Johnson E E, Urist M R, Schmalzried T P, Chotivichit A, Huang H K, Finerman G A
Division of Orthopaedic Surgery, University of California, Los Angeles.
Clin Orthop Relat Res. 1989 Jun(243):254-65.
Xenogeneic (bovine) bone morphogenetic protein (bBMP) and associated insoluble noncollagenous proteins (NCP) were implanted in inbred adult beagle dogs with 3-4 cm diaphyseal defects in the ulna. Defects were stabilized with internal plate fixation, and the control defects were not stabilized. The defects were implanted with either autogeneic cancellous bone grafts (ACG), bBMP/NCP, or a composite of ACG and bBMP/NCP. Of the plated ulnae, 18 of 19 ACG controls restored bone continuity; six of seven defects healed under the influence of bBMP/NCP plus ACG. Two of four defects with bBMP/NCP plus ACG healed and two were filled with osseous tissue, but fibrous tissue developed at one or both bone ends. Eight of nine defects implanted with bBMP/NCP capsules alone were repaired with fibrous tissue only. Of the nonplated defects, four were implanted with bBMP/NCP plus ACG and only one regenerated; three of four showed hypertrophic bone growth around a pseudarthrosis. Of six nonplated defects implanted with bBMP/NCP without ACG, all developed atrophic bone ends and fibrous tissue repair. Thus, to restore continuity of large segmental defects three times greater than the critical size for spontaneous regeneration, xenogeneic bBMP/NCP failed to induce bone regeneration in dogs. To exclude cell-mediated immune reactions and soft-tissue ingrowth, one defect was bridged with a polytetrafluoroethylene semipermeable tube (pore size 0.45 micron) containing implants of bBMP/NCP. In response to bBMP/NCP, cells from the host bone ends produced ossicles of induced woven bone formation. The observation that bBMP/NCP induced bone formation across the defect inside of semipermeable cylindrical chambers suggests that the experiments on bone defects larger than the critical size for spontaneous repair should be repeated with: (1) allogeneic dog BMP/NCP; (2) semipermeable cylinders to protect against muscle interposition; (3) compartment angiograms to evaluate blood supply; (4) treatment of the recipient with immunosuppressants and immunostaining to observe the concentration gradient of BMP; and (5) histologic observations on the first three days after implantation to evaluate cell-mediated immune barriers to the response of BMP.
将异种（牛）骨形态发生蛋白（bBMP）及相关不溶性非胶原蛋白（NCP）植入成年近交系比格犬尺骨骨干有3 - 4厘米骨缺损处。缺损处采用内固定钢板固定，对照缺损处未固定。缺损处分别植入自体松质骨移植片（ACG）、bBMP/NCP或ACG与bBMP/NCP的复合物。在采用钢板固定的尺骨中，19个ACG对照组中有18个恢复了骨连续性；7个在bBMP/NCP加ACG影响下愈合。bBMP/NCP加ACG的4个缺损中有2个愈合，2个被骨组织填充，但在一端或两端出现了纤维组织。单独植入bBMP/NCP胶囊的9个缺损中有8个仅通过纤维组织修复。在未采用钢板固定的缺损中，4个植入了bBMP/NCP加ACG，只有1个再生；4个中有3个在假关节周围出现肥大性骨生长。6个未采用钢板固定且未植入ACG的bBMP/NCP缺损，均出现萎缩性骨端和纤维组织修复。因此，为恢复大于自发再生临界尺寸三倍的大段骨缺损的连续性，异种bBMP/NCP未能在犬体内诱导骨再生。为排除细胞介导的免疫反应和软组织长入，用一根含bBMP/NCP植入物的聚四氟乙烯半透膜管（孔径0.45微米）桥接一个缺损。对bBMP/NCP的反应是，宿主骨端的细胞产生诱导编织骨形成的小骨。bBMP/NCP在半透性圆柱形腔室内诱导缺损处骨形成这一观察结果表明，对于大于自发修复临界尺寸的骨缺损实验，应重复进行，条件如下：（1）同种异体犬BMP/NCP；（2）用半透性圆柱体防止肌肉长入；（3）进行隔室血管造影评估血供；（4）用免疫抑制剂治疗受体并进行免疫染色观察BMP浓度梯度；（5）植入后前三天进行组织学观察，评估细胞介导的免疫屏障对BMP反应的影响。
