Enzyme‐Responsive Porous Scaffolds by Electrospinning Polyalanine

ABSTRACT Porous polymeric materials are essential for applications ranging from tissue regeneration to controlled drug delivery, with a growing demand for them to be biodegradable and synthesized via environmentally responsible methods. In this work, we present a novel approach that addresses these needs by first synthesizing polyalanine (PAla) through a green and cost‐effective ring‐opening polymerization of its 2,5‐diketopiperazine monomer. The resulting PAla was then co‐electrospun with poly(ε‐caprolactone) (PCL) to create robust, nanofibrous scaffolds. The inclusion of PAla resulted in a 399% increase in the material's maximum tensile stress compared to PCL alone, creating a tough material suitable for mechanically demanding applications. Crucially, these scaffolds demonstrated ‘smart’ behavior, exhibiting selective degradation in the presence of human neutrophil elastase (HNE), an enzyme overexpressed in chronic wounds. This work pioneers the creation of mechanically competent, enzyme‐responsive biomaterials from a sustainable poly(amino acid) source, presenting a significant advance for potential PCL applications.