| There is a need in medicine for the development of cost effective alternatives in treatment of diseases like liver failure, diabetes, Parkinson's, as well as reconstruction of damaged tissues and organs like skin, cartilage, bone and blood vessels. Materials that serve as analogs for the native extracellular matrix (ECM) can be utilized for this purpose. Important characteristics of artificial matrices for tissue engineering include the ability to control the microarchitecture, allow neovascularization, cellular infiltration, cell adhesion, cell spreading and expression of their normal phenotype. Furthermore, the ability to incorporate and release drugs or proteins from these matrices in a controlled manner is crucial. An emulsion freeze-drying method for processing porous, biodegradable scaffolds of polylactide and polyglycolide and their copolymers with controlled median pore sizes, and very high porosity and specific surface areas has been developed. These scaffolds with median pore sizes as low as 16 {dollar}mu{dollar}m were used without growth factors to regenerate bone in a rat calvarial critical sized defect via haematoma stabilization. This demonstrated that it was not necessary to have a minimum average pore size of 200 to 400 {dollar}mu{dollar}m for bone regeneration as specified by the current paradigm, but instead control of the whole microarchitecture was important. The mechanisms that govern the processing technique and hence the scaffold microarchitecture were further established using Taguchi experimental analysis. Effects of the addition of water phase additives like polyethylene glycol, CaCl{dollar}sb2{dollar}, and protein on pore size were investigated to produce scaffolds with different pore sizes but similar protein loading and visa versa. These scaffolds were used to test their ability to control protein release. The viability of a clinically relevant bioactive factor, bone morphogenetic protein (rhBMP)-2, released from these scaffolds was verified in vivo by regenerating bone in a rat ectopic site. This thesis demonstrated that control of scaffold microarchitecture affected tissue regeneration and protein release kinetics. That these scaffolds are suitable for regeneration of various tissues. |
