It is well known that stem cells reside within tissue engineering functional microenvironments that physically localize them and direct their stem cell fate. Recent efforts in the development of more complex and engineered scaffold technologies, together with new understanding of stem cell behavior in vitro, have provided a new impetus to study regulation and directing stem cell fate. A variety of tissue engineering technologies have been developed to regulate the fate of stem cells. Traditional methods to change the fate of stem cells are adding growth factors or some signaling pathways. In recent years, many studies have revealed that the geometrical microenvironment played an essential role in regulating the fate of stem cells, and the physical factors of scaffolds including mechanical properties, pore sizes, porosity, surface stiffness, three-dimensional structures, and mechanical stimulation may affect the fate of stem cells. Chemical factors such as cell-adhesive ligands and exogenous growth factors would also regulate the fate of stem cells. Understanding how these physical and chemical cues affect the fate of stem cells is essential for building more complex and controlled scaffolds for directing stem cell fate.
Biofabrication of personalized titanium scaffold mimicking that of the osteocyte microenvironment is challenging due to its complex geometrical cues. The effect of scaffolds geometrical cues and implantation sites on osteogenesis is still not clear. In this study, personalized titanium scaffolds with homogeneous diamond-like structures mimicking that of the osteocyte microenvironment were precisely designed and fabricated by selected laser melting method. The effects of different geometric cues, including porosity, pore sizes and interconnection properties, on cellular behavior were investigated. Biomimetic mechanical properties of porous titanium alloy scaffold were predesigned and simulated by finite element analysis. In vitro experiment revealed that homogeneous diamond-like structures mimicking that of the osteocyte microenvironment triggered osteocyte adhesion and migration behavior. Typical implantation sites, including rabbit femur, beagle femur, and beagle skull, were used to study the implantation sites effects on bone regeneration. In vivo experimental results indicated that different implantation sites showed significant differences. This study helps to understand the scaffolds geometrical microenvironment and implantation sites effects on osteogenesis mechanism. And it is beneficial to the development of bone implants with better bone regeneration ability.
Large-segment bone defect caused by trauma or tumor is one of the most challenging problems in orthopedic clinics. Biomimetic materials for bone tissue engineering have developed dramatically in the past few decades. The organic combination of biomimetic materials and stem cells offers new strategies for tissue repair, and the fate of stem cells is closely related to their extracellular matrix (ECM) properties. In this study, a photocrosslinked biomimetic methacrylated gelatin (Bio-GelMA) hydrogel scaffold was prepared to simulate the physical structure and chemical composition of the natural bone extracellular matrix, providing a three-dimensional (3D) template and extracellular matrix microenvironment. Bone marrow mesenchymal stem cells (BMSCS) were encapsulated in Bio-GelMA scaffolds to examine the therapeutic effects of ECM-loaded cells in a 3D environment simulated for segmental bone defects. In vitro results showed that Bio-GelMA had good biocompatibility and sufficient mechanical properties (14.22kPa). A rat segmental bone defect model was constructed in vivo. The GelMA-BMSC suspension was added into the PDMS mold with the size of the bone defect and photocured as a scaffold. BMSC-loaded Bio-GelMA resulted in maximum and robust new bone formation compared with hydrogels alone and stem cell group. In conclusion, the bio-GelMA scaffold can be used as a cell carrier of BMSC to promote the repair of segmental bone defects and has great potential in future clinical applications.
Scaffolds
with a biomimetic hierarchy micro/nanoscale pores play
an important role in bone tissue regeneration. In this study, multilevel
porous calcium phosphate (CaP) bioceramic orthopedic implants were
constructed to mimic the micro/nanostructural hierarchy in natural
wood. The biomimetic hierarchical porous scaffolds were fabricated
by combining three-dimensional (3D) printing technology and hydrothermal
treatment. The first-level macropores (∼100–600 μm)
for promoting bone tissue ingrowth were precisely designed using a
set of 3D printing parameters. The second-level micro/nanoscale pores
(∼100–10,000 nm) in the scaffolds were obtained by hydrothermal
treatment to promote nutrient/metabolite transportation. Micro- and
nanoscale-sized pores in the scaffolds were recognized as in situ formation of whiskers, where the shape, diameter,
and length of whiskers were modulated by adjusting the components
of calcium phosphate ceramics and hydrothermal treatment parameters.
These biomimetic natural wood-like hierarchical structured scaffolds
demonstrated unique physical and biological properties. Hydrophilicity
and the protein adsorption rate were characterized in these scaffolds. In vitro studies have identified micro/nanowhisker coating
as potent modulators of cellular behavior through the onset of focal
adhesion formation. In addition, histological results indicate that
biomimetic scaffolds with porous natural wood hierarchical pores exhibited
good osteoinductive activity. In conclusion, these findings combined
suggested that micro/nanowhisker coating is a critical factor to modulate
cellular behavior and osteoinductive activity.
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