Zhang Weibo, Zhang Zheng, Chen Shuang, Macri Lauren, Kohn Joachim, Yelick Pamela C
1 Department of Orthodontics, Division of Craniofacial and Molecular Genetics, Tufts University School of Dental Medicine , Boston, Massachusetts.
2 New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey , Piscataway, New Jersey.
Tissue Eng Part A. 2016 Jul;22(13-14):985-93. doi: 10.1089/ten.TEA.2016.0166.
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, 5.0 × 10(5) hDPCs/scaffold (CH); (2) E1001(1k)/β-TCP scaffolds seeded with a lower density of hDPCs, 2.5 × 10(5) hDPCs/scaffold (CL); (3) acellular E1001(1k)/β-TCP scaffolds (SA); (4) acellular E1001(1k)/β-TCP scaffolds supplemented with 4 μg recombinant human bone morphogenetic protein-2 (BMP); and (5) empty defects (EDs). Replicate hDPC-seeded and acellular E1001(1k)/β-TCP scaffolds were cultured in vitro in osteogenic media for 1 week before implantation for 3 and 6 weeks. Live microcomputed tomography (μCT) 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)/β-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.
在此，我们展示了一种用于牙槽颌骨再生的新模型，该模型使用人牙髓细胞（hDPCs）与含有β-磷酸三钙（β-TCP）的酪氨酸衍生聚碳酸酯聚合物支架[E1001(1k)] [E1001(1k)/β-TCP]相结合。制作了直径5毫米×厚度1毫米的E1001(1k)/β-TCP支架，以适配5毫米大鼠下颌支临界骨缺损。本研究中检测了五个实验组：（1）接种高密度hDPCs的E1001(1k)/β-TCP支架，5.0×10⁵个hDPCs/支架（CH）；（2）接种低密度hDPCs的E1001(1k)/β-TCP支架，2.5×10⁵个hDPCs/支架（CL）；（3）无细胞E1001(1k)/β-TCP支架（SA）；（4）补充有4μg重组人骨形态发生蛋白-2（BMP）的无细胞E1001(1k)/β-TCP支架；以及（5）空白缺损（ED）。接种hDPCs的和无细胞的E1001(1k)/β-TCP支架复制品在植入前于成骨培养基中体外培养1周，并植入3周和6周。植入后3周和6周的活体微型计算机断层扫描（μCT）成像显示BMP植入组有强劲的骨再生。CH组和CL组在整个缺损处均表现出类似的均匀分布的矿化组织覆盖，但少于BMP植入组。相比之下，SA处理的缺损处矿化组织再生区域稀疏。ED组缺损尺寸略有减小。组织学分析未显示免疫反应迹象。此外，在接种hDPCs的支架中观察到牙本质和骨分化标志物的强劲表达，而相比之下，BMP和SA植入物仅表现出骨而非牙本质分化标志物的表达。在接种hDPCs的支架组3周时检测到hDPCs，但6周时未检测到，表明它们至少存活了3周。总之，这些结果表明接种hDPCs的E1001(1k)/β-TCP支架支持类骨牙本质矿化颌组织的快速再生，为牙槽颌骨修复和再生提出了一种有前景的新疗法。
