Use of Human Dental Pulp and Endothelial Cell Seeded Tyrosine-Derived Polycarbonate Scaffolds for Robust in vivo Alveolar Jaw Bone Regeneration

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 osteodentinlike 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

Bioactive Scaffolds as a Promising Alternative for Enhancing Critical-Size Bone Defect Regeneration in the Craniomaxillofacial Region

“…In this case, cellular scaffolds showed more homogeneous bone formation and vascularization when compared to defects grafted with acellular scaffolds. 55 Further research showed that hDPSCs seeded on PCL/BCP scaffolds and then implanted into rabbit cranial CSDs promoted bone formation and maturation. 246 5III).…”

Tyrosine-Derived Polymers as Potential Biomaterials: Synthesis Strategies, Properties, and Applications

“…Notably, HDPC seeded scaffolds strongly expressed dentin sialophosphoprotein, along with osteocalcin and angiogenic marker F8, which was found absent in acellular scaffolds after 3 months of implantation. 161 Recently, Saxena et al investigated craniomaxillofacial bone regeneration in an E1001(1k) scaffold, incorporated with dicalcium phosphate dihydrate (DCPD), an osteoconductive coating to overcome the limitations of traditionally used BGS. Herein, the fabricated E1001(1k)/DCPD, E1001(1k)/β-TCP, and E1001(1k) scaffolds showed bimodal porous structures with interconnected micro-and macropores.…”

“…(iv) Rabbit mandible defect model created by drilling the buccal cortex, and the subsequent replacement with E1001­(1k)/β-TCP scaffolds. Reprinted with permission under a Creative Commons (CC-BY 4.0) License from ref . Copyright 2020 Frontiers Media S.A.…”

“…In addition, HDPC or HUVEC seeded E1001­(1k)/β-TCP demonstrated active cell remodeling and a response to mechanical forces and imparts proper size as well as shape to affected bones. Notably, HDPC seeded scaffolds strongly expressed dentin sialophosphoprotein, along with osteocalcin and angiogenic marker F8, which was found absent in acellular scaffolds after 3 months of implantation …”

Potential application of dental stem cells in regenerative reconstruction of oral and maxillofacial tissues: a narrative review

“…Using a mandibular distraction model in New Zealand white rabbits, Alkaisi et al showed that SHED can significantly enhance mandibular distraction osteogenesis (DO) (79). Most recently, Zhang et al showed that transplantation of hDPSC/endothelial cells (HUVEC)seeded E1001(1K)/β-TCP scaffolds significantly enhance bone formation in critical-sized alveolar bone defects in an in vivo rabbit mandible defect model (77). Gutiérrez-Quintero reported that transplantation of DPSCs seeded with hydroxyapatite matrix and polylactic polyglycolic acid (HA/PLGA) scaffolds also significantly augmented bone regeneration in bilateral mandibular critical-sized defects in rabbits (78) (96).…”