Easy, Scalable, Robust, Micropatterned Silk Fibroin Cell Substrates

Abstract

DOI: 10.1002/admi.201801822 diffusion barriers, friction reduction, etc.[1] Recently, such films and sheets have been explored for biomedical uses such as drug delivery, biofiltration, biosensors, wound healing, and tissue regeneration.[2] Of specific interest are flexible, free-standing sheets, which can be formed with controllable thickness (ultrathin (tens of nanometers) to thin (few to tens of micrometers)). Sheets with mechanical flexibility and adhesiveness may be suitable for sealing wounds, or for the development of biomimetic cellular constructs. They can be stacked to form functional 3D tissues to form cell sheets as biomembranes or tissue/organ models.[3] They can also be used as substrates for wearable devices, soft robotics, and smart skins.[4] At the nanoscale thickness, such films can directly conform to the underlying surface, whereas at the microscale, adhesive layers may be needed for attachment to tissue.[5] Integrating thin films as dynamic cell culture platforms is of great interest because of applications in biosensing, regenerative medicine, and soft robotics.[6] Cell culture substrates capable of physically supporting cell growth with topographical and spatial cellular control can provide insight into the dynamics of cell interactions, while forming scaffolds and cell-based biosensors.[6] A significant Thin polymeric films are being explored for biomedical uses such as drug delivery, biofiltration, biosensors, and tissue regeneration. Of specific interest is the formation of mechanically flexible sheets, which can be formed with controllable thickness for sealing wounds, or as biomimetic cellular constructs. Flexible substrates with precise microand nanopatterns can function as supports for cell growth with conformal contact at the biointerface. To date, approaches to form free-standing, thin sheets are limited in the ability to present patterned architectures and micro/nanotextured surfaces. Other materials have a lack of degradability, precluding their application as cellular scaffolds. An approach is suggested using biocompatible and biodegradable films fabricated from silk fibroin. This work presents the fabrication and characterization of flexible, micropatterned, and biodegradable 2D fibroin sheets for cell adhesion and proliferation. A facile and scalable technique using photolithography is shown to fabricate optically transparent, strong, and flexible fibroin substrates with tunable and precise micropatterns over large areas. By controlling the surface architectures, the control of cell adhesion and spreading can be observed. Additionally, the base material is fully degradable via proteolysis. Through mechanical control and directing the adherent cells, it is possible to explore interactions of cells and the microscale geometric topography.