Wildemann B, Kandziora F, Krummrey G, Palasdies N, Haas N P, Raschke M, Schmidmaier G
Center for Musculoskeletal Surgery, Charité-University Medicine, Campus Virchow-Clinic, Augustenburger Platz 1, D-13353, Berlin, Germany.
J Control Release. 2004 Mar 5;95(2):249-56. doi: 10.1016/j.jconrel.2003.11.014.
The osteoinductive potential of growth factors leads not only to a stimulated bone formation in bony tissue but also in extra skeletal tissue. This potential depends on the dosage and potentially on the application method and may limit the clinical use. The aim of the present study was to investigate the potential of IGF-I, TGF-beta1 and BMP-2 released from a newly developed application systems of orthopaedic implants to induce ectopic bone formation in muscles. This bioactive coating showed a stimulating effect on fracture healing in several experimental studies before. Titanium discs were coated on one side with the drug carrier poly(d,l-lactide) (PDLLA), with the carrier plus IGF-I and TGF-beta1 or with the carrier plus BMP-2. The discs were implanted in the Musculus cleidomastoideus of sheep and followed up for 3 months. X-rays were taken after the operation and the day of sacrifice. The muscles plus implant were harvested and prepared for histology. Neither the radiology nor the histology revealed any signs of ectopic ossification in the implant/muscle interface or in a distance to the plate in any group. An influence of the locally applied growth factor, however, was seen in the formation of a soft tissue capsule. Histomorphometric analysis revealed a significantly larger capsule area over the growth factor coated side in comparison to the uncoated side or the pure titanium plate, indicating an effect of the applied growth factors on cells, however, not resulting in osteoinduction in muscle. The result showed that the local and controlled release of growth factors from PDLLA coated implants does not induce ectopic bone formation in sheep muscle and could be used in orthopaedic surgery to increase healing without the risk of ectopic bone formation in the surrounding soft tissue.
生长因子的骨诱导潜能不仅能刺激骨组织中的骨形成，还能刺激骨骼外组织中的骨形成。这种潜能取决于剂量，可能还取决于应用方法，这可能会限制其临床应用。本研究的目的是调查从新开发的骨科植入物应用系统中释放的胰岛素样生长因子-I（IGF-I）、转化生长因子-β1（TGF-β1）和骨形态发生蛋白-2（BMP-2）在肌肉中诱导异位骨形成的潜能。这种生物活性涂层在之前的几项实验研究中对骨折愈合显示出刺激作用。将钛盘的一侧用药物载体聚（d，l-丙交酯）（PDLLA）涂层，或用载体加IGF-I和TGF-β1涂层，或用载体加BMP-2涂层。将这些盘植入绵羊的胸锁乳突肌中，并随访3个月。术后及处死当天拍摄X线片。取出肌肉加植入物并准备进行组织学检查。在任何组中，无论是放射学检查还是组织学检查，均未在植入物/肌肉界面或距钢板一定距离处发现异位骨化的迹象。然而，在软组织包膜的形成中观察到了局部应用生长因子的影响。组织形态计量学分析显示，与未涂层侧或纯钛板相比，生长因子涂层侧的包膜面积明显更大，这表明所应用的生长因子对细胞有影响，但未导致肌肉中的骨诱导。结果表明，从PDLLA涂层植入物中局部和控释生长因子不会在绵羊肌肉中诱导异位骨形成，可用于骨科手术以促进愈合，而不会有周围软组织异位骨形成的风险。
