Abstract
Herein,
a
novel
extracellular
matrix
(ECM)
hydrogel
is
proposed
fabricated
solely
from
decellularized,
human
fibroblast‐derived
(FDM)
toward
advanced
wound
healing.
This
FDM‐gel
physically
very
stable
and
viscoelastic,
while
preserving
the
natural
ECM
diversity
various
bioactive
factors.
Subcutaneously
transplanted
provided
permissive
environment
for
innate
immune
cells
infiltration.
Compared
to
collagen
hydrogel,
excellent
healing
indications
of
treated
in
full‐thickness
wounds
are
noticed,
particularly
hair
follicle
formation
via
highly
upregulated
β‐catenin.
Sequential
analysis
regenerated
tissues
disclosed
that
significantly
alleviated
pro‐inflammatory
cytokine
promoted
M2‐like
macrophages,
along
with
elevated
vascular
endothelial
growth
factor
(VEGF)
basic
fibroblast
(bFGF)
level.
A
mechanistic
study
demonstrated
macrophages‐FDM
interactions
through
cell
surface
integrins
α5β1
α1β1
resulted
significant
production
VEGF
bFGF,
increased
Akt
phosphorylation,
metalloproteinase‐9
activity.
Interestingly,
blocking
such
using
specific
inhibitors
(ATN161
obtustatin
α1β1)
negatively
affected
those
pro‐healing
factors
secretion.
Macrophages
depletion
animal
model
attenuated
effect
FDM‐gel.
demonstrates
an
immunomodulatory
material
host
infiltration,
resorbable
time,
interactive
where
it
thus
enables
regenerative
remodeling
complete
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
173, С. 116458 - 116458
Опубликована: Март 19, 2024
Osteoarthritis
(OA)
is
a
multifaceted
disease
characterized
by
imbalances
in
extracellular
matrix
metabolism,
chondrocyte
and
synoviocyte
senescence,
as
well
inflammatory
responses
mediated
macrophages.
Although
there
have
been
notable
advancements
pharmacological
surgical
interventions,
achieving
complete
remission
of
OA
remains
formidable
challenge,
oftentimes
accompanied
significant
side
effects.
Mesenchymal
stem
cells
(MSCs)
emerged
promising
avenue
for
treatment,
given
their
ability
to
differentiate
into
chondrocytes
facilitate
cartilage
repair,
thereby
mitigating
the
impact
an
microenvironment
induced
This
comprehensive
review
aims
provide
concise
overview
diverse
roles
played
MSCs
treatment
OA,
while
elucidating
underlying
mechanisms
behind
these
contributions.
Specifically,
include:
(a)
Promotion
regeneration;
(b)
Inhibition
degradation;
(c)
Attenuating
macrophage-induced
microenvironment;
(d)
Alleviation
pain.
Understanding
paramount
developing
novel
therapeutic
strategies.
By
harnessing
regenerative
potential
immunomodulatory
properties
MSCs,
it
may
be
possible
devise
more
effective
safer
approaches
managing
OA.
Further
research
clinical
studies
are
warranted
optimize
utilization
realize
full
field
therapeutics.
Abstract
Hyaluronic
acid
(HA)
is
a
naturally
occurring
polysaccharide
found
in
the
extracellular
matrix
with
broad
applications
disease
treatment.
HA
possesses
good
biocompatibility,
biodegradability,
and
ability
to
interact
various
cell
surface
receptors.
Its
wide
range
of
molecular
weights
modifiable
chemical
groups
make
it
an
effective
drug
carrier
for
delivery.
Additionally,
overexpression
specific
receptors
on
surfaces
many
states
enhances
accumulation
drugs
at
pathological
sites
through
receptor
binding.
In
this
review,
modification
drugs,
major
proteins,
latest
advances
receptor‐targeted
nano
delivery
systems
(DDS)
treatment
tumors
inflammatory
diseases
are
summarized.
Furthermore,
functions
varying
vivo
selection
methods
different
discussed.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 16, 2024
The
extracellular
matrix
(ECM)
is
a
complex
three-dimensional
structure
composed
of
proteins,
glycans,
and
proteoglycans,
constituting
critical
component
the
tumor
microenvironment.
Complex
interactions
among
immune
cells,
matrix,
cells
promote
development
metastasis,
consequently
influencing
therapeutic
efficacy.
Hence,
elucidating
these
interaction
mechanisms
pivotal
for
precision
cancer
therapy.
T
lymphocytes
are
an
important
system,
exerting
direct
anti-tumor
effects
by
attacking
or
releasing
lymphokines
to
enhance
effects.
ECM
significantly
influences
function
infiltration
within
microenvironment,
thereby
impacting
behavior
biological
characteristics
cells.
involved
in
regulating
synthesis,
degradation,
remodeling
through
secretion
cytokines
enzymes.
As
result,
it
affects
proliferation
invasive
ability
as
well
efficacy
immunotherapy.
This
review
discusses
underlying
lymphocyte-ECM
microenvironment
their
potential
application
It
provides
novel
insights
innovative
strategies
drug.
Abstract
Herein,
a
novel
extracellular
matrix
(ECM)
hydrogel
is
proposed
fabricated
solely
from
decellularized,
human
fibroblast‐derived
(FDM)
toward
advanced
wound
healing.
This
FDM‐gel
physically
very
stable
and
viscoelastic,
while
preserving
the
natural
ECM
diversity
various
bioactive
factors.
Subcutaneously
transplanted
provided
permissive
environment
for
innate
immune
cells
infiltration.
Compared
to
collagen
hydrogel,
excellent
healing
indications
of
treated
in
full‐thickness
wounds
are
noticed,
particularly
hair
follicle
formation
via
highly
upregulated
β‐catenin.
Sequential
analysis
regenerated
tissues
disclosed
that
significantly
alleviated
pro‐inflammatory
cytokine
promoted
M2‐like
macrophages,
along
with
elevated
vascular
endothelial
growth
factor
(VEGF)
basic
fibroblast
(bFGF)
level.
A
mechanistic
study
demonstrated
macrophages‐FDM
interactions
through
cell
surface
integrins
α5β1
α1β1
resulted
significant
production
VEGF
bFGF,
increased
Akt
phosphorylation,
metalloproteinase‐9
activity.
Interestingly,
blocking
such
using
specific
inhibitors
(ATN161
obtustatin
α1β1)
negatively
affected
those
pro‐healing
factors
secretion.
Macrophages
depletion
animal
model
attenuated
effect
FDM‐gel.
demonstrates
an
immunomodulatory
material
host
infiltration,
resorbable
time,
interactive
where
it
thus
enables
regenerative
remodeling
complete
