Human-derived cytokine functionalized sericin/agarose composite gel material with cell proliferation-promoting activity fabricated using genetically engineered silk for medical application

Abstract

Functional biomaterials have great potential for future medical application. Although functional biomaterials produced from genetically engineered silk are promising, it can be challenging to simultaneously maintain their structural stability and functionality. Herein, a stable and functional sericin protein-based composite gel biomaterial with improved cell-proliferation activity was designed and fabricated using a genetically engineered silk material containing human-derived cytokines combined with agarose molecules. This composite gel material is porous and consists of a sericin protein network, agarose molecular network, and sericin-agarose crossing (by hydrogen bond linkage) network; a complex structure that improved the stability and mechanical performance of the final material by approximately 2-fold. Moreover, the composite material showed to efficiently and gradually release the active cytokines FGF-1 and FGF-2 for up to 3 weeks, thereby promoting significant fibroblast proliferation by activating the extracellular signal-regulated kinase pathway. Notably, this composite gel caused no obvious cytotoxicity or severe inflammation responses in vitro nor in vivo. Taken together, this composite gel material has medical application potential for damaged tissue repair and regeneration. Moreover, this report demonstrates that application of agarose in biomaterials can aid on the clinical application of genetically engineered silk materials in the future.