Characterization of PEG Incorporated Flexible Scaffolds of Poly-DL-lactide-co-caprolactone as Potential Biomaterials for Bone Tissue Engineering

Biopharmaceutical proteins have enormous therapeutic potential due to their natural occurrence and highly specific mechanism of action. DNA recombinant technologies employing a variety of expression hosts ranging from prokaryotic E. coli to eukaryotic complex mammalian cells have been used as robust tools for mass production of these biopharmaceuticals. Bone Morphogenetic Prortein-2 is an US FDA approved biopharmaceutical drug with applications in bone fracture repair and spinal fusion when delivered using a polymer-based graft device. Chapter 1 focuses on the expression of BMP-2 using genetically engineered E. coli. We also report a novel, fast and easy-to-scale up method utilizing cation exchange resin for refolding BMP-2.;There is a need for suitable bone substitutes for applications in bone fracture repair and polymers have been widely used as biomaterials to guide bone wound healing process. However, biocompatibility is a huge limitation to these polymeric devices, especially those made from polyester, due to accumulation of acidic degradation products in the surrounding tissues resulting in chronic inflammation. In Chapter 2, we study biocompatibility of a synthetic poly-DL-lactide-co-caprolactone (DLCL) copolymer by implanting it in the subcutaneous tissue of rats and evaluate the surrounding tissues for inflammatory responses. Histology analysis revealed the tendency of the polymer to provoke both acute and chronic inflammatory reactions, suggesting the need for surface modifications to improve tissue acceptance. We, hence, investigate blending of DLCL with a hydrophilic, biocompatible polymer polyethylene glycol (PEG) using thermal and IR spectroscopy (Chapter 3). This chapter highlights effects of two blending procedures namely, heat molding and solvent evaporation, on the physical properties of the composite blends. Additionally, we present a comprehensive analysis on the mixing tendencies of the two polymers. Chapter 4 describes the in vitro response of PEG blended DLCL scaffolds to pre-osteoblast and macrophage cell lines. Biofunctionality of the blended materials was evaluated based on their tendency to exhibit attachment and proliferation of cells.