(181a) One-Pot Approach for Generating Drug Loaded Nano-Thin Silk Fibroin Coatings for Tissue Engineering Applications
AIChE Annual Meeting
Tuesday, November 9, 2021 - 3:30pm to 3:48pm
Electrospun scaffolds have been highly utilized in various tissue engineering applications due to their ability to recapitulate the length scale and architecture of the extracellular matrix (ECM). Great advancements have been made in producing scaffolds that better mimic the ECM and enhance cell-scaffold interactions by manipulating scaffold structural and topographical properties. Despite these efforts, when in contact with biological systems the surface properties of many synthetic and natural electrospinning materials adversely affect cell-scaffold interactions. Current covalent surface modification strategies of these topographically complex substrates, such as grafting-to or grafting-from chemistries, are limited to specific materials, often result in low grafting densities, and can potentially result in drastic changes in fiber morphology. Recent work in our group has developed a non-covalent bottom-up self-assembly approach for generating homogeneous, stable, and dense nano-thin coatings of silk fibroin, a natural biopolymer derived from the threads of the domesticated silkworm Bombyx mori. This coating strategy has been shown to uniformly coat electrospun poly-l-lactic acid scaffolds without drastically changing fiber diameter and alignment or altering the fine surface nanotopographies engineered on fiber surfaces for improving nerve cell attachment. Importantly, the presence of the silk fibroin coating, even without any specific cell adhesion motifs, led to an overall enhancement of dorsal root ganglia adhesion and neurite extension, therefore improving the neuroregenerative efficacy of these scaffolds. Here, we demonstrate the the ability to further enhance the bioactivity of these nano-thin silk coatings by non-covalently incorporating a therapeutic payload during the coating assembly process. Using fluorophores and dye-conjugated proteins as models for small molecule and biologic drugs, respectively, we show that the total amount of drug loaded into the nano-thin coating can be controlled by varying its concentration in the coating solution. Additionally, we show that the size, hydrophobicity, and overall charge of the loaded molecules directly affect their incorporation and subsequent release. Specifically, smaller molecular weight, hydrophobic, and overall positively charged molecules lead to higher loading efficiencies. Importantly, with enzyme payloads, the mild coating conditions used does not cause a high loss of activity, as suggested from data using lysozyme as a model enzyme. Ultimately, this work demonstrates a substrate-tolerant one-pot method of producing nano-thin silk fibroin coatings that can incorporate a therapeutic payload to further enhance the regenerative efficacy of electrospun scaffolds.