The use of heparin/polycation coacervate sustain release system to compare the bone regenerative potentials of 5 BMPs using a critical sized calvarial bone defect model.
The use of heparin/polycation coacervate sustain release system to compare the bone regenerative potentials of 5 BMPs using a critical sized calvarial bone defect model.
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DOI：
10.1016/j.biomaterials.2022.121708
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发表时间：
2022-09
期刊：
影响因子：
14
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中科院分区：
文献类型：
--
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骨折后的骨不连和节段性骨缺损是具有挑战性的临床条件。为了克服这一临床困境，开发新的骨组织工程疗法是可取的，该疗法使用生物相容材料来传递骨生长因子。本研究的目的是使用肝素/聚阳离子凝聚缓释平台比较5种骨形态发生蛋白(BMPs)在临界大小的颅骨缺损模型中促进骨缺损愈合的作用。体外三维成骨颗粒培养结果显示，BMP2、4、6、7和9均能促进体外矿化。BMP2的矿化体积大于BMP4和BMP6。所有BMP和对照组均激活pSMAD5信号通路并表达Osterix(OSX)。BMP2与凝聚体的结合显著增加了凝聚体的平均粒径。BMP2、BMP4、BMP6和BMP7与凝聚体结合可显著提高凝聚体的Zeta电位，而结合BMP9的作用不明显。此外，单层培养成骨实验发现，与对照组和BMPs4、6、7、9相比，在聚集型BMP2成骨培养液中培养的hMDSCs表达更高水平的RUNX2、OSX、ALP和COX-2。此外，凝聚型BMP2成骨复合体中可以负载高达2μg的BMP蛋白以进行持续释放。在体内，BMP2是最强的促进骨再生的BMP，其再生能力是BMP4、6和9的10倍。与BMP4、6和9相比，BMP7还能刺激强健的骨再生。凝聚体输送的所有BMPs所生成的新骨的质量相当于由骨基质和具有正常骨结构的骨髓组成的宿主骨。虽然6周后骨缺损尚未完全愈合，但凝聚缓释BMPs，尤其是BMP2和BMP7，可能成为治疗骨缺损和骨不连的一种新策略。
Nonunion following bone fracture and segmental bone defects are challenging clinical conditions. To combat this clinical dilemma, development of new bone tissue engineering therapies using biocompatible materials to deliver bone growth factors is desirable. This aim of this study is to use a heparin/polycation coacervate sustained-release platform to compare 5 bone morphogenetic proteins (BMPs) for promoting bone defect healing in a critical sized calvarial defect model. The in vitro 3D osteogenic pellet cultures assays demonstrated that BMPs 2, 4, 6, 7 and 9 all enhanced mineralization in vitro compared to the control group. BMP2 resulted in higher mineralized volume than BMP4 and BMP6. All BMPs and the control group activated the pSMAD5 signaling pathway and expressed osterix (OSX). The binding of BMP2 with coacervate significantly increased the coacervate average particle size. BMP2, 4, 6, & 7 bound to coacervate significantly increased the Zeta potential of the coacervate while BMP9 binding showed insignificant increase. Furthermore, using a monolayer culture osteogenic assay, it was found that hMDSCs cultured in the coacervate BMP2 osteogenic medium expressed higher levels of RUNX2, OSX, ALP and COX-2 compared to the control and BMPs 4, 6, 7 & 9. Additionally, the coacervate complex can be loaded with up to 2 μg of BMP proteins for sustained release. In vivo, when BMPs were delivered using the coacervate sustained release system, BMP2 was identified to be the most potent BMP promoting bone regeneration and regenerated 10 times of new bone than BMPs 4, 6 & 9. BMP7 also stimulated robust bone regeneration when compared to BMPs 4, 6 & 9. The quality of the newly regenerated bone by all BMPs delivered by coacervate is equivalent to the host bone consisting of bone matrix and bone marrow with normal bone architecture. Although the defect was not completely healed at 6 weeks, coacervate sustain release BMPs, particularly BMP2 and BMP7, could represent a new strategy for treatment of bone defects and non-unions.
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影响因子：
17.1
作者：
Bez M;Sheyn D;Tawackoli W;Avalos P;Shapiro G;Giaconi JC;Da X;David SB;Gavrity J;Awad HA;Bae HW;Ley EJ;Kremen TJ;Gazit Z;Ferrara KW;Pelled G;Gazit D
通讯作者：
Gazit D
影响因子：
4.8
作者：
Gao, Xueqin;Usas, Arvydas;Huard, Johnny
通讯作者：
Huard, Johnny
影响因子：
14
作者：
Gao, Xueqin;Usas, Arvydas;Tang, Ying;Lu, Aiping;Tan, Jian;Schneppendahl, Johannes;Kozemchak, Adam M.;Wang, Bing;Cummins, James H.;Tuan, Rocky S.;Huard, Johnny
通讯作者：
Huard, Johnny
影响因子：
4.7
作者：
Hasenbein I;Sachse A;Hortschansky P;Schmuck KD;Horbert V;Anders C;Lehmann T;Huber R;Maslaris A;Layher F;Braun C;Roth A;Plöger F;Kinne RW
通讯作者：
Kinne RW
DOI：
10.1111/wrr.12319
发表时间：
2015-07
期刊：
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
影响因子：
--
作者：
Johnson NR;Wang Y
通讯作者：
Wang Y