Non-invasive monitoring of BMP-2 retention and bone formation in composites for bone tissue engineering using SPECT/CT and scintillation probes.
Non-invasive monitoring of BMP-2 retention and bone formation in composites for bone tissue engineering using SPECT/CT and scintillation probes.
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DOI：
10.1016/j.jconrel.2008.11.023
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发表时间：
2009-03-19
影响因子：
10.8
通讯作者：
Lu, Lichun
中科院分区：
文献类型：
--
作者：
Kempen, Diederik H. R.;Yaszemski, Michael J.;Heijink, Andras;Hefferan, Theresa E.;Creemers, Laura B.;Britson, Jason;Maran, Avudaiappan;Classic, Kelly L.;Dhert, Wouter J. A.;Lu, Lichun
关键词：
非侵入性成像可以为优化新的基于药物递送的骨再生策略以修复受损或受损的骨组织提供重要信息。本研究探讨了核医学和放射技术的适用性，以监测生长因子的保留概况和随后对骨形成的影响。将重组人骨形态发生蛋白-2（BMP-2，6.5 μ g/支架）掺入由聚乳酸-羟基乙酸共聚物微球组成的缓释载体中，该微球包埋在聚富马酸丙二醇酯支架中，周围为明胶水凝胶，并皮下植入9只大鼠的5 mm节段性股骨缺损中，持续56天。为了确定药代动力学特征，用125I放射性标记BMP-2，并通过单光子发射计算机断层扫描（SPECT）、闪烁探针和离体闪烁分析测量125I-BMP-2的局部保留。通过微型计算机断层扫描（μ CT）监测骨形成。支架在56天的植入期内以持续的方式释放BMP-2。SPECT和闪烁探针测量之间的相关性良好，随访8周后，无创和离体计数方法之间没有显着差异。全身和甲状腺计数的SPECT分析显示125 I在体内的累积有限。支架材料能诱导异位成骨，骨缺损完全愈合。体内μ CT成像分别在第14天和第28天检测到原位和异位植入物的骨形成的最初迹象，并提供了骨形成率的详细曲线。总体而言，本研究通过在有限数量的动物中提供不同植入部位生长因子保留和骨形成的详细和可靠特征，清楚地证明了在基于药物递送的骨再生策略中应用非侵入性技术的益处。
Non-invasive imaging can provide essential information for the optimization of new drug delivery-based bone regeneration strategies to repair damaged or impaired bone tissue. This study investigates the applicability of nuclear medicine and radiological techniques to monitor growth factor retention profiles and subsequent effects on bone formation. Recombinant human bone morphogenetic protein-2 (BMP-2, 6.5 μg/scaffold) was incorporated into a sustained release vehicle consisting of poly(lactic-co-glycolic acid) microspheres embedded in a poly(propylene fumarate) scaffold surrounded by a gelatin hydrogel and implanted subcutaneously and in 5-mm segmental femoral defects in 9 rats for a period of 56 days. To determine the pharmacokinetic profile, BMP-2 was radiolabeled with 125I and the local retention of 125I-BMP-2 was measured by single photon emission computed tomography (SPECT), scintillation probes and ex vivo scintillation analysis. Bone formation was monitored by micro-computed tomography (μCT). The scaffolds released BMP-2 in a sustained fashion over the 56-day implantation period. A good correlation between the SPECT and scintillation probe measurements was found and there were no significant differences between the non-invasive and ex-vivo counting method after 8 weeks of follow up. SPECT analysis of the total body and thyroid counts showed a limited accumulation of 125I within the body. Ectopic bone formation was induced in the scaffolds and the femur defects healed completely. In vivo μCT imaging detected the first signs of bone formation at days 14 and 28 for the orthotopic and ectopic implants, respectively, and provided a detailed profile of the bone formation rate. Overall, this study clearly demonstrates the benefit of applying non-invasive techniques in drug delivery-based bone regeneration strategies by providing detailed and reliable profiles of the growth factor retention and bone formation at different implantation sites in a limited number of animals.
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影响因子：
14
作者：
Takahashi, Y;Yamamoto, M;Tabata, Y
通讯作者：
Tabata, Y
影响因子：
5.8
作者：
Friess, W;Uludag, H;Sargeant, C
通讯作者：
Sargeant, C
DOI：
10.1115/1.429662
发表时间：
2000-06-01
影响因子：
1.7
作者：
Oldham, JB;Lu, L;Yaszemski, MJ
通讯作者：
Yaszemski, MJ
影响因子：
56.9
作者：
LANGER, R;VACANTI, JP
通讯作者：
VACANTI, JP
DOI：
10.1016/0047-0740(81)90071-1
发表时间：
1981-01-01
期刊：
INTERNATIONAL JOURNAL OF NUCLEAR MEDICINE & BIOLOGY
影响因子：
--
作者：
BLOOMER, WD;ADELSTEIN, SJ
通讯作者：
ADELSTEIN, SJ