Resorbable polyesters and –ethers; structures, controlled release and regeneration

Resorbable polymers are widely used in tissue regeneration and controlled drug delivery due to their excellent modification possibilities. The aims of this thesis are to synthetize hydrolytically-degradable polymers, study the effect of polymer composition and structure on drug release and prepare controlled 3D-structures for the purpose of nerve and bone regenerative scaffolds. In this thesis, both thermoplastic and photo-crosslinkable polyesters and –ethers were synthetized. Thermoplastic polyesters were modified by adjusting the monomer ratio and incorporating poly(ethylene glycol) (PEG) to the molecular structure to tailor the degradation rate and hydrophilicity of the polymers. The polymers were used to prepare interconnected, porous structures via supercritical carbon dioxide foaming. Photo-crosslinkable polycaprolactone (PCL) -macromers were synthetized and pre-designed structures with high accuracy were built via 3D-fabrication method stereolithography (SLA). Furthermore, anhydride-modified, photo-crosslinkable PCL and PEG -macromers were synthetized and used in preparation of pH-sensitive networks. The application areas of the polymers are in controlled drug delivery and tissue regeneration. Thermoplastic polyester foams were used to release bone growth inducing active agents. One of the polymer/active agent combinations resulted in near zero-order drug release, which is favored in drug releasing applications. pH-sensitive networks were used to study the release of model drugs. In vitro drug release studies showed that the polymers have potential as pH sensitive, colon-targeted drug delivery devices for macromolecules. SLA was used to build drug releasing PCL-structures with defined porosities and surface to volume ratios. Porous structures released the model drug with a burst, whereas solid samples had a slower drug release rate. PCL-based nerve guidance channels were also prepared via SLA. The channels were filled with cryogel and they exhibited excellent nerve regeneration in vivo. In conclusion, polymers were modified to suit the specific needs of each application. The degradation rate of polymers was tailored and they were modified to be more hydrophilic, photo-crosslinkable or pH-sensitive.