Available Technology
Osteoinductive peptides to enhance bone regeneration
Technology:
Novel screening method for the unbiased selection of peptides that bind to components of the extracellular matrix (ECM)
Markets Addressed
Use of biomaterials to enhance bone regeneration has broad clinical applications that include spinal fusions and dental implants. Currently, surgical implants are coated with components of the ECM to enhance bone healing around metallic implants. These methods are problematic due to difficulties in obtaining stable attachment to the material and instability towards enzymatic degradation in the organism.
An alternative approach is to coat implants using small peptides containing only the binding sequences of known natural protein ligands. However, this approach has been limited because neither the ECM protein that induces osteoblast differentiation, nor the receptor proteins of osteoblast progenitor cells, is clearly defined.
Dr. Nagai’s mesh chambers provide a method to screen peptide and small molecule libraries in order to study the ECM and its role in tissue formation, cell mobility and differentiation. Further, the discovery of proteins that induce osteoblast differentiation is important for the development of new biomaterials that actively and selectively stimulate cellular functions important for tissue growth and healing. Use of osteoinductive peptides to enhance bone regeneration will offer several advantages, including:
• Increased stability
• Simple syntheses of short sequences
• Ability to incorporate them at much higher concentrations than full proteins
Innovations and Advantages
Dr. Nagai developed a novel high throughput screening method for the unbiased selection of peptides that bind to components of the extracellular matrix (ECM). The method uses a cell growing chamber with a mesh support that allows for cell attachment as well as delivery of reagents through the mesh. The chamber is exposed to a phage library in which each phage expresses a random peptide sequence on its surface. Phages with affinity for receptors on the target cells, such as ECM receptors on osteogenic cells, are then amplified and analyzed.
Researchers in Dr. Nagai’s laboratory then used secondary and tertiary screens on ECM-binding phages to identify peptide sequences that 1) attach to osteoblast precursors and 2) support the proliferation and differentiation of osteoblast progenitor cells. The laboratory screened 180 million random dodecamer peptides, and selected and sequenced 21 osteoinductive peptides shown to be specific to osteoblasts.
Further investigations in Dr. Nagai’s laboratory will study the acceleration of bone regeneration by novel peptides compared to commercially available peptides known to help with bone defects. This will be addressed by conducting 1) in vitro experiments to assay the functional activity and stability of each peptide, and 2) in vivo experiments to assess bone regeneration capacity of each peptide. In addition, the laboratory plans to determine the optimal delivery system for the peptides, as well as the optimal combination of multiple peptides.
Methods for the biopanning assay, as well as the osteoinductive peptides are available for worldwide, exclusive licensing.
Additional Information
Intellectual Property Status: Patent(s) pending
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Inventor(s):
Gil, Mindy
Nagai, Masazumi
Nagai, Shigemi
Categories:
For further information, please contact:
Grant Zimmermann, Director of Business Development
(617) 495-3067
Reference Harvard Case #3473