Novel functionalised biodegradable polymeric micro- and nano-structures for tissue engineering and drug delivery applications

Abstract

The focus of the work present in this thesis is the preparation of well-defined polymeric micro- and nano-structures for use in biomedical applications. Each of the polymers in this work was prepared using reversible addition fragmentation chain-transfer (RAFT) polymerisation or a combination of ring opening polymerisation (ROP) and RAFT polymerisation. Functional groups were incorporated into the polymer chain for subsequent covalent conjugation of biologically important molecules.

Chapter One provides a detailed look at ‘living’ polymerisation techniques, RAFT polymerisation and ROP and their use in the preparation of polymers for biomedical applications.

In Chapter Two, one poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and three poly(oligo(ethylene glycol)methacrylate)) (POEGMA) homopolymers were prepared using RAFT polymerisation. Two of the POEGMA homopolymers were prepared using two different functional groups, disulphide and n-hydroxysuccinimide (NHS), to allow subsequent cell-adhesive arginine-glycine-aspartic acid-cysteine (RGDC) peptide conjugation using different chemistries. The series of four homopolymers was used to prepare segmented conetworks, also by RAFT polymerisation. The homopolymers were cross-linked with either the aciddegradable di(methacryloyloxy-1-ethoxy)methane (DMOEM) or the nondegradable ethylene glycol dimethacrylate (EGDMA). Segmented conetworks were prepared from one cross-linked homopolymer or a combination of PMPC and one of the POEGMA homopolymers with various molar ratios of POEGMA to PMPC. The phase separation of the POEGMA and PMPC homopolymers was determined. The degradability of the segmented conetwork cross-linked with DMOEM was investigated and the conjugation of the cell-adhesive RGDC peptide to the functionalised POEGMA homopolymers and segmented conetworks were examined.

In Chapter Three a series of polylactide-b-poly(oligo(ethylene glycol)methacrylate)) (PLA-b-POEGMA) amphiphilic diblock copolymers were prepared using a one-pot simultaneous ROP and RAFT polymerisation method. A series of PLA-b-PMPC amphiphilic diblock copolymers are also prepared using a one-pot two-step ROP and RAFT polymerisation procedure. Two of the PLA-b-PMPC amphiphilic diblock copolymers were prepared with two different functional groups, benzaldehyde and NHS, for subsequent attachment of biologically important molecules by different chemistries. The morphologies formed after self-assembly of the PLA-b-POEGMA and PLA-bPMPC amphiphilic diblock copolymers in aqueous solutions using a solvent switch method were examined. The morphologies formed after self-assembly of a mixture of a PLA-b-POEGMA and PLA-b-PMPC were determined and the phase separation of POEGMA and PMPC was investigated.

In the Chapter Four several PLA-b-POEGMA and PLA-b-PMPC amphiphilic diblock copolymers (prepared in Chapter Three) and some of their mixtures, were electrospun and the resulting morphologies were investigated. Optimum electrospinning conditions for nanofibre production were determined for each polymer. The phase separation of the two hydrophilic blocks, POEGMA and PMPC on the surface of the nanofibres was determined. The conjugation of the cell-adhesive RGDC peptide to the benzaldehyde functional groups of nanofibres consisting of benzaldehyde-functionalised PLA-b-PMPC and PLA-b-POEGMA copolymers in a 1:1 molar ratio was investigated.

In Chapter Five, the NHS-functionalised PLA-b-PMPC amphiphilic diblock copolymer prepared in Chapter Three was electrosprayed and the optimum electrospraying conditions for microparticle formation were determined. The encapsulation during electrospraying and the kinetic release profile of Rhodamine B dye was examined, followed by conjugation of cysteine (thiol functionalisation) to the electrosprayed microparticles.

In the final chapter, Chapter Six, the conclusions of the thesis and the future work are presented.

Date of Award	Jul 2020
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Engineering and Physical Sciences Research Council
Supervisor	Efrosyni Themistou (Supervisor) & Amilra De Silva (Supervisor)