Acta Biomaterialia,
Journal Year:
2024,
Volume and Issue:
192, P. 260 - 278
Published: Dec. 12, 2024
Regeneration
of
large
bone
defects
remains
a
clinical
challenge
until
today.
While
existing
biomaterials
are
predominantly
addressing
healing
via
direct,
intramembranous
ossification
(IO),
tissue
formation
cartilage
phase,
so-called
endochondral
(EO)
has
been
shown
to
be
promising
alternative
strategy.
However,
pure
biomaterial
approaches
for
EO
induction
sparse
and
the
knowledge
how
material
components
can
have
bioactive
contribution
required
is
limited.
Here,
we
combined
previously
developed
purely
architecture-driven
approach
with
release
therapeutic
metal
ions
from
tailored
silicate
microparticles.
The
delivery
platform
was
free
calcium
phosphates
(CaP)
that
known
support
IO
but
not
employed
lithium
(Li),
magnesium
(Mg),
strontium
(Sr)
or
zinc
(Zn)
ions.
We
identified
an
ion-specific
cellular
response
in
which
certain
strongly
enhanced
cell
recruitment
into
showed
superior
chondrogenesis
deposition
collagen
II
by
human
mesenchymal
stromal
cells
(MSCs).
At
same
time,
some
cases
microparticle
incorporation
altered
mechanical
properties
consequences
cell-induced
contraction
scaffold
wall
deformation.
Collectively,
results
suggest
metal-doped
microparticles
potential
further
improve
bioactivity
architectured
defect
EO.
STATEMENT
OF
SIGNIFICANCE:
Endochondral
healing,
process
resembles
embryonic
skeletal
development,
gained
prominence
regenerative
medicine.
most
strategies
optimized
instead
target
direct
through
IO.
report
on
novel
accelerate
biomaterial-guided
combining
cell-guiding
scaffolds
other
strategies,
such
as
hypoxia-mimic
drugs
iron-chelating
biomaterials,
documented
literature
before
enhance
EO,
our
uniquely
implements
strategy
regeneration.
Enhanced
more
pronounced
were
observed
specific
hybrid
formulations,
suggesting
high
relevance
this
new
improved
healing.
Cells,
Journal Year:
2023,
Volume and Issue:
12(16), P. 2039 - 2039
Published: Aug. 10, 2023
Mesenchymal
stromal
cells
nowadays
emerge
as
a
major
player
in
the
field
of
regenerative
medicine
and
translational
research.
They
constitute,
with
their
derived
products,
most
frequently
used
cell
type
different
therapies.
However,
heterogeneity,
including
subpopulations,
anatomic
source
isolation,
high
donor-to-donor
variability,
constitutes
controversial
issue
that
affects
use
clinical
applications.
Furthermore,
intrinsic
extrinsic
molecular
mechanisms
underlying
self-renewal
fate
specification
are
still
not
completely
elucidated.
This
review
dissects
heterogeneity
aspects
tissue
associated
distinct
developmental
origin
need
to
be
considered
when
generating
homogenous
products
before
usage
for
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: May 4, 2024
Abstract
Excessive
bone
marrow
adipocytes
(BMAds)
accumulation
often
occurs
under
diverse
pathophysiological
conditions
associated
with
deterioration.
Estrogen-related
receptor
α
(ESRRA)
is
a
key
regulator
responding
to
metabolic
stress.
Here,
we
show
that
adipocyte-specific
ESRRA
deficiency
preserves
osteogenesis
and
vascular
formation
in
adipocyte-rich
upon
estrogen
or
obesity.
Mechanistically,
adipocyte
interferes
E2/ESR1
signaling
resulting
transcriptional
repression
of
secreted
phosphoprotein
1
(
Spp1
);
yet
positively
modulates
leptin
expression
by
binding
its
promoter.
abrogation
results
enhanced
SPP1
decreased
secretion
from
both
visceral
BMAds,
concertedly
dictating
stromal
stem
cell
fate
commitment
restoring
type
H
vessel
formation,
constituting
feed-forward
loop
for
formation.
Pharmacological
inhibition
protects
obese
mice
against
loss
high
adiposity.
Thus,
our
findings
highlight
therapeutic
approach
via
targeting
preserve
especially
detrimental
milieu.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Jan. 20, 2025
Abstract
Reconstructing
large,
inflammatory
maxillofacial
defects
using
stem
cell-based
therapy
faces
challenges
from
adverse
microenvironments,
including
high
levels
of
reactive
oxygen
species
(ROS),
inadequate
oxygen,
and
intensive
inflammation.
Here,
inspired
by
the
reaction
mechanisms
intracellular
antioxidant
defense
systems,
we
propose
de
novo
design
an
artificial
antioxidase
Ru-doped
layered
double
hydroxide
(Ru-hydroxide)
for
efficient
redox
homeostasis
bone
regeneration.
