nanowires were deposited for single nanowire FETs (Step A, Fig.4.1). Second,
individual nanowire FET devices were lithographically patterned and integrated
into free-standing macroporous scaffolds (Step B, Fig.4.1), the nanoES. The
nanoES were designed to mimic ECM structures, and specifically, to be 3D, to have
nanometer to micrometer features with high (>99%) porosity, and to be highly
flexible and biocompatible. NanoES were then combined with synthetic or natural
macroporous ECMs. Finally, cells were cultured within the nanoES (Step C,
Fig.4.1) to yield 3D nanoelectronics innervated synthetic tissue, in which nano-
electronic devices innervates cells at the subcellular level throughout whole 3D
tissue. The nanoES are distinct from conventional 2D multi-electrode arrays
(MEA) [ 23 ], carbon nanotube/nanofiber arrays [ 24 , 25 ], implantable microelec-
trodes [ 23 ] andflexible or stretchable electrodes [ 13 – 17 ] in that the sensors are
nanoscale semiconductors, and critically, that the sensor network isflexible,
macroporous and 3D.
4.2 Experimental
4.2.1 NanoES/Tissue Scaffold..........................
NanoES: Kinked and uniform silicon nanowires were synthesized by the methods
described previously. The fabrication for nanoES with uniform nanowire as
nanoFET device was described in Chaps. 2 and 3. The fabrication for nanoES with
kinked and modulated doped nanowire as nanoFET device employs electron beam
lithography (EBL) to pattern SU-8 supporting and passivation layer, and metal
contact and interconnects. All the other processes are the same as that for fabri-
cation of uniform nanowire nanoES.
NanoES/collagen (Matrigel™) hybrid matrix: Prior to gel casting, collagen
type-I (Sigma-Aldrich Corp., St. Louis, MO) was diluted (1:2–1:5) with culture
media or phosphate buffered saline solution (PBS) and the pH was adjusted to
7.4. Matrigel™was used as received or diluted (1:2–1:5). The Matrigel™solu-
tions were allowed to form gels around nanoES.
NanoES/alginate hybrid scaffold: The 3D nanoES/alginate scaffolds were
prepared from pharmaceutical-grade alginate, Protanal LF5/60, which has a high
guluronic acid (G) content (65%). Sodium alginate solutions were drop casted on
nanoES, frozen and treated by lyophilization to produce sponge like scaffolds.
NanoES/PLGA hybrid scaffold: Poly(lactic-co-glycolic acid) (PLGA) elec-
trospunfibers were used as a secondary scaffold in several experiments. The PLGA
fibers were prepared based on reported procedures [ 26 ]. To prepare hybrid scaf-
folds, a sheet of PLGAfibers with diameters of 1 – 3 μm was deposited on both
sides of the mesh nanoES.
4.1 Introduction 41