Abstract
Human adipose-derived stem cells (hASCs) have been shown to differentiate down many lineages including endothelial lineage. We hypothesized that hASCs would more efficiently differentiate toward the endothelial lineage when formed as three-dimensional (3D) spheroids and with the addition of vascular endothelial growth factor (VEGF). Three conditions were tested: uncoated tissue culture polystyrene (TCPS) surfaces that induced a 2D monolayer formation; elastin-like polypeptide (ELP)-collagen composite hydrogel scaffolds that induced encapsulated 3D spheroid culture; and ELP-polyethyleneimine-coated TCPS surfaces that induced 3D spheroid formation in scaffold-free condition. Cells were exposed to endothelial differentiation medium containing no additional VEGF or 20 and 50 ng/mL of VEGF for 7 days and assayed for viability and endothelial differentiation markers. While endothelial differentiation media supported endothelial differentiation of hASCs, our 3D spheroid cultures augmented this differentiation and produced more von Willebrand factor than 2D cultures. Likewise, 3D cultures were able to uptake LDL, whereas the 2D cultures were not. Higher concentrations of VEGF further enhanced differentiation. Establishing angiogenesis is a key factor in regenerative medicine. Future studies aim to elucidate how to produce physiological changes such as neoangiogenesis and sprouting of vessels which may enhance the survival of regenerated tissues.
Highlights
Dental infection, disease, or aging can lead to complex soft and hard tissue defects
Alternative strategies range from alloplastic bone grafting to the application of growth factors to stem cells supported by biodegradable scaffolds for creating elaborate three-dimensional (3D) constructs for tissue regeneration
When the Human adipose-derived stem cells (hASCs) were cultured in various hydrogel conditions for 7 days, a significant number of live cells can be seen (Figure 1A)
Summary
Disease, or aging can lead to complex soft and hard tissue defects. The oral cavity does not readily regenerate the loss of soft and hard tissue, neither does it return to its original form. The lost tissue is replaced by a fibrous network with no restoration in form or function. In order to restore form and function, regeneration must take place by grafting the tissue [1]. Autogenous bone is the gold standard for regeneration of hard tissue defects. Autogenous bone has the critical properties for regeneration such as osteoinductivity, osteogenicity, and osteoconductivity. Alternative strategies range from alloplastic bone grafting to the application of growth factors to stem cells supported by biodegradable scaffolds for creating elaborate three-dimensional (3D) