Bioactive peptide nanofibers for bone tissue regeneration

Abstract

Replacement and repair of bone tissue that is lost due to fractures, tumor resection, degenerative diseases and infections still remain major clinical challenges. Autografting, allografting and xenografting are the current strategies for the treatment of bone defects. However, these strategies cause problems such as immunological response and disease transmission in clinical applications. To overcome these limitations, regeneration of new bone can be induced by the use of synthetic bioactive materials. One of the most promising strategies is to develop synthetic scaffolds mimicking the functional components of the extracellular matrix (ECM). Biomineralization is mineralization carried out by living organisms. Glycosaminoglycans have crucial roles in biomineralization and enhance the functions of growth factors involved in biomineralization. Success in bone regeneration studies requires a thorough understanding of the necessary conditions for triggering biomineralization during the bone tissue formation process. In this study, the effect of bioactive and biocompatible peptide nanofibers on osteogenic differentiation, biomineralization and bone tissue regeneration are investigated under in vitro and in vivo conditions. In the first chapter, bone tissue composition, the clinical need for bone regeneration and general principles in bone tissue engineering are discussed. Bone tissue regeneration strategies are also highlighted in this part, with emphasis on peptide amphiphiles and self-assembly behavior. In the second chapter, a fully synthetic, extracellular matrix-mimetic peptide nanofiber system is described for enhancing the biomineralization and regeneration of bone tissue. This nanostructural environment forms artificial intracellular networks and supports biomineralization by providing cell-material and protein-material interactions. In the third chapter, effect of osteoinductive peptide nanofibers on osteogenic differentiation of rat mesenchymal stem cells (MSCs) were investigated. In the fourth chapter, the natural biomineralization process in bone tissue was mimicked on peptide nanofibers and the effect of this system on the osteogenic differentiation of osteoblast-like cells was investigated. In the fifth chapter, a dentin-mimetic peptide amphiphile (SpDSp-PA) molecule that is capable of emulating the structure and function of dentin phosphoprotein was designed and its capacity to support the deposition of hydroxyapatite and survival and biomineralization of osteoblast-like cells was evaluated.