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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journal contribution
posted on 2020-03-24, 16:13 authored by David Walsh, Rosanne Raftery, Gang ChenGang Chen, Andreas HeiseAndreas Heise, Fergal O'BrienFergal O'Brien, Sally-Ann CryanSally-Ann CryanThe 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.