All ETDs from UAB

Advisory Committee Chair

Ho-Wook Jun

Advisory Committee Members

Renato P Camata

Dale S Feldman

Shawn R Gilbert

Amjad Javed

Timothy M Wick

Document Type

Dissertation

Date of Award

2011

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Formation of the native bone extracellular matrix (ECM) provides an attractive template for bone tissue engineering. At the cellular level, structural support and biological complexity of bone ECM are provided within a composite microenvironment that consists of an organic fibrous network reinforced by inorganic hydroxyapatite (HA) nanostructured crystals. To synthetically recreate this biphasic assembly, a bone ECM analogous scaffold comprised of self-assembling peptide amphiphile (PA) nanofibers and interspersed HA nanoparticles was investigated. The PAs have been endowed with biomolecular ligand signaling using synthetically inscribed peptide sequences (i.e. RGDS, DGEA) derived from the native bone ECM and integrated with HA nanoparticles throughout the self-assembled fibrous network to form a biphasic nanomatrix hydrogel. It was hypothesized that the biphasic hydrogel scaffold would promote enhanced osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro and improved bone healing in vivo as mediated by the inscribed ligand sequences within the PA nanofibers and embedded HA mineral source. First, bioactive PA nanomatrix coatings (i.e. PA-RGDS, PA-DGEA) were studied for osteoinductive potential with or without conditioned media, containing exogenous osteogenic supplements, to better assess the differentiating potential of inscribed ligand signaling. Then, the PA nanomatrix was transitioned to three-dimensional hydrogels, along with incorporating the biphasic HA component. Viscoelastic stability of the biphasic PA hydrogels was evaluated with different weight concentrations of HA for improved gelation, followed by confirmation of PA nanostructure self-assembly with the included HA nanoparticles. After demonstrating initial cellular viability, long-term cellularity and osteogenic differentiation of encapsulated hMSCs in different PA hydrogels were subsequently studied under in vitro conditions. Temporal progression of osteogenic maturation was assessed by gene expression of key markers. Finally, a preliminary animal study was conducted to demonstrate the bone healing capacity of the biphasic PA nanomatrix under physiological conditions using a critical size femoral defect rat model. The combination of RGDS ligand signaling and HA nanoparticles within the biphasic PA nanomatrix hydrogel demonstrated the most effective osteoinduction and comparative bone healing response. Therefore, the biphasic PA nanomatrix establishes a well-organized scaffold with increased similarity to natural bone ECM with the prospect for improved bone tissue regeneration.

Included in

Engineering Commons

Share

COinS