Precise Protein Photolithography (P³): High Performance Biopatterning Using Silk Fibroin Light Chain as the Resist

Abstract

Precise patterning of biomaterials has widespread applications, including drug release, degradable implants, tissue engineering, and regenerative medicine. Patterning of protein‐based microstructures using UV‐photolithography has been demonstrated using protein as the resist material. The Achilles heel of existing protein‐based biophotoresists is the inevitable wide molecular weight distribution during the protein extraction/regeneration process, hindering their practical uses in the semiconductor industry where reliability and repeatability are paramount. A wafer‐scale high resolution patterning of bio‐microstructures using well‐defined silk fibroin light chain as the resist material is presented showing unprecedent performances. The lithographic and etching performance of silk fibroin light chain resists are evaluated systematically and the underlying mechanisms are thoroughly discussed. The micropatterned silk structures are tested as cellular substrates for the successful spatial guidance of fetal neural stems cells seeded on the patterned substrates. The enhanced patterning resolution, the improved etch resistance, and the inherent biocompatibility of such protein‐based photoresist provide new opportunities in fabricating large scale biocompatible functional microstructures.

Engineering the Future of Silk Materials through Advanced Manufacturing

“…To be specific, the means of modification includes direct feeding, gene modification, chemical conjugation, mesoscopic assembly, and macroscopic mixing, spanning from molecular level to macroscopic level. By selecting the appropriate method, new opportunities become available to attain new functions of silk biomaterials or silk‐based devices, such as strength‐enhanced silk fibers, photosensitive silk photoresist, silk screw with the function of drug sustained release, and so on.…”

“…More interestingly, hierarchical assembly of the DNA‐spider silk conjugates into ribbons and rafts could be triggered by the temperature ( Figure ). Other types of functional molecules have also been successfully conjugated to the silk protein for a variety of applications such as photo‐sensitization, and cell attachment . In particular, the biomedical applications of the chemically modified silk protein have been well documented and summarized in another review article .…”

“…Copyright 2015, Springer Nature. UVL: Reproduced under the terms of the Creative Commons Attribution 4.0 License . Copyright 2017, The Authors, published by Wiley‐VCH.…”

Degradation Behavior of Silk Fibroin Biomaterials - A Review

“…produce functional materials [144]. Wanpeng Liu et al [145] have been investigated the UV-reactive silk L-fibroin doping and its stabilization model using the horseradish peroxidase (HRP) enzyme and its bioactivities as the effect of the process of UV-reactive silk L-fibroin photolithography. The bioactivity of sample attached in biological molecules to UV with HRP doping model shift blue after exposure to tetramethylbenzidine during UVreactive silk L-fibroin photolithography.…”

“…Silks have been considerably used as biomaterials especially in tissue engineering such as regenerated silk fibroin [4][5][6][7][8][9][10][11][12][13][14][15] as well as degummed silk [16][17][18]. Various forms of materials made of fibroin and sericin such as films, hydrogels, particles, and fibers [19][20][21] have been developed through several methods such as electrospinning [22], Electron-beam lithography [23,24], printing [25][26][27][28], and photolithography [29,30]. The latter method is the most interesting for compatible biomechanics [31][32][33][34][35].…”