LAUSR

&NA; Porous silk protein scaffolds are designed to display shape memory characteristics and volumetric recovery following compression. Two strategies are utilized to realize shape recovery: addition of hygroscopic plasticizers like glycerol, and tyrosine modifications with hydrophilic sulfonic acid chemistries. Silk sponges are evaluated for recovery following 80% compressive strain, total porosity, pore size distribution, secondary structure development, in vivo volume retention, cell infiltration, and inflammatory responses. Glycerol‐modified sponges recover up to 98.3% of their original dimensions following compression, while sulfonic acid/glycerol modified sponges swell in water up to 71 times their compressed volume, well in excess of their original size. Longer silk extraction times (lower silk molecular weights) and higher glycerol concentrations yielded greater flexibility and shape fidelity, with no loss in modulus following compression. Sponges are over 95% porous, with secondary structure analysis indicating glycerol‐induced β‐sheet physical crosslinking. Tyrosine modifications with sulfonic acid interfere with β‐sheet formation. Glycerol‐modified sponges exhibit improved rates of cellular infiltration at subcutaneous implant sites with minimal immune response in mice. They also degrade more rapidly than unmodified sponges, a result posited to be cell‐mediated. Overall, this work suggests that silk sponges may be useful for minimally invasive deployment in soft tissue augmentation procedures. &NA; Silk protein sponges show enhanced shape memory properties and elasticity when modified with hydrophilic plasticizers, making them ideal for minimally invasive deployment in soft tissue augmentation procedures. Figure. No caption available.