Development of Bioactive Soft Tissue Scaffold Systems

Abstract

There is a need for development of versatile soft tissue scaffolds which can interface with tissue junctions and a range of tissue architectures. Two approaches were developed. A bone capable ceramic scaffold was infused with gel and polymer components to suit cartilage resurfacing. Several biphasic prototypes were successfully developed and evaluated mechanically and biologically. Whilst they supported chondrocyte culture within the infused gel layer they lacked sufficient mechanical stability. Two therapeutic agents were investigated for potential roles in modulating cartilage degradation. Gene expression (RT-PCR) measurements demonstrated that whilst zoledronic acid reduced cartilage degradation, S100A9 increased ECM breakdown. In a subsequent more substantive approach, a versatile polymer composite scaffold (variotis™) was designed and synthesised using a novel, high-throughput batch coagulation method. Methods were developed for formation of scaffolds with a range of shapes and properties. This novel scaffold could be readily post formed to impart graded interconnected porosity and mechanical response. Characterisation was undertaken for physical structure and mechanical behavior. The soft, elastic scaffolds were highly porous with excellent void interconnectivity and tensile properties within the range of skin. A range of novel bioactive glass compositions were developed for incorporation with the scaffolds. Glasses were analysed compositionally, mechanically, for bioactivity and radiopacity. During in vitro studies, composites with bioactive glass and bulk metallic glass constituents were shown to support fibroblast cell culture and exhibited less inflammation than stainless steel and cell controls, negligible inflammation. In vivo subcutaneous implantation of 124 polymer and polymer-composite variotis™ scaffolds into rats demonstrated complete tissue filling by 14 days. Histological staining confirmed high proportions of mature collagen content and vascularization within the polymer-Bioglass® composite scaffolds. Low inflammatory levels were confirmed by circulating and wound fluid cell counts.