Conductive Peptide‐Based MXene Hydrogel as a Piezoresistive Sensor

Abstract

Wearable pressure sensors have become increasingly popular for personal healthcare and motion detection applications due to recent advances in materials science and functional nanomaterials. In this study, a novel composite hydrogel is presented as a sensitive piezoresistive sensor that can be utilized for various biomedical applications, such as wearable skin patches and integrated artificial skin that can measure pulse and blood pressure, as well as monitor sound as a self‐powered microphone. The hydrogel is composed of self‐assembled short peptides containing aromatic, positively‐ or negatively charged amino acids combined with 2D Ti3C2Tz MXene nanosheets. This material is low‐cost, facile, reliable, and scalable for large areas while maintaining high sensitivity, a wide detection range, durability, oxidation stability, and biocompatibility. The bioinspired nanostructure, strong mechanical stability, and ease of functionalization make the assembled peptide‐based composite MXene‐hydrogel a promising and widely applicable material for use in bio‐related wearable electronics.

Full text

RESEARCH ARTICLE
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Conductive Peptide-Based MXene Hydrogel as a
Piezoresistive Sensor
Dana Cohen-Gerassi, Or Messer, Gal Finkelstein-Zuta, Moran Aviv, Bar Favelukis,
Yosi Shacham-Diamand, Maxim Sokol,* and Lihi Adler-Abramovich*
Wearable pressure sensors have become increasingly popular for personal
healthcare and motion detection applications due to recent advances in
materials science and functional nanomaterials. In this study, a novel
composite hydrogel is presented as a sensitive piezoresistive sensor that can
be utilized for various biomedical applications, such as wearable skin patches
and integrated artificial skin that can measure pulse and blood pressure, as
well as monitor sound as a self-powered microphone. The hydrogel is
composed of self-assembled short peptides containing aromatic, positively- or
negatively charged amino acids combined with 2D Ti3C2TzMXene
nanosheets. This material is low-cost, facile, reliable, and scalable for large
areas while maintaining high sensitivity, a wide detection range, durability,
oxidation stability, and biocompatibility. The bioinspired nanostructure, strong
mechanical stability, and ease of functionalization make the assembled
peptide-based composite MXene-hydrogel a promising and widely applicable
material for use in bio-related wearable electronics.
1. Introduction
Healthcare and the maintenance of quality of life, particularly for
the elderly, have now emerged as major societal challenges. In
this context, wearable devices and pressure sensors have shown
promising results and possess versatile potential for various
applications, including electronic skin,[1]disease diagnostics,[2]
human–machine interfaces,[3]healthcare biomonitoring,[4]
and artificial intelligence.[5]Unfortunately, conventional health
D. Cohen-Gerassi, M. Aviv, L. Adler-Abramovich
Department of Oral Biology
The Goldschleger School of Dental Medicine
Faculty of Medical and Health Sciences
Tel Aviv University
Tel Aviv , Israel
E-mail: lihia@tauex.tau.ac.il
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/./adhm.
©  The Authors. Advanced Healthcare Materials published by
Wiley-VCH GmbH. This is an open access article under the terms of the
Creative Commons Attribution-NonCommercial-NoDerivs License,
which permits use and distribution in any medium, provided the original
work is properly cited, the use is non-commercial and no modifications
or adaptations are made.
DOI: 10.1002/adhm.202303632
systems suffer from deficiencies in wear-
ability, wireless technology, and stability,
thus hindering the individual real-time
monitoring required for accurate diag-
nosis. Despite widespread interest from
researchers and the rapid development
of high-performance smart materials, it
remains a critical challenge to achieve all
characteristics in one device that exhibits
high sensitivity, a broad sensing range, me-
chanical stability, a fast response/recovery
time, and reliability required for long-
term, low-cost, comfortable full-scale
biomonitoring.[6]
Self-assembled peptide-based nanomate-
rials have exhibited wide application poten-
tial in the fields of materials science, nan-
odevices, biomedicine, tissue engineering,
energy storage, biosensors, and others.[7–12]
In particular, their relatively facile synthe-
sis, bioinspired structure, tunable phys-
ical properties, intrinsic biocompatibility,
and ease of functionalization provide short peptide-based
self-assembled hydrogels with potential for bio-related
applications.[13–15]The ability to self-assemble into fibrillar
networks and 3D hydrogels, mimicking the extracellular ma-
trix, can facilitate the development of novel biomaterials.[16,17]
Moreover, a co-assembled nanomaterial composed of two or
more peptides often displays unique properties that significantly
impact its functionality.[18,19]
D. Cohen-Gerassi, G. Finkelstein-Zuta, M. Aviv, L. Adler-Abramovich
The Center for Nanoscience and Nanotechnology
Tel Aviv University
Tel Aviv , Israel
D. Cohen-Gerassi, O. Messer, G. Finkelstein-Zuta, B. Favelukis, M. Sokol
Department of Materials Science and Engineering
Tel Aviv University
Tel Aviv , Israel
E-mail: sokolmax@tauex.tau.ac.il
M. Aviv
School of Mechanical Engineering
Afeka Tel Aviv Academic College of Engineering
Tel Aviv , Israel
Y. Shacham-Diamand
The Scojen Institute for Synthetic Biology
Director
Reichman University
 University St., Herzliya , Israel
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One such extensively studied peptide hydrogelator is N-
fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF), charac-
terized by intrinsic biocompatibility and outstanding tunable
gelation capabilities.[20,21]In particular, when combined
with hyaluronic acid, Fmoc-FF has recently been demon-
strated to serve as a scaffold for bone regeneration and
immunomodulation.[22]In a recent development, our research
showcased that Fmoc-FF hydrogels possess the ability to encap-
sulate an oxygen-sensitive enzyme, protecting its activity against
oxygen-induced damage. The peptide’s supramolecular structure
features aromatic pockets with a high affinity for oxygen through
hydrophobic interactions, effectively mitigating the enzyme’s
vulnerability to oxygen damage within the hydrogel matrix.[23]
MXenes are a new group of 2D layered nanomaterials, with
a chemical composition of Mn+1XnTz, where M represents a
transition metal, X represents carbon (C) and/or nitrogen (N),
T represents surface functional groups (such as ─O, ─OH,
or ─F),andnisaninteger.
[24–27]These materials exhibit dis-
tinct properties, including high electrical conductivity, active
surfaces, a large specific surface area, and good hydrophilic-
ity, which make them ideal for fabricating pressure sensors.
