Functional Degradable Polymers by a Radical Chemistry approach

Sammanfattning: One class of polymers that is inherently of great value for many applications is the aliphatic polyesters. Such polymers are very suitable for use as temporary guides, scaffolds, for tissue formation and other biomedical applications, due to their biocompatibility, degradability and appropriate mechanical properties. A prominent way to incorporate sites that allow alterations and modifications of the polymer backbone could be by copolymerization of functional monomers. The focus in this thesis is the development of new monomers and subsequent polymers bestowed with functional groups.Radical ring-opening polymerization (RROP) of cyclic ketene acetals through a free-radical mechanism presents an alternative route to conventional ring-opening polymerization for the synthesis of aliphatic polyesters. By RROP, it is possible to incorporate ester functionality into the backbone of non-degradable polymers by copolymerize cyclic ketene acetals with vinyl monomers.The possibility of creating materials with high degree of functionality is achieved by copolymerization with other and possible functional monomers. Three different copolymerizations including cyclic ketene acetals were performed. First, to increase hydrophilicity of a hydrophobic polymer by copolymerization of two cyclic ketene acetals, 2-methylene-1,3,6-trioxocane (MTC) and 2-methylene-1,3-dioxepane (MDO). Second, to introduce degradability into a non-degradable backbone by copolymerize MDO and vinyl acetal (VAc). Subsequently, the acetate side-group was hydrolyzed into the more hydrophilic alcohol group. Third, to introduce reactive functionalities into the degradable backbone of poly(2-methylene-1,3-dioxepane) (PMDO), by copolymerize MDO and glycidyl methacrylate (GMA). The epoxide side-groups, originating from GMA, were subsequently used in post-polymerization reactions by coupling with the bioactive molecule heparin.The degradability of this class of copolymers was evaluated using the MDO/GMA-based material as model, showing that the materials degrade during 133 days without a rapid release of acidic degradation products or any substantial lowering of the pH. Methylthiazol tetrazolium (MTT) assays were also performed to confirm the innocuousness of the material. The results from the degradation study together with the MTT assays showed that these materials would be interesting for use in biomedical applications.Finally, a combination of controlled radical polymerization with controlled ring-opening polymerization was performed. α-Bromo-γ-butyrolactone (αBrγBL) together with ε-caprolactone (εCL) or L-lactide (LLA) was successfully copolymerized to achieve copolymers with active and available grafting sites for single electron transfer living radical polymerization (SET-LRP). Different acrylates, ranging from the hydrophobic n-butyl acrylate and methyl methacrylate to the hydrophilic 2-hydroxyethyl methacrylate, were subsequently grafted via SET-LRP. All designated acrylate monomers were successfully grafted onto the polymer backbone, thereby emphasizing the versatility and ability of αBrγBL to act as a bridge between SET-LRP and ROP for a wide range of monomers.