权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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），通过融合纤维连接蛋白胶原结合结构域（CBD）赋予胶原结合活性。所得到的工程生长因子具有稳定的结合活性。当它们与胶原蛋白结合时，细胞生长促进活性也有所提高。其中一种固定在培养血管上的融合蛋白（CBD-HGF）在不改变培养基的情况下继续刺激内皮细胞的生长。也就是说，在长时间培养过程中，不需要额外的因素。这将适合于开发用于细胞植入治疗的大量细胞培养系统（或生物反应器）。我们结合组织工程材料进一步考察了CBD-HGF在再生医学中的适用性。1)小口径人工血管（直径3mm， ePTFE）与CBD-HGF联合植入犬股动脉。与对照血管和原生HGF处理血管相比，移植血管内皮化时间更早（4周）。融合HGF可用于冠状动脉旁路移植术中长通畅的可植入血管的培养。2)在植入大鼠皮下组织2周后，含CBD-HGF的胶原海绵可诱导大量血管生成，而对照组和含hgf的海绵血管生成极少。海绵可用于修复缺血心脏组织、腿部溃疡等。3)大鼠颈动脉球囊损伤后注入CBD-HGF可促进脱落区内皮化。它可用于防止球囊导管血管成形术后再狭窄。本研究结果表明胶原结合生长因子在以下几个方面的适用性：1)细胞治疗培养系统，2)生物材料结合生长因子活性诱导组织修复，3)药物诱导组织修复。