Fibrin scaffolds for angiogenesis in soft tissue models: a systematic review.

Background: Fibrin is a biocompatible, angiogenic biomaterial widely used in soft tissue engineering, with outcomes influenced by scaffold formulation and design. Aim: This systematic review evaluates how fibrin scaffold composition and design affect angiogenesis in Methods: PubMed, Scopus, and OVID were searched on 28/Oct/2024. A two-step screening process by three independent researchers identified original studies on fibrin scaffolds assessing endothelial formation and/or migration. Studies without experimental data or focused solely on grafts were excluded. Data on scaffold composition, manufactured objects, cell-embedding strategies, angiogenic outcomes, and a subset of muscle-specific studies were narratively synthesised. Risk of bias (RoB) and study quality were assessed using SYRCLE's RoB tool and a modified CAMARADES checklist. Results & discussion: The 81 studies highlight the impact of scaffold composition on angiogenic outcomes, with human-derived fibrinogen and pre-embedding cells consistently supporting successful outcomes. While tube and network formation outcomes typically aligned, endothelial migration exhibited different patterns. Thrombin often contributed positively, but crosslinker effects were less clear. Muscle-focused studies mainly used hydrogels and often included non-endothelial cells. Conclusions: Fibrin scaffolds are highly relevant for soft tissue engineering, with outcomes influenced by formulation, fibrinogen source, and cell embedding. However, experimental design variability and lack of standardised reporting hinder reproducibility and clinical translation. To support future research, a minimum information checklist was created to promote consistent reporting, while aggregated success rates across design parameters could guide scaffold design. Registration & funding: PROSPERO [CRD42025612994] and OSF [10.17605/osf.io/nvfdj]. No funding body was directly involved.