Rapid healing of a critical-sized bone defect using a collagen-hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery.pdf (1.03 MB)
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Rapid healing of a critical-sized bone defect using a collagen-hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery

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posted on 24.03.2020 by David Walsh, Rosanne Raftery, Gang Chen, Andreas Heise, Fergal O'Brien, Sally-Ann Cryan
The healing of large, critically sized bone defects remains an unmet clinical need in modern orthopaedic medicine. The tissue engineering field is increasingly using biomaterial scaffolds as 3D templates to guide the regenerative process, which can be further augmented via the incorporation of recombinant growth factors. Typically, this necessitates supraphysiological doses of growth factor to facilitate an adequate therapeutic response. Herein, we describe a cell-free, biomaterial implant which is functionalised with a low dose, combinatorial growth factor therapy that is capable of rapidly regenerating vascularised bone tissue within a critical-sized rodent calvarial defect. Specifically, we demonstrate that the dual delivery of the growth factors bone morphogenetic protein-2 (osteogenic) and vascular endothelial growth factor (angiogenic) at a low dose (5 μg/scaffold) on an osteoconductive collagen-hydroxyapatite scaffold is highly effective in healing these critical-sized bone defects. The high affinity between the hydroxyapatite component of this biomimetic scaffold and the growth factors functions to sequester them locally at the defect site. Using this growth factor-loaded scaffold, we show complete bridging of a critical-sized calvarial defect in all specimens at a very early time point of 4 weeks, with a 28-fold increase in new bone volume and seven-fold increase in new bone area compared with a growth factor-free scaffold. Overall, this study demonstrates that a collagen-hydroxyapatite scaffold can be used to locally harness the synergistic relationship between osteogenic and angiogenic growth factors to rapidly regenerate bone tissue without the need for more complex controlled delivery vehicles or high total growth factor doses.

Funding

Science Foundation Ireland Investigators Program 13/IA/1840

Advanced Materials and Bioengineering Research (AMBER) Centre through SFI/12/RC/2278

History

Comments

This is the pre-peer reviewed version of the following article: Walsh DP, Raftery RM, Chen G, Heise A, O’Brien FJ, Cryan SA. Rapid healing of a critical-sized bone defect using a collagen-hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery. Journal of Tissue Engineering and Regenerative Medicine. 2019;13(10):1843-1853 which has been published in final form at https://doi.org/10.1002/term.2934. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Published Citation

Walsh DP, Raftery RM, Chen G, Heise A, O’Brien FJ, Cryan SA. Rapid healing of a critical-sized bone defect using a collagen-hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery. Journal of Tissue Engineering and Regenerative Medicine. 2019;13(10):1843-1853

Publication Date

08/08/2019

Publisher

Wiley

PubMed ID

31306563

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