Bioactive IGF-1 release from collagen-GAG scaffold to enhance cartilage repair in vitro.
Bioactive IGF-1 release from collagen-GAG scaffold to enhance cartilage repair in vitro.
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DOI：
10.1007/s10856-014-5325-y
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Cameron RE
中科院分区：
文献类型：
--
作者：
Mullen LM;Best SM;Ghose S;Wardale J;Rushton N;Cameron RE
组织工程是一种很有前途的软骨修复技术。为了实现这一目标，多孔胶原-糖胺聚糖（CG）支架装载有不同浓度的胰岛素样生长因子-1（IGF-1），并作为生长因子递送装置进行评估。通过监测植入支架内的软骨细胞合成的II型胶原和蛋白聚糖的量来评估生物学反应。IGF-1释放取决于用于将IGF-1吸附到CG支架上的IGF-1负载浓度，并且释放到培养基中的IGF-1的量在第4天最高。该初始IGF-1释放可以使用线性回归分析建模。骨关节炎（OA）软骨细胞接种在含有吸附的IGF-1的支架内，以剂量依赖性方式沉积核心蛋白聚糖和II型胶原，并且通过用50 μg/ml IGF-1加载支架实现最高的II型胶原沉积。与无生长因子对照组相比，接种在IGF-1负载支架内的细胞也沉积更多的细胞外基质，因此从支架释放的IGF-1保持生物活性并对OA软骨细胞发挥合成代谢作用。将IGF-1吸附到支架上的有效性可能是由于保护分子免受蛋白水解消化，与添加多剂量的外源性生长因子相比，允许IGF-1随时间更持续地释放。将IGF-1插入CG支架中提供了IGF-1的初始治疗性爆发释放，这在该体外模型中有利于启动ECM沉积和修复，并显示出在体内开发该递送装置的潜力。
Tissue engineering is a promising technique for cartilage repair. Toward this goal, a porous collagen–glycosaminoglycan (CG) scaffold was loaded with different concentrations of insulin-like growth factor-1 (IGF-1) and evaluated as a growth factor delivery device. The biological response was assessed by monitoring the amount of type II collagen and proteoglycan synthesised by the chondrocytes seeded within the scaffolds. IGF-1 release was dependent on the IGF-1 loading concentration used to adsorb IGF-1 onto the CG scaffolds and the amount of IGF-1 released into the media was highest at day 4. This initial IGF-1 release could be modelled using linear regression analysis. Osteoarthritic (OA) chondrocytes seeded within scaffolds containing adsorbed IGF-1 deposited decorin and type II collagen in a dose dependent manner and the highest type II collagen deposition was achieved via loading the scaffold with 50 μg/ml IGF-1. Cells seeded within the IGF-1 loaded scaffolds also deposited more extracellular matrix than the no growth factor control group thus the IGF-1 released from the scaffold remained bioactive and exerted an anabolic effect on OA chondrocytes. The effectiveness of adsorbing IGF-1 onto the scaffold may be due to protection of the molecule from proteolytic digestion allowing a more sustained release of IGF-1 over time compared to adding multiple doses of exogenous growth factor. Incorporating IGF-1 into the CG scaffold provided an initial therapeutic burst release of IGF-1 which is beneficial in initiating ECM deposition and repair in this in vitro model and shows potential for developing this delivery device in vivo.
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