bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 31, 2025
Abstract
Extracellular
vesicles
(EVs)
are
versatile
transporters
of
genetic
cargo
with
enormous
potential
in
the
therapeutic
setting.
Scalable
production
EVs,
and
routes
to
overcome
rapid
clearance
required.
Biocompatible
hydrogels
may
support
precise,
localized
delivery
EVs
target
sites.
This
study
aimed
establish
sustained
a
scalable
3D
dynamic
bioreactor
fabricate
using
tyramine-modified
hyaluronic
acid
(HA-TA)
EV
integration
release
patterns.
MDA-MB-231
cells
transduced
lentiviral
GFP
fused
CD63,
were
cultured
20kD
hollow
fiber
GFP-EVs
harvested
over
five
weeks.
characterized
by
Nanoparticle
Tracking
Analysis(NTA),
Western
Blot(WB)
Transmission
Electron
Microscopy(TEM).
Tyramine
modified
acid(HA-TA)
formulated
via
enzymatic
crosslinking
hydrogen
peroxide
horseradish
peroxidase,
investigate
patterns
static
conditions.
Hydrogel
swelling
was
recorded
at
1-72
hrs
loaded
assess
distribution
Scanning
Microscopy(SEM)
NTA
respectively.
GFP-EV
uptake
assessed
confocal
microscopy.
Longitudinal
expression
demonstrated
released
throughout
culture.
TEM
successful
isolation
30-200
nm
size
intact
lipid
bilayers
(average
4×10
9
EVs/harvest).
Initial
harvests
exhibited
subpopulations
larger
which
disappeared
upon
serum
withdrawal.
WB
verified
presence
markers
TSG101,
CD81.
HA-TA
successfully
formed
assays
revealed
requirement
for
higher
concentrations
crosslinkers
scaffold
stability
continued
swelling.
incorporated
into
variable
observed
time,
depending
on
concentration
hydrogel
formulation.
clusters
visualized
SEM.
Investigation
under
conditions
highlighted
significant
increase
fluid
flow
Efficient
transfer
recipient
also
vitro
.
The
data
demonstrate
engineered
free
subsequent
incorporation
release.
These
biocompatible
hold
promise
tuneable
variety
disease
settings.
Biomaterials Research,
Journal Year:
2023,
Volume and Issue:
27(1)
Published: Feb. 9, 2023
Currently,
the
clinical
treatment
of
critical
bone
defects
attributed
to
various
causes
remains
a
great
challenge,
and
repairing
these
with
synthetic
substitutes
is
most
common
strategy.
In
general,
tissue
engineering
materials
that
mimic
structural,
mechanical
biological
properties
natural
have
been
extensively
applied
fill
promote
in
situ
regeneration.
Hydrogels
extracellular
matrix
(ECM)-like
are
materials,
among
which
methacrylate-based
gelatin
(GelMA)
hydrogels
widely
used
because
their
tunable
properties,
excellent
photocrosslinking
capability
good
biocompatibility.
Owing
lack
osteogenic
activity,
however,
GelMA
combined
other
types
activities
improve
current
composites.
There
three
main
aspects
consider
when
enhancing
regenerative
performance
composite
materials:
osteoconductivity,
vascularization
osteoinduction.
Bioceramics,
bioglass,
biomimetic
scaffolds,
inorganic
ions,
bionic
periosteum,
growth
factors
two-dimensional
(2D)
nanomaterials
combinations
achieve
enhanced
regeneration
activities.
Three-dimensional
(3D)-bioprinted
scaffolds
popular
research
topic
(BTE),
printed
customized
suitable
for
restoring
large
irregular
due
shape
structural
tunability,
Herein,
recent
progress
on
GelMA-based
hydrogel
as
multifunctional
platforms
plastic
or
orthopedic
clinics
systematically
reviewed
summarized.
These
strategies
pave
way
design
effective
reconstruction
biosafety.
This
review
provides
novel
insights
into
development
trends
(BTE)
correcting
defects,
contents
summarized
emphasized
from
perspectives
(osteoconductivity,
vascularization,
osteoinduction
3D-bioprinting).
addition,
advantages
deficiencies
put
forward,
corresponding
improvement
measures
presented
prior
application
near
future
(created
BioRender.com).
International Journal of Nanomedicine,
Journal Year:
2023,
Volume and Issue:
Volume 18, P. 4751 - 4778
Published: Aug. 1, 2023
Abstract:
Exosomes,
as
natural
nanocarriers,
characterized
with
low
immunogenicity,
non-cytotoxicity
and
targeted
delivery
capability,
which
have
advantages
over
synthetic
nanocarriers.
