bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 18, 2024
Abstract
Cells
dynamically
modify
their
local
extracellular
matrix
by
expressing
proteases
that
degrade
proteins.
This
enables
cells
to
spread
and
migrate
within
tissues,
this
process
is
often
mimicked
in
hydrogels
through
the
incorporation
of
peptide
crosslinks
can
be
degraded
cell-secreted
proteases.
However,
cleavage
hydrogel
will
also
reduce
mechanical
properties,
most
crosslinking
peptides,
such
as
widely
used
GPQGIWGQ
“PanMMP”
sequence,
lead
bulk
degradation
hydrogel.
A
subset
are
localized
cell
membrane
only
active
pericellular
region
immediate
vicinity
surface.
These
membrane-type
have
important
physiological
roles
enable
tissues.
In
work
we
developed
an
approach
identify
optimize
sequences
specifically
We
utilized
a
proteomic
screen
targets,
coupled
with
functional
assay
both
quantifies
individual
types
elucidate
whether
peptides
primarily
cleaved
soluble
or
then
split-and-pool
synthesis
generate
more
than
300
variants
target
improve
behavior.
identified
optimized
KLVADLMASAE,
which
proteases,
but
endothelial
stem
grown
KLVADLMASAE-crosslinked
viabilities
similar
gels
crosslinked
PanMMP
peptide.
Notably,
biological
performance
KLVADLMASAE
peptide-cross
linked
was
significantly
improved
from
initial
found
screen.
introduces
identifying
refining
protease-substrate
way
enhance
properties
matrices.
Polymer-based
hydrogels
are
hydrophilic
polymer
networks
with
crosslinks
widely
applied
for
drug
delivery
applications
because
of
their
ability
to
hold
large
amounts
water
and
biological
fluids
control
release
based
on
unique
physicochemical
properties
biocompatibility.
Current
trends
in
the
development
hydrogel
systems
involve
drugs
response
specific
triggers
such
as
pH,
temperature,
or
enzymes
targeted
reduce
potential
systemic
toxicity.
In
addition,
developing
injectable
formulations
that
easily
used
sustain
during
this
extended
time
is
a
growing
interest.
Another
emerging
trend
synthesis
nano
other
functional
substances
improving
loading
efficacy.
Following
these
trends,
advanced
possessing
mechanically
improved
properties,
controlled
rates,
biocompatibility
focus
field.
More
complex
multi-drug
combination
therapies
will
be
developed
advancements.
polymer-based
gaining
increasing
attention
personalized
medicine
tailored
patient,
example,
combinations,
target-specific
delivery,
improvement
disease
treatment
effectiveness,
healthcare
cost
reduction.
Overall,
application
advancing
rapidly,
towards
more
efficient
effective
future.
Head
and
neck
cancers
(HNCs)
rank
as
the
sixth
most
common
cancer
globally
result
in
over
450
000
deaths
annually.
Despite
considerable
advancements
diagnostics
treatment,
5-year
survival
rate
for
types
of
HNCs
remains
below
50%.
Poor
prognoses
are
often
attributed
to
tumor
heterogeneity,
drug
resistance,
immunosuppression.
These
characteristics
difficult
replicate
using
vitro
or
vivo
models,
culminating
few
effective
approaches
early
detection
therapeutic
development.
Organs-on-a-chip
offer
a
promising
avenue
studying
HNCs,
serving
microphysiological
models
that
closely
recapitulate
complexities
biological
tissues
within
highly
controllable
microfluidic
platforms.
Such
systems
have
gained
interest
advanced
experimental
tools
investigate
human
pathophysiology
assess
efficacy,
providing
deeper
understanding
pathophysiology.
This
review
outlines
current
challenges
opportunities
replicating
systems,
focusing
on
mimicking
soft,
glandular,
hard
head
neck.
We
further
delve
into
major
applications
organ-on-a-chip
including
fundamental
research,
discovery,
translational
approaches,
personalized
medicine.
emphasizes
integration
organs-on-a-chip
repertoire
model
available
researchers.
enables
exploration
unique
aspects
thereby
accelerating
discoveries
with
potential
improve
outcomes
HNC
patients.
ACS Applied Bio Materials,
Год журнала:
2024,
Номер
7(5), С. 2620 - 2636
Опубликована: Апрель 9, 2024
Salivary
glands
(SGs)
play
a
vital
role
in
maintaining
oral
health
through
the
production
and
release
of
saliva.
Injury
to
SGs
can
lead
gland
hypofunction
decrease
saliva
secretion
manifesting
as
xerostomia.
While
symptomatic
treatments
for
xerostomia
exist,
effective
permanent
solutions
are
still
lacking,
emphasizing
need
innovative
approaches.
Significant
progress
has
been
made
field
three-dimensional
(3D)
SG
bioengineering
applications
regeneration.
This
achieved
major
focus
on
cell
culture
techniques,
including
soluble
cues
biomaterial
components
3D
niche.
Cells
derived
from
both
adult
embryonic
have
highlighted
key
vitro
characteristics
models.
its
first
decade
exploration,
spheroids
organoids
so
far
served
crucial
tools
study
pathophysiology.
review,
based
literature
search
over
past
decade,
covers
importance
types
realm
their
isolation,
sourcing,
conditions
that
modulate
microenvironment.
We
discuss
different
biomaterials
employed
current
advances
models
using
them.
The
success
these
cellular
further
evaluated
context
organ
transplantation
disease
modeling.
ACS Applied Materials & Interfaces,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 17, 2025
Toward
the
goal
of
in
vitro
engineering
functional
salivary
gland
tissues,
we
cultured
primary
human
stem/progenitor
cells
(hS/PCs)
hyaluronic
acid-based
matrices
with
varying
percentages
proteolytically
degradable
crosslinks
presence
Rho
kinase
(ROCK)
inhibitor.
