Controlled release of growth factors using synthetic glycosaminoglycans in a modular macroporous scaffold for tissue regeneration

使用合成的氨基葡聚糖在模块化大孔支架中控制释放生长因子,用于组织再生

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作者:Z Söderlund, A Ibáñez-Fonseca, S Hajizadeh, J C Rodríguez-Cabello, J Liu, L Ye, E Tykesson #, L Elowsson #, G Westergren-Thorsson

Abstract

Healthy regeneration of tissue relies on a well-orchestrated release of growth factors. Herein, we show the use of synthetic glycosaminoglycans for controlled binding and release of growth factors to induce a desired cellular response. First, we screened glycosaminoglycans with growth factors of interest to determine kon (association rate constant), koff (dissociation rate constant), and Kd (equilibrium rate constant). As proof-of-concept, we functionalized an elastin-like recombinamer (ELR) hydrogel with a synthetic glycosaminoglycan and immobilized fibroblast growth factor 2 (FGF2), demonstrating that human umbilical vein endothelial cells cultured on top of ELR hydrogel differentiated into tube-like structures. Taking this concept further, we developed a tunable macroporous ELR cryogel material, containing a synthetic glycosaminoglycan and FGF2 that showed increased blood vessel formation and reduced immune response compared to control when implanted in a subcutaneous mouse model. These results demonstrated the possibility for specific release of desired growth factors in/from a modular 3D scaffold in vitro and in vivo.

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