Enhancing Bone Regeneration by Mimicking the Osteogenic Niche
To coax human mesenchymal stem cells toward an osteogenic lineage, we inhibit the adipogenic transcription factor peroxisome proliferator activated receptor-γ (PPAR-γ) with the small molecule GW9662. The cells secrete an extracellular matrix that mimics the composition of regenerating bone tissue. We integrating this matrix into microcarriers minimally-invasive injection of hMSCs into bone defects.
Multiscale Nanocomposite Scaffolds and Non-invasive Characterization for Bone Regeneration
We are developing a multiscale hMSC delivery scaffold that provides steady release of osteogenic small molecules and proteins from nanoparticles integrated into hydrogel scaffolds. In one project, collagen fibrils are coated with Mg-doped hydroxyapatite displaying nanoscale crystal structure closely resembling that of mineralize collagen in bone. Combined Raman and Brillouin imaging is being developed as a non-invasive method to quantify the chemical and mechanical properties of the scaffolds following mineralization in culture and after implantation in a bone defect.
High-throughput Testing of Cell Behavior in Mechanically-Loaded 3D Nanocomposites
A long-standing interest of our laboratory is cell mechanosensing of tensile mechanical loads. Our current efforts focus on cell behavior in 3-dimensional nanocomposite scaffolds. We employ nanoparticles that significantly stiffen polymer hydrogels in a concentration-dependent manner. Using gradient scaffolds and 3D printed scaffolds, we are studying the interactive effects of tensile load and matrix stiffness to influence cell structure and function.