Our
studies
demonstrate
that
Ru-hydroxide
consists
hydroxyls-synergistic
monoatomic
Ru
centers,
which
efficiently
react
with
collaborate
hydroxyls
rapid
proton
electron
transfer,
thus
exhibiting
efficient,
broad-spectrum,
robust
ROS
scavenging
performance.
Moreover,
can
effectively
sustain
cell
viability
osteogenic
differentiation
in
elevated
environments,
modulating
microenvironment
during
tissue
regeneration
male
mice.
We
believe
this
development
offers
a
promising
avenue
designing
antioxidase-like
materials
to
treat
various
inflammation-associated
disorders,
arthritis,
diabetic
wounds,
enteritis,
fractures.
Advanced Healthcare Materials,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 2, 2025
With
the
global
population
aging,
awareness
of
oral
health
is
rising.
Periodontitis,
a
widespread
bacterial
infectious
disease,
gaining
attention.
Current
novel
biomaterials
address
key
clinical
issues
like
infection,
gum
inflammation,
tooth
loosening,
and
loss,
focusing
on
antibacterial,
anti-inflammatory,
tissue
regeneration
properties.
However,
strategies
that
integrate
advantages
these
to
achieve
synergistic
therapeutic
effects
by
clearing
biofilms,
inhibiting
inflammation
activation,
restoring
periodontal
soft
hard
functions
remain
very
limited.
Recent
studies
highlight
link
between
periodontitis
systemic
diseases,
underscoring
complexity
disease.
There
an
urgent
need
find
comprehensive
treatment
plans
requirements.
Whether
integrating
new
enhance
existing
treatments
or
developing
approaches
replace
traditional
therapies,
efforts
will
drive
advancements
in
treatment.
Therefore,
this
review
compares
with
treatments.
It
highlights
design
concepts
mechanisms
functional
materials,
their
properties,
discusses
importance
strategies.
This
aims
provide
guidance
for
emerging
research
promote
development
precise
efficient
Biomaterials,
Journal Year:
2023,
Volume and Issue:
303, P. 122387 - 122387
Published: Nov. 6, 2023
Endochondral
ossification
(ECO),
the
major
process
during
embryogenesis
and
bone
repair,
involves
formation
of
a
cartilaginous
template
remodelled
into
functional
organ.
Adipose-derived
stromal
cells
(ASC),
non-skeletal
multipotent
progenitors
from
vascular
fraction
(SVF)
human
adipose
tissue,
were
shown
to
recapitulate
ECO
generate
organs
in
vivo
when
primed
hypertrophic
cartilage
tissue
(HCT)
vitro.
However,
reproducibility
was
limited
triggers
remain
unknown.
We
studied
effect
expansion
maturation
HCT
on
induction
process.
SVF
or
expanded
ASC
seeded
onto
collagen
sponges,
cultured
chondrogenic
medium
for
3–6
weeks
implanted
ectopically
nude
mice
evaluate
their
bone-forming
capacities.
all
tested
donors
formed
mature
3
whereas
needed
4–5
weeks.
A
longer
increased
degree
HCT,
with
gradually
denser
matrix
mineralization.
This
highly
predictive
capacity
vivo,
achieved
only
an
intermediate
degree.
In
parallel,
expanding
also
resulted
enrichment
characterized
by
rapid
change
proteomic
profile
quiescent
proliferative
state.
Inducing
quiescence
rescued
potential.
Our
findings
emphasize
role
monolayer
provides
simple,
yet
reproducible
effective
approach
be
specific
clinical
models.
Cells,
Journal Year:
2022,
Volume and Issue:
11(6), P. 946 - 946
Published: March 10, 2022
Donor
variation
is
a
prominent
critical
issue
limiting
the
applicability
of
cell-based
therapies.
We
hypothesized
that
batch
effects
during
propagation
bone
marrow
stromal
cells
(BMSCs)
in
human
platelet
lysate
(hPL),
replacing
fetal
bovine
serum
(FBS),
can
affect
phenotypic
and
functional
variability.
therefore
investigated
impact
donor
variation,
hPL-
vs.
FBS-driven
exhaustive
proliferation,
on
BMSC
epigenome,
transcriptome,
phenotype,
coagulation
risk
osteochondral
regenerative
function.
Notably,
hPL
significantly
increased
created
different
gene
expression
trajectories
distinct
surface
marker
signatures,
already
after
just
one
passage.
confirmed
declining
proliferative
potential
FBS-expanded
challenge.
