35 research outputs found
Fractal Structure of Hydrogels Modulates Stem Cell Behavior
Fractal
dimension (<i>D</i><sub>f</sub>) is an index
to describe the irregular continuous structure by quantifying the
complexity. The concept of fractals has been employed to describe
the complicated structure of polymer gel and human tissue. This study
examined the effect of <i>D</i><sub>f</sub> on cell proliferation
and stem cell differentiation in six polymer hydrogels with <i>D</i><sub>f</sub> ranging from 1.2 to 2.1. It was observed that
fibroblasts and mesenchymal stem cells (MSCs) grew faster in hydrogels
with higher <i>D</i><sub>f</sub>. Moreover, hydrogels with
a fractal structure of <i>D</i><sub>f</sub> ≤ 1.4,
≥1.6, and ≥1.8 promoted the neural, osteogenic, and
chondrogenic differentiation of MSCs, respectively. The fractal structure
of gel can modulate cell proliferation and fate, which provides an
insight into designing the appropriate fractal and molecular structure
of polymer hydrogel for biomedical applications
Biodegradable Water-Based Polyurethane Shape Memory Elastomers for Bone Tissue Engineering
Shape
memory polymers (SMPs) are polymers with the shape memory
effect. The biodegradable SMPs are candidate materials for making
biomedical devices and scaffolds for tissue engineering. Superparamagnetic
iron oxide nanoparticles (SPIO NPs) have recently been reported to
promote the osteogenic induction of human mesenchymal stem cells (hMSCs).
In this study, we synthesized water-based biodegradable shape memory
polyurethane (PU) as the main component of the 3D printing ink for
fabricating bone scaffolds. The 3D printing ink contained 500 ppm
of SPIO NPs to promote osteogenic induction and shape fixity, and
it also contained polyethylene oxide (PEO) or gelatin for the improvement
of printability. Scaffolds were printed by the microextrusion-based
low-temperature fuse deposition manufacturing (LFDM) platform. Both
PU–PEO and PU–gelatin ink showed excellent printability.
Shape memory properties were evaluated in 50 °C air and 37 °C
water. PU–PEO scaffolds showed better shape fixity and recovery
than PU–gelatin scaffolds, while the shape memory properties
in water were better than those in air. hMSCs were seeded for evaluation
of bone regeneration. The proliferation of the hMSCs in PU/gelatin
and PU/gelatin/SPIO scaffolds was greater than that in PU/PEO and
PU/PEO/SPIO scaffolds, confirming the better compatibility of gelatin
vs PEO as the viscosity enhancer of the ink. The gradual release of
SPIO NPs from the scaffolds promoted the osteogenesis of seeded hMSCs.
With SPIO in the scaffolds, the osteogenesis increased 2.7 times for
PU/PEO and 1.5 times for PU/gelatin scaffolds based on the collagen
content. Meanwhile, SPIO release from PU/PEO/SPIO scaffolds was faster
than that from PU/gelatin/SPIO scaffolds at 14 days, consistent with
the better osteogenesis observed in PU/PEO/SPIO scaffolds. We concluded
that 3D printed PU scaffolds with shape memory properties, biodegradability,
and osteogenic effect may be employed to the minimally invasive surgical
procedures as customized-bone substitutes for bone tissue engineering
Modulation of Macrophage Phenotype by Biodegradable Polyurethane Nanoparticles: Possible Relation between Macrophage Polarization and Immune Response of Nanoparticles
Nanomaterials with
surface functionalized by different chemical groups can either provoke
or attenuate the immune responses of the nanomaterials, which is critical
to their biomedical efficacies. In this study, we demonstrate that
synthetic waterborne polyurethane nanoparticles (PU NPs) can inhibit
the macrophage polarization toward the M1 phenotype but not M2 phenotype.
The surface-functionalized PU NPs decrease the secretion levels of
proinflammatory cytokines (TNF-α and IL-1β) for M1 macrophages.
