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基于纤维蛋白水凝胶的骨替代物与骨形态发生蛋白-2（BMP-2）和BMP-2/7异二聚体相连

Fibrin Hydrogel Based Bone Substitute Tethered with BMP-2 and BMP-2/7 Heterodimers.

作者信息

Karfeld-Sulzer Lindsay S, Siegenthaler Barbara, Ghayor Chafik, Weber Franz E

机构信息

Oral Biotechnology & Bioengineering, University Hospital, Division of Cranio-Maxillofacial and Oral Surgery and Center for Dental Medicine, University of Zurich, Plattenstrasse 11, Zurich CH-8032, Switzerland.

Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich CH-8006, Switzerland.

出版信息

Materials (Basel). 2015 Mar 6;8(3):977-991. doi: 10.3390/ma8030977.

DOI:10.3390/ma8030977
PMID:28787983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5455435/
Abstract

Current clinically used delivery methods for bone morphogenetic proteins (BMPs) are collagen based and require large concentrations that can lead to dangerous side effects. Fibrin hydrogels can serve as osteoinductive bone substitute materials in non-load bearing bone defects in combination with BMPs. Two strategies to even further optimize such a fibrin based system include employing more potent BMP heterodimers and engineering growth factors that can be covalently tethered to and slowly released from a fibrin matrix. Here we present an engineered BMP-2/BMP-7 heterodimer where an N-terminal transglutaminase substrate domain in the BMP-2 portion provides covalent attachment to fibrin together with a central plasmin substrate domain, a cleavage site for local release of the attached BMP-2/BMP-7 heterodimer under the influence of cell-activated plasmin. and results revealed that the engineered BMP-2/BMP-7 heterodimer induces significantly more alkaline phosphatase activity in pluripotent cells and bone formation in a rat calvarial model than the engineered BMP-2 homodimer. Therefore, the engineered BMP-2/BMP-7 heterodimer could be used to reduce the amount of BMP needed for clinical effect.

摘要

目前临床上用于递送骨形态发生蛋白（BMP）的方法是以胶原蛋白为基础的，需要高浓度使用，这可能会导致危险的副作用。纤维蛋白水凝胶可与BMP联合用作非承重骨缺损中的骨诱导性骨替代材料。进一步优化这种基于纤维蛋白的系统的两种策略包括使用更有效的BMP异二聚体以及构建可以共价连接到纤维蛋白基质并从其缓慢释放的生长因子。在此，我们展示了一种工程化的BMP-2/BMP-7异二聚体，其中BMP-2部分的N端转谷氨酰胺酶底物结构域与中央纤溶酶底物结构域一起提供与纤维蛋白的共价连接，该中央纤溶酶底物结构域是在细胞激活的纤溶酶影响下附着的BMP-2/BMP-7异二聚体局部释放的切割位点。结果显示，与工程化的BMP-2同二聚体相比，工程化的BMP-2/BMP-7异二聚体在多能细胞中诱导出显著更多的碱性磷酸酶活性，并在大鼠颅骨模型中诱导更多的骨形成。因此，工程化的BMP-2/BMP-7异二聚体可用于减少产生临床效果所需的BMP用量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/d420b1b80ab7/materials-08-00977-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/fcb3da35ee0f/materials-08-00977-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/4939b74767f5/materials-08-00977-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/bc64322081b2/materials-08-00977-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/6878df249779/materials-08-00977-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/41aab53d45f6/materials-08-00977-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/0046e66e9965/materials-08-00977-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/d420b1b80ab7/materials-08-00977-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/fcb3da35ee0f/materials-08-00977-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/4939b74767f5/materials-08-00977-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/bc64322081b2/materials-08-00977-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/6878df249779/materials-08-00977-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/41aab53d45f6/materials-08-00977-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/0046e66e9965/materials-08-00977-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/588e/5455435/d420b1b80ab7/materials-08-00977-g007.jpg

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本文引用的文献

1
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J Tissue Eng Regen Med. 2017 Feb;11(2):425-433. doi: 10.1002/term.1926. Epub 2014 Jun 12.
2
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Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4563-8. doi: 10.1073/pnas.1221602110. Epub 2013 Mar 4.
3
BMP2/7 heterodimer is a stronger inducer of bone regeneration in peri-implant bone defects model than BMP2 or BMP7 homodimer.
BMP 异源二聚体通过不同的 I 型受体类别功能发挥信号作用。
Proc Natl Acad Sci U S A. 2021 Apr 13;118(15). doi: 10.1073/pnas.2017952118.
4
Rational design of hydrogels to enhance osteogenic potential.用于增强成骨潜能的水凝胶的合理设计。
Chem Mater. 2020 Nov 24;32(22):9508-9530. doi: 10.1021/acs.chemmater.0c03018. Epub 2020 Nov 5.
5
Human Fresh Fibrin Membrane with Bone Morphogenetic Protein-2 (BMP-2) Induces Bone Formation in the Subcutaneous Tissues of Nude Mice.含骨形态发生蛋白-2（BMP-2）的人新鲜纤维蛋白膜在裸鼠皮下组织中诱导骨形成。
Materials (Basel). 2020 Dec 31;14(1):150. doi: 10.3390/ma14010150.
6
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7
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4
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5
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6
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7
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8
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Macromol Biosci. 2011 Sep 9;11(9):1149-63. doi: 10.1002/mabi.201000505. Epub 2011 Apr 20.
9
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10
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Tissue Eng Part A. 2010 Mar;16(3):879-87. doi: 10.1089/ten.TEA.2009.0312.