As such, they have been extensively exploited for various ap-
plications, including sensing,[28]electromagnetic shielding,[29,30 ]
wearable textile,[31,32]ceramic nanocomposites,[33–35 ]optoelec-
tronic functionality,[36,37]and energy storage.[38–41]However, the
relatively low aspect ratio makes it challenging to assemble MX-
ene nanosheets into a continuous macrostructure in order to pro-
vide the desired mechanical properties for wearable biomonitor-
ing devices. Few-layered MXenes have good water dispersibil-
ity, which makes them the ideal nanomaterial to enhance the
conductivity of hydrogels.[42]When incorporated into hydrogels,
the MXene serves as an electroactive and mechanical nano-
reinforcer capable of converting nonconductive scaffolds into ex-
cellent conductors of electricity while also having a significant
effect on the mechanical properties of engineered electroactive
organs and tissues,[43]such as skin[44 ]bone,[45,46]cardiac[47]and
skeletal muscle.[43]However, numerous studies have demon-
strated that MXene nanosheets have poor chemical durability
in water and in ambient conditions due to the structural trans-
formation caused by collective effects from air, moisture, and
light, resulting in unwanted oxidation and alternation of the
properties.[48,49]
Here, we designed composite MXene/peptide hydrogels based
on the Fmoc-FF peptide hydrogelator. To improve the peptide in-
teraction with the MXene, we studied two peptide derivatives and
examined the effects of the addition of positively- and negatively-
charged amino acids, namely Lysine (K) and Aspartic acid (D), on
the self-assembly, self-healing, mechanical, and electrical prop-
erties. Notably, the MXene/Fmoc-FF hydrogel exhibits superior
mechanical and electrical properties compared to the other pep-
tide derivatives, which prompted us to utilize it for sensing ap-
plications. We have successfully fabricated a piezoresistive sen-
sor with a wide detection range of 0–400 kPa, good sensitiv-
ity of 38.5 kPa−1, an extremely fast response/recovery time of
0.64/0.61 ms, excellent durability of more than 20 000 pressing
cycles and oxidation stability. This piezoresistive biocompatible
sensor can be applied to human health monitoring needs, includ-
ing pulse and blood pressure analysis, and can also be used in
sound monitoring as a self-powered microphone.
2. Results and Discussion
2.1. Fabrication of Composite MXene/Peptide Hydrogels
For the fabrication of the composite MXene/peptide hydrogels,
three peptides were selected: a) Fmoc-FF, containing two aro-
matic amino acids and an ─OH group at the C-terminus, b)
Fmoc-Phe-Phe-Asp-OH (Fmoc-FFD), with the addition of the
negatively-charged amino acid, Aspartic acid, at the C-terminus,
and c) Fmoc-Phe-Phe-Lys-OH (Fmoc-FFK), with the addition of
the positively-charged amino acid, Lysine, at the C-terminus
(Figure 1a–c). The tripeptide Fmoc-FFD has been shown to self-
assemble into nanofilaments in water at neutral pH[50]and Fmoc-
FFK was used to stabilize disordered proteins for the formation
of membranes.[51]
Figure 1illustrates the fabrication process of the compos-
ite MXene/peptide hydrogels. First, a biocompatible Ti3C2Tz
MXene was synthesized and dispersed in an aqueous solution
(Figure 1d), following a previously described protocol.[52]The ob-
tained 2D Ti3C2TzMXene nanosheets have a lateral size of ≈2μm
(Figure S1, Supporting Information). The biocompatible peptide-
based hydrogels were formulated with biocompatible Ti3C2Tz
MXene nanosheets. The self-assembly of the composite MX-
ene/peptide into a 3D hydrogel was triggered using the solvent-
switch method.[53]Each peptide was dissolved in dimethyl sulfox-
ide (DMSO) to form a stock solution, which was then diluted into
the colloidal suspension of the MXene to trigger self-assembly.
Figure 1e schematically illustrates the formation of the compos-
ite MXene/peptide hydrogel.
2.2. Morphological Characterization and Interfacial Interactions
of the Composite MXene/Peptide Hydrogels
At a concentration of 1% (w/v), the pristine Fmoc-FF and Fmoc-
FFD self-assembled into a fibrillary hydrogel. Adding MXene at
concentrations of 0.3%, 0.15%, and 0.05% (w/v) to the Fmoc-FF
or Fmoc-FFD peptides solution resulted in the formation of self-
supporting hydrogels (Figures S2,S3a, Supporting Information).
Moreover, while the pristine Fmoc-FFK self-assembled into a
weak hydrogel (1% (w/v)), which was not self-supporting, the ad-
dition of MXene at relatively low concentrations of 0.3%, 0.15%,
and 0.05% (w/v) resulted in a self-supporting hydrogel (Figure
S3b, Supporting Information). The successful integration of the
MXene nanosheets into the Fmoc-FFK could be due to electro-
static interactions between the positive charge of the peptide and
the negative charge of the MXene surface. The MXene also serves
as a mechanical nano-reinforcer for the peptide hydrogels, where
the MXene/peptide composites of all three peptides gelate within
minutes to form self-supporting hydrogels. This is demonstrated
in Figure 2a–d, which presents the inverted tubes of the MXene
suspension and the MXene/peptide hydrogels at a concentration
of 1% (w/v) peptide and 0.3% (w/v) MXene. Scanning electron
microscopy (SEM) and transmission electron microscopy (TEM)
morphological characterization of the 2D MXene nanosheets and
the composite MXene/peptide hydrogels representative images
confirmed that the MXene nanosheets are homogeneously dis-
tributed within the peptide fibril network (Figure 2). The corre-
sponding selected area electron diffraction patterns (Figure S4,
Supporting Information), taken from the same regions presented
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Figure 1. Schematic illustration of the fabrication of the composite MXene/peptide hydrogels. a–c) Molecular structures of a) Fmoc-FF, b) Fmoc-FFD,
and c) Fmoc-FFK. d) A schematic illustration of the preparation of D TiCTzMXene nanosheets. e) A schematic representation of the formation of
MXene/peptide composite hydrogels.
in Figure 2e–h, clearly show the hexagonal pattern of Ti3C2Tz
MXene as viewed from the (0001) basal plane direction. The
powder X-ray diffraction patterns of free-standing films of pris-
tine Ti3C2TzMXene, MXene/Fmoc-FF, MXene/Fmoc-FFD, and
MXene/Fmoc-FFK are presented in Figure S5 (Supporting Infor-
mation). The presence of the (002) peak ≈7°2𝜃and its higher-
order reflections confirm the presence of MXene. More impor-
tantly, these peaks are absent in all composite MXene/peptide
hydrogels, which exhibit a diffraction pattern typical of an amor-
phous material, implying that the Ti3C2TzMXene nanosheets are
successfully embedded within the peptide assemblies and dis-
tributed homogeneously between the fibrils of the hydrogels.
In addition, we characterized the surface electrical charges of
the MXene and the composite MXene gels using zeta poten-
tial measurements. The average zeta potential values of the MX-
ene, MXene/Fmoc-FF, MXene/Fmoc-FFD, and MXene/Fmoc-
FFK were −24.2 ±8.78, −18.0 ±10.1, 19.8 ±8.53 and
−9.73 ±4.32 mV, respectively. The MXene/Fmoc-FFK compos-
ite displayed the lowest zeta potential value probably due to the
positively charged amino acid Lysine.
The biocompatibility of composite materials is essential for
their utilization in electronics for health monitoring devices.[54]
We studied the cytocompatibility of the MXene/peptide hydro-
gels in vitro using the MC3T3-E1 cell line (Figure S6, Figure 2i–l,
Supporting Information). An elusion method[55]was applied
in which the cell medium was incubated with the hydrogels
overnight and then used to culture the MC3T3-E1 cells for 24 h.
