Many biological tissues contain colloids within a fibrillar structure. Here, we develop and characterize colloidal-fibrillar scaffolds through examination of the effects of relative colloid and fiber ratios within a fibrin-based model system composed of fibrin-based nanoparticles (FBNs) within a natural fibrin scaffold. At lower concentrations, FBNs primarily integrate into the fibrillar fibrin matrix, strengthening it. At high concentrations, colloid-colloid interactions dominate and FBNs primarily form a highly aligned secondary structure that does not strengthen the fibrillar matrix. At intermediate concentrations, both reinforcement of the fibrin matrix and colloid-colloid interactions are observed. Our characterization of this colloidal-fibrillar system provides insight into new avenues for wound healing biomaterial development. Using structural and mechanical results, we developed a biomimetic surgical sealant. When applied to a vascular healing model, FBN gel resulted in improved vessel healing. This colloidal-fibrillar composite can greatly improve healing outcomes and should be applied to other tissues.