2024 AIChE Annual Meeting

Thiol-Functionalized Silk Biomaterials, a Study of Two Different Synthetic Routes

Biomaterials are extremely useful for local and controlled delivery of therapeutics as well as for tissue engineering purposes. In this work, brush-like polymers are generated on the surface of biomaterials, and two different synthetic approaches are explored to enable the generation of brush-like polymers containing thiol groups. The thiol groups are compatible with a wide range of molecules, including bioactive molecules and various drugs, to enable the use of the materials in drug delivery and tissue engineering applications. We use Bombyx mori silk fibroin, as it has been widely researched and used for its biocompatibility, controlled degradation, and drug release properties.

We are comparing two methods of forming thiol-functionalized silk biomaterials. Both methods result in the formation of brush-like polymers on the surface of silk biomaterials. Method A began with hydroxyl-enriched silk films, which were subsequently modified to attach a chain transfer agent (RAFT agent). The films were then polymerized with AEMA (amino ethyl methacrylate) using reversible addition-fragmentation chain transfer polymerization, to result in the formation of brush-like polymers. Traut’s Reagent was subsequently utilized to convert the primary amines present on the brush side chains to thiol groups.

Method B begins by forming a thiol-containing monomer via a two-step synthesis reaction. The films were then modified to enrich hydroxyl groups and attach the chain transfer agent (RAFT agent). The brush-like polymer was then synthesized from the thiol-containing monomer. It is hypothesized that forming brushes from a thiol-containing monomer directly on the silk films (Method B) will lead to brushes with greater thiol content than converting primary amines to thiols on existing brushes (Method A). The enhanced thiol content is expected to effectively allow a greater amount of drug product to attach to the biomaterial.

To quantify the difference between Method A and Method B, a variety of characterizations and assays were conducted. ATR-FTIR and Raman spectra were used to characterize the films before and after the attachment of the RAFT agent. Contact angle studies using sessile drop method showed increased angles after polymerizing the films with a hydrophobic monomer. Ellman’s Assay was used to quantify the amount of thiol contained in the molecule and a ninhydrin assay was used to quantify the amount of primary amine present. The ability to form a thiol functionalized biomaterial with a greater thiol content is expected to enable increased drug attachment that is suitable for various biomedical applications.