Rapid healing of a critical-sized bone defect using a collagen-hydroxyapatite scaffold to facilitate low dose, combinatorial growth factor delivery
David P. Walsh
Drug Delivery and Advanced Materials Team, School of Pharmacy, RCSI, Dublin, Ireland
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland
Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin, Ireland
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Search for more papers by this authorRosanne M. Raftery
Drug Delivery and Advanced Materials Team, School of Pharmacy, RCSI, Dublin, Ireland
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland
Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin, Ireland
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Search for more papers by this authorGang Chen
Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders, Microsurgical Research and Training Facility (MRTF), RCSI, Dublin, Ireland
Search for more papers by this authorAndreas Heise
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Department of Chemistry, RCSI, Dublin, Ireland
Centre for Research in Medical Devices (CURAM), RCSI, Dublin and National University of Ireland, Galway, Ireland
Search for more papers by this authorFergal J. O'Brien
Drug Delivery and Advanced Materials Team, School of Pharmacy, RCSI, Dublin, Ireland
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland
Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin, Ireland
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Centre for Research in Medical Devices (CURAM), RCSI, Dublin and National University of Ireland, Galway, Ireland
Search for more papers by this authorCorresponding Author
Sally-Ann Cryan
Drug Delivery and Advanced Materials Team, School of Pharmacy, RCSI, Dublin, Ireland
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland
Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin, Ireland
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Centre for Research in Medical Devices (CURAM), RCSI, Dublin and National University of Ireland, Galway, Ireland
Correspondence
Professor Sally-Ann Cryan, School of Pharmacy, Royal College of Surgeons in Ireland, 1st Floor, Ardilaun House (Block B), Dublin 2, Ireland.
Email: [email protected]
Search for more papers by this authorDavid P. Walsh
Drug Delivery and Advanced Materials Team, School of Pharmacy, RCSI, Dublin, Ireland
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland
Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin, Ireland
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Search for more papers by this authorRosanne M. Raftery
Drug Delivery and Advanced Materials Team, School of Pharmacy, RCSI, Dublin, Ireland
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland
Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin, Ireland
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Search for more papers by this authorGang Chen
Department of Physiology and Medical Physics, Centre for the Study of Neurological Disorders, Microsurgical Research and Training Facility (MRTF), RCSI, Dublin, Ireland
Search for more papers by this authorAndreas Heise
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Department of Chemistry, RCSI, Dublin, Ireland
Centre for Research in Medical Devices (CURAM), RCSI, Dublin and National University of Ireland, Galway, Ireland
Search for more papers by this authorFergal J. O'Brien
Drug Delivery and Advanced Materials Team, School of Pharmacy, RCSI, Dublin, Ireland
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland
Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin, Ireland
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Centre for Research in Medical Devices (CURAM), RCSI, Dublin and National University of Ireland, Galway, Ireland
Search for more papers by this authorCorresponding Author
Sally-Ann Cryan
Drug Delivery and Advanced Materials Team, School of Pharmacy, RCSI, Dublin, Ireland
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, RCSI, Dublin, Ireland
Trinity Centre for Biomedical Engineering, Trinity College Dublin (TCD), Dublin, Ireland
Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI, TCD, Dublin, Ireland
Centre for Research in Medical Devices (CURAM), RCSI, Dublin and National University of Ireland, Galway, Ireland
Correspondence
Professor Sally-Ann Cryan, School of Pharmacy, Royal College of Surgeons in Ireland, 1st Floor, Ardilaun House (Block B), Dublin 2, Ireland.
Email: [email protected]
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST
The authors have no conflict of interest to declare.
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