Single
encapsulated
hydrogel
grew
into
organized
multicellular
structures
by
day
15,
and
over
60%
developed
nondegradable
50%
hydrogels
contained
a
central
lumen.
Importantly,
ROCK
inhibition
led
to
establishment
that
were
correctly
polarized,
as
evidenced
apical
localization
Golgi
marker
GM130,
apical/lateral
tight
junction
protein
zonula
occludens-1
(ZO-1),
basal
integrin
β1
basement
membrane
proteins
laminin
α1
collagen
IV.
Cultures
maintained
gels
exhibited
an
increased
expression
acinar
markers
aquaporin
5
(AQP5,
AQP5)
sodium–potassium–chloride
cotransporter
1
(SLC12A2,
NKCC1)
at
transcript
levels,
respectively,
compared
those
without
inhibition.
Upon
stimulation
isoproterenol,
α-amylase
secretion
lumen
was
observed.
Particle-tracking
microrheology
employed
analyze
stiffness
using
mitochondria
passive
tracer
particles.
Our
results
indicated
grown
100%
stiffer
than
gels,
inhibitor
softer
We
conclude
reducing
cellular
contractility
via
while
retaining
some
degree
matrix
confinement
promotes
containing
pro-acinar
correct
apicobasal
polarization.
Journal of Biomedical Materials Research Part A,
Год журнала:
2025,
Номер
113(5)
Опубликована: Май 1, 2025
Solid
phase
peptide
synthesis
(SPPS)
techniques
are
critical
for
developing
and
using
peptides
in
various
biomedical
applications.
However,
typical
routes
used
SPPS
either
resource-intensive
(e.g.,
with
automated
or
commercial
services)
time-consuming
manual
benchtop
synthesis).
Here,
a
rapid
method
was
developed
to
produce
up
8
fast
cycle
times
simultaneously.
Peptides
synthesized
manually
were
of
equivalent
superior
quality
those
produced
by
in-house
microwave-assisted
synthesis,
higher
average
crude
purity
70%
compared
50%.
The
significantly
reduced
time,
enabling
the
parallel
coupling
amino
acids
simultaneously
15-20
min,
as
opposed
traditional
which
requires
80-150
min
per
acid.
This
approach
offers
an
intermediate
throughput
between
milligram-scale
libraries
gram-scale
single
iteration
novel
designs
without
need
expensive
systems.
As
result,
modifications,
including
incorporation
unnatural
acids,
can
be
explored,
accelerating
development
wide
range
Abstract
Objective
Salivary
gland
(SG)
hypofunction
is
a
common
clinical
condition
arising
from
radiotherapy
to
suppress
head
and
neck
cancers.
The
radiation
often
destroys
the
SG
secretory
acini,
glands
are
left
with
limited
regenerative
potential.
Due
complex
architecture
of
acini
ducts,
three-dimensional
(3D)
bioprinting
platforms
have
emerged
spatially
define
these
in
vitro
epithelial
units
develop
mini-organs
or
organoids
for
regeneration.
body
evidence,
this
comprehensive
review
highlights
advantages
challenges
Methods
microtissue
engineering
strategies
such
as
magnetic
3D
bioassembly
cells
microfluidic
coaxial
cell-laden
microfibers
microtubes
been
proposed
replace
damaged
acinar
units,
avoid
use
xenogeneic
matrices
(like
Matrigel),
restore
salivary
flow.
Results
Replacing
organ
challenging
due
its
architecture,
which
combines
ductal
network
facilitate
unidirectional
flow
saliva.
Our
research
group
was
first
functional
innervation
respond
both
cholinergic
adrenergic
stimulation.
More
recently,
using
hydrogel
could
also
supported
formation
viable
units.
Both
approaches
overcome
need
Matrigel
by
facilitating
assembly
adult
stem
cells,
human
dental
pulp
primary
into
micro-sized
constructs
able
produce
their
own
matrix
self-organize
micro-modular
tissue
clusters
lumenized
areas.
Furthermore,
extracellular
vesicle
(EV)
therapies
organoid-derived
secretome
were
designed
validated
ex
vivo
regeneration
after
damage.
Conclusion
Magnetic
potential
create
applications
via
organoid
transplantation
EV
therapies.
eXPRESS Polymer Letters,
Год журнала:
2023,
Номер
18(2), С. 160 - 192
Опубликована: Дек. 6, 2023
Polymer-based
hydrogels
are
hydrophilic
polymer
networks
with
a
remarkable
capacity
to
absorb
substantial
amounts
of
water
and
biological
fluids,
rendering
them
highly
attractive
for
drug
delivery
applications.The
COVID-19
pandemic
has
acted
as
catalyst
research
innovation
in
the
realm
polymer-based
delivery,
particular
emphasis
on
antiviral
therapeutics,
vaccines,
diagnostics,
precision
respiratory
system.The
distinctive
attributes
hydrogels,
such
their
biocompatibility,
customizable
release
profiles,
ease
functionalization,
establish
versatile
platforms
development
advanced
systems
combat
not
only
but
also
spectrum
other
infectious
diseases.This
study
is
dedicated
scruti-nizing
evaluating
characteristics
employed
treatment
diseases
associated
SARS-CoV-2
virus.Furthermore,
investigation
introduces
novel
classification
system
deployed
SARS-CoV-2-related
diseases.Additionally,
paper
provides
an
up-to-date
evaluation
latest
developed
utilized
dis-eases
linked
virus,
based
conducted
through
recent
months
2023.