480546 Inductive Properties of Simple Signaling Molecules
Inductive Properties of Simple Signaling Molecules
Brittany N. Allen1, Soheila Aliakbarighavimi2, Ram Rao Tata2, Andrew J. Greenwald2, Bret D. Ulery1,2
1Department of Bioengineering, University of Missouri, Columbia, MO 65211
2Department of Chemical Engineering, University of Missouri, Columbia, MO 65211
Regenerative engineering is an exciting field that combines expertise from materials science, developmental biology, and stem cell science to achieve the repair of complex tissues. While many advances have been made over the past quarter of a century in this field, engineered solutions capable of achieving higher-order tissue regeneration have yet to be translated to the clinic. Nowhere is this more apparent than in bone regeneration for which commercially available solutions improve small fracture healing but are sub-optimal for the large volume repair necessary for non-union bone defects due to traumatic injury or tumor removal. One reason for this bottleneck is that most technologies focus on the use of polymeric scaffolds loaded with proteinaceous growth factors which have significant drawbacks including their cost, fragility, poor processability, potential immunogenicity, and high dosage requirements. An alternative to protein growth factors are simple signaling molecules which are a group of ions, redox reagents, and gases that have been found to possess potent bioactivity. In specific, calcium and phosphate ions have been found to induce osteogenesis in mesenchymal stem cells (MSCs) and hydrogen peroxide has been found to induce angiogenesis in endothelial progenitor cells (EPCs). It was hypothesized that controllably delivering these simple signaling molecules can allow for the regeneration of high-quality, complex bone tissue.
To controllably deliver single signaling molecules, we fabricated a variety of novel polyesters and infused them with a rapidly decomposing ceramic (monobasic calcium phosphate MCP) to form a composite material. Calcium and phosphate ion release from each polymer/ceramic composite was evaluated over the course of 14 days as well as the release products impact on MSC health and differentiation. At selected time points, alkaline phosphatase production and Alizarin Red staining were measured to determine differentiation and mineralization, respectively. Cell viability and proliferation were assessed by commercial colorimetric and fluorometric assays. All composites materials as well as MCP alone showed stable cell numbers indicating a lack of cellular division commonly found in differentiated cells. Further assessment showed that MSCs exposed to the composite materials had enhanced alkaline phosphatase expression and more quickly mineralized compared to MCP alone. Experiments with hydrogen peroxide generating molecules like barium peroxide and strontium peroxide have shown controllable release of this simple signaling molecule. Preliminary cell experiments show the existence of a biocompatible range with this molecule though further studies need to be conducted to determine its therapeutic window. Taken together, these results provide considerable evidence for the utility of materials-based release of simple signaling molecules for bone regenerative engineering applications.
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