Development of Smoothened Agonist Non Phospholipid Liposomal Nanoparticles for Bone Repair

Abstract

Non-healing bone defects remain a significant problem for combat casualties and military veterans. A principle challenge is to develop therapeutic agents that safely and effectively improve growth and differentiation factor (GDF) based skeletal regeneration. The manipulation of Hedgehog signaling is a promising alternative to BMP2 for improved bone repair outcomes. Recently, we observed that the small molecule Hedgehog agonist SAG demonstrates pro-osteogenic / pro-vasculogenic effects to induce mouse calvarial defect healing. Independently, we have developed innately osteoinductive Stearylamine and Oxysterol (SA/Oxy) nanoparticles (NPs), and showed their high drug loading efficiency and synergistic osteoinductive potential with the small molecule SAG. In the current proposal, we will combine these recent breakthroughs to develop a next generation NP packaged small molecule as a bone graft substitute product to jumpstart endogenous bone repair.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2020
Accession Number
AD1114533

Entities

People

  • Aaron W James

Organizations

  • Johns Hopkins University

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Bone Regeneration
  • California
  • Cells
  • Cells (Biology)
  • Chemical Reactions
  • Department Of Defense
  • Electron Microscopy
  • Engineering
  • Materials
  • Medical Personnel
  • Membrane Lipids
  • Military Medicine
  • Molecules
  • Nanoparticles
  • Osteogenesis
  • Polymerase Chain Reaction
  • Scanning Electron Microscopy
  • Self Assembly
  • Small Molecules
  • Stem Cells
  • Surgery
  • Therapy
  • Three Dimensional
  • Tissue Engineering

Readers

  • Immunology and Pathology
  • Nanocomposite Materials Science
  • Trauma Surgery or Emergency Medicine.

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech