Pekkarinen Tarmo, Hietala Oili, Jämsä Timo, Jalovaara Pekka
Bone Transplantation Research Group, Department of Orthopaedic and Trauma Surgery, University of Oulu, Oulu, Finland.
Acta Orthop. 2005 Apr;76(2):231-6. doi: 10.1080/00016470510030625.
Bone morphogenetic proteins (BMPs), which are capable of stimulating the production of new bone, must be sterilized before preclinical and clinical use to reduce the risk of infections and associated complications. In this study, we investigated the effects of gamma sterilization on the osteoinductivity of native reindeer BMP extract in the Balb/C mouse thigh muscle pouch model.
5 mg of native reindeer BMP extract and 5 mg of bovine serum albumin were administered separately either in gelatine capsules or mixed with gelatine as injections. The dose of gamma irradiation was 4.1 Mrad. Unsterile capsules and injections served as controls. New bone formation was evaluated based on the incorporation of Ca45 and also radiographically 3 weeks after implantation.
Albumin-containing implants and injections did not induce new bone formation, as monitored in radiographs. Gamma sterilization did not reduce the osteoinductivity of native BMP extract in capsules, but a significant decrease in osteoinductivity--measured as area (50%) and Ca45 incorporation of new bone (27%)--was seen after injection. Gamma sterilization had no effect on the optical density of new bone induced by native BMP extract administered in capsules or by injection.
We conclude that, as gamma irradiation did not reduce the osteoinductivity of reindeer BMP extract in gelatine capsules, this method appears to be suitable for sterilization of BMPs to be given in capsule form. Native reindeer BMP extract was more sensitive to irradiation in soluble collagen (gelatine) than BMP in gelatine capsules. This finding must be given serious consideration regarding treatment of patients, but the remaining activity may be sufficient for the induction of bone formation in preclinical and clinical situations.
骨形态发生蛋白（BMPs）能够刺激新骨生成，在临床前和临床应用前必须进行灭菌处理，以降低感染及相关并发症的风险。在本研究中，我们在Balb/C小鼠大腿肌肉袋模型中研究了γ射线灭菌对天然驯鹿BMP提取物骨诱导活性的影响。
将5mg天然驯鹿BMP提取物和5mg牛血清白蛋白分别装入明胶胶囊中给药，或与明胶混合后注射给药。γ射线辐照剂量为4.1兆拉德。未灭菌的胶囊和注射剂作为对照。植入3周后，根据Ca45的掺入情况以及X线片评估新骨形成情况。
X线片监测显示，含白蛋白的植入物和注射剂未诱导新骨形成。γ射线灭菌并未降低胶囊中天然BMP提取物的骨诱导活性，但注射后骨诱导活性显著降低，以新骨面积（50%）和Ca45掺入量（27%）衡量。γ射线灭菌对胶囊给药或注射的天然BMP提取物诱导的新骨光密度没有影响。
我们得出结论，由于γ射线辐照并未降低明胶胶囊中驯鹿BMP提取物的骨诱导活性，该方法似乎适用于对以胶囊形式给药的BMP进行灭菌。天然驯鹿BMP提取物在可溶性胶原蛋白（明胶）中比在明胶胶囊中的BMP对辐照更敏感。这一发现对于患者治疗必须予以认真考虑，但剩余活性可能足以在临床前和临床情况下诱导骨形成。
