integration of this biomimetic 3D nanoelectronic network with synthetic tissue
scaffolds as hybrid nanoelectronic scaffold (nanoES) and growth of synthetic tissues
within nanoES. Through this way, we can, for thefirst time, seamlessly and
non-invasively innervate nanoelectronic units with cells throughout the whole tis-
sue at single cell level. We show that nanoelectronic units can sense and stimulate
activities at single cell and single spike level from neurons and cardiomyocytes
throughout the whole 3D tissue, which cannot be achieved by traditional MEA,
patch-clamp and optical technologies. More importantly, this integration will not
alter the chemical and physical properties of synthetic tissue due to the
ultra-flexibility and lowfilling ratio of nanoelectronic networks, which have been
proved by imaging results and sensing experiments of chemical diffusion inside
tissue. Therefore, this work has been widely considered as thefirst example of
“cyborg tissue”[ 6 ].
This part of work can be further benefited by following studies. One is to
incorporate nanodevices that can be delivered into intracellular environment for
interrogation of intracellular activity. Building intracellular-nanoelectronics inter-
face inside tissue is very challenging, yet important forfields from drug delivery to
neuroscience. It requires a good mechanical match between the supporting structure
and tissue to minimize the movement between cells and nanodevice that bridging
intracellular environment and external connections. This seamlessly integration and
bending stiffness match between nanoES and tissue provide an idea platform for
this study. Second study is to incorporate vascular structure in synthetic tissue.
Current synthetic tissue suffer from the size limitation due to the under developed
synthetic vascular system. Therefore, the failure to deliver oxygen and nutrition into
the central regions of synthetic tissues could cause cells death in synthetic tissue,
limiting the size that tissue can grow. To further enhance this, microfluidic channels
can be incorporated into nanoES to facilitate the delivery of oxygen and nutrition
during synthetic tissue. The third study is to incorporate Complementary metal–
oxide–semiconductor (CMOS) technique into flexible nanoES to dramatically
increase the number of sensors to individually address all the cells throughout the
whole tissue.
To move forward to applications, one direction is to develop cyborg tissues for
drug screening assays [ 7 ]. Current drug screening assays employ 2D planar MEA or
single-cell patch-clamp to record the response of tissue activities from drug stim-
ulation, which lacks the capability to study the diffusion of drugs throughout the
tissue. Optical imaging methods yet provide the 3D imaging, still suffer from a
limited penetration depth and relatively low temporal resolution due to the
requirement of 3D scanning. The results in our experiments that cells can form tight
networks within nanoES and show similar behaviors, compared with synthetic
tissues, to the external drug stimulation show potentials to use cyborg tissues as
drug screen assays to study the diffusion effect of drug. The second direction is to
make cyborg synthetic tissues for cellular therapies and employ the seamlessly
integrated nanoelectronics as tools to locally monitoring and promote the process of
integration between synthetic tissues and implanted systems. As example, a cyborg
cardiac patch can be used to implant into patients’malfunctioned heart for repairing
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