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Translating the role of osteogenic-angiogenic coupling in bone formation: Highly efficient chitosan-pDNA activated scaffolds can accelerate bone regeneration in critical-sized bone defects.

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posted on 2021-10-01, 16:45 authored by Rosanne Raftery, Irene Mencía Castaño, Gang Chen, Brenton CavanaghBrenton Cavanagh, Brian Quinn, Caroline CurtinCaroline Curtin, Sally-Ann CryanSally-Ann Cryan, Fergal O'BrienFergal O'Brien

The clinical translation of bioactive scaffolds for the treatment of large segmental bone defects has remained a challenge due to safety and efficacy concerns as well as prohibitive costs. The design of an implantable, biocompatible and resorbable device, which can fill the defect space, allow for cell infiltration, differentiation and neovascularisation, while also recapitulating the natural repair process and inducing cells to lay down new bone tissue, would alleviate the problems with existing treatments. We have developed a gene-activated scaffold platform using a bone-mimicking collagen hydroxyapatite scaffold loaded with chitosan nanoparticles carrying genes encoding osteogenic (BMP-2) and angiogenic (VEGF) proteins. With a single treatment, protein expression by mesenchymal stem cells (MSCs) seeded onto the scaffold is sustained for up to 28 days and is functional in inducing MSC osteogenesis. The in vivo safety and efficacy of this gene-activated scaffold platform was demonstrated resulting in the successful transfection of host cells, abrogating the requirement for multiple procedures to isolate cells or ex vivo cell culture. Furthermore, the level of bone formation at the exceptionally early time-point of 28 days was comparable to that achieved following recombinant BMP-2 protein delivery after 8 weeks in vivo, without the adverse side effects and at a fraction of the cost. This naturally derived cell-free gene-activated scaffold thus represents a new 'off-the-shelf' product capable of accelerating bone repair in critical-sized bone defects.

Funding

This work was funded by Science Foundation Ireland (SFI) Research Frontiers Programme (Grant No. 11/RFP/ENM/3053) and the SFI AMBER research centre.

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This article is also available at https://www.journals.elsevier.com/biomaterials/

Published Citation

Raftery RM, Mencía Castaño I, Chen G, Cavanagh B, Quinn B, Curtin CM, Cryan SA, O'Brien FJ. Translating the role of osteogenic-angiogenic coupling in bone formation: Highly efficient chitosan-pDNA activated scaffolds can accelerate bone regeneration in critical-sized bone defects. Biomaterials. 2017;149:116-127.

Publication Date

2017-12-01

PubMed ID

29024837

Department/Unit

  • Tissue Engineering Research Group (TERG)
  • Anatomy and Regenerative Medicine
  • Amber (Advanced Material & Bioengineering Research) Centre
  • School of Pharmacy and Biomolecular Sciences
  • Physiology and Medical Physics

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