The cells were visualized using a confocal microscope following
Live/Dead staining (Figure S6a–l, Figure 2i–l, Supporting Infor-
mation). The cells showed excellent viability, with a high pop-
ulation of live cells (green stained) and an elongated morphol-
ogy demonstrating cell adhesion capacity. In addition, a cell via-
bility assay using alamarBlue reagent was performed after 24 h
and 4 days, showing excellent cell viability similar to the con-
trol group for all MXene/peptide hydrogels (Figure S6m,Sup-
porting Information). In particular, the survival rates of the cells
with the hydrogels MXene/Fmoc-FF, MXene/Fmoc-FFD, and
MXene/Fmoc-FFK were 87.2 ±1.4%, 89.5 ±0.8%, 95.3 ±2.8%,
after 24 h, respectively.
Next, we characterized the surface chemical compositions of
pristine Ti3C2TzMXene, Fmoc-FF, Fmoc-FFD, and Fmoc-FFK,
as well as the interfacial interactions in the composite MX-
ene/peptide hydrogels, using X-ray photoelectron spectroscopy
(XPS). The Ti2p spectrum of pristine Ti3C2Tzrevealed the
presence of ─Oand─OH groups in addition to Ti and C, as
evidenced by the C-Ti-Tzpeaks at 455.8 and 461.3 eV (Figure
S7, Supporting Information).[56]The ─OH and ─Ogroupson
Ti3C2TzMXene contribute to its high hydrophilicity and strong
negative charges, facilitating hydrogen bonding and electrostatic
interactions with the peptides.[57]In the O1s spectrum of pris-
tine Fmoc-FF, a peak at 532 eV indicates the presence of C─O
(Figure 3a). In the MXene/Fmoc-FF composite, an additional
peak at 530.4 eV is observed in the O1s spectrum, which can be
attributed to the Ti–OC interaction (Figure 3a). The appearance
of this new peak in the Ti2p spectrum of the MXene/Fmoc-FF
composite (Figure 3b) confirms that Fmoc-FF interacts with Ti
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Figure 2. Morphological characterization of the composite MXene/peptide hydrogels. a–d) SEM images of a) TiCTzMXene sheets, b) MXene/Fmoc-
FF, c) MXene/Fmoc-FFD, and d) MXene/Fmoc-FFK. The MXene nanosheets are marked with red arrows. e–h) TEM micrographs of e) Pristine TiCTz
MXene sheets, f) MXene/Fmoc-FF, g) MXene/Fmoc-FFD, and h) MXene/Fmoc-FFK. i–l) Confocal images of MCT-E cells stained with fluorescein
diacetate cultured for  h i) Control j) MXene/Fmoc-FF, k) MXene/Fmoc-FFD, and l) MXene/Fmoc-FFK (Scale bar  μm).
during the self-assembly process. The C1s spectrum of pristine
Fmoc-FFD displayed a peak at 288.1 eV, indicating the presence
of a C═O bond on the D-residue. However, this peak was not
observed in the MXene/Fmoc-FFD composite (as shown in
Figure 3c). In addition, the Ti2p spectrum of the composite
hydrogel (as shown in Figure 3d) displayed a new peak at
458.6 eV, corresponding to a Ti–O interaction. This additional
peak could be attributed to the electron density function of the
carbonyl bond fluctuating toward the carbon upon the addition
of the available Ti 2p electrons. These electrons then bind in a
coordinative bond to the oxygen, resulting in the appearance of
the new Ti─O peak while simultaneously causing a degradation
of the presence of the C═O bond peak. The N1s spectra showed
two peaks at 398.95 and 400.7 eV, which corresponded to the
C─N bond and the cationic C─(NH3)+group, respectively.
These peaks were observed in both the pristine Fmoc-FFK and
MXene/Fmoc-FFK composite hydrogels (as shown in Figure 3e).
The peak associated with C─(NH3)+slightly increased from 33%
to 41% after the self-assembly of the negatively charged Ti3C2Tz
and the positively charged Fmoc-FFK. This increase could be at-
tributed to the electrostatic interactions of the positively charged
C─(NH3)+with the MXene surface, resulting in a shift toward
the protonated species of the Lysine residue in Fmoc-FFK. There
were no apparent differences between the Ti2p spectrum of the
MXene/Fmoc-FFK composite hydrogel and that of the pristine
Fmoc-FFK (Figure 3f). Overall, by comparing the three-hydrogel
system, it can be observed that the MXene/Fmoc-FF creates new
Ti–OC interactions, the MXene/Fmoc-FFD displays oxidation
of the Ti, and the MXene/Fmoc-FFK assembly occurs through
simple electrostatic interactions. These findings may provide
guidance for designing composite MXene/peptide hydrogels.
2.3. Electrical Performance and Oxidation Protection of MXene in
Composite MXene/Peptide Hydrogels
The current–voltage (I–V) conductivity curves of the hydrogels
are presented in Figure 4a. The pristine hydrogels exhibited
no change in current when the voltage was varied, thereby re-
sembling a typical insulator. In contrast, pristine MXene and
the composite MXene/peptide hydrogels exhibited ohmic be-
havior in the measured voltage range. Under 2 V, the currents
obtained for the MXene, MXene/Fmoc-FF, MXene/Fmoc-FFD,
and MXene/Fmoc-FFK hydrogels were 9.7 ×10−2, 3.0 ×10−2,
2.1 ×10−2, and 1.2 ×10−3A, respectively. Notably, the current
of the MXene/Fmoc-FFK, which contains a positively charged
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Figure 3. XPS analysis and interfacial interactions of the composite MXene/peptide hydrogels. a) XPS Os spectra of pristine Fmoc-FF (top) and
MXene/Fmoc-FF composite (bottom). b) XPS Tip spectra of the MXene/Fmoc-FF composite. c) XPS Cs spectra of pristine Fmoc-FFD (top) and
MXene/Fmoc-FFD composite (bottom). d) XPS Tip spectra of the pristine TiCTzand the MXene/Fmoc-FFD composite. e) XPS Ns spectra of pris-
tine Fmoc-FFK (top) and MXene/Fmoc-FFK composite (bottom). f ) XPS Tip spectra of the pristine TiCTzand the MXene/Fmoc-FFK composite.
amino acid, was one order of magnitude lower. This effect on
material conductivity could be due to the new charge interac-
tion formed during the self-assembly process between the pos-
itive charge of the Lysine residue and the MXene surface charge.
This new charge interaction creates spatial separation between
the MXene nanosheets and interferes with their conductance
properties. The small difference in conductivity between the
MXene/Fmoc-FF and the MXene/Fmoc-FFD composites is prob-
ably due to the oxidation of the Ti in the MXene/Fmoc-FFD,
as evident in the XPS analysis (Figure 3d). In Figure 4b, the
resistance values of the MXene-based hydrogels are presented.
