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Expanded skeletal stem and progenitor cells promote and participate in induced bone regeneration at subcritical BMP-2 dose


Papageorgiou, Panagiota; Vallmajo-Martin, Queralt; Kisielow, Malgorzata; Sancho-Puchades, Alejandro; Kleiner, Esther; Ehrbar, Martin (2019). Expanded skeletal stem and progenitor cells promote and participate in induced bone regeneration at subcritical BMP-2 dose. Biomaterials, 217:119278.

Abstract

The regeneration of large bone defects remains an unsolved clinical problem, which could benefit from recent findings on the biology of skeletal stem and progenitor cells. The elucidation of conditions to specifically control their dynamic and function will likely enable the development of novel treatment strategies. In this study, we aimed at dissecting the role of osteogenic cues and skeletal stem (SSC) and progenitor cell (BCSP) recruitment during biomimetic hydrogel-assisted bone regeneration. To do so, we employed a biomimetic synthetic hydrogel based on poly (ethylene glycol) (PEG), highly controllable and enzymatically crosslinkable. We show that hydrogel-released bone morphogenetic protein-2 (BMP-2) dose-dependently promoted the enrichment of both SSCs and BCSPs within bone defects. Furthermore, we demonstrate that prospectively isolated neonatal bone-derived, as well as expanded SSCs and BCSPs, differentiate into osteogenic cells and enhance the healing of bone defects by low BMP-2 releasing biomaterials. These results indicate that growth factor releasing materials should be designed to first augment the number of SSCs and BCSPs, followed by their osteogenic differentiation to potentiate the healing of bone defects. Additionally, we demonstrate that expanded SSCs and BCSPs are easily accessible cell sources that allow the study of novel bone healing regimen under controlled in vitro and in vivo conditions.

Abstract

The regeneration of large bone defects remains an unsolved clinical problem, which could benefit from recent findings on the biology of skeletal stem and progenitor cells. The elucidation of conditions to specifically control their dynamic and function will likely enable the development of novel treatment strategies. In this study, we aimed at dissecting the role of osteogenic cues and skeletal stem (SSC) and progenitor cell (BCSP) recruitment during biomimetic hydrogel-assisted bone regeneration. To do so, we employed a biomimetic synthetic hydrogel based on poly (ethylene glycol) (PEG), highly controllable and enzymatically crosslinkable. We show that hydrogel-released bone morphogenetic protein-2 (BMP-2) dose-dependently promoted the enrichment of both SSCs and BCSPs within bone defects. Furthermore, we demonstrate that prospectively isolated neonatal bone-derived, as well as expanded SSCs and BCSPs, differentiate into osteogenic cells and enhance the healing of bone defects by low BMP-2 releasing biomaterials. These results indicate that growth factor releasing materials should be designed to first augment the number of SSCs and BCSPs, followed by their osteogenic differentiation to potentiate the healing of bone defects. Additionally, we demonstrate that expanded SSCs and BCSPs are easily accessible cell sources that allow the study of novel bone healing regimen under controlled in vitro and in vivo conditions.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Obstetrics
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Biophysics, Mechanics of Materials, Bioengineering, Biomaterials, Ceramics and Composites
Language:English
Date:1 October 2019
Deposited On:25 Jul 2019 08:51
Last Modified:25 Sep 2019 00:37
Publisher:Elsevier
ISSN:0142-9612
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.biomaterials.2019.119278
Project Information:
  • : FunderFP7
  • : Grant ID607868
  • : Project TitleITERM - Training scientists to develop and Image materials for Tissue Engineering and Regenerative Medicine

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