Recently,
exosomes
shown
great
potential
diagnostic
markers
for
diseases
are
also
considered
a
promising
cell-free
therapy.
Engineered
significantly
enhanced
the
efficacy
precision
of
delivering
therapeutic
agents,
currently
being
extensively
employed
in
investigations
various
ailments,
including
oncology,
inflammatory
disorders,
degenerative
conditions.
Particularly,
engineered
enable
agent
loading,
modification,
evasion
MPS
phagocytosis,
intelligent
control,
bioimaging,
been
developed
multifunctional
nano-delivery
platforms
recent
years.
The
utilization
bioactive
scaffolds
that
loaded
exosome
has
to
substantially
augment
retention,
extend
release,
enhance
efficacy.
This
approach
advanced
from
conventional
hydrogels
nanocomposite
hydrogels,
nanofiber
3D
printing,
resulting
superior
physical
biological
properties
effectively
address
limitations
scaffolds.
Additionally,
plant-derived
exosomes,
can
participate
gut
flora
remodeling
via
oral
administration,
an
ideal
platform
treatment
intestinal
diseases.
Consequently,
there
is
interest
nanocarriers
applications.
comprehensive
review
provides
overview
biogenesis,
composition,
isolation
methods
exosomes.
it
examines
pathological
mechanisms
diseases,
tumors,
Furthermore,
this
highlights
significance
microbial-derived
Strategies
specific
applications
scaffold-loaded
further
summarized,
especially
some
new
techniques
such
large-scale
loading
technique,
macromolecular
development
nano-scaffold-loaded
delivery.
benefits
using
gut-related
discussed.
challenges,
opportunities,
prospects
exosome-based
disease
diagnosis
summarized
both
preclinical
clinical
viewpoints.
Keywords:
diagnosis,
Bone Research,
Journal Year:
2024,
Volume and Issue:
12(1)
Published: Jan. 23, 2024
Abstract
Osteoporosis
is
a
widely
observed
condition
characterized
by
the
systemic
deterioration
of
bone
mass
and
microarchitecture,
which
increases
patient
susceptibility
to
fragile
fractures.
The
intricate
mechanisms
governing
homeostasis
are
substantially
impacted
extracellular
vesicles
(EVs),
play
crucial
roles
in
both
pathological
physiological
contexts.
EVs
derived
from
various
sources
exert
distinct
effects
on
osteoporosis.
Specifically,
released
osteoblasts,
endothelial
cells,
myocytes,
mesenchymal
stem
cells
contribute
formation
due
their
unique
cargo
proteins,
miRNAs,
cytokines.
Conversely,
secreted
osteoclasts
immune
promote
resorption
inhibit
formation.
Furthermore,
use
as
therapeutic
modalities
or
biomaterials
for
diagnosing
managing
osteoporosis
promising.
Here,
we
review
current
understanding
impact
homeostasis,
including
classification
biogenesis
regulatory
present
an
overview
latest
research
progress
treating
using
EVs.
Finally,
discuss
challenges
prospects
translational
Theranostics,
Journal Year:
2024,
Volume and Issue:
14(5), P. 2099 - 2126
Published: Jan. 1, 2024
Exosomes,
which
are
small
vesicles
enclosed
by
a
lipid
bilayer
and
released
many
cell
types,
widely
dispersed
have
garnered
increased
attention
in
the
field
of
regenerative
medicine
due
to
their
ability
serve
as
indicators
diseases
agents
with
therapeutic
potential.
Exosomes
play
crucial
role
mediating
intercellular
communication
through
transfer
biomolecules,
including
proteins,
lipids,
RNA,
other
molecular
constituents,
between
cells.
The
targeted
transport
proteins
nucleic
acids
specific
cells
has
potential
enhance
or
impair
biological
functions.
applications,
they
can
be
used
alone
combination
approaches.
examination
unique
attributes
functions
these
factors
emerged
prominent
study
realm
biomedical
research.
This
manuscript
summarizes
origins
properties
exosomes,
structural,
biological,
physical,
chemical
aspects.
paper
offers
complete
recent
progress
tissue
repair
medicine,
emphasizing
possible
implications
methods
forthcoming
regeneration
attempts.
Journal of Nanobiotechnology,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: Feb. 12, 2025
Senescent
mandibular
bone
repair
poses
a
formidable
challenge
without
completely
satisfactory
strategy.
Endogenous
cell
recruitment
and
osteogenic
differentiation
are
two
sequential
stages
in
regeneration,
disruptions
these
processes
present
significant
obstacles
to
senescent
repair.
To
address
issues,
engineered
extracellular
vesicles
(EV)
with
stem
functions
were
developed.
