Silk Fibroin and Sericin Differentially Potentiate the Paracrine and Regenerative Functions of Stem Cells Through Multiomics Analysis

Abstract

emerging as a potential alternative to these problems. The tissue engineering triad involves the effective integration of cells, scaffolds, and signals for the development of biological substitutes to restore, maintain, and replace injured tissues and organs. [2] The scaffold plays a substantial role in the field of tissue engineering, primarily by providing physical support (structures and substrates) for cells to attach and grow, subsequently resulting in tissue formation. [3] A variety of natural and synthetic biomaterials have been explored to develop tissue-engineered scaffolds. By incorporating exogenous growthstimulating signals, such as growth factors or small molecules, scaffolds can provide specific bioactivities, that is, biochemical signals required for cellular behaviors and tissue regeneration. [4] As biomaterials are essentially comprised of chemical molecules, they are capable of supplying inherent biochemical signals to guide and influence cells. For example, cells residing in tissue-engineered scaffolds can establish cell-biomaterial communication networks partially through biochemical signaling. The degradation products of various biodegradable biomaterials after implantation in vivo also provide specific biochemical signals to the cells in and around the Silk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials with great potential in tissue engineering and regenerative medicine. However, their biochemical interactions with stem cells remain unclear. In this study, multiomics are employed to obtain a global view of the cellular processes and pathways of mesenchymal stem cells (MSCs) triggered by SF and SS to discern cell-biomaterial interactions at an in-depth, high-throughput molecular level. Integrated RNA sequencing and proteomic analysis confirm that SF and SS initiate widespread but distinct cellular responses and potentiate the paracrine functions of MSCs that regulate extracellular matrix deposition, angiogenesis, and immunomodulation through differentially activating the integrin/PI3K/Akt and glycolysis signaling pathways. These paracrine signals of MSCs stimulated by SF and SS effectively improve skin regeneration by regulating the behavior of multiple resident cells (fibroblasts, endothelial cells, and macrophages) in the skin wound microenvironment. Compared to SS, SF exhibits better immunomodulatory effects in vitro and in vivo, indicating its greater potential as a carrier material of MSCs for skin regeneration. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling the future development of silk-based therapeutics for tissue engineering and stem cell therapy.

Direct Assembly of Bioactive Nanoparticles Constructed from Polyphenol-Nanoengineered Albumin

“…Two other proteins (sericin and transferrin) were employed to fabricate UNP nanoparticles and similar trends of size changes and stability were observed, indicating the versatility of the UNP nanoparticle assembly strategy (Figure S2). 29,30 Subsequently, we assessed the crucial role of TA in promoting protein assembly. To remove the excess free TA in the solution, the UNP nanoparticle was dialyzed with the molecular weight cutoff at 14 kDa.…”

“…Two other proteins (sericin and transferrin) were employed to fabricate UNP nanoparticles and similar trends of size changes and stability were observed, indicating the versatility of the UNP nanoparticle assembly strategy (Figure S2). , …”

Waste to Wealth: Exploring the Versatile Prospects of Discarded Silk Sericin

“…However, mesenchymal stem cell respond differently to fibroin and sericin as observed by Zhang et al They found that fibroin had better effects on the immune system compared with sericin, suggesting it has more potential as a material for carrying mesenchymal stem cells in skin regeneration treatments. In a similar study, Tao et al developed a sericin/poly­(vinyl alcohol) based hydrogel as a drug delivery carrier for wound healing purposes.…”

Biomimetic Structural Proteins: Modular Assembly and High Mechanical Performance

“…Inspired by these unique molecules, resulting diverse protein materials, such as spider silk, elastin, collagen, and mussel proteins, are favored in multiple industries. 5 For example, spider silk protein materials have been utilized for supertough electro-tendon 6 and cardiac tissue engineering 7 due to the extraordinary mechanical properties and biological features. However, the preparation of protein materials remains far behind the increasing demands.…”

“…Proteins are accurately synthesized from 20 amino acid monomers, forming materials with precise structures and versatile functionalities by subsequent supramolecular self-assembly to realize their biological roles. Inspired by these unique molecules, resulting diverse protein materials, such as spider silk, elastin, collagen, and mussel proteins, are favored in multiple industries . For example, spider silk protein materials have been utilized for supertough electro-tendon and cardiac tissue engineering due to the extraordinary mechanical properties and biological features.…”