Flow
cytometry
verified
canonical
fibroblastic
phenotype
culture-expanded
BMSCs.
observed
limited
DNA
methylation,
preferentially
cultures,
irrespective
culture
duration.
The
clotting
over
time.
Moreover,
expansion
xenogenic
resulted
significant
loss
function
3D
cartilage
disk
formation
risk.
Superior
chondrogenic
under
hPL-conditions
was
maintained
culture.
blood
group
isoagglutinins
had
minor
These
data
demonstrate
pronounced
due
to
factors,
partly
outcompeting
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: April 11, 2023
Heterotopic
ossification
is
a
disorder
caused
by
abnormal
mineralization
of
soft
tissues
in
which
signaling
pathways
such
as
BMP,
TGFβ
and
WNT
are
known
key
players
driving
ectopic
bone
formation.
Identifying
novel
genes
related
to
the
process
important
steps
for
future
gene
therapy
disorders.
In
this
study,
we
detect
an
inter-chromosomal
insertional
duplication
female
proband
disrupting
topologically
associating
domain
causing
ultra-rare
progressive
form
heterotopic
ossification.
This
structural
variant
lead
enhancer
hijacking
misexpression
ARHGAP36
fibroblasts,
validated
here
orthogonal
vitro
studies.
addition,
overexpression
inhibits
TGFβ,
activates
hedgehog
genes/proteins
extracellular
matrix
production.
Our
work
on
genetic
cause
case
has
revealed
that
plays
role
formation
metabolism,
outlining
first
details
contributing
bone-formation
-disease.
Basic Research in Cardiology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 14, 2024
Abstract
Anthracyclines
are
highly
potent
anti-cancer
drugs,
but
their
clinical
use
is
limited
by
severe
cardiotoxic
side
effects.
The
impact
of
anthracycline-induced
cardiotoxicity
(AIC)
on
left
ventricular
(LV)
microarchitecture
and
diffusion
properties
remains
unknown.
This
study
sought
to
characterize
AIC
cardiovascular
magnetic
resonance
tensor
imaging
(DTI).
Mice
were
treated
with
Doxorubicin
(DOX;
n
=
16)
for
induction
or
saline
as
corresponding
control
(
15).
Cardiac
function
was
assessed
via
echocardiography
at
the
end
period.
Whole
hearts
8
per
group)
scanned
ex
vivo
high-resolution
DTI
7
T.
Results
correlated
histopathology
mass
spectrometry
imaging.
demonstrated
systolic
dysfunction
(LVEF
52
±
3%
vs.
43
6%,
P
<
0.001),
impaired
global
longitudinal
strain
(−19.6
2.0%
−16.6
3.0%,
0.01),
cardiac
atrophy
(LV
index
[mg/mm],
4.3
0.1
3.6
0.2,
0.01).
Regional
sheetlet
angles
significantly
lower
in
AIC,
whereas
helix
angle
relative
helicity
remained
unchanged.
In
fractional
anisotropy
increased
(0.12
0.01
0.14
0.02,
0.05).
DOX-treated
mice
displayed
higher
planar
less
spherical
C
Planar
0.07
0.09
0.01,
0.01;
Spherical
0.89
0.87
yielded
good
discriminatory
power
distinguish
between
without
(c-index
0.91
0.84,
respectively,
both
associated
regional
changes
no
major
abnormalities
LV
microarchitecture.
geometric
shape
altered
AIC.
may
provide
a
new
tool
myocardial
characterization
patients
which
warrants
future
studies
evaluate
its
diagnostic
utility.
Advanced Healthcare Materials,
Journal Year:
2024,
Volume and Issue:
13(29)
Published: June 24, 2024
Critical-sized
segmental
bone
defects
cannot
heal
spontaneously,
leading
to
disability
and
significant
increase
in
mortality.
However,
current
treatments
utilizing
grafts
face
a
variety
of
challenges
from
donor
availability
poor
osseointegration.
Drugs
such
as
growth
factors
cancer
risk
are
very
costly.
Here,
porous
bioceramic
scaffold
that
promotes
regeneration
via
solely
mechanobiological
design
is
reported.
Two
types
scaffolds
with
high
versus
low
pore
curvatures
created
using
high-precision
3D
printing
technology
fabricate
radius
the
100s
micrometers.
While
both
able
support
formation,
high-curvature
pores
induce
higher
ectopic
formation
increased
vessel
invasion.
Scaffolds
also
promote
faster
critical-sized
by
activating
mechanosensitive
pathways.
High-curvature
recruits
skeletal
stem
cells
type
H
vessels
periosteum
marrow
during
early
phase
repair.
have
survival
transplanted
GFP-labeled
(SSCs)
recruit
more
host
SSCs.
Taken
together,
defined
micrometer-scale
demonstrate
approach
for
orthopedic
design.