1 Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University , Taipei, Taiwan .
Tissue Eng Part A. 2014 Jan;20(1-2):356-64. doi: 10.1089/ten.TEA.2012.0687. Epub 2013 Oct 17.
Timely augmentation of the physiological events of dentoalveolar repair is a prerequisite for the optimization of the outcome of regeneration. This study aimed to develop a treatment strategy to promote dentoalveolar regeneration by the combined delivery of the early mitogenic factor platelet-derived growth factor (PDGF) and the late osteogenic differentiation factor simvastatin.
By using the coaxial electrohydrodynamic atomization technique, PDGF and simvastatin were encapsulated in a double-walled poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) (PDLLA-PLGA) microspheres in five different modes: microspheres encapsulating bovine serum albumin (BB), PDGF alone (XP), simvastatin alone (SB), PDGF-in-core and simvastatin-in-shell (PS), and simvastatin-in-core and PDGF-in-shell (SP). The microspheres were characterized using scanning electronic microscopy, and the in vitro release profile was evaluated. Microspheres were delivered to fill large osteotomy sites on rat maxillae for 14 and 28 days, and the outcome of regeneration was evaluated by microcomputed tomography and histological assessments.
Uniform 20-μm controlled release microspheres were successfully fabricated. Parallel PDGF-simvastatin release was noted in the PS group, and the fast release of PDGF followed by the slow release of simvastatin was noted in the SP group. The promotion of osteogenesis was observed in XP, PS, and SP groups at day 14, whereas the SP group demonstrated the greatest bone fill, trabecular numbers, and thickest trabeculae. Bone bridging was evident in the PS and SP group, with significantly increased osteoblasts in the SP group, and osteoclastic cell recruitment was promoted in all bioactive molecule-treated groups. At day 28, osteogenesis was promoted in all bioactive molecule-treated groups. Initial corticalization was noted in the XP, PS, and SP groups. Osteoblasts appeared to be decreased in all groups, and significantly, a greater osteoclastic cell recruitment was noted in the SB and SP groups.
Both PDGF and simvastatin facilitate dentoalveolar regeneration, and sequential PDGF-simvastatin release (SP group) further accelerated the regeneration process through the enhancement of osteoblastogenesis and the promotion of bone maturation.
及时增强牙牙槽修复的生理事件是优化再生效果的前提。本研究旨在通过联合递送早期有丝分裂因子血小板衍生生长因子（PDGF）和晚期成骨分化因子辛伐他汀来开发一种促进牙牙槽再生的治疗策略。
通过使用共轴电动力学雾化技术，将 PDGF 和辛伐他汀包封在双层聚（D，L-丙交酯）和聚（D，L-丙交酯-共-乙交酯）（PDLLA-PLGA）微球中，有五种不同的模式：包封牛血清白蛋白的微球（BB）、单独的 PDGF（XP）、单独的辛伐他汀（SB）、PDGF 核-辛伐他汀壳（PS）和辛伐他汀核-PDGF 壳（SP）。通过扫描电子显微镜对微球进行了表征，并评估了体外释放情况。将微球输送到大鼠上颌骨的大截骨部位，持续 14 和 28 天，并通过微计算机断层扫描和组织学评估评估再生的结果。
成功制备了均匀的 20μm 控释微球。在 PS 组中观察到 PDGF-辛伐他汀的平行释放，在 SP 组中观察到 PDGF 的快速释放随后是辛伐他汀的缓慢释放。在第 14 天观察到 XP、PS 和 SP 组促进成骨，而 SP 组显示出最大的骨填充、小梁数量和最厚的小梁。在 PS 和 SP 组中可见骨桥形成，SP 组中骨细胞明显增多，所有生物活性分子处理组均促进破骨细胞募集。在第 28 天，所有生物活性分子处理组均促进成骨。在 XP、PS 和 SP 组中观察到初始皮质化。所有组的成骨细胞似乎减少，并且在 SB 和 SP 组中观察到破骨细胞募集显著增加。
PDGF 和辛伐他汀均促进牙牙槽再生，PDGF-辛伐他汀顺序释放（SP 组）通过增强成骨细胞生成和促进骨成熟进一步加速了再生过程。
