Essa, Abdulrahman
(2018)
A new biodegradable elastomeric polyester amide for soft tissue engineering applications.
PhD thesis, University of Nottingham.
Abstract
Elastomeric scaffolds play an important role in the field of soft tissue engineering, and recently, studies investigating different medical applications for these scaffolds have been increasing rapidly. New thermoset bioelastomers have demonstrated promising applications for myocardial, vascular and nerve tissue engineering. Nevertheless, these elastomers have several disadvantages, including the toxicity of the degradation products of the polyester family and the poor solubility of the poly(ester amide) (PEAs) family in the most commonly used polar and nonpolar solvents, which restricts fabrication. Therefore, this PhD project aims to develop a novel biodegradable and biocompatible elastomer to overcome the disadvantages of currently available PEA elastomers, such as the poor solubility of the PEA pre-polymer and the limitations of its mechanical properties, in order to create an elastomer which is similar to protein-based polymers, thus allowing for wider use in soft tissue engineering applications.
The major outcomes of this project include:
(1) In order to build biodegradable and biocompatible elastomers with a satisfactory combination of a soluble pre-polymer, mechanical flexibility and an improved biodegradation profile, an amino alcohol, serinol, was used to synthesise poly(serinol sebacate) (PSS). The synthesised PSS pre-polymer exhibited excellent solubility in a variety of solvents, including methanol, dimethyl sulfoxide and dimethylformamide, while the crosslinked PSS became insoluble in any type of solvent. More importantly, the mechanical properties of PSS could be fine-tuned by changing the curing conditions. In addition, the 3T3 fibroblast cells cultured in the PSS demonstrated good cell attachment and proliferation. No cytotoxicity responses were detected for the PSS samples.
(2) In order to build fibrous elastic materials that resemble the extracellular matrix architecture and mechanical properties of soft tissues, an elastomeric PSS scaffold was fabricated by utilising an electrospinning technique using polyvinyl alcohol (PVA) as a carrier polymer to facilitate fibre formation. After electrospinning, the PSS was cured via thermal treatment and the PVA was partially removed by water. The newly fabricated PSS fibrous scaffold demonstrated diverse characteristics with respect to its mechanical properties, with average rapture elongation (450%) and tensile modulus (∼200 kPa) as soft as many types of soft tissues.
(3) The correlation between solution rheology and electro-spinnability, fibre morphology and fibre alignment of polycaprolactone (PCL) with different molecular weights was studied. The produced PCL scaffolds were then treated with an uncured PSS polymer to improve their hydrophilicity and biocompatibility. The PCL/PSS composite scaffolds were fabricated using a safe and cost-effective method. The results showed that cell adhesion and proliferation improved for the PCL/PSS composite scaffolds, which may be attributed to the higher hydrophilicity of these scaffolds in comparison to the pure PCL scaffolds.
In conclusion, novel biodegradable PEA elastomers were successfully designed and synthesised from serinol and sebacic acid by polycondensation reaction. The PSS elastomers exhibited tuneable degradation and mechanical profiles by varying the curing time. Thus, the developed PSS polymer shows excellent potential for various biomedical applications, including tissue engineering applications, drug delivery and coating material.
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