This
study
demonstrated
that
Apt19s-engineered
(Apt19s-EV)
recognize
recruit
marrow
mesenchymal
cells
derived
from
old
rats
(O-BMSCs)
specifically
effectively.
MiR-376b-5p,
identified
by
RNA
sequencing
transfection,
was
significantly
decreased
O-BMSCs,
it
selected
construct
miR-376b-5p-engineered
(376b-EV).
376b-EV
could
promote
osteogenesis
alleviate
senescence
of
O-BMSCs
targeting
Camsap1.
combine
the
advantages
Apt19s
miR-376b-5p,
dual
(Apt-376b-EV)
comprising
both
miR-376b-5p
modifications
constructed.
further
validate
its
function,
Gelatin
methacryloyl
(GelMA)
hydrogel
used
as
carrier
Apt-376b-EV@GelMA
delivery
system.
The
vitro
results
have
sequentially.
Notably,
vivo
also
showed
sequentially
endogenous
enhance
new
formation
fracture
critical-sized
defect
models.
In
summary,
vesicles,
Apt-376b-EV,
offer
an
appealing
solution
for
recruiting
promoting
microenvironment,
which
may
broaden
clinical
applications
EV
provide
valuable
strategies
treating
bone-related
diseases
future
work.
Gels,
Journal Year:
2023,
Volume and Issue:
9(7), P. 533 - 533
Published: June 30, 2023
Injectable
hydrogels
have
gained
popularity
for
their
controlled
release,
targeted
delivery,
and
enhanced
mechanical
properties.
They
hold
promise
in
cardiac
regeneration,
joint
diseases,
postoperative
analgesia,
ocular
disorder
treatment.
Hydrogels
enriched
with
nano-hydroxyapatite
show
potential
bone
addressing
challenges
of
defects,
osteoporosis,
tumor-associated
regeneration.
In
wound
management
cancer
therapy,
they
enable
accelerated
closure,
drug
delivery.
also
find
applications
ischemic
brain
injury,
tissue
cardiovascular
personalized
immunotherapy.
This
manuscript
highlights
the
versatility
injectable
hydrogel
nanocomposites
biomedical
research.
Moreover,
it
includes
a
perspective
section
that
explores
future
prospects,
emphasizes
interdisciplinary
collaboration,
underscores
promising
research
applications.
Bioactive Materials,
Journal Year:
2024,
Volume and Issue:
39, P. 302 - 316
Published: May 24, 2024
Diabetic
wounds,
characterized
by
prolonged
inflammation
and
impaired
vascularization,
are
a
serious
complication
of
diabetes.
This
study
aimed
to
design
gelatin
methacrylate
(GelMA)
hydrogel
for
the
sustained
release
netrin-1
evaluate
its
potential
as
scaffold
promote
diabetic
wound
healing.
The
results
showed
that
was
highly
expressed
during
proliferation
phases
normal
whereas
it
synchronously
exhibited
aberrantly
low
expression
in
wounds.
Neutralization
inhibited
healing,
topical
application
accelerated
Mechanistic
studies
demonstrated
regulated
macrophage
heterogeneity
via
A2bR/STAT/PPARγ
signaling
pathway
promoted
function
endothelial
cells,
thus
accelerating
These
data
suggest
is
therapeutic
target
Life,
Journal Year:
2024,
Volume and Issue:
14(3), P. 287 - 287
Published: Feb. 21, 2024
Segmental
bone
defects
that
are
caused
by
trauma,
infection,
tumor
resection,
or
osteoporotic
fractures
present
significant
surgical
treatment
challenges.
Host
autograft
is
considered
the
gold
standard
for
restoring
function
but
comes
with
cost
of
harvest
site
comorbidity.
Allograft
a
secondary
option
has
its
own
limitations
in
incorporation
host
as
well
cost.
Therefore,
developing
new
tissue
engineering
strategies
to
treat
critically
needed.
In
past
three
decades,
use
stem
cells
delivered
different
scaffolds
growth
factors
made
tremendous
progress.
Many
varieties
have
been
isolated
from
tissues
engineering.
This
review
summarizes
progress
using
postnatal
cells,
including
marrow
mesenchymal
muscle-derived
adipose-derived
dental
pulp
cells/periodontal
ligament
periosteum
umbilical
cord-derived
peripheral
blood
urine-derived
apical
papilla,
and
induced
pluripotent
repair.
also
exosomes
extracellular
vesicles
various
The
advantages
disadvantages
each
type
cell
discussed
explained
detail.
It
hoped
future,
these
preclinical
results
will
translate
into
regenerative
therapies
defect