These values were extrapolated from the slopes of the I–Vcurves
following Ohm’s law, where V=IR. MXene, MXene/Fmoc-FF,
and MXene/Fmoc-FFD demonstrated a similar resistance of 30–
100 Ω, while the MXene/Fmoc-FFK composite demonstrated
a higher resistance of ≈1600 Ω. To understand the influence
of the MXene concentration on the conductivity of the com-
posite hydrogel, three formulations of MXene/Fmoc-FF hydro-
gels were prepared with variable concentrations of the MXene
nanosheets (0.3%, 0.15%, and 0.05% (w/v)) while maintaining a
peptide concentration of 1% (w/v). As shown in Figure 4c, the
conductivity of the MXene/Fmoc-FF hydrogel exhibited a pro-
portional increase as the MXene concentration was elevated. In
addition, we examined the conductivity in relation to tempera-
ture variations between room temperature and 50 °C, indicating
no significant alteration in conductivity (Figure S8, Supporting
Information).
To further study the durability of the materials, we re-
peated the I–Vmeasurements using aged MXene and MX-
ene/peptide hydrogel samples that had been stored under ambi-
ent conditions for a period of 4 weeks (Figure 4d). Under 2 V,
the currents obtained for the pristine MXene, MXene/Fmoc-
FF, MXene/Fmoc-FFD, and MXene/Fmoc-FFK hydrogels were
5.64 ×10−10, 3.1 ×10−2, 1.4 ×10−2,and7×10−4A, respectively.
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Figure 4. Electrical performance and oxidation protection of MXene in the composite MXene/peptide hydrogels. a) I–Vcharacteristic curves of the hydro-
gels with and without MXene, measured between two gold electrodes separated by a  μm gap. b) Resistance values of the MXene and MXene/peptide
hydrogels extrapolated from the slopes of the curves shown in (a). c) I–Vcharacteristic curves of the MXene/Fmoc-FF composite hydrogel containing
dierent MXene concentrations. d) I–Vcharacteristic curves of aged MXene and the MXene/peptide composite hydrogels stored under ambient condi-
tions for a period of  weeks. e) Resistance values of the MXene and MXene/peptide hydrogels extrapolated from the slopes of the curves shown in (d).
f) Inverted vials of MXene solution and the MXene peptide hydrogels at dierent time points, t= (top) and after  month (bottom). Vials from left to
right: MXene, MXene/Fmoc-FF, MXene/Fmoc-FFD, MXene/Fmoc-FFK. g) Absorbance kinetics of Fmoc-FF, MXene, and MXene/Fmoc-FF at  nm. h)
XPS Tip Ti─C atomic % of the MXene/peptide aged hydrogels that had been stored under ambient conditions for a period of two months versus etch
time. i) XPS Tip Ti─O atomic % of the MXene/peptide aged hydrogels versus etch time.
Interestingly, while pristine MXene completely loses its con-
ductivity within one month under ambient conditions, the MX-
ene/peptide hydrogels retain a conductivity similar to the values
observed for the fresh samples. The resistance values of the MX-
ene, MXene/Fmoc-FF, MXene/Fmoc-FFD, and MXene/Fmoc-
FFK hydrogels were 2.6 ×109, 62.5, 132, and 2522 Ω, respectively
(Figure 4e). The ability of peptide hydrogels to sustain MXene
conductivity in a wet state presents a notable advantage, partic-
ularly in the context of device and sensor development, distin-
guishing them from other MXene-based hydrogels.
Since peptide hydrogels have exhibited the capability to pre-
serve MXene conductivity, we set out to delve deeper into the ox-
idation process of MXene within the composite MXene/peptide
hydrogels. Figure 4f presents inverted vials of MXene suspen-
sion in water and of the different MXene/peptide hydrogels at
two-time points: t=0(Figure4f top), immediately after prepa-
ration of the hydrogels, and after 4 weeks under ambient con-
ditions (Figure 4f bottom). As previously shown, MXene un-
derwent a conspicuous color loss and became transparent after
4 weeks due to the oxidation of the Ti2C3into TiO2.[48]In contrast,
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MXene/Fmoc-FF and MXene/Fmoc-FFK hydrogels retained a
black color, demonstrating the prevention of MXene oxidation by
the hydrogels. As for the MXene/Fmoc-FFD hydrogel, there was
a slight reduction in color intensity, resulting in a subdued gray
appearance. Kinetics of absorbance analysis was used for quan-
tification of the color change in the MXene and MXene/Fmoc-
FF hydrogels (Figure 4g). The Fmoc-FF hydrogel displayed trans-
parency at 350 nm, exhibiting an optical density (OD) of approx-
imately zero. In contrast, both MXene and MXene/Fmoc-FF hy-
drogels exhibited significantly higher OD levels, approximately
reaching 4 a.u., during the initial two weeks. After 4 weeks, there
was a notable decrease in the OD of the MXene, and this trend
continued over time. In contrast, the MXene/Fmoc-FF main-
tained its elevated OD for six weeks before gradually declining.
To further investigate the hydrogel’s capacity to protect MXene
from oxidation, we conducted XPS measurements using aged
samples of MXene/peptide hydrogels that had been stored un-
der ambient conditions for a period of two months. Given that
the MXene nanosheets within the hydrogels are covered by fib-
rils composed of organic material, we employed ion beam sput-
tering on the samples to reveal the surface of the MXene. Figure
S9 (Supporting Information) demonstrates the Ti2p spectrum of
the MXene/peptide hydrogels as a function of the sputter etch-
ing time. Figure 4h,i present a comprehensive overview of the
atomic percentages of Ti─CandTi─O, respectively, within the
Ti2p spectrum, depicting their variations with respect to the etch
time. The observed trend indicates that the atomic percentage
of Ti─C is most prominent in MXene/Fmoc-FF, while it is least
pronounced in MXene/Fmoc-FFD. Conversely, the Ti─Oatomic
percentage follows the opposite pattern. This indicates that the
Fmoc-FF can mitigate the oxidation of the MXene nanosheets in-
side the hydrogel for a period of two months. This represents a
highly promising attribute of Fmoc-FF and Fmoc-FFK hydrogels,
as they exhibit the capability to protect the MXene nanosheets
from oxidation within the hydrogel while effectively impeding
and decelerating the oxidation and degradation processes in a
wet state. The significant Ti─CtoTi─O oxidation observed in
MXene/Fmoc-FFD is in correlation with the XPS analysis pre-
sented in Figure 3. This analysis revealed that during the self-
assembly of Fmoc-FFD with MXene, an initial oxidation of Ti oc-
curs due to the negatively charged aspartate (D) residues. Conse-
quently, as time progresses, this oxidation process intensifies.
Notably, these observations highlight the ability of the MX-
ene/peptide hydrogels to effectively shield MXene against oxida-
tion in a wet state under ambient conditions. This feature dis-
tinguishes peptide assemblies compared to other MXene-based
hydrogels, particularly in terms of preserving the electrical prop-
erties of MXene over time. We hypothesize that this distinctive
attribute is based on the presence of pockets formed between the
aromatic rings of the phenylalanine and the Fmoc group, as pre-
viously shown by molecular dynamic simulation.[23]
2.4. Mechanical Properties of the Composite MXene/Peptide
Hydrogels
Based on the electrical characterization of the composite hydro-
gels containing different concentrations of MXene (Figure 4c),
the mechanical properties of the composite MXene/peptide hy-
drogels at a peptide concentration of 1% (w/v) and an MXene con-
centration of 0.3% (w/v) were analyzed by rheological methods.
