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.

Confluent hMSCs on PEEK, coated with hMatrix. SEM. Courtesy of Robert Reese.
Confluent hMSCs on PEEK, coated with hMatrix. SEM. Courtesy of Robert Reese.

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.

Scanning-electron micrograph of fabricated gelatin/hydroxyapatite nanocomposite scaffold. Azami et al. From "Gelatin/hydroxyapatite nanocomposite scaffolds for bone repair". 9 August 2010.
Scanning-electron micrograph of fabricated gelatin/hydroxyapatite nanocomposite scaffold. Azami et al. From "Gelatin/hydroxyapatite nanocomposite scaffolds for bone repair". 9 August 2010.

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.

Osteogenically differentiated hMSCs. Courtesy of Biological Industries.