Design of Peptides with Targeted Apatite and Human Bone Marrow Stromal CellAdhesion for Bone Tissue Engineering.

Bone Tissue Engineering;Phage Display;Peptide;Cell Attachment;Bone-like Mineral;Biomedical Engineering;Engineering;Biomedical Engineering

Segvich, Sharon JanellTakayama, Shuichi ;

University of Michigan

关键词: Bone Tissue Engineering;    Phage Display;    Peptide;    Cell Attachment;    Bone-like Mineral;    Biomedical Engineering;    Engineering;    Biomedical Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/61615/ssegvich_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

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.