First, strain sweep experiments (1 Hz frequency) were carried
out to determine the material’s linear viscoelastic regime (Figure
5a–c). Figure S10a–c (Supporting Information) shows the results
of the dynamic frequency sweep experiment carried out on the
MXene/peptide hydrogels at 0.1% strain, which demonstrates a
wide linear viscoelastic regime. The observation that the G′value
of all the MXene/peptide hydrogels is independent of the fre-
quency, confirms the viscoelastic nature of the hydrogels. The
G′values (measured at a frequency of 1 Hz) of the correspond-
ing hydrogels increased in the following order: MXene/Fmoc-
FFK (3.7 kPa), MXene/Fmoc-FFD (13 kPa), and MXene/Fmoc-FF
(100 kPa). Interestingly, these values are higher than the G′val-
ues of the pristine hydrogels: Fmoc-FFK (0.05 kPa), Fmoc-FFD
(6.8 kPa), and Fmoc-FF (78 kPa) (Figure S11; Table S1, Support-
ing Information). Moreover, the addition of MXene nanosheets
to Fmoc-FFD and Fmoc-FFK increased the storage modulus by
1 and 2 orders of magnitude, respectively. Thus, the MXene
nanosheets influence the self-assembly process and serve as a
mechanical nano-reinforcer, thereby improving the rigidity of the
hydrogels. The effect of the MXene nanosheets on the mechan-
ical properties of the hydrogels could also be due to the new
charge interaction, which provides additional driving forces for
self-assembly and stabilizes the composite hydrogels. Notably,
the G′value of the MXene/Fmoc-FF composite, 100 kPa, is con-
siderably higher than that of other previously reported peptide-
based hydrogels,[58,59]or other MXene composite hydrogels[59–61]
and is comparable to that of several biological tissues.[62]Te m-
perature sweep experiments carried out on the MXene/peptide
hydrogels (Figure 5d–f) demonstrated the stable behavior of G′
and G″over a temperature range of 25–100 °C. As no crossover
of the modulus values was observed, it can be stated that the hy-
drogels did not exhibit breakage at the tested temperature range
and that they are stable at biologically relevant temperatures.
As the next step, we assessed the self-healing or shear-
responsive behavior of the composite MXene/peptide hydro-
gels by monitoring the reformation of the bulk hydrogels after
breaking the networks under mechanical stress. For this pur-
pose, a step-strain experiment was conducted in which the MX-
ene/peptide hydrogels were subjected to seven cycles of time
sweep experiments with alternate low (0.1%) and high (100%)
strain values (Figure 5g–i). At 100% strain, the hydrogels were
converted to a quasi-liquid (sol) state, as evident from the mod-
ulus values (G′<G″). However, the gel reformed (G′>G″)
when the strain was reduced to 0.1% (i.e., in the linear vis-
coelastic regime). This behavior was consistent over multiple cy-
cles, thereby demonstrating the reproducibility of the self-healing
ability of all the MXene/peptide composites. We have also per-
formed continuous step strain measurements on the Fmoc-FF,
Fmoc-FFD, and Fmoc-FFK hydrogels without MXene under iden-
tical conditions (Figure S12, Supporting Information) to exam-
ine their self-healing ability. It was evident that the Fmoc-FF and
Fmoc-FFD exhibited self-healing properties. Therefore, it can be
surmised that the self-healing properties of the MXene/Fmoc-
FF and MXene/Fmoc-FFD hydrogels are attributable to the pris-
tine hydrogels. The pristine Fmoc-FFK is a very viscose and elas-
tic hydrogel that, under these conditions, didn’t exhibit break-
age (as can also be evident from the strain sweep experiment
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Figure 5. Mechanical properties of the composite MXene/peptide hydrogels. a–c) Strain dependence of the storage and loss moduli of a) MXene/Fmoc-
FF, b) MXene/Fmoc-FFD, and c) MXene/Fmoc-FFK hydrogels at a frequency of  Hz. d–f) Storage and loss moduli as a function of temperature for
d) MXene/Fmoc-FF, e) MXene/Fmoc-FFD, and f) MXene/Fmoc-FFK hydrogels. g–i) Continuous step strain measurement at alternate .% and %
strains over time for g) MXene/Fmoc-FF h) MXene/Fmoc-FFD i) MXene/Fmoc-FFK hydrogels. j) Demonstration of the self-healing property. Two separate
blocks of Fmoc-FF and MXene/Fmoc-FF hydrogels healed after being kept in contact for  min. k) Shear viscosity versus shear rate plot of the hydrogels.
(Figure S11c, Supporting Information)). Nevertheless, we can as-
sume that the self-healing ability is driven by the peptide’s strong
supramolecular interactions. A block of Fmoc-FF (semitranspar-
ent) was brought into contact with a block of MXene/Fmoc-FF
(black) hydrogel (Figure 5j) fused together within 5 min with-
out the use of any external healing agent. This heterogeneous
fusion behavior, combined with the thixotropic rheological re-
sults (Figure 5g–i), demonstrates the excellent self-healing ca-
pability of the Fmoc-FF hydrogel, which is also present in the
composite MXene/Fmoc-FF hydrogel. The rheological analysis
demonstrated that the peptide hydrogel component contributed
to the self-healing ability of the MXene/peptide hydrogels. There-
fore, it can be concluded that the peptide fibers have an inher-
ent tendency to reform after being detached by mechanical force
or separation, and this property remains intact after being com-
bined with MXene nanosheets. This re-entanglement occurs due
to the supramolecular interactions of the peptides, which re-
sult in the fibril network formation.[63]When two heterogeneous
blocks of Fmoc-FF and MXene/Fmoc-FF hydrogels were fused,
the dynamic nature of the self-healing process allowed the re-
entanglement of the fibers at the fusion interface, thus trigger-
ing the healing. Figure 5k presents the viscosity versus strain rate
plot of the composite MXene/peptide hydrogels, which demon-
strates their shear-thinning property. This property remained un-
changed after the addition of the MXene nanosheets. As the
MXene/Fmoc-FF hydrogel demonstrates self-healing properties,
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Figure 6. Sensing performance of the MXene/peptide composite as a piezoresistive sensor. a) A schematic illustration of the composite MXene/Fmoc-
FF piezoresistive sensor fabrication. b) A schematic illustration of the structural change of the MXene/Fmoc-FF sensor under pressure. c) Electrical circle
illustration of the MXene/Fmoc-FF sensor connected to an LED. d) Photographs showing the sensing ability of the piezoresistive sensor by pressing
and releasing to produce the “On” and “O” states of the LED, respectively.
we sought to explore its ability to restore conductivity after macro-
scopic separation and rejoining of gel blocks. In this experi-
ment, we connected a light-emitting diode (LED) in series with
an MXene/Fmoc-FF hydrogel block, allowing for LED activation
(Figure S13a, Supporting Information). Subsequently, we phys-
ically separated the hydrogel block into two parts, interrupting
the circuit and deactivating the LED. After rejoining the two
blocks, the LED was successfully reactivated (Figure S13a,Sup-
porting Information). To further confirm the restoration of con-
ductivity during the healing process, we monitored the resistance
changes of the MXene/Fmoc-FF hydrogel block (Figure S13b,
Supporting Information). Upon cutting the hydrogel block into
two pieces, resistance values increased, reaching the instrumen-
tal limit (3 GΩ). However, upon rejoining the pieces, the resis-
tance decreased and returned to values similar to those obtained
before the cutting procedure. This demonstrates the ability of the
MXene/Fmoc-FF hydrogel to reinstate its conductivity after self-
healing. Thus, the MXene/Fmoc-FF hydrogel not only preserves
its mechanical integrity but also restores its bulk conductivity fol-
lowing macroscopic disruption.
