biostudies-literatureUnknown10Boucard EIn tissue engineering, cell origin is important to ensure outcome quality. However, the impact of the cell type chosen for seeding in a biocompatible matrix has been less investigated. Here, we investigated the capacity of primary and immortalized fibroblasts of distinct origins to degrade a gelatin/alginate/fibrin (GAF)-based biomaterial. We further established that fibrin was targeted by degradative fibroblasts through the secretion of fibrinolytic matrix-metalloproteinases (MMPs) and urokinase, two types of serine protease. Finally, we demonstrated that besides aprotinin, specific targeting of fibrinolytic MMPs and urokinase led to cell-laden GAF stability for at least forty-eight hours. These results support the use of specific strategies to tune fibrin-based biomaterials degradation oFrontiers in bioengineering and biotechnology920929https://www.ebi.ac.uk/biostudies/studies/S-EPMC9355319biostudies-literatureThe degradation of gelatin/alginate/fibrin hydrogels is cell type dependent and can be modulated by targeting fibrinolysis.PMC9355319Boucard EHalary FMota CCoulon FVidal LHascoet JYfalseThe degradation of gelatin/alginate/fibrin hydrogels is cell type dependent and can be modulated by targeting fibrinolysis.In tissue engineering, cell origin is important to ensure outcome quality. However, the impact of the cell type chosen for seeding in a biocompatible matrix has been less investigated. Here, we investigated the capacity of primary and immortalized fibroblasts of distinct origins to degrade a gelatin/alginate/fibrin (GAF)-based biomaterial. We further established that fibrin was targeted by degradative fibroblasts through the secretion of fibrinolytic matrix-metalloproteinases (MMPs) and urokinase, two types of serine protease. Finally, we demonstrated that besides aprotinin, specific targeting of fibrinolytic MMPs and urokinase led to cell-laden GAF stability for at least forty-eight hours. These results support the use of specific strategies to tune fibrin-based biomaterials degradation o2022-01-01T00:00:00Z20222025-04-21T22:35:27.311Z2025-02-19T04:54:02.714ZS-EPMC93553193593548610.3389/fbioe.2022.920929