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


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.

Abstract

Regenerative medicine requires innovative therapeutic designs to accommodate hight 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-glutaminase 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.

Abstract

Regenerative medicine requires innovative therapeutic designs to accommodate hight 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-glutaminase 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.

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42 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Equine Department
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Language:English
Date:March 2009
Deposited On:13 Mar 2009 13:56
Last Modified:05 Apr 2016 13:01
Publisher:Elsevier
ISSN:0142-9612
Publisher DOI:https://doi.org/10.1016/j.biomaterials.2008.12.023
PubMed ID:19124152

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