Tricalcium Phosphate Binding Peptides and Proteins

Technology 

The technology operates by first identifying peptides with high affinity for β-tricalcium phosphate (β-TCP) through phage display screening. These β-TCP binding peptides are genetically fused to therapeutic proteins or peptides such as epidermal growth factor (EGF) to form fusion constructs. When applied to β-TCP scaffolds, the peptides facilitate stable, non-covalent attachment of the fusion proteins to the scaffold surface. This immobilization enables localized delivery of the therapeutic agents directly at the site of implantation or cell culture. The functionalized scaffolds can then be used to support mesenchymal stem cell (MSC) proliferation, enhance survival under stress conditions, and promote tissue regeneration such as bone repair. The platform is also highly adaptable, allowing for different proteins or peptides to be tethered depending on the desired therapeutic outcome. 

Problem Addressed 

β-TCP (or BTCP) is a widely used biomaterial in bone repair, commonly employed to fill bone voids and featured in orthopedic products like putties and pastes due to its ability to conform to irregular wound geometries. However, its clinical utility is limited by its lack of modifiable surface chemistry and suboptimal handling characteristics. Traditional bone repair strategies often rely on combining β-TCP with soluble growth factors to stimulate tissue regeneration. Unfortunately, these growth factors tend to diffuse away from the implantation site and degrade rapidly, diminishing their therapeutic effectiveness. As a result, higher doses and repeated administrations are often required, which increases the risk of side effects and raises the overall cost of treatment.  This technology addresses these limitations by enabling the stable, surface-tethered delivery of bioactive molecules to β-TCP scaffolds, enhancing localized therapeutic effects, reducing growth factor loss, and improving regenerative outcomes in challenging conditions such as osteoporosis-related fractures. 

Advantages 

• Enables localized delivery of therapeutic agents, enhancing efficacy. 
• Improves MSC proliferation and survival under stress conditions, creating a supportive microenvironment for regeneration. 
• Adaptable platform allows for the tethering of various therapeutic proteins and peptides, supporting a broad range of applications.  
• Prolongs therapeutic effect by preventing rapid diffusion and degradation of growth factors, reducing the need for high doses or repeat administration. 

Publications

Alvarez, L. M., J. J. Rivera, L. Stockdale, S. Saini, R. T. Lee, and others. "Tethering of Epidermal Growth Factor (EGF) to Beta Tricalcium Phosphate (βTCP) via Fusion to a High Affinity, Multimeric βTCP-Binding Peptide: Effects on Human Multipotent Stromal Cells/Connective Tissue Progenitors." PLOS ONE 10, no. 6 (2015): e0129600. https://doi.org/10.1371/journal.pone.0129600.