Design and optimization of a biodegradable nanofiber based polymer and polymer/composite matrix for bone tissue engineering

Autografts and allografts are the most commonly used bone graft substitutes for bone injuries and traumas. However, the potential problems with autografts include donor site morbidity, harvesting, complications and discomfort for patients. Additionally, the allografts have chances of potential disease transmission and adverse immune response when implanted. Tissue engineering is a promising alternative to current bone grafts that employs the use of biodegradable and biocompatible transient scaffolds in conjunction with cells and growth factors. Recent concerns about the acidic degradation products of the traditional biodegradable polymers such as poly (alpha-hydroxyesters) spurred the quest for novel polymers for biomedical applications with neutral and non-toxic degradation products.; The present thesis describes the synthesis of such novel biodegradable polymers from polyphosphazene platform by a macromolecular substitution route with different ratio of side groups of ethyl alanato and p-methyl phenoxy groups. The effects of the different ratio of side groups of on the properties of the synthesized co-substituted polyphosphazene were investigated. The polymers were characterized by nuclear magnetic resonance spectroscopy, x-ray photoelectron spectroscopy and attenuated total reflectance fourier transform infrared spectroscopy to elucidate their structures. Other polymer properties, such as glass transition temperature increased with an increment of the ratio of the bulkier side group in the co-substituted polymer. The molecular weight of the polymer, with lower ratio of methyl phenoxy group was found to be comparatively higher. The extracellular matrix of the natural bone contains hydroxyapatite nanocrystals as the major inorganic mineral component with a size range of 20-80 rim along with collagen nanofibrls as the organic matrix. Towards this end, a design of the scaffold was conceived and developed via electrospinning to mimic the natural nanofibrous bone tissue architecture. The fabrications of both purely polymeric and composite nanofibrous scaffolds with 20-40 nm hydroxyapatite crystals from the polymer were described. These scaffolds were extensively characterized for properties pertinent to tissue engineering scaffolds such as fiber diameter, porosity, degradation properties, surface wettability, mechanical properties etc. The nanohydroxyapatite content in the composite fibers along with the distribution of the same within the fibers were also investigated.; Fabricated nanofiber scaffolds and composites were evaluated for primary osteoblast interaction in vitro. This work provides the concept and groundwork of novel polyphosphazene nanofiber scaffolds with biomimetic, bioactive and osteoconductive properties via electrospinning and paves the way for future developmental works.