Inadequate bone cell-surface interactions associated with existing synthetic materials have hindered the development of biologically active osseous implants. The objective of this application is to engineer advanced bioadhesive materials presenting fibronectin (FN)- and collagen (COL-I)-mimetic motifs that direct osteoblast function to promote bone formation and osseointegration. Our central hypothesis is that controlled presentation of mixed integrin-specific ligands will direct cell adhesion and signaling to upregulate osteoblast differentiation and matrix mineralization thereby enhancing bone repair. The rationale for this work is that it will establish a robust biomolecular approach to overcome inadequate cell-material interactions associated with current synthetic materials.
Aim 1 : Identify surface formulations of mixed FN- and COL-I-mimetic ligands that promote osteoblastic differentiation and matrix mineralization. We hypothesize that controlled presentation of mixed integrin-specific ligands will direct osteogenic cell adhesion, osteoblast-specific gene expression, and nineralization compared to single ligand and non-functionalized surfaces. These surface formulations will then be ased to engineer biomimetic implant coatings.
Aim 2 : Evaluate the ability of integrin-specific biomimetic surfaces to promote osseointegration. It is hypothesized that titanium implants functionalized with non-fouling polymer brushes that present mixed FN- and COL-I-mimetic ligands will exhibit enhanced bone apposition and pull-out strength compared to single ligand-functionalized and unmodified implants. This work is fundamentally different from current biomimetic approaches using short adhesive peptides (e.g. RGD) in that it concentrates on engineering integrin specificity. This is a key consideration because different integrin receptors activate different signaling pathways and gene expression programs. This research is expected to yield the following outcomes: (1) valuate the extent to which presentation of multiple integrin-binding ligands enhances osteoblastic differentiation !and mineralization, and (2) establish the potential of this biomolecular approach as a robust surface treatment for osseous implants. Collectively, these studies will validate this biomolecular surface engineering approach for developing biologically active implants for enhanced bone repair.
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