2.5. Sensing Performance of the Composite MXene/Peptide as a
Piezoresistive Sensor
The MXene/Fmoc-FF hydrogel demonstrated markedly en-
hanced mechanical and electrical characteristics compared to the
charged hydrogels, MXene/Fmoc-FFD and MXene/Fmoc-FFK,
with a storage modulus of 100 kPa notably surpassing those of the
charged hydrogels as well as other MXene composite hydrogels.
Additionally, the electrical properties of the MXene/Fmoc-FF hy-
drogel proved to be superior to those of the charged hydrogels,
particularly compared to the MXene/Fmoc-FFK hydrogel, show-
casing an order-of-magnitude difference in performance. Fur-
thermore, it is worth noting that Fmoc-FFD exhibits Ti oxidation,
resulting in decreased conductivity, while Fmoc-FFK induces spa-
tial separation among the MXene nanosheets, adversely impact-
ing their conductance properties. In contrast, MXene/Fmoc-FF
fosters the formation of novel Ti-OC interactions, which could
be a contributing factor to the enhanced properties observed in
this composite material. Hence, we selected the MXene/Fmoc-
FF composite for the fabrication of a piezoresistive sensor device,
as outlined in the schematic representation shown in Figure 6a.
For this purpose, the MXene/Fmoc-FF hydrogel was drop-cast in
a circular void of a Kapton tape layer and sandwiched between
indium tin oxide-coated polyethylene glycol terephthalate (PET)
substrates. A schematic illustration of the structural change of
the sensor under pressure is presented in Figure 6b. In the initial
state, there were only a few contact points, and therefore conduc-
tive paths, between adjacent MXene nanosheets within the com-
posite hydrogel, resulting in a very high overall resistance. When
external force was applied, the distance between the neighboring
fibrils in the 3D matrix of the hydrogel was reduced, and the con-
tact area between the MXene nanosheets increased accordingly,
resulting in a more conductive and reduced resistance compos-
ite MXene/Fmoc-FF hydrogel. The 3D matrix of the hydrogel re-
turned to its original state on completion of the dynamic pres-
sure cycle. The resistance change of the sensor under pressure
was measured using a light-emitting diode (LED) serially con-
nected to the MXene/Fmoc-FF sensor (Figure 6c). Applying man-
ual pressure on the sensor activated the LED (ON) while releas-
ing the pressure resulted in LED deactivation (OFF) (Figure 6d,
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Movie S1, Supporting Information). This process was repeated
multiple times.
2.6. Performance and Applications of the Composite
MXene/Peptide Piezoresistive Sensor
A custom-made measurement system designed to apply contin-
uous external pressure and record electrical signals in real time
was constructed based on previous work (Figure S14, Support-
ing Information).[64]This was used for a series of experiments
designed to detect and analyze the electrical properties of the
composite MXene/Fmoc-FF-based piezoresistive sensor under
dynamic and static conditions. The results of I–Vcharacteris-
tic curves of the MXene/Fmoc-FF sensor under different pres-
sures ranging from 0 to 400 kPa are presented in Figure 7a.The
I–Vcurve showed a clear linear relationship to an increase in
the applied force, indicating that the pressure-sensing response
of the sensor is stable under different external pressures. Un-
der 5 V, the currents at 0 and 400 kPa were 2.0 ×10−6and
5×10−2A, respectively, reflecting a 4 orders of magnitude in-
crease. An essential part of estimating the sensing ability of a
device is to estimate the sensitivity, which can be calculated by
the equation S=(ΔI
I0
)∕ΔP,whereΔI=I−I0,I
0is the ini-
tial current without pressure, and ΔPis the pressure change.[65]
The sensitivity of the MXene/Fmoc-FF-based piezoresistive sen-
sor contains three areas: S1 (0–34 kPa−1) in the low-pressure
range, S2 (50–190 kPa−1) in the medium-pressure range, and S3
(190–400 kPa−1) in the high-pressure range (Figure 7b). The sen-
sitivity of the S1, S2, and S3 areas was 38.5, 3.5, and 0.25 kPa−1,
respectively. These sensitivities are superior to those of other pre-
viously reported MXene-based piezoresistive sensors, as detailed
in Table 1. We postulate that the distance between the neighbor-
ing nanofibrils in the 3D matrix of the hydrogel is reduced in the
S1 area (0–0.34 kPa−1), thereby providing more contact positions
with adjacent sheets of MXene, generating a significant num-
ber of conductive routes, and leading to a quick rise in current.
As the pressure increases (area S2, 50–190 kPa−1), the increase
in contact areas between the sheets of MXene is relatively re-
duced, and the sensitivity decreases. In contrast, in area S3 (190–
400 kPa−1), when the applied force reaches a certain point, the
3D structure evolves into a layered structure. Consequently, the
tighter contact between the sheets becomes the primary factor in
the elevation in conductivity, and the sensitivity approaches sat-
uration. The MXene/Fmoc-FF-based piezoresistive sensor exhib-
ited response/recovery time of 0.641/0.614 ms, respectively (De-
fined as a 90% increase and/or decrease of total current change;
Figure 7c), which are extremely short compared to other MXene-
based piezoresistive sensors (Table 1). The fast response to the
external force indicates that the sensor can be used to monitor
human motion and other minor stresses in real-time. The sta-
bility of a sensor is also a crucial factor that affects its perfor-
mance. Under continuous loading and unloading conditions, the
MXene/Fmoc-FF-based piezoresistive sensor was tested for over
20 000 cycles at a high intensity (100 cycles per 1 s over 200 s)
(Figure 7d). The sensing response was found to be retained even
after 20 000 cycles, as shown in the insert of Figure 7d.Thisin-
dicates the potential use of the MXene/Fmoc-FF device for ro-
bust and stable human motion biomonitoring. We were able to
adjust the force speed by changing the frequency of the pres-
sure actuator while maintaining the same pressure, as demon-
strated in Figure 7e. According to the formula f=1/T,wheref
is the frequency and Tis the response time, it is apparent that
under the settled force of 2 kPa, the response time tends to stay
the same even when the frequency is increased, indicating the
excellent and stable response of the sensor. Moreover, the sens-
ing responses synchronized with the input signal under a pres-
sure of 2 kPa (Figure S15, Supporting Information), indicating
that the output sensing signals can be accurately tracked and re-
flect the input loading forces. To evaluate the long-term dura-
bility and performance of the device, we repeated the response
and recovery analysis, along with frequency-related parameters,
after one year at standard room temperature and shelf storage
conditions. We observed remarkably consistent results. The re-
sponse and recovery times, crucial indicators of the sensor’s per-
formance, exhibited remarkable stability, with response/recovery
time of 0.121/0.124 ms, respectively (defined as a 90% increase
and/or decrease of total current change; Figure S16a, Supporting
Information). Notably, these findings were not confined to spe-
cific conditions or frequencies. Regardless of variations in the fre-
quency of operation, the device exhibited a robust performance
profile (Figure S16b, Supporting Information). This not only un-
derscores the durability of the device but also reinforces its suit-
ability for long-term applications where consistent and stable per-
formance is a key requirement.
