The aim of this PhD research project was to synthesise and characterize water soluble linear and hyperbranched biodegradable polymers based on bio-compatible (macro )molecules of poly(ethylene glycol) (PEG) and (D,L)-lactide using modem polymer synthesis approaches. The targeted P_DLLA-PEG-P_DLLA polymers are aimed for use in the preparation of biodegradable hydrogels for tissue engineering and drug delivery. By changing the composition, topology and molecular weights of the copolymers, hydrogels with tailored biodegradability, swelling and mechanical properties can be achieved.
In the course of this project, a series of P_DLLA-PEG-P_DLLA linear copolymers from poly( ethylene glycol) (PEG) (M_w = 1000 g/mol) and (D,L)-lactide (LA) were prepared with various LA chain lengths by ring opening polymerisation (ROP) of lactide and then functionalised with diacrylate groups. These reactions have been studied systematically in order to find optimised reaction conditions to obtain P_DLLA- PEG- P_DLLA copolymers and P_DLLA-PEG-P_DLLA diacrylate macromers with tailored composition and molecular weight. These linear block copolymers and macromers were fully characterised by Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared spectroscopy (FTIR), Differential Scanning
Calorimetry (DSC), Thermogravimetric analysis (TGA) and Gel Permeation Chromatography (GPC).
Since diacrylated P_DLLA-PEG-P_DLLA have photocrosslinkable and biodegradable properties, biodegradable hydrogels were prepared by directly photocrosslinking diacrylated P_DLLA-co-PEG-co-P_DLLA copolymers alone and in conjugation with poly(ethylene glycol) methyl ethyl methacrylate (PEGMEMA) at different ratios. Hydrogels with tailored swelling and biodegradability were obtained and studied.
Diacrylated P_DLLA-PEG-P_DLLA macromers were also used as branching agents to synthesize novel water soluble hyperbranched polymers with PEG-based monomers. Different copolymerisation approaches were used and these include Free Radical Polymerisation (FRP), Atom Transfer Radical Polymerisation (ATRP) and the Reversible Addition Fragmentation Chain Transfer (RAFT) Polymerisation. Challenges were found for the ATRP of P_DLLA-PEG-P_DLLA macromers as it was found that acidic conditions interfere due to hydrolysis with the catalysis. RAFT approach has been found to be a better method for V the polymerisation of PEG-co-PLA macromers and the resulting novel hyperbranched polymers have also been characterised by NMR, FTIR, DSC, TGA and GPC.
The resulting hyperbranched polymers with multivinyl functional groups can be used to prepare biodegradable hydrogels and are envisioned to have more advanced properties compared to those obtained directly from photocrosslinking of diacrylated P_DLLA-PEG-P_DLLA macromers. Fine tuning of the P_DLLA-PEG-P_DLLA macromer constituents and their combination with co-monomers, for example PEGMEMA, can result in hydrogels with balanced hydrophobic and hydrophilic properties as well as tailored swelling and drug release profiles. These biodegradable hydrogels prepared by hyperbranched polymers have promising potentials for applications in tissue engineering and drug delivery.
The first chapter is an introduction to the topics covered in the project and a summary of state-of-art research and findings in the relevant areas. The second chapter is in three parts and concerns the materials used, the experimental procedures employed and the methods for characterising the products obtained. Chapter 3 presents a discussion driven by the results of the experimental work. The final chapter sums up the conclusions and how the work suggests
possible future work.