Silk proteins for 3D bioprinting: Integrating fibroin structural support with sericin cell-supportive capability

Three-dimensional (3D) bioprinting requires inks and bioinks that combine appropriate processing and mechanical properties with a biologically supportive environment capable of sustaining cell viability and proliferation. Silk-based biomaterials have attracted considerable attention in biofabrication due to their tunable properties, processability, and structural similarity to extracellular matrix components. While most silk-based inks/bioinks rely primarily on silk fibroin (SF) for structural integrity, the use of silk sericin (SS) as a cell-supportive component remains comparatively underexplored in bioprinting. As a hydrophilic protein, SS has been associated with favorable cell responses, including cell adhesion and proliferation. Additionally, SS has been reported to support cell growth in culture media, or to replace fetal bovine serum (FBS). These characteristics have motivated the exploration of sericin in formulations intended for cell encapsulation Furthermore, as a by-product of the silk industry, SS is a sustainable protein source, providing an environmental dimension to its biomedical use. In the current study, we combined both silk proteins to develop a proof-of-concept bilayer silk-based printed construct. SS-based hydrogels were formulated with gelatin and glycerol to encapsulate human dermal fibroblasts (HDFs), while SF-based ink was incorporated into the 3D printing process as a structurally supportive biomaterial. The inks/bioinks were processed using extrusion-based 3D bioprinting and subsequently crosslinked through an enzymatic horseradish peroxidase/hydrogen peroxide (HRP/H₂O₂) system to stabilize the hydrogel network. These structures supported HDF viability and proliferation under the tested in vitro conditions. Overall, these results highlight the potential of silk proteins as a proof-of-concept 3D bioprinting platform that combines a SF-based structural support ink with a sericin-containing cell-laden bioink in which HDF viability and proliferation were supported under the tested in vitro conditions.