Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice
Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice
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DOI：
10.1016/j.bone.2014.07.007
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发表时间：
2014-10-01
期刊：
影响因子：
4.1
通讯作者：
Cray, James J.
中科院分区：
文献类型：
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作者：
Herberg, Samuel;Kondrikova, Galina;Cray, James J.
背景：颅面外科的一个主要问题是骨缺损的不愈合。自体再造仍然是这些病例的标准治疗。骨形态发生蛋白-2（BMP-2）治疗已证明其临床实用性，尽管由于使用的高毫克级剂量而发生非靶向不良事件。正在进行的努力探索使用不同的生长因子，细胞因子，或趋化因子，以及共同治疗，以增强healing.Methods：在这里，我们利用基于喷墨的生物图案化加载无细胞DermaMatrix交付矩阵与纳克级剂量的BMP-2，基质细胞衍生因子-1 β（SDF-1 β），转化生长因子-β 1（TGF-β 1），或其共同治疗。我们测试了生物打印的SDF-1 β共同递送增强BMP-2和TGF-β 1驱动的骨生成的假设，在体外和体内使用小鼠颅骨临界尺寸缺损（CSD）model.Results：我们的数据表明，BMP-2在低剂量生物打印诱导显着的新骨形成的四周后手术。与BMP-2相比，TGF-β 1的效果较差，SDF-1 β治疗并没有增强骨生成超过对照水平。然而，与单独的BMP-2相比，BMP-2 + SDF-1 β的共递送显示出增加BMP-2诱导的骨形成。相比之下，与单独的TGF-1 β相比，TGF-β 1 + SDF-1 β的共递送减少了骨愈合。这进一步证实了在体外成骨分化研究使用MC 3 T3-E1 pre-osteoblasts.Conclusions：我们的数据表明，持续释放交付的低剂量的生长因子治疗使用biopatterning技术可以帮助愈合CSD损伤。SDF-1 β增强了BMP-2驱动愈合的能力，这一结果在体内和体外都得到了证实;然而，由于SDF-1 β对TGF-1 β驱动的骨生成有害，因此其对骨生成的影响并不普遍。(C)2014爱思唯尔公司All rights reserved.
Background: A major problem in craniofacial surgery is non-healing bone defects. Autologous reconstruction remains the standard of care for these cases. Bone morphogenetic protein-2 (BMP-2) therapy has proven its clinical utility, although non-targeted adverse events occur due to the high milligram-level doses used. Ongoing efforts explore the use of different growth factors, cytokines, or chemokines, as well as co-therapy to augment healing.Methods: Here we utilize inkjet-based biopatterning to load acellular DermaMatrix delivery matrices with nanogram-level doses of BMP-2, stromal cell-derived factor-1 beta (SDF-1 beta), transforming growth factor-beta 1 (TGF-beta 1), or co-therapies thereof. We tested the hypothesis that bioprinted SDF-1 beta co-delivery enhances BMP-2 and TGF-beta 1-driven osteogenesis both in-vitro and in-vivo using a mouse calvarial critical size defect (CSD) model.Results: Our data showed that BMP-2 bioprinted in low-doses induced significant new bone formation by four weeks post-operation. TGF-beta 1 was less effective compared to BMP-2, and SDF-1 beta therapy did not enhance osteogenesis above control levels. However, co-delivery of BMP-2 + SDF-1 beta was shown to augment BMP-2-induced bone formation compared to BMP-2 alone. In contrast, co-delivery of TGF-beta 1 + SDF-1 beta decreased bone healing compared to TGF-1 beta alone. This was further confirmed in vitro by osteogenic differentiation studies using MC3T3-E1 pre-osteoblasts.Conclusions: Our data indicates that sustained release delivery of a low-dose growth factor therapy using biopatterning technology can aid in healing CSD injuries. SDF-1 beta augments the ability for BMP-2 to drive healing, a result confirmed in vivo and in vitro; however, because SDF-1 beta is detrimental to TGF-1 beta-driven osteogenesis, its effect on osteogenesis is not universal. (C) 2014 Elsevier Inc. All rights reserved.