Abstract
The ability to effectively repair craniomaxillofacial (CMF) bone defects in a fully functional and aesthetically pleasing manner is essential to maintain physical and psychological health. Current challenges for CMF repair therapies include the facts that craniofacial bones exhibit highly distinct properties as compared to axial and appendicular bones, including their unique sizes, shapes and contours, and mechanical properties that enable the ability to support teeth and withstand the strong forces of mastication. The study described here examined the ability for tyrosine-derived polycarbonate, E1001(1K)/β-TCP scaffolds seeded with human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) to repair critical sized alveolar bone defects in an in vivo rabbit mandible defect model. Human dental pulp stem cells are uniquely suited for use in CMF repair in that they are derived from the neural crest, which naturally contributes to CMF development. E1001(1k)/β-TCP scaffolds provide tunable mechanical and biodegradation properties, and are highly porous, consisting of interconnected macro- and micropores, to promote cell infiltration and attachment throughout the construct. Human dental pulp stem cells/HUVECs seeded and acellular E1001(1k)/β-TCP constructs were implanted for one and three months, harvested and analyzed by micro-computed tomography, then demineralized, processed and sectioned for histological and immunohistochemical analyses. Our results showed that hDPSC seeded E1001(1k)/β-TCP constructs to support the formation of osteodentin-like mineralized jawbone tissue closely resembling that of natural rabbit jaw bone. Although unseeded scaffolds supported limited alveolar bone regeneration, more robust and homogeneous bone formation was observed in hDPSC/HUVEC-seeded constructs, suggesting that hDPSCs/HUVECs contributed to enhanced bone formation. Importantly, bioengineered jaw bone recapitulated the characteristic morphology of natural rabbit jaw bone, was highly vascularized, and exhibited active remodeling by the presence of osteoblasts and osteoclasts on newly formed bone surfaces. In conclusion, these results demonstrate, for the first time, that E1001(1K)/ β-TCP scaffolds pre-seeded with human hDPSCs and HUVECs contributed to enhanced bone formation in an in vivo rabbit mandible defect repair model as compared to acellular E1001(1K)/β-TCP constructs. These studies demonstrate the utility of hDPSC/HUVEC-seeded E1001(1K)/β-TCP scaffolds as a potentially superior clinically relevant therapy to repair craniomaxillofacial bone defects.
Highlights
The most common cause for craniomaxillofacial (CMF) bone damage is acute trauma, which can result in serious health problems with respect to both the physical and psychological well-being of civilians and military personnel (Grayson et al, 2015; Gaihre et al, 2017)
The studies described here demonstrate the potential for hDPSCHUVEC seeded E1001(1k)/β-tricalcium phosphate (β-TCP) constructs as a potentially new and improved therapy to repair CMF defects
The formulation used in the studies described here, E1001(1k) derived porous scaffolds fabricated from 90 mol% desaminotyrosyl-tyrosine ethyl ester (DTE), 10 mol% DT, and 1 mol% poly(ethylene glycol) (PEG) with 1 kDa molecular weight, were shown to support robust bone regeneration in calvarial and long bone defect repair models, when the E1001(1k) scaffolds contained calcium phosphate (Kim et al, 2012, 2015; Guda et al, 2014)
Summary
The most common cause for craniomaxillofacial (CMF) bone damage is acute trauma, which can result in serious health problems with respect to both the physical and psychological well-being of civilians and military personnel (Grayson et al, 2015; Gaihre et al, 2017). Craniofacial defects are a common birth defect (1:700), which poses significant challenges for the health and development of, and reparative therapies for, affected children whose facial bones are actively growing (Caballero et al, 2017). Large CMF boney defects caused by tumor resection, trauma, and birth defects commonly require highly specialized surgical interventions due to the limited regenerative potential of craniofacial bones. Clinical approaches to repair craniofacial bone reconstruction remain quite challenging. Xenograft and allograft therapies are commonly used, clinical applications for these approaches are limited due to concerns about potential immune rejection and often inadequate bone regeneration
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