein for application as a novel acellular implant to aid in neural tissue regeneration.
This system is unique in the sense that it captures the multi-scale, multi-porous (micro/meso/macro porous), intricate properties of native ECM (a key component of neural regeneration) in its design.
Therefore, the results herein are unique to the composition and architecture of the novel 3-in-1
scaffold design, and thus contribute to potentially furthering knowledge influencing neural tissue
regeneration research in comparison to any other previously reported CNS scaffolds in literature
Description
A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, Johannesburg, 2021