Презентация на тему Nano-enabled biological tissues

cultured in matrigel clusters
Guided cell aggregation. COURTESY: “Modular tissue

Nano-scale biofunctional surfaces
(cell membrane) http://www.nanowerk.
com/spotlight/spotid=12717.php

Flexible electronics
embedded in contact lens

Self-organized
collagen fibrils

Formation (above) and function
(below) of contractile organoids.
Biomedical Microdevices, 9, 149–
157 (2007).

DNA/protein sensor, example
of BioNEMS device (left).

“Bioprinting” to
construct a heart
(left).

surfaces

Cell colonies and
biomaterial clusters
Single molecule monitoring
and bio-functionalization

Embedded and

Self-assembled and
bioprinted organs

~ 1 nm

10-100 nm

1-100 μm

1-100 cm

1-100 mm

Soft Matter, 6,
1092-1110 (2010)

NanoLetters, 5(6),
1107-1110 (2005)

+ 1m

NanoBiotechnology, DOI: 10.1385/Nano:1:
2:153 (2005).

systems.

Nature has evolved things better
than humans can design

Polylactic Acid
Coating

Cyclomarin
Source

Hydroxyapatite
(Collagen)

Parylene
(Smart Skin)

circuitry for low- voltage macroscale artificial skin”. Nature Materials,

“Tissue-Engineered Skin Containing Mesenchymal Stem Cells Improves Burn Wounds”. Artificial Organs, 2008.

Stem cells better than synthetic polymers (latter does not allow for vascularization).

* stem cells need cues to differentiate.

* ECM matrix, “niche” important.

* biomechanical structure hard to approximate.

Skin has important biomechanical, sensory functions (pain, touch, etc).

* approximated using electronics (nanoscale sensors embedded in a complex geometry).

* applied force, should generate electrophysiological-like signal.

electronic skin:

Output signal from electronic skin, representation is close

9, 359 (2010)
Bio-integrated Electronics. J. Rogers,
Nature Materials, 9,

Nanoconfinement (Buehler group, MIT):
* confine material to a layer ~ 1nm thick (e.g. silk, water).

* confinement can change material, electromechanical properties.

Bio-integrated electronics (Rogers group, UIUC):
Silk used as durable, biocompatible substrate for implants, decays in vivo:
* spider web ~ steel (Young’s modulus).

* in neural implants, bare Si on tissue causes inflammation, tissue damage, electrical interference.

* a silk outer layer can act as an insulator (electrical and biological).

the need for compliance in a device that requires

Flexible e-reader

Flexible circuit board

Nano Letters, 3(10), 1353-1355 (2003)

Sparse network
of NTs.

Nano version (Nano Letters, 3(10), 1353-1355 - 2003):


* transistors fabricated from sparse networks of nanotubes, randomly oriented.


* transfer from Si substrate to flexible polymeric substrate.

polymers with semiconducting properties.



Thin-film Transistors (TFTs):
* semiconducting, dielectric

PNAS, 102(35), 12321–
12325 (2005).

PNAS, 102(35), 12321–
12325 (2005).

Create a bendable array of pressure, thermal sensors.

Integrate them into a single device (B, C – on right).

Embedded array
of pressure and
thermal sensors

Conformal network of pressure sensors

in culture to form complex geometries?

PNAS 107(2),
565 (2010)
We

Gratings at
nanoscale dimensions

Alignment and protrusions w.r.t
nanoscale substrate

HC neurons: Nano Letters, 5(6), 1107-1110 (2005).

Improvement in electrophysiology:
IPSCs

Neuronal density similar between CNTs and control.

* increase in electrical
activity due to gene expression, ion channel changes in neuron.

CNTs functionalized, purified, deposited on
glass (pure carbon network desired).

there are two basic approaches to building tissues:





bottom-up:

Nature Reviews Microbiology 5,
209-218 (2007).

(2003).
Left: “Nanotechnology and Tissue Engineering: the scaffold”. Chapter 9.
Electrospinning

Align nanofibers using electrostatic repulsion forces
(review, see Biomedical Materials, 3, 034002 - 2008).

Contact guidance theory:
Cells tend to migrate along orientations associated with chemical, structural, mechanical properties of substrate.

used.

Protein approach – see review, Progress in
Materials Science,

Nature Nanotechnology,
3, 8 (2008).

Filament network, in vivo. PLoS ONE,
4(6), e6015 (2009).

Hierarchical Network Topology, MD simulations. PLoS ONE, 4(6), e6015 (2009).

α-helix protein networks in cytoskeleton withstand strains of 100-1000%.

* synthetic materials catastrophically fail at much lower values.

* due to nanomechanical properties, large dissipative yield regions in proteins.

Si-based) at nanoscale.

* conductance incrementally modified by controlling change,

Nano Letters, 10, 1297–1301 (2010).

Nano Letters, 10, 1297–1301 (2010).

Memristor response

Biological Neuronal
response

Learning = patterned
(time domain) analog modifications at synapse (pre-post junction).

Array of pre-neurons (rows), connect with post-neurons (columns) at junctions.

* theory matches experiment!

on a substrate in patterned fashion.

* 3D printers (rapid

PNAS, 105(13), 4976 (2008).

Optical
Microscopy

Atomic
Microscopy

Sub-femtoliter (nano) inkjet printing:
* microfabrication without a mask.

* amorphous Si thin-film transistors (TFTs), conventionally hard to control features smaller than 100nm.

* p- and n-channel TFTs with contacts (Ag nanoparticles) printed on a substrate.