Structure-guided and sustainable engineering silk sericin powder with improved storability, redissolution, and biocompatibility

Silk sericin (SS), a highly biocompatible and biodegradable byproduct of the silk industry, is valuable yet underutilized due to its poor thermal and storage stability, leading to thermal degradation and function loss. Here, a structure-guided sustainable strategy is proposed to extract, stabilize, and preserve SS, enhancing its utilization via high-temperature and high-pressure (HTHP, 121 °C and 0.1 MPa) processing followed by spray drying. The controlled HTHP processing duration drives a morphological transition of SS from stacked lamellae to fibrillar, rodlike, and eventually spherical nanoparticle assemblies, accompanied by chemical changes such as molecular weight reduction, β-sheet transition in secondary structure, and modifications of polar, which are closely associated with biological outcomes, including solubility, antioxidant capacity, and cell biocompatibility, thereby indicating diverse potential applications. Based on these insights, spray drying is employed to trap metastable conformations, yielding amorphous SS powders with enhanced storage stability. Importantly, these powders exhibit complete redissolution (100 % usability), outperforming conventional freeze-dried products (20 %–70 % solubility). Moreover, redissolved SS samples significantly promote the proliferation and migration of different cell types, maintaining biological functions comparable to the original liquid SS. Overall, the HTHP-induced structural transitions of SS provide mechanistic insights into its underlying disassembly. Furthermore, this green and scalable method with low energy consumption and equipment cost facilitates the practical value of SS and offers a broadly applicable framework for stabilizing thermally labile proteins, particularly in biomedical and composite material fields.