The MXene/Fmoc-FF-based piezoresistive sensor demon-
strated good sensitivity, an extremely rapid response time, a
wide detection range, good durability, and simple preparation.
Therefore, the sensor can provide a promising potential for
application in wearable devices, including the monitoring of
physiological signals. As an example of a prototype pressure
sensor, we detected the pulse of a human by locating the piezore-
sistive sensor over the radial artery of a human wrist as a skin
patch. As shown in Figure 7f, when the pulse was stable, the
sensor could accurately record a pulse waveform with a heart rate
of 80 beats per minute. Furthermore, the heart rate could also
be measured when the MXene/Fmoc-FF-based piezoresistive
sensor was applied to the carotid artery on the neck (Figure 7g).
Indeed, the high sensitivity of the pressure response of the
piezoresistive sensor allowed the percussion (P1), tidal (P2), and
dicrotic (P3) waves of the heart rate curve to be distinguished.
The magnification of a single peak with the typical systolic peak
(P1) and diastolic peak (P2) is shown in Figure 7h. These data
provide the radial enhancement index (P2/P1),whichisanim-
portant parameter for arterial stiffness. The health status of the
human body can be easily determined by analyzing the obtained
pulse data using the radial enhancement index AIr =P2/P1.
This gives the necessary conditions for extracting blood pressure
signals and suggests the potential for applications concerning
vital signal monitoring. Moreover, good sensitivity and quick re-
sponse were obtained by high-frequency finger-induced tapping
on the piezoresistive sensor, while the relatively consistent peak
intensities indicated the good stability of the device (Figure 7i,
Movie S2, Supporting Information). The MXene/Fmoc-FF-based
piezoresistive sensor can also be used for sound monitoring
as a self-powered microphone. The device can record sound
vibrations at different frequencies and translate them into
electrical signals, which can then be recorded by an oscilloscope
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Figure 7. Performance and applications of the composite MXene/peptide piezoresistive sensor. a) I–Vcurves of the piezoresistive sensor under dierent
pressures ranging from – kPa. b) The sensitivity curve of the piezoresistive sensor is divided into  areas: S, S, and S. c) Response time (. ms)
and recovery time (. ms) of the piezoresistive sensor. d) Durability of the piezoresistive sensor over   loading–unloadingcycles. e) The response
performance of the piezoresistive sensors at dierent frequencies. f) Measurement of pulse using the piezoresistive sensor located on the wrist. Inset:
a photograph of the sensor attached to the wrist. g) Blood pressure measurement with the piezoresistive sensor on the neck. Inset: a photograph of the
sensor attached to the neck. h) An enlarged version of the blood pulse waveform from (g). i) Finger-induced tapping on the sensor. Inset: a photograph
of the tapping. j) The response performance of the piezoresistive sensors as self-powered microphones with dierent sound frequencies.
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Tabl e 1. Comparison of dierent MXene-based piezoresistive sensors per-
formance.
Materials Pressure range
[kPa]
Sensitivity
[kPa−]
Response
time [ms]
Durability
[cycles]
MXene/Fmoc-FF – . ./. Over k
MXene/PLA[]– .  k
MXene/Aramid[]– . / k
SF@MXene[]– . / .k
MXene/Chitosan[]– . / .k
MXene/CS/PU[]– . /– k
(Figure 7j). The sensitive response to sound vibrations of the
piezoresistive sensor can be used for human voice monitoring.
3. Conclusion
A bioinspired, sensitive, and robust composite peptide-based
MXene-hydrogel piezoresistive sensor was fabricated by combin-
ing the Fmoc-FF peptide with 2D Ti3C2TzMXene nanosheets.
Utilizing the simple preparation and functionality of the aro-
matic dipeptide, the piezoresistive sensor exhibits good mechan-
ical properties and pressure-sensing, stability against oxidation
damage, a self-healing ability, a wide detection range (0–400 kPa),
good sensitivity (38.5 kPa−1), extremely fast response/recovery
time (0.641/0.614 ms), and excellent durability for more than
20 000 cycles. The piezoresistive sensor can be attached directly to
human skin to collect various human vital signs, even those man-
ifesting as small deformations, such as wrist pulses and voice
sounds. We were able to simultaneously achieve high sensitivity,
a broad sensing range, a fast response/recovery time, and reli-
ability suitable for long-term, biomonitoring. Furthermore, the
sensor can be used for sound monitoring and as a self-powered
microphone. These results demonstrate the great potential of the
MXene/peptide hydrogel for next-generation artificial skin and
personal healthcare wearable devices.
4. Experimental Section
Ti3AlC2MAX and Ti3C2TzMXene Synthesis:TiCTzMXene was syn-
thesized by selectively etching the metallic Al layer of the TiAlCMAX
precursor.[,]The TiAlCMAX precursor was synthesized by mixing ti-
tanium carbide (Alfa Aesar, .%,  μm), aluminum (Alfa Aesar, .%,
 mesh), and titanium (Alfa Aesar, .%,  mesh) powders in a
:.: molar ratio, respectively. The elementary powders were mixed in
a tumbler ball mixer at  rpm for  h until a homogeneous mixture was
obtained. The mixed powders were then heat-treated in a tube furnace at
 °C at a heating rate of  °Cmin
−for  h under a flowing Ar atmo-
sphere ( sccm). Finally, the resulting TiAlCMAX phase was milled
to a fine powder in a planetary ball mill and sieved through a -mesh
screen (< μm) to attain a homogeneous powder.
The TiAlCpowder was etched in an HCl and LiF solution, which re-
acted to form in situ HF. Initially, . g of LiF (Alfa Aesar, .%,  mesh)
was dissolved in  mL of   HCl (Fisher Scientific). This was followed
by the slow addition of  g of the TiAlCpowder to avoid a violent re-
action, and the solution was then stirred for  h at  °C and  rpm.
