Two-dimensional (2D) materials have
emerged as a new promising
research topic for tissue engineering because of their ability to
alter the surface properties of tissue scaffolds and thus improve
their biocompatibility and cell affinity. Multiple 2D materials, such
as graphene and graphene oxide (GO), have been widely reported to
enhance cell adhesion and proliferation. Recently, a newly emerged
black phosphorus (BP) 2D material has attracted attention in biomedical
applications because of its unique mechanical and electrochemical
characteristics. In this study, we investigated the synergistic effect
of these two types of 2D materials on cell osteogenesis for bone tissue
engineering. BP was first wrapped in negatively charged GO nanosheets,
which were then adsorbed together onto positively charged poly(propylene
fumarate) three-dimensional (3D) scaffolds. The increased surface
area provided by GO nanosheets would enhance cell attachment at the
initial stage. In addition, slow oxidation of BP nanosheets wrapped
within GO layers would generate a continuous release of phosphate,
an important osteoblast differentiation facilitator designed to stimulate
cell osteogenesis toward the new bone formation. Through the use of
3D confocal imaging, unique interactions between cells and BP nanosheets
were observed, including a stretched cell shape and the development
of filaments around the BP nanosheets, along with increased cell proliferation
when compared with scaffolds incorporating only one of the 2D materials.
Furthermore, the biomineralization of 3D scaffolds, as well as cellular
osteogenic markers, was all measured and improved on scaffolds with
both BP and GO nanosheets. All these results indicate that the incorporation
of 2D BP and GO materials could effectively and synergistically stimulate
cell proliferation and osteogenesis on 3D tissue scaffolds.
Injectable hydrogels
have unique advantages for the repair of irregular
tissue defects. In this study, we report a novel injectable carbon
nanotube (CNT) and black phosphorus (BP) gel with enhanced mechanical
strength, electrical conductivity, and continuous phosphate ion release
for tissue engineering. The gel utilized biodegradable oligo(poly(ethylene
glycol) fumarate) (OPF) polymer as the cross-linking matrix, with
the addition of cross-linkable CNT-poly(ethylene glycol)-acrylate
(CNTpega) to grant mechanical support and electric conductivity. Two-dimensional
(2D) black phosphorus nanosheets were also infused to aid in tissue
regeneration through the steady release of phosphate that results
from environmental oxidation of phosphorus in situ. This newly developed
BP-CNTpega-gel was found to enhance the adhesion, proliferation, and
osteogenic differentiation of MC3T3 preosteoblast cells. With electric
stimulation, the osteogenesis of preosteoblast cells was further enhanced
with elevated expression of several key osteogenic pathway genes.
As monitored with X-ray imaging, the BP-CNTpega-gel demonstrated excellent
in situ gelation and cross-linking to fill femur defects, vertebral
body cavities, and posterolateral spinal fusion sites in the rabbit.
Together, these results indicate that this newly developed injectable
BP-CNTpega-gel owns promising potential for future bone and broad
types of tissue engineering applications.
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