Dataset Information

Mandibular Jaw Bone Regeneration Using Human Dental Cell-Seeded Tyrosine-Derived Polycarbonate Scaffolds.

ABSTRACT: Here we present a new model for alveolar jaw bone regeneration, which uses human dental pulp cells (hDPCs) combined with tyrosine-derived polycarbonate polymer scaffolds [E1001(1k)] containing beta-tricalcium phosphate (?-TCP) [E1001(1k)/?-TCP]. E1001(1k)/?-TCP scaffolds (5?mm diameter?×?1?mm thickness) were fabricated to fit a 5?mm rat mandibular ramus critical bone defect. Five experimental groups were examined in this study: (1) E1001(1k)/?-TCP scaffolds seeded with a high density of hDPCs, 5.0?×?10(5) hDPCs/scaffold (CH); (2) E1001(1k)/?-TCP scaffolds seeded with a lower density of hDPCs, 2.5?×?10(5) hDPCs/scaffold (CL); (3) acellular E1001(1k)/?-TCP scaffolds (SA); (4) acellular E1001(1k)/?-TCP scaffolds supplemented with 4??g recombinant human bone morphogenetic protein-2 (BMP); and (5) empty defects (EDs). Replicate hDPC-seeded and acellular E1001(1k)/?-TCP scaffolds were cultured in vitro in osteogenic media for 1 week before implantation for 3 and 6 weeks. Live microcomputed tomography (?CT) imaging at 3 and 6 weeks postimplantation revealed robust bone regeneration in the BMP implant group. CH and CL groups exhibited similar uniformly distributed mineralized tissue coverage throughout the defects, but less than the BMP implants. In contrast, SA-treated defects exhibited sparse areas of mineralized tissue regeneration. The ED group exhibited slightly reduced defect size. Histological analyses revealed no indication of an immune response. In addition, robust expression of dentin and bone differentiation marker expression was observed in hDPC-seeded scaffolds, whereas, in contrast, BMP and SA implants exhibited only bone and not dentin differentiation marker expression. hDPCs were detected in 3-week but not in 6-week hDPC-seeded scaffold groups, indicating their survival for at least 3 weeks. Together, these results show that hDPC-seeded E1001(1k)/?-TCP scaffolds support the rapid regeneration of osteo-dentin-like mineralized jaw tissue, suggesting a promising new therapy for alveolar jaw bone repair and regeneration.

SUBMITTER: Zhang W

PROVIDER: S-EPMC4985268 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Mandibular Jaw Bone Regeneration Using Human Dental Cell-Seeded Tyrosine-Derived Polycarbonate Scaffolds.

Zhang Weibo W Zhang Zheng Z Chen Shuang S Macri Lauren L Kohn Joachim J Yelick Pamela C PC

Tissue engineering. Part A 20160701 13-14

Here we present a new model for alveolar jaw bone regeneration, which uses human dental pulp cells (hDPCs) combined with tyrosine-derived polycarbonate polymer scaffolds [E1001(1k)] containing beta-tricalcium phosphate (β-TCP) [E1001(1k)/β-TCP]. E1001(1k)/β-TCP scaffolds (5 mm diameter × 1 mm thickness) were fabricated to fit a 5 mm rat mandibular ramus critical bone defect. Five experimental groups were examined in this study: (1) E1001(1k)/β-TCP scaffolds seeded with a high density of hDPCs, 5 ...[more]

PMID: 27369635

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Project description: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)/?-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)/?-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)/?-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)/?-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)/ ?-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)/?-TCP constructs. These studies demonstrate the utility of hDPSC/HUVEC-seeded E1001(1K)/?-TCP scaffolds as a potentially superior clinically relevant therapy to repair craniomaxillofacial bone defects.

Dataset Information

Mandibular Jaw Bone Regeneration Using Human Dental Cell-Seeded Tyrosine-Derived Polycarbonate Scaffolds.

Publications

Mandibular Jaw Bone Regeneration Using Human Dental Cell-Seeded Tyrosine-Derived Polycarbonate Scaffolds.

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