Specifically, PU NPs with carboxyl groups on the surface exhibit a
greater extent of inhibition on M1 polarization than those with amine
groups. These water-suspended PU NPs reduce the nuclear factor-κB
(NF-κB) activation and suppress the subsequent NLR family pyrin
domain containing 3 (NLRP3) inflammasome signals. Furthermore, the
dried PU films assembled from PU NPs have a similar effect on macrophage
polarization and present a smaller shifting foreign body reaction
(FBR) in vivo than the conventional polyÂ(l-lactic acid).
Taken together, the biodegradable waterborne PU NPs demonstrate surface-dependent
immunosuppressive properties and macrophage polarization effects.
The findings suggest potential therapeutic applications of PU NPs
in anti-inflammation and macrophage-related disorders and propose
a mechanism for the low FBR observed for biodegradable PU materials
Preparation, Characterization, and Mechanism for Biodegradable and Biocompatible Polyurethane Shape Memory Elastomers
Thermally induced
shape memory is an attractive feature of certain
functional materials. Among the shape memory polymers, shape memory
elastomers (SMEs) especially those with biodegradability have great
potential in the biomedical field. In this study, we prepared waterborne
biodegradable polyurethane SME based on polyÂ(ε-caprolactone)
(PCL) oligodiol and polyÂ(l-lactic acid) (PLLA) oligodiol
as the mixed soft segments. The ratio of the soft segments in polyurethanes
was optimized for shape memory behavior. The thermally induced shape
memory mechanism of the series of polyurethanes was clarified using
differential scanning calorimeter (DSC), X-ray diffraction (XRD),
and small-angle X-ray scattering (SAXS). In particular, the in situ
SAXS measurements combined with shape deformation processes were employed
to examine the stretch-induced (oriented) crystalline structure of
the polyurethanes and to elucidate the unique mechanism for shape
memory properties. The polyurethane with optimized PLLA crystalline
segments showed a diamond-shape two-dimensional SAXS pattern after
being stretched, which gave rise to better shape fixing and shape
recovery. The shape memory behavior was further tested in 37 °C
water. The biodegradable polyurethane comprising 38 wt % PCL segments
and 25 wt % PLLA segments and synthesized at a relatively lower temperature
by the waterborne procedure showed ∼100% shape recovery in
37 °C water. The biodegradable polyurethane SME also demonstrated
good endothelial cell viability as well as low platelet adhesion/activation.
We conclude that the waterborne biodegradable polyurethane SME possesses
a unique thermally induced shape memory mechanism and may have potential
applications in making shape memory biodegradable stents or scaffolds
Evaluation of the Antibacterial Activity and Biocompatibility for Silver Nanoparticles Immobilized on Nano Silicate Platelets
Silver nanoparticles
(AgNPs) are known for their bactericidal abilities. The antibacterial
potency is dependent on the particle size and dispersion status. In
this study, we synthesized AgNP/NSP nanohybrids in two different weight
ratios (1/99 and 8/92) using the fully exfoliated clay, i.e., nanosilicate
platelets (NSP), as a dispersing agent and carrier for AgNPs. Due
to the size of NSP, the immobilized AgNPs do not enter cells readily,
which may lower the risk associated with the cellular uptake of AgNPs.
