Bone allografts provide an essential alternative to autografts. However, there is a significant need
to improve host osteointegration of allografts, as without it, allografts have no mechanism of
repair, eventually rendering them incompetent to support a structural load. The critical barriers of
allograft osteointegration are limited techniques to i) support either pre- or post-transplant graft
loading with host progenitor cells and ii) drive osteogenesis within the graft. To overcome these
barriers, we hypothesize that the application of a ‘synthetic periosteum’ composed of ceramic
polyphosphate (polyP), contained within a hydrogel to the outer surface of a structural allograft,
is sufficient to recruit host progenitor cells and instigate osteointegration of the graft. This
approach is innovative as it takes account i) the novel capacity of ceramic-polyP to drive
progenitor recruitment and osteogenesis, ii) the physical design of applying the biologic to the
periphery of the graft in order to harness the main pool of host progenitor cells located in the
periosteum and muscle, and iii) that ossification is driven by endochondral mechanisms, which is
well suited to overcome hypoxia within the grafting microenvironment. In Aim 1 we will use
innovative genetic tracing animal models, in vivo imaging, and sensitive endpoint measures, to
design the optimal hydrogel-ceramic-polyP construct that promotes their required biological
potential (progenitor cell recruitment/expansion and endochondral ossification), while limiting
possible toxicity (inflammation/apoptosis). Guided by these results, in Aim 2 we will then examine
the optimized hydrogel-polyP-NP coating on allografts implanted in a femoral murine critical size
defect model. If our hypothesis is proven true, the application of a hydrogel-ceramic-polyP as a
synthetic periosteum offers a practical and cost-effective alternative to directly implanting
progenitor cells pre-transplant. Compared to previously proposed organic biological constructs
(rBMP2, mesenchymal stem cells, etc.), this hydrogel-polyP-NP construct is designed to be cost-
effective, shelf-stable, and result in limited toxicity and host-rejection, making it promising for
clinical translation. Therefore, these materials are well positioned for rapid, cost-effective, clinical
application globally, not just in first-world medical communities that can afford medical
technologies such as recombinant proteins.