Growth Factor Immobilization to Synthetic Hydrogels: Bioactive bFGF-Functionalized Polyisocyanide Hydrogels

生长因子固定化合成水凝胶:生物活性 bFGF 功能化聚异氰化物水凝胶

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作者:Melissa J J van Velthoven, Aksel N Gudde, Evert Arendsen, Jan-Paul Roovers, Zeliha Guler, Egbert Oosterwijk, Paul H J Kouwer

Abstract

With its involvement in cell proliferation, migration and differentiation basic fibroblast growth factor (bFGF) has great potential for tissue engineering purposes. So far, however, clinical translation of soluble bFGF-based therapies is unsuccessful, because the required effective doses are often supraphysiological, which may cause adverse effects. An effective solution is growth factor immobilization, whereby bFGF retains its bioactivity at increased efficacy. Studied carriers include films, solid scaffolds, and particles, as well as natural and synthetic hydrogels. However, these synthetic hydrogels poorly resemble the characteristics of the native extracellular matrix (ECM). In this work, bFGF is covalently conjugated to the synthetic, but highly biocompatible, polyisocyanide-based hydrogel (PIC-bFGF), which closely mimics the architecture and mechanical properties of the ECM. The growth factor conjugation protocol is straightforward and readily extrapolated to other growth factors or proteins. The PIC-bFGF hydrogel shows a prolonged bioactivity up to 4 weeks although no clear effects on the ECM metabolism are observed. Beyond the future potential of the PIC-bFGF hydrogel toward various tissue engineering applications, this work underlines that simple biological conjugation procedures are a powerful strategy to induce additional bioactivity in 3D synthetic cell culture matrices.

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