Toriumi D M, O'Grady K, Horlbeck D M, Desai D, Turek T J, Wozney J
Division of Facial Plastic and Reconstructive Surgery, University of Illinois College of Medicine, Chicago 60612, USA.
Laryngoscope. 1999 Sep;109(9):1481-9. doi: 10.1097/00005537-199909000-00023.
To determine the degree of bone resorption and stability of 3-cm, full-thickness canine mandibular defects reconstructed with recombinant human bone morphogenetic protein 2 (rhBMP-2) and a bioerodible particle carrier followed for 30 months after reconstruction.
Nine dogs, divided into three groups, underwent reconstruction of surgically created 3-cm, full-thickness defects of the body of the mandible.
Mandibular reconstruction was performed via a combined intraoral and extraoral approach. Using standard plating techniques, a unilateral full-thickness, 3-cm defect was created in the body of the mandible. After stabilizing the defects with titanium reconstruction plates, test implants composed of rhBMP-2 and poly(lactide-co-glycolide) bioerodible particles were placed in the mandibular defects of six animals. Reconstruction plates were removed from test animals at 10 weeks. Three short-term test animals were sacrificed 3 months after reconstruction. Three long-term test animals were sacrificed 30 months after reconstruction to determine the degree of resorption and long-term stability of the rhBMP-2-induced bone. Control implants (carrier without rhBMP-2) were used in three animals and were sacrificed at 3 months. At 9 months, long-term animals were advanced to a solid diet. Masticatory function and body weight were monitored periodically to assess diet tolerance. Roentgenographic photodensitometry was performed on serial dental roentgenograms of the reconstructed segments to determine bone density and the degree of bone resorption over 30 months. After sacrifice, reconstructed segments were harvested and embedded in plastic for histological analysis and histomorphometry to determine the percentage of the defect replaced by mineralized bone (area density) and degree of resorption from 3 to 30 months after reconstruction. The main outcome measures were bone density and bone height determined from serial roentgenograms and percentage of the reconstructed segment replaced by mineralized bone (area density) determined from histomorphometry.
Control animals without rhBMP-2 showed no evidence of bone formation across the defect. Histological examination revealed good bone formation in two of three of the short-term test animals with a mean area density of 41.0%. The long-term test animals treated with rhBMP-2 demonstrated good bone formation that was comparable to that of normal host bone by 3 months. The roentgenographic photodensity measurements stabilized at 5 months without evidence of persistent bone resorption. The height of the reconstructed segment (rhBMP-2-induced bone) initially decreased, then stabilized by 11 months after reconstruction with no indication of resorption or failure. Histological examination of the long-term test animals revealed good bone formation across the mandibular defects. However, there were localized areas of thinning of the cortical bone as compared with the short-term test animals sacrificed at 3 months. Histological examination verified the loss of height of the bone in the reconstructed segments. The area density (mean) of the long-term test animals was 56.5%. Despite the decrease in height of the induced bone, there was an increase in area density of the bone over time.
This study demonstrated that rhBMP-2 in a bioerodible particle carrier induced new host bone formation across critical-size mandibular defects. The newly formed bone successfully integrated with existing host bone creating a stable union capable of withstanding the forces of masticatory function in a canine. There was some evidence of early bone resorption (thinning of the cortical bone and decrease in height) in the rhBMP-2-induced bone. The rhBMP-2-induced bone stabilized by 11 months after reconstruction and no further resorption was noted. The percentage of area of the defect replaced by rhBMP-2-induced bone (area density) increased over 30 months. (ABSTRACT TRUNCATED)
确定用重组人骨形态发生蛋白2（rhBMP - 2）和可生物降解颗粒载体重建3厘米全层犬下颌骨缺损后30个月的骨吸收程度和稳定性。
将9只犬分为三组，对手术造成的下颌骨体部3厘米全层缺损进行重建。
通过口内和口外联合入路进行下颌骨重建。采用标准接骨板技术，在下颌骨体部制造单侧全层3厘米缺损。用钛重建接骨板稳定缺损后，将由rhBMP - 2和聚（丙交酯 - 共 - 乙交酯）可生物降解颗粒组成的测试植入物置于6只动物的下颌骨缺损处。10周时从测试动物身上取出重建接骨板。三只短期测试动物在重建后3个月处死。三只长期测试动物在重建后30个月处死，以确定rhBMP - 2诱导骨的吸收程度和长期稳定性。三只动物使用对照植入物（不含rhBMP - 2的载体），并在3个月时处死。9个月时，长期测试动物改为固体饮食。定期监测咀嚼功能和体重以评估饮食耐受性。对重建节段的系列牙科X线片进行X线光密度测定，以确定30个月内的骨密度和骨吸收程度。处死动物后，取出重建节段并包埋于塑料中进行组织学分析和组织形态计量学分析，以确定重建后3至30个月矿化骨替代缺损的百分比（面积密度）和吸收程度。主要观察指标为从系列X线片确定的骨密度和骨高度，以及从组织形态计量学确定的矿化骨替代重建节段的百分比（面积密度）。
未使用rhBMP - 2的对照动物在缺损处未显示骨形成迹象。组织学检查显示，三只短期测试动物中有两只骨形成良好，平均面积密度为41.0%。用rhBMP - 2治疗的长期测试动物在3个月时显示出良好的骨形成，与正常宿主骨相当。X线光密度测量在5个月时稳定，无持续性骨吸收迹象。重建节段（rhBMP - 2诱导骨）的高度最初下降，然后在重建后11个月稳定，无吸收或失败迹象。长期测试动物的组织学检查显示下颌骨缺损处骨形成良好。然而，与3个月时处死的短期测试动物相比，皮质骨有局部变薄区域。组织学检查证实了重建节段中骨高度的降低。长期测试动物的面积密度（平均值）为56.5%。尽管诱导骨高度降低，但随着时间推移骨的面积密度增加。
本研究表明，可生物降解颗粒载体中的rhBMP - 2可诱导临界大小下颌骨缺损处形成新的宿主骨。新形成的骨成功地与现有宿主骨整合，形成了能够承受犬咀嚼功能力量的稳定连接。有一些证据表明rhBMP - 2诱导骨存在早期骨吸收（皮质骨变薄和高度降低）。rhBMP - 2诱导骨在重建后11个月稳定，未观察到进一步吸收。rhBMP - 2诱导骨替代缺损的面积百分比（面积密度）在30个月内增加。（摘要截断）
