Bone healing induced by local delivery of an engineered parathyroid hormone prodrug

Isabelle Arrighi, Silke Mark, Monica Alvisi, Brigitte von Rechenberg, Jeffrey A. Hubbell, Jason C. Schense

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Regenerative medicine requires innovative therapeutic designs to accommodate high morphogen concentrations in local depots, provide their sustained presence, and enhance cellular invasion and directed differentiation. Here we present an example for inducing local bone regeneration with a matrix-bound engineered active fragment of human parathyroid hormone (PTH1-34), linked to a transglutaminase substrate for binding to fibrin as a delivery and cell-invasion matrix with an intervening plasmin-sensitive link (TGplPTH1-34). The precursor form displays very little activity and signaling to osteoblasts, whereas the plasmin cleavage product, as it would be induced under the enzymatic influence of cells remodeling the matrix, was highly active. In vivo animal bone-defect experiments showed dose-dependent bone formation using the PTH-fibrin matrix, with evidence of both osteoconductive and osteoinductive bone-healing mechanisms. Results showed that this PTH-derivatized matrix may have potential utility in humans as a replacement for bone grafts or to repair bone defects.

Original languageEnglish (US)
Pages (from-to)1763-1771
Number of pages9
JournalBiomaterials
Volume30
Issue number9
DOIs
StatePublished - Mar 2009

Keywords

  • Bone graft
  • Bone healing
  • Fibrin
  • Osteoblast
  • Peptide

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Fingerprint Dive into the research topics of 'Bone healing induced by local delivery of an engineered parathyroid hormone prodrug'. Together they form a unique fingerprint.

  • Cite this

    Arrighi, I., Mark, S., Alvisi, M., von Rechenberg, B., Hubbell, J. A., & Schense, J. C. (2009). Bone healing induced by local delivery of an engineered parathyroid hormone prodrug. Biomaterials, 30(9), 1763-1771. https://doi.org/10.1016/j.biomaterials.2008.12.023