The etching was done in an open container to avoid pressure buildup and
to allow the release of hydrogen produced during the reaction. The black
slurry was transferred to a -mL centrifuge vial, and type I deionized (DI)
water was added to fill the vial. The slurry was centrifuged at  RCF for
 min, and the resulting clear supernatant was discarded while retaining
the bottom sediment. To remove the excess LiF, the etched material was
washed twice with   diluted HCl and centrifuged after each wash. After
the HCl washing, the material was washed with DI water and centrifuged
several times until the pH of the solution reached >. This step yielded
multilayered TiCTzMXene. To exfoliate to a single layer of MXene, the
mixture was sonicated under a bubbling Ar flow for  h, with the tempera-
ture of the sonication bath maintained below  °C. The solution was then
centrifuged for  min at  RCF, and only the upper half of the solution
was taken while the rest was discarded.
Preparation of Composite MXene/Peptide Hydrogels:Fmoc-FF (Sigma-
Aldrich, Israel), Fmoc-FFD, and Fmoc-FFK (GL Biochem, Shanghai) stock
solutions were prepared in dimethyl sulfoxide (DMSO) and then diluted
in the required ratios in the TiCTzMXene solution. The final Fmoc-FFX
concentration in the MXene gels was % (w/v) unless otherwise noted.
Scanning Electron Microscopy:Hydrogel samples were placed on glass
coverslips and left to dry under ambient conditions. The samples were
then coated with Au for conductance and viewed using a scanning electron
microscope (JEOL, Tokyo, Japan) operating at  kV.
Transmission Electron Microscopy:Hydrogel samples ( μL) were ap-
plied to -mesh copper grids (Electron Microscopy Sciences, Ltd) and
left to air dry under ambient conditions. Samples were examined using a
JEOL EX electron microscope (JEOL), operating at  kV.
Powder X-Ray Diffraction:The diraction patterns were collected us-
ing a PANalytical AERIS research Edition diractometer with CuK𝛼radi-
ation ( kV and  mA), a step size of ≈.°𝜃, and scan speed
≈.°sec−in the range of –°𝜃.
X-Ray Photoelectron Spectroscopy:XPS measurements were per-
formed using an ESCALAB QXi (Thermo Scientific, USA) system. The
samples were irradiated with a monochromatic Al K𝛼radiation. High-
resolution spectra of Cs, Ns, and Tip were collected with a pass energy
of  eV with a -micron spot size. Samples were cleaned using an Ar
cluster ion beam with an energy of  kV and a minimum cluster size of
.
Dynamic Light Scattering (DLS):Surface charges were measured us-
ing ZetaPALS dynamic light scattering (DLS) (Malvern Instruments Ltb.
Worcestershire, UK) with appropriate viscosity and refractive index set-
tings. The temperature was maintained at  °C during the measurement.
Rheological Analysis:The rheological studies of the hydrogel were per-
formed on an ARES-G rheometer (TA Instruments, New Castle, DE,
U.S.A.) using an  mm parallel-plate geometry with a gap of  μm.
The measurements were repeated on at least three independent samples
to ensure reproducibility.
Conductivity Analysis:The hydrogels were drop-cast on prefabricated
field-eect transistor substrates (Ossila, U.K.) with an electrode gap of
μm and dried under ambient conditions. Current–voltage (I–V)mea-
surements were performed on a Keithley B source-meter using the
two-probe method. All measurements were taken from  to  V with . V
steps, . s hold time, and a . s sweep delay. Conductance values were
extracted from the slope of the linear curves. The measurements were re-
peated on at least three independent samples to ensure reproducibility.
Piezoresistive Performance and Analysis:The measurements of the
piezoresistive sensor performance were done using a series circuit con-
sisting of a resistor R=kΩ, a power source V=. V, and the device,
connected to an oscilloscope measuring the voltage that drops across the
resistor. When a voltage was applied across the series circuit, the resulting
current flowed through the resistor and the piezoresistive sensor. As the
sensor underwent deformation or pressure, its resistance changed, which
altered the voltage drop across the sensor and the resistor.
Experiments on Human Subjects:On-skin experiments were con-
ducted under the approval from the Institutional Review Board at Tel Aviv
University (protocol number: -). Informed consent of all partici-
pating subjects was obtained.
Cell Viability Assay:MCT-E mouse fibroblast cells were pur-
chased from ATCC and cultured in Dulbecco’s Modified Eagle’s Medium
(DMEM) supplemented with  wt.% fetal calf serum,  U mL−peni-
cillin,  U mL−streptomycin, and  mmol L−L-glutamine (all from
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Biological Industries, Israel). The cells were cultured in a petri dish at  °C
in a humidified atmosphere containing % CO. Hydrogels ( μL) were
prepared in  well-plate and incubated with  μLDMEMforhafter
its full gelation. The hydrogels were washed five times with  μLDMEM
for  min each, on an orbital shaker at room temperature. The extracted
medium was kept in a refrigerator overnight. Afterward,  μLofextracted
medium was added to a new  well-plate and used to grow the cells
(K per well). Cell viability was evaluated using the alamarBlue reagent
(thermofisher). At  and  days post seeding, the cells were stained by
replacing the cell medium with alamarBlue diluted : in DMEM and
incubating for  h ( °C, % CO). Then, absorbance was measured
using a Tecan Spark Infinite MPRO plate reader at 𝜆= nm and
𝜆= nm. The results were presented as the percentage of viable cells
relative to the control group of normal cells cultured on  day.
Live/Dead Staining:Cells were cultured as outlined above. Briefly,
 μL of the extracted medium was added to a  well-plate and used
to grow the cells (K per well). One day post-seeding, a fluorescent
Live/Dead staining assay (Sigma Aldrich) containing fluorescein diacetate
(. μgml
−) and propidium iodide ( μgml
−) was used to visualize the
proportion of viable versus non-viable cells. The labeled cells were imme-
diately viewed using a confocal microscope ZEISS LSM  (ZEISS, Ger-
many).
Statistical Analysis:All the data were performed using Prism ..
(GraphPad) and expressed as the mean ±SD based on at least three inde-
pendent experiments. Specific comparisons were indicated in the respec-
tive figure legends.
Supporting Information
Supporting Information is available from the Wiley Online Library or from
the author.
Acknowledgements
This work was supported by the European Research Council (ERC), un-
der the European Union’s Horizon  research and innovation program
(grant agreement no.  ) (L.A.-A.). This work was supported by the
Israel Science Foundation (grant No. /) (M.S.). The authors ac-
knowledge the support of the Zimin Institute. D.C.-G. acknowledges the
Marian Gertner Institute for Medical Nano systems at Tel Aviv University.
D.C.-G. gratefully acknowledges the support of the Colton Foundation. The
authors acknowledge the Chaoul Center for Nanoscale Systems of Tel Aviv
University for the use of instruments and sta assistance. The authors
thank Dr. Pini Shekhter for the assistance and helpful discussion on XPS
analysis. The authors thank Ariel Halperin for her assistance. The authors
thank Sigal Rencus-Lazar for editing assistance. The authors thank the
members of the Adler-Abramovich, Shacham-Diamand, and Sokol groups
for the helpful discussions.
Conflict of Interest
The authors declare no conflict of interest.
Data Availability Statement
The data that support the findings of this study are available from the cor-
responding author upon reasonable request.
Keywords
D materials, biosensors, hydrogels, self-assembly, wearable electronics
Received: March , 
Published online: April , 
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