The biocompatibility, immunological response, and antimicrobial activities
of AgNP/NSP hybrids were evaluated. The results revealed that AgNP/NSP
hybrids elicited merely mild inflammatory response and retained the
outstanding antibacterial activity. The hybrids were further embedded
in polyÂ(ether)Âurethane (PEU) to increase the biocompatibility. At
the same silver content (20 ppm), the PEU-AgNP/NSP nanocomposites
were nontoxic to mouse skin fibroblasts, while simultaneously exhibiting
nearly complete bacterial growth reduction (99.9%). PEU containing
the same amount of free AgNPs did not display such an effect. Our
results verify the better biosafety of the AgNPs/NSP hybrids and their
polymer nanocomposites for further clinical use
Interaction of vascular endothelial cells with hydrophilic fullerene nanoarchitectured structures in 2D and 3D environments
The interaction between diverse nanoarchitectured fullerenes and cells is crucial for biomedical applications. Here, we detailed the preparation of hydrophilic self-assembled fullerenes by the liquid-liquid interfacial precipitation (LLIP) method and hydrophilic coating of the materials as a possible vascularization strategy. The interactions of vascular endothelial cells (ECs) with hydrophilic fullerene nanotubes (FNT-P) and hydrophilic fullerene nanowhiskers (FNW-P) were investigated. The average length and diameter of FNT-P were 16 ± 2 μm and 3.4 ± 0.4 μm (i.e. aspect ratios of 4.6), respectively. The average length and diameter of FNW-P were 65 ± 8 μm and 1.2 ± 0.2 μm (i.e. aspect ratios of 53.9), respectively. For two-dimensional (2D) culture after 7 days, the ECs remained viable and proliferated up to ~ 420% and ~ 400% with FNT-P and FNW-P of 50 μg/mL, respectively. Furthermore, an optimized chitosan-based self-healing hydrogel with a modulus of ~400 Pa was developed and used to incorporate self-assembled fullerenes as in vitro three-dimensional (3D) platforms to investigate the impact of FNT-P and FNW-P on ECs within a 3D environment. The addition of FNW-P or FNT-P (50 μg/mL) in the hydrogel system led to proliferation rates of ECs up to ~323% and ~280%, respectively, after 7 days of culture. The ECs in FNW-P hydrogel displayed an elongated shape with aligned morphology, while those in FNT-P hydrogel exhibited a rounded and clustered distribution. Vascular-related gene expressions of ECs were significantly upregulated through interactions with these fullerenes. Thus, the combined use of different nanoarchitectured self-assembled fullerenes and self-healing hydrogels may offer environmental cues influencing EC development in a 3D biomimetic microenvironment, holding promise for advancing vascularization strategy in tissue engineering. Self-assembled fullerenes with large aspect ratios modulate the morphology and gene expression of endothelial cells within a soft biomimetic 3D microenvironment, representing a promising new vascularization strategy in tissue engineering.</p
Synthesis of Thermoresponsive Amphiphilic Polyurethane Gel as a New Cell Printing Material near Body Temperature
Waterborne polyurethane (PU) based
on polyÂ(ε-caprolactone)
(PCL) diol and a second oligodiol containing amphiphilic blocks was
synthesized in this study. The microstructure was characterized by
dynamic light scattering (DLS), small-angle X-ray scattering (SAXS),
and rheological measurement of the PU dispersion. The surface hydrophilicity
measurement, infrared spectroscopy, wide-angle X-ray diffraction,
mechanical and thermal analyses were conducted in solid state. It
was observed that the presence of a small amount of amphiphilic blocks
in the soft segment resulted in significant changes in microstructure.
When 90 mol % PCL diol and 10 mol % amphiphilic blocks of polyÂ(l-lactide)–polyÂ(ethylene oxide) (PLLA–PEO) diol
were used as the soft segment, the synthesized PU had a water contact
angle of ∼24° and degree of crystallinity of ∼14%.
The dispersion had a low viscosity below room temperature. As the
temperature was raised to body temperature (37 °C), the dispersion
rapidly (∼170 s) underwent sol–gel transition with excellent
gel modulus (<i>G</i>′ ≈ 6.5 kPa) in 20 min.
PU dispersions with a solid content of 25–30% could be easily
mixed with cells in sol state, extruded by a 3D printer, and deposited
layer by layer as a gel. Cells remained alive and proliferating in
the printed hydrogel scaffold. We expect that the development of novel
thermoresponsive PU system can be used as smart injectable hydrogel
and applied as a new type of bio-3D printing ink
Synthesis of Thermoresponsive Amphiphilic Polyurethane Gel as a New Cell Printing Material near Body Temperature
Waterborne polyurethane (PU) based
on polyÂ(ε-caprolactone)
(PCL) diol and a second oligodiol containing amphiphilic blocks was
synthesized in this study. The microstructure was characterized by
dynamic light scattering (DLS), small-angle X-ray scattering (SAXS),
and rheological measurement of the PU dispersion. The surface hydrophilicity
measurement, infrared spectroscopy, wide-angle X-ray diffraction,
mechanical and thermal analyses were conducted in solid state. It
was observed that the presence of a small amount of amphiphilic blocks
in the soft segment resulted in significant changes in microstructure.
When 90 mol % PCL diol and 10 mol % amphiphilic blocks of polyÂ(l-lactide)–polyÂ(ethylene oxide) (PLLA–PEO) diol
were used as the soft segment, the synthesized PU had a water contact
angle of ∼24° and degree of crystallinity of ∼14%.
The dispersion had a low viscosity below room temperature. As the
temperature was raised to body temperature (37 °C), the dispersion
rapidly (∼170 s) underwent sol–gel transition with excellent
gel modulus (<i>G</i>′ ≈ 6.5 kPa) in 20 min.
PU dispersions with a solid content of 25–30% could be easily
mixed with cells in sol state, extruded by a 3D printer, and deposited
layer by layer as a gel. Cells remained alive and proliferating in
the printed hydrogel scaffold. We expect that the development of novel
thermoresponsive PU system can be used as smart injectable hydrogel
and applied as a new type of bio-3D printing ink
Biocompatibility and Favorable Response of Mesenchymal Stem Cells on Fibronectin-Gold Nanocomposites
<div><p>A simple surface modification method, comprising of a thin coating with gold nanoparticles (AuNPs) and fibronectin (FN), was developed to improve the biocompatibility required for cardiovascular devices. The nanocomposites from FN and AuNPs (FN-Au) were characterized by the atomic force microscopy (AFM), UV-Vis spectrophotometry (UV-Vis), and Fourier transform infrared spectroscopy (FTIR). The biocompatibility of the nanocomposites was evaluated by the response of monocytes and platelets to the material surface in vitro. FN-Au coated surfaces demonstrated low monocyte activation and platelet activation. The behavior of human umbilical cord-derived mesenchymal stem cells (MSCs) on FN-Au was further investigated. MSCs on FN-Au nanocomposites particularly that containing 43.5 ppm of AuNPs (FN-Au 43.5 ppm) showed cell proliferation, low ROS generation, as well as increases in the protein expression levels of matrix metalloproteinase-9 (MMP-9) and endothelial nitric oxide synthase (eNOS), which may account for the enhanced MSC migration on the nanocomposites. These results suggest that the FN-Au nanocomposite thin film coating may serve as a potential and simple solution for the surface modification of blood-contacting devices such as vascular grafts.</p></div
Water-Soluble Fullerene Derivatives as Brain Medicine: Surface Chemistry Determines If They Are Neuroprotective and Antitumor
Delivering drugs
to the central nervous system (CNS) is a major challenge in treating
CNS-related diseases. Nanoparticles that can cross blood–brain
barrier (BBB) are potential tools. In this study, water-soluble C<sub>60</sub> fullerene derivatives with different types of linkages between
the fullerene cage and the solubilizing addend were synthesized (compounds <b>1</b>–<b>3</b>: C–C bonds, compounds <b>4</b>–<b>5</b>: C–S bonds, compound <b>6</b>: C–P bonds, and compounds <b>7</b>–<b>9</b>: C–N bonds). Fullerene derivatives <b>1</b>–<b>6</b> were observed to induce neural stem cell (NSC)
proliferation <i>in vitro</i> and rescue the function of
injured CNS in zebrafish. Fullerene derivatives <b>7</b>–<b>9</b> were found to inhibit glioblastoma cell proliferation <i>in vitro</i> and reduce glioblastoma formation in zebrafish.
These effects were correlated with the cell metabolic changes. Particularly,
compound <b>3</b> bearing residues of phenylbutiryc acids significantly
promoted NSC proliferation and neural repair without causing tumor
growth. Meanwhile, compound <b>7</b> with phenylalanine appendages
significantly inhibited glioblastoma growth without retarding the
neural repair. We conclude that the surface functional group determines
the properties as well as the interactions of C<sub>60</sub> with
NSCs and glioma cells, producing either a neuroprotective or antitumor
effect for possible treatment of CNS-related diseases