Integrated construction of silkworm cocoon-inspired 3D scaffold for improving cell manufacture and cryopreservation

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Although cellular therapy holds enormous promise in treating intractable diseases, its application potential has been significantly hampered due to the scarcity of reliable and consistent cell sources. Therefore, a high-efficiency strategy that improves cell production and storage is desperately needed. Herein, we develop a versatile 3D bioinspired scaffold (Cryosilk) for improving scalable cell manufacture and cryopreservation. A bottom-up fabrication technique integrating electrospinning, in situ surface functionalization and freeze-shaping was explored to construct Cryosilk with biomimetic features and functions of silkworm cocoons. Cryosilk is composed of a core-shell heterostructure with silk fibroin/poly alanine fiber core and silk sericin shell, generating a 3D cocoon-mimicking fibrous structure. Importantly, Cryosilk possesses improved thermal conductivity and ice crystal resistance capability, thus enabling to cryopreserve biological samples with minimal cryodamage. Furthermore, Cryosilk not only promotes cell adhesion and growth, but achieves rapid and uniform rewarming process, which provides high cryopreservation efficacy for immune cells and stem cells. Particularly, Cryosilk can maintain cell viability and biofunctions of stem cell-scaffold constructs after freeze-thawing, which can be directly implanted to promote wound healing. Thus, Cryosilk offers unprecedented efficacy in cell manufacture and cryopreservation, which provides sufficient and high-quality precious cells and tissue engineered scaffolds for cellular therapy.