一种具有趋化功能的支架，其表面结合有释放 VEGF 的肽两亲体，可通过 BMP-2 在大型啮齿动物颅骨缺损模型中促进骨再生。
A Chemotactic Functional Scaffold with VEGF-Releasing Peptide Amphiphiles Facilitates Bone Regeneration by BMP-2 in a Large-Scale Rodent Cranial Defect Model.
机构信息
From the Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles; the Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tsukuba; and the Simpson Querrey Institute and the Departments of Materials Science and Engineering, Chemistry, Medicine, and Biomedical Engineering, Northwestern University.
出版信息
Plast Reconstr Surg. 2021 Feb 1;147(2):386-397. doi: 10.1097/PRS.0000000000007551.
BACKGROUND
Current common techniques for repairing calvarial defects by autologous bone grafting and alloplastic implants have significant limitations. In this study, the authors investigated a novel alternative approach to bone repair based on peptide amphiphile nanofiber gels that are engineered to control the release of vascular endothelial growth factor (VEGF) to recruit circulating stem cells to a site of bone regeneration and facilitate bone healing by bone morphogenetic protein-2 (BMP-2).
METHODS
VEGF release kinetics from peptide amphiphile gels were evaluated. Chemotactic functional scaffolds were fabricated by combining collagen sponges with peptide amphiphile gels containing VEGF. The in vitro and in vivo chemotactic activities of the scaffolds were evaluated by measuring mesenchymal stem cell migration, and angiogenic capability of the scaffolds was also evaluated. Large-scale rodent cranial bone defects were created to evaluate bone regeneration after implanting the scaffolds and other control materials.
RESULTS
VEGF was released from peptide amphiphile in a controlled-release manner. In vitro migration of mesenchymal stem cells was significantly greater when exposed to chemotactic functional scaffolds compared to control scaffolds. In vivo chemotaxis was evidenced by migration of tracer-labeled mesenchymal stem cells to the chemotactic functional scaffolds. Chemotactic functional scaffolds showed significantly increased angiogenesis in vivo. Successful bone regeneration was noted in the defects treated with chemotactic functional scaffolds and BMP-2.
CONCLUSIONS
The authors' observations suggest that this bioengineered construct successfully acts as a chemoattractant for circulating mesenchymal stem cells because of controlled release of VEGF from the peptide amphiphile gels. The chemotactic functional scaffolds may play a role in the future design of clinically relevant bone graft substitutes for large-scale bone defects.
背景
目前自体骨移植和同种异体植入物修复颅骨缺损的常用技术存在显著局限性。在这项研究中，作者研究了一种基于肽两亲纳米纤维凝胶的新型骨修复替代方法，该方法设计用于控制血管内皮生长因子（VEGF）的释放，以募集循环干细胞到骨再生部位，并通过骨形态发生蛋白-2（BMP-2）促进骨愈合。
方法
评估肽两亲凝胶中 VEGF 的释放动力学。通过将胶原海绵与含有 VEGF 的肽两亲凝胶结合来制备趋化功能支架。通过测量间充质干细胞迁移来评估支架的体外和体内趋化活性，并评估支架的血管生成能力。创建大规模啮齿动物颅骨缺损，以评估植入支架和其他对照材料后的骨再生情况。
结果
VEGF 以受控释放方式从肽两亲物中释放。与对照支架相比，暴露于趋化功能支架时，间充质干细胞的体外迁移明显更大。体内趋化作用通过示踪标记的间充质干细胞向趋化功能支架的迁移得到证明。趋化功能支架在体内显示出明显增加的血管生成。在用趋化功能支架和 BMP-2 治疗的缺陷中观察到成功的骨再生。
结论
作者的观察结果表明，由于肽两亲凝胶中 VEGF 的受控释放，这种生物工程构建体成功地作为循环间充质干细胞的趋化剂发挥作用。趋化功能支架可能在未来设计用于大规模骨缺损的临床相关骨移植物替代品方面发挥作用。
Zotero 插件