Huang Zhinong, Ryu Wonhyoung, Ren Peigen, Fasching Rainer, Goodman Stuart B
Department of Orthopaedic Surgery, Stanford University Medical Center, Edwards Building R116, 300 Pasteur Drive, Stanford, CA 94305, USA.
Clin Orthop Relat Res. 2008 Aug;466(8):1905-11. doi: 10.1007/s11999-008-0290-8. Epub 2008 May 29.
Allografts are important alternatives to autografts for treating defects after major bone loss. Bone growth factors have both local autocrine and paracrine effects and regulate the growth, proliferation, and differentiation of osteoprogenitor cells. To study the effects of prolonged, continuous, local delivery of growth factors on bone growth, we developed a new microelectromechanical system (MEMS) drug delivery device. Bone marrow cells from mice were seeded on mouse allograft discs and cultured in osteogenic media with osteogenic protein 1 (OP-1) and/or basic fibroblast growth factor (FGF-2) delivered from MEMS devices for 6 weeks. We monitored bone formation by changes of bone volume using micro-CT scanning and release of osteocalcin using ELISA. The data suggest the MEMS devices delivered constant concentrations of OP-1 and FGF-2 to the media. Bone marrow cells grew on the allografts and increased bone volume. Addition of OP-1 increased bone formation whereas FGF-2 decreased bone formation. Local delivery of growth factors over a prolonged period modulated the differentiation of osteoprogenitor cells on allograft bone.
同种异体骨移植是治疗严重骨缺损后自体骨移植的重要替代方法。骨生长因子具有局部自分泌和旁分泌作用,可调节骨祖细胞的生长、增殖和分化。为了研究生长因子长期、持续、局部递送对骨生长的影响,我们开发了一种新型微机电系统(MEMS)药物递送装置。将小鼠骨髓细胞接种在小鼠同种异体骨移植盘上,并在含有从MEMS装置递送的成骨蛋白1(OP-1)和/或碱性成纤维细胞生长因子(FGF-2)的成骨培养基中培养6周。我们通过使用微型计算机断层扫描(micro-CT)扫描监测骨体积变化以及使用酶联免疫吸附测定(ELISA)监测骨钙素释放来监测骨形成。数据表明,MEMS装置向培养基中递送了恒定浓度的OP-1和FGF-2。骨髓细胞在同种异体骨上生长并增加了骨体积。添加OP-1增加了骨形成,而FGF-2则减少了骨形成。长时间局部递送生长因子可调节同种异体骨上骨祖细胞的分化。