| The restoration and repair of orofacial and large bone defects resulting from extreme trauma, disease, or genetic inheritance is a clinical challenge in need of new solutions, as current grafting techniques can result in donor site morbidity, graft rejection, and/or inadequate bone formation and quality. Because bone is a complex organ, its hierarchical structure may only be restored in such defects if a temporary material guides tissue formation. Bone tissue engineering explores combinations of materials, biological signals, and cell sources to achieve guided tissue formation with structure-function properties matching those of native tissue.;By using nature's building blocks, or amino acids, as a design platform to synthesize multi-dimensional biomolecules in the form of peptides, biological function can be influenced. The idea is to provide specificity to induce a desired biological activity. In addition, coating a material with biomimetic bone-like mineral can provide a surface morphology and composition similar to the native hydroxyapatite in bone. While bone-like mineral can increase bone growth in vivo, the tissue formed is not uniform or spatially controlled, suggesting the need for better-designed scaffolding to spatiotemporally influence bone tissue development.;No studies have investigated the potential impact biomolecule-laden bone-like mineral has on influencing cell behavior. The work presented in this thesis is first to design dual-functioning peptides to increase in vitro cell attachment on bone-like mineral. Using a combinatorial phage library, computational modeling, and biological assays, specific peptide sequences that preferentially adsorb to bone-like mineral and attach to clonally derived human bone marrow stromal cells (hBMSCs) were identified. When combined, these sequences formed a dual-functioning peptide that exhibited an increased ability to attach hBMSCs compared to previous peptide designs. Additionally, a bioreactor was designed to coat three-dimensional porous scaffolds with uniform, continuous bone-like mineral, addressing a need for improved biomimetic coating fabrication techniques. The presented strategies can influence guided bone growth and advance the current methodologies in bone engineering. This work provides a new paradigm for peptide development linking organics to inorganics, not only for bone tissue engineered constructs, but also for any system requiring temporary or guided adhesion. |
