Design of High-Payload Silk/Butyrate Materials for Immunomodulation

Area of Science:

• Biomaterials Science
• Immunology
• Drug Delivery Systems

Background:

• Short-chain fatty acids (SCFAs), such as butyrate, are potent immunomodulators.
• Therapeutic application of SCFAs is hindered by poor bioavailability, volatility, and rapid metabolism.
• Conventional polymeric delivery systems often fail to provide sustained, biologically relevant SCFA exposure.

Purpose of the Study:

• To introduce silk fibroin (SF) as a versatile carrier for volatile metabolites.
• To develop SF-based delivery systems with tunable loading and release profiles for SCFAs.
• To investigate the impact of material morphology on the immunomodulatory efficacy of delivered SCFAs.

Main Methods:

• Fabrication of butyrate-loaded silk fibroin nanoparticles and porous sponges.
• Characterization of SCFA loading and multi-day release profiles.
• In vitro assessment of macrophage reprogramming and cytokine production (IL-10).

Main Results:

• SF carriers enabled sustained, Fickian release of butyrate over multiple days.
• Nanoparticle-mediated delivery was essential for reprogramming inflammatory macrophages.
• SF nanoparticles induced significant anti-inflammatory IL-10 production and M1-to-M2 macrophage polarization, unlike sponge formats.

Conclusions:

• Material morphology, specifically nanoparticle form factor, is critical for SCFA immunomodulatory efficacy, independent of release rate.
• Silk fibroin is a promising platform for delivering volatile and rapidly metabolized endogenous metabolites.
• This work enables novel therapeutic strategies in immunomodulation and metabolic medicine using SF-based delivery systems.