Functional Design of Soft Tissue Engineered Replacements using Novel Bioactive Polymeric Scaffolds

Limited options are available to treat articular cartilage defects of the knee caused by trauma and degenerative diseases such as osteoarthritis. Attempts at joint resurfacing using several surgical techniques have had variable results, but eventually lead to a total joint replacement. One method of cartilage repair involves growing replacement tissue ex vivo for subsequent implantation, so called Tissue Engineering. Three components are needed to successfully engineer replacement tissue; cells to generate extracellular matrix, a scaffold to support growth and a scaffold which enables the release of bioactive factors to stimulate the desired cellular response. Thus far, tissue engineered constructs have not been able to match the mechanical properties, and hence the functionality of the surrounding native cartilage tissue, neither have they had the ability to fully integrate with the native tissue. Through the development of novel polymeric scaffolds, it should be possible to provide mechanical integrity to the defect site, to support tissue growth and to release growth factors in a timed manner. This thesis presents the design, development and testing of a novel bioactive polymeric scaffold intended to maintain long-term mechanical integrity to a cartilage defect site and to facilitate the generation of viable cartilaginous matrix from included cells. Non-degradable Poly (vinyl alcohol)-based scaffolds combined with degradable microparticles made of either Alginate, a naturally-derived polymer, or Poly (lactic-co-glycolic acid), a synthetic polymer, have been developed. Partly-degradable PVA-based composite scaffolds have been also developed using a blend of PVA and Gelatin, a naturally-derived polymer. Degradable microparticles have been developed for the incorporation of Insulin (hydrophilic drug) and Dexamethasone (non-hydrophilic drug) to control the drug release and to improve the mechanical properties of the scaffold. The scaffolds were manufactured and their morphological properties, biological factor release rates, mechanical characteristics, and cell reponse characterized. The data herein presented demonstrate that a scaffold which can support cell growth and carry mechanical loads has been designed.