Establishing an aligned nanofibre platform to deliver synergistic topographical and biochemical signalling

• Main Author: Chin, Jiah Shin
• Other Authors: Chew Sing Yian
• Format: Final Year Project
• Language: English
• Published: 2016
• Subjects: DRNTU::Engineering
• Online Access: http://hdl.handle.net/10356/68407
• Institution: Nanyang Technological University

Given the complexity of the nervous system, mechanisms to promote functional recovery at injury sites have yet been completely understood by both clinicians and researchers. Tissue engineering approaches serve as a potential therapy for neural regeneration. In particular, aligned sub-micron and nan-scale fibrous scaffolds which accurately mimic the topography of natural extracellular matrix can function as prospective scaffold candidates to facilitate recovery. In this study, a fiber fabrication technique, Electrospinning, was adopted and electrospun fibers were collected across an electrically charged air gap. Parameters were optimized to achieve aligned poly (Ɛ-caprolactone) (PCL) fiber with diameters ranging from 390nm to 1.14um. Though this fabrication technique has been proven efficient, the use of organic solvents, which are highly cytotoxic, to dissolve PCL is unfavorable for both in vitro and in vivo use. Hence, a solvent-free electrospinning technique, melt electrospinning, was established. Several configurations were explored and a stable heating system was obtained through a combination of proportional integral derivative (PID) controlling system coupled with the use of a solid state relay switching mechanism. This established setup was subsequently evaluated and proven to be feasible for melting low molecular weight PCL pallets to achieve a stable melt flow at high flow rates along with high heating temperature. Bio-functionality of aligned fibrous scaffolds can be established through incorporation of biochemical cue delivery. Gene silencing through RNA interference can be achieved with the use of small-interfering RNA (siRNA) and this technique has revealed immense potential in silencing inhibitory intrinsic factors of axonal regeneration at injury sites. Micellar Nanoparticles (MNP) has recently been developed and engaged in delivery of nucleic acids. Two copolymers, poly (Ɛ-caprolactone)-poly (ethylene glycol) (PCL-PEG) and poly (Ɛ-caprolactone)-poly (2-aminoethyl ethylene phosphate) (PCL-PPEEA), were used for MNP synthesis weight ratios of both copolymers were varied to obtain a range of MNPs exhibiting different particle sizes and charges. Upon siRNA loading, siRNA/MNP complexes were formed and these complexes had a general reduction in overall size as well as charge. Combination of MNPs with aligned fibrous scaffolds could serve as an efficient scaffold-mediated delivery system to induce functional recovery at injury sites especially within the non-permissive environment of the central nervous system (CNS).