复合rhBMP-2可注射磷酸钙骨水泥在椎体成形术中应用的实验研究

Histological changes of an injectable rhBMP-2/calcium phosphate cement in vertebroplasty of rhesus monkey

目的探讨自主研发的复合rhBMP-2可注射磷酸钙骨水泥（复合材料）替代注射型聚甲基丙烯酸甲酯（PMMA）应用于猕猴椎体成形术的可行性。方法将4只成年猕猴分为Ⅰ、Ⅱ两组，每组2只。每组猕猴T10～L7的20个椎体经皮穿刺，按处理方法不同分为复合材料组（A组，8个椎体）、可注射型PMMA组（B组，6个椎体）和手术空白对照组（C组，6个椎体）。分别于术后即刻和术后1、2,4、6个月行放射学检查。Ⅰ组于术后2个月、Ⅱ组于术后6个月处死，取出单个椎体，每个椎体取含材料骨样本2份，1份用于光镜检查，另1份用于扫描电镜。观察两种材料强化椎体的早期和后期效果和变化。结果A组2个月时材料部分降解，未见界面缝隙、纤维增生、炎性浸润或硬化骨痂现象，大量类骨质形成并长人材料，可见新生血管；6个月后大部分材料吸收完全，大部分软骨钙化形成成熟骨组织，有完整的骨小梁及哈佛系统。B组2个月时未见材料降解，中度炎性浸润，纤维组织膜包裹，界面缝隙明显，未见新骨生长；6个月时，炎性浸润消失，纤维界膜变薄，界面缝隙变窄，仍无材料降解和新骨生长。C组2个月后椎体骨隧道被新生骨质填充，骨小梁排列紊乱，边界硬化骨痂形成；6个月后，骨小梁排列整齐，边界骨痂消失，不能辨认，骨重建完成。结论复合rhBMP-2的注射型磷酸钙骨水泥植入椎体后能够获得良好的诱导生长活性，材料降解和新骨替代同步，周期接近于正常椎体的骨愈合，可望替代PMMA获得椎体成形后早期和远期更好的组织学效果。

Objective The histological changes of rhBMP-2/calcium phosphate cement （CPC） were evaluated in vertebroplasty on nonhuman primate models in order to determine the feasibility of this carrier formulation instead of PMMA. Methods Percutaneous vertebroplasty （PVP） was performed in 4 adult rhesus monkeys which were evenly distributed in two groups. Ten vertebral bodies（VBs） from Tl0 to L7 of each rhesus were selected, and the 20 VBs in each group were randomly divided into 3 sub-groups. Group A：8 VBs, filled with rhBMP-2/CPC; Group B：6 VBs, filled with injectable PMMA; Group C：6 VBs, as control, Idled with normal saline. The 2 rhesus monkeys in each group were killed at 2 and 6 months after operation, respectively, and the specimens of all the 40 VBs were collected for histological examination. Results In group A, radiographic and histologic studies confirmed that part of the rhBMP-2/CPC cement degraded with new bone and new vessels ingrowth into the material after 2 months. No gap, fibrous hyperplasia or sclerotic callus was found in the interface. After six months, the cement was almost completely replaced by mature bone tissue. In group B, no new bone formation and material degradation but inflammatory cell infiltration and fibrous membrane gapping were found 2 months after operation. After 6 months, the inflammatory cell infiltration subsided, the fibrous membrane gapping became narrower, but there were still no new bone formation and material degradation. In group C, the tunnels were filled with irregular new trabeculae after 2 months and unrecognizable from the surrounding mature bone after 6 months, indicating the completion of bone healing. Conclusions With the characteristic of osteoinductivity, the rhBMP-2/CPC can accelerate the healing of vertebral bone in nonhuman primates. Bone substitution is synchronous with material degradation, and the complete degradation of this material in late stage can avoid the potential adverse effects of polymethylmethacylate on contiguous vertebral fracture and annulus degeneration. It might be a perfect bone substitute material for vertebroplasty instead of PMMA in the future.