Biomaterials combined with Engineered Growth Factors with collagen binding affinity for tissue regeneration.

生物材料与具有胶原蛋白结合亲和力的工程生长因子相结合，可促进组织再生。

基本信息

批准号：
18500371
负责人：
KITAJIMA Takashi
金额：
$ 1.96万
依托单位：
The Institute of Physical and Chemical Research (2007)Kanagawa Academy of Science and Technology (2006)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500371/
关键词：
Regenerative Medicine Tissue Engineering Growth Factors Blood Vessels

项目摘要

We engineered growth factors (EGF, HGF, VEGF etc) to confer collagen binding activity by fusion of fibronectin collagen-binding domain (CBD). Resulting engineered growth factors showed stable binding activity. Cell growth promotion activity was also improved when they were combined with collagen. One of such fusion protein (CBD-HGF) immobilized to the culture vessels continued to stimulate growth of endothelial cells without medium change. That is, additional factor was unnecessary during prolonged culture. This will be suitable for developing culture system (or bioreactor) of growing large number of cells for cell-implantation therapy.We further examined CBD-HGF on the applicability to regenerative medicine by combining with tissue engineering materials as follows.1) Small caliber artificial blood vessels (3mm in diameter, ePTFE) were combined with CBD-HGF and implanted into dog femoral artery. The implanted vessels showed earlier endothelialization (4weeks) as compared to control vessels and native HGF treated vessels. The fusion HGF may be used to develop implantable vessels with long patency for bypass graft of coronary artery.2) Collagen sponges combined with CBD-HGF induced extensive angiogenesis by 2 weeks after implantation into rat subcutaneous tissue, while control and HGF-treated sponge showed minimal angiogenesis. The sponge may be useful to repair ischemic cardiac tissues, leg ulcer etc.3) CBD-HGF infused to balloon-injured carotid artery of rats promoted endothelialization of denuded areas. It may be used to prevent restenosis after angioplasty using balloon catheter.The results of the present study indicated the applicability of collagen-binding growth factor (s) in the following ways;1) Culture system for cell therapy, 2) biomaterial combined with growth factor activity to induce tissue repair and 3) medicine to induce tissue repair.

我们设计了生长因子（EGF，HGF，VEGF等），以通过纤连蛋白胶原结合结构域（CBD）融合来赋予胶原蛋白结合活性。由此产生的工程生长因子显示出稳定的结合活性。当细胞生长与胶原蛋白结合时，还可以改善它们。固定在培养血管上的这种融合蛋白之一（CBD-HGF）继续刺激内皮细胞的生长而没有中等变化。也就是说，在长期文化期间，其他因素是不必要的。这将适用于开发大量细胞的培养系统（或生物反应器），用于细胞植入术治疗。我们通过与组织工程材料结合使用，进一步研究了CBD-HGF对再生医学的适用性，如下1）小口径人造血管（直径3mm，Eptfe，Eptfe，Eptfe，Eptfe，Eptfe，Eptfe，Eptfe）与cbd-Hgf和dogor养殖混合在一起。与对照血管和本地HGF处理的血管相比，植入的血管显示早期的内皮化（4周）。融合HGF可用于开发具有较长通畅的冠状动脉移植物的植入式血管。2）胶原蛋白海绵与CBD-HGF结合在大鼠皮下组织后2周结合了CBD-HGF诱导的广泛的血管生成，而对照和HGF造成的SPONGE则显示出微生的质量。海绵可能有助于修复缺血性心脏组织，腿部溃疡等。3）CBD-HGF注入大鼠气球受伤的颈动脉，促进了裸露区域的内皮化。该研究的结果表明，它可用于预防血管成形术后血管成形术后再狭窄。