We show that tuning the kinetics of a dynamic hindered urea bond in polyurethanes to match competitive isocyanate hydrolysis results in the formation of new, unhindered urea bonds upon incubation of the material in water (Figure 1). This significantly increases thermomechanical performance of the pristine material on demand. Most notably, strains at break could be increased up to 10x while elongations at break remained equal or even increased compared to the pristine material, which led us to term the effect “self-reinforcement”. We have elucidated the mechanism of self-reinforcement in small molecule studies and investigated its matrix-dependent effects on material properties of both, thermoplastic and thermoset materials. Self-strengthening materials provide a unique opportunity to reconcile the contradicting properties of mechanical performance vs processability and highly porous design of final parts, which is particularly important for highly porous biomedical scaffolds. Here we show the application of self-reinforcing thermoplastic poly(urethane urea) for electrospun biodegradable vascular grafts. Notably, biodegradability of such scaffolds is enhanced compared to reference grafts despite their superior mechanical performance.