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

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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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Söderlund, Z., Ibáñez-Fonseca, A., Hajizadeh, S., Rodríguez-Cabello, J. C., Liu, J., Ye, L., … Westergren-Thorsson, G. (2022). Controlled release of growth factors using synthetic glycosaminoglycans in a modular macroporous scaffold for tissue regeneration. Communications Biology, 5(1). https://doi.org/10.1038/s42003-022-04305-9

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