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

59 Citations (Scopus)

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
Pages (from-to)1763-1771
Number of pages9
JournalBiomaterials
Volume30
Issue number9
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

Fingerprint

Prodrugs
Parathyroid Hormone
Bone
Bone and Bones
Fibrinolysin
Fibrin
Bone Regeneration
Transglutaminases
Regenerative Medicine
Osteoblasts
Osteogenesis
Defects
Transplants
Grafts
Animals
Repair
Substrates
Therapeutics
Experiments

Keywords

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

ASJC Scopus subject areas

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

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

Bone healing induced by local delivery of an engineered parathyroid hormone prodrug. / Arrighi, Isabelle; Mark, Silke; Alvisi, Monica; von Rechenberg, Brigitte; Hubbell, Jeffrey A.; Schense, Jason C.

In: Biomaterials, Vol. 30, No. 9, 01.03.2009, p. 1763-1771.

Research output: Contribution to journalArticle

Arrighi, I, Mark, S, Alvisi, M, von Rechenberg, B, Hubbell, JA & Schense, JC 2009, 'Bone healing induced by local delivery of an engineered parathyroid hormone prodrug', Biomaterials, vol. 30, no. 9, pp. 1763-1771. https://doi.org/10.1016/j.biomaterials.2008.12.023
Arrighi I, Mark S, Alvisi M, von Rechenberg B, Hubbell JA, Schense JC. Bone healing induced by local delivery of an engineered parathyroid hormone prodrug. Biomaterials. 2009 Mar 1;30(9):1763-1771. https://doi.org/10.1016/j.biomaterials.2008.12.023
Arrighi, Isabelle ; Mark, Silke ; Alvisi, Monica ; von Rechenberg, Brigitte ; Hubbell, Jeffrey A. ; Schense, Jason C. / Bone healing induced by local delivery of an engineered parathyroid hormone prodrug. In: Biomaterials. 2009 ; Vol. 30, No. 9. pp. 1763-1771.
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