Into the groove: instructive silk-polypyrrole films with topographical guidance cues direct DRG neurite outgrowth.

Instructive biomaterials capable of controlling the behaviour of the cells are particularly interesting scaffolds for tissue engineering and regenerative medicine. Novel biomaterials are particularly important in societies with rapidly aging populations, where demand for organ/tissue donations is greater than their supply. Herein we describe the preparation of electrically conductive silk film-based nerve tissue scaffolds that are manufactured using all aqueous processing. Aqueous solutions of Bombyx mori silk were cast on flexible polydimethylsiloxane substrates with micrometer-scale grooves on their surfaces, allowed to dry, and annealed to impart ß-sheets to the silk which assures that the materials are stable for further processing in water. The silk films were rendered conductive by generating an interpenetrating network of polypyrrole and polystyrenesulfonate in the silk matrix. Films were incubated in an aqueous solution of pyrrole (monomer), polystyrenesulfonate (dopant) and iron chloride (initiator), after which they were thoroughly washed to remove low molecular weight components (monomers, initiators, and oligomers) and dried, yielding conductive films with sheet resistances of 124 ± 23 kΩ square(-1). The micrometer-scale grooves that are present on the surface of the films are analogous to the natural topography in the extracellular matrix of various tissues (bone, muscle, nerve, skin) to which cells respond. Dorsal root ganglions (DRG) adhere to the films and the grooves in the surface of the films instruct the aligned growth of processes extending from the DRG. Such materials potentially enable the electrical stimulation (ES) of cells cultured on them, and future in vitro studies will focus on understanding the interplay between electrical and topographical cues on the behaviour of cells cultured on them.

Instructive Conductive 3D Silk Foam-Based Bone Tissue Scaffolds Enable Electrical Stimulation of Stem Cells for Enhanced Osteogenic Differentiation.

Stimuli-responsive materials enabling the behavior of the cells that reside within them to be controlled are vital for the development of instructive tissue scaffolds for tissue engineering. Herein, we describe the preparation of conductive silk foam-based bone tissue scaffolds that enable the electrical stimulation of human mesenchymal stem cells (HMSCs) to enhance their differentiation toward osteogenic outcomes.

Patterned silk film scaffolds for aligned lamellar bone tissue engineering.

The alignment and osteogenic differentiation of MSCs on patterned silk films (PF) is investigated as a bottom-up approach toward engineering bone lamellae. Screening PF with various groove dimensions shows that cell alignment is mediated by both the pattern width and depth. MSCs are differentiated in osteogenic medium for four weeks on flat films and on the PF that produce the best alignment. The PF support osteogenic differentiation while also inducing lamellar alignment of cells and matrix deposition. A secondary alignment effect is noted on the PF where a new layer of aligned cells grows over the first layer, but rotated obliquely to the underlying pattern. This layering and rotation of the MSCs resembles the cellular organization observed in native lamellar bone.