摘要
目的研制复合重组人骨形态发生蛋白2（rhBMP-2）壳聚糖水凝胶的新型HA／ZrO2多孔泡沫陶瓷人工椎体，并观察其修复beagle犬椎体骨缺损的能力。方法离子交联法制备壳聚糖水凝胶作为rhBMP-2的缓释载体，扫描电镜下观察其微观形态，检测其载药量、包封率及缓释速率。将HA／ZrO2多孔泡沫陶瓷人工椎体复合rhBMP-2壳聚糖水凝胶，构建新型HA／ZrO2多孔泡沫陶瓷人工椎体。将12只beagle犬按数字表法随机分为3组，每组4只；均采用手术造成半径9mm、高23mm的半圆柱状IJ4椎骨缺损模型，其中A组植入复合rhBMP-2壳聚糖水凝胶的新型HA／ZrO2多孔泡沫陶瓷人工椎体，B组植入复合空白干燥壳聚糖的新型HA／ZrO，多孔泡沫陶瓷人工椎体，C组植入实验犬自体髂骨。术后6、12、24周对实验犬行大体观察、X线影像学观察；术后24周取实验犬椎体标本行离体MicroCT新生骨量检测及生物力学检测。结果制备所得壳聚糖水凝胶扫描电镜下呈3D网状结构，内部均匀分布壳聚糖微球，其负载rhBMP-2后包封率达91．88％±1．53％，载药量为（39．84±2．34）ng／mg；释放率第1天为28．32％±3．01％，第3天为48．92％±6．27％，第12天为74．40％±6．29％。术后6周C组动物平均活动度恢复较A组和B组快（P值均〈0．05），A、B组差异无统计学意义（P〉0．05）；术后12、24周B组与C组活动度比较差异均有统计学意义（P值均〈0．05），A、C组差异均无统计学意义（P值均〉0．05）。术后6、12、24周x线影像学观察显示，A组椎体置换术后骨痂生成逐渐增多，植入材料与宿主骨之间的界线逐渐模糊，至24周时人工椎体周围新生骨与自体骨融为一体；C组在24周时出现明显非承重部位的骨吸收，出现较快的自体骨塑形；B组椎体置换术后人工椎体与自体骨的融合速度慢于A组和C组。术后24周标本MicroCT新生骨量检测结果
Objective To prepare the chitosan hydrogel as release carrier of recombinant human bone morphogenetic protein 2 （rhBMP-2） , and loaded the prepared recombinant human bone morphogenetic protein 2 chitosan hydrogel in novel HA/ZrO2 gradient biocomposite artificial vertebrae and study bone reparation effect of it in a beagle dog＇ vertebral defect model. Methods To prepar rhBMP-2 chitosan hydroge｜ by ion-crosslinked method. Scanning electron microscopy was used to observe lyophilized chitosan microscopic surface morphology, test its swelling coefficient and detect drug loading mass, encapsulation efficiency and sustained release characteristics of the chitosan hydrogel loaded with rhBMP-2. Loaded the rhBMP-2 chitosan hydrogel onto novel HA/ZrO2 gradient biocomposite artificial vertebrae. Then 12 beagle dogs were randomly divided into three groups （A, B, and C ） by number table, each group included four dogs. Afterwards, a 23 mm radius and 9 mm high semi-cylindrical bone defect model was caused by surgery in each dog. While the bone defect location was implanted artificial vertebral body composite rhBMP-2 cbitosan gel in group A, implanted artificial vertebral body composite blank dried chitosan in group B, and implanted autologous bone in group C. After operations, general observation and X-ray observation were carried out at week 6,12, and 24. At week 24, all beagle dogs were sacrificed and taken vertebral body specimens, then detect new bone volume in the artificial vertebral body by Micro-CT and detect ultimate compressive strength by biomechanical testing. Results SEM scanning showed the lyophilized chitosan was a three-dimensional network structure with uniform distribution of chitosan microspberes internal. When loaded with rhBMP-2, chitosan hydrogel encapsulation efficiency was 91.88%± 1.53%, the loaded mass of drug was （39.84± 2.34） ng/mg; the release rate was 28.32% ±3.01% at day 1, 48.92%± 6.27% at day 3, and 74.40% ±6.29% at day 12. The average recovery ratio of group C was faster than
出处
《中华解剖与临床杂志》
2016年第1期57-63,共7页
Chinese Journal of Anatomy and Clinics
基金
浙江省重大科技专项（2014c03031）
浙江省科学技术厅公益技术研究社会发展项目（2012C33114）
杭州市重大科技专项（20122513A14）
关键词
羟基磷灰石类
锆
组织工程
人工椎体
重组人骨形态发生蛋白2
Hydroxyapatites
Zirconia
Tissue engineering
Artificial vertebrae
Recombinant human bone morphogenetie protein 2
