Biomaterials for Orthopaedic Implants and Bone RegenerationPublic Deposited
For bone regeneration, there is need for biodegradable, synthetic scaffolds that direct the formation of <em>de novo</em> mineralized tissue. Orthopaedic implants additionally require mechanical function. The work described herein attempts to address both of these needs. The general strategy involves integrating molecularly designed tissue engineering scaffolds with porous metallic foams to create hybrid materials to direct cellular behavior. Peptide amphiphiles (PAs) that self-assemble into nanofibers were designed to template hydroxyapatite mineral under biological conditions. The molecular design incorporated either serine (S) or phosphoserine S(P) and was mixed with RGDS-bearing PA to evaluate of the key parameters for mineral formation. This led to the discovery of nanoscale hydroxyapatite spheres templated on both S- and S(P)-bearing PA nanofibers. Stem cells were encapsulated in these gels and RT-PCR showed osteoblastic differentiation in all samples. Osteoblast maturation was increased in S-bearing PA compared to S(P)-bearing PA, although the reason is not yet understood. A method to create robust PA nanofiber coatings on NiTi was developed by optimizing the NiTi oxide surface chemistry, optimizing silane vapor deposition, and covalently attaching the PAs to the silanized substrate. The surfaces were characterized by XPS, SIMS, AFM, and fluorimetry. <em>In vitro</em> experiments demonstrated the importance of covalent attachment for cellular adhesion and proved the materials were not cytotoxic. Orthopaedic hybrid materials were created by triggering PA self-assembly within the interconnected pores of Ti foams developed by the Dunand research group. <em>In vitro</em> experiments demonstrate that pre-osteoblasts adhere to, proliferate on, and migrate into PA-Ti hybrids made with S(P)- and RGDS-bearing PA mixtures. The cells differentiate into mature osteoblasts and remain viable up to 28 days. In vivo</em> studies using a rat model demonstrate osteointegration and boney ingrowth into bare Ti foams and PA-Ti hybrids. Histology suggests that the PA-filled Ti foams may improve <em>de novo</em> bone formation and boney ingrowth compared to bare Ti foams, particularly with the serine PA, which correlates with the <em>in vitro</em> results. These findings suggest that molecularly designed self-assembling PAs are an excellent system to study biomimetic mineralization and offer potential as an osteogenic material for bone regeneration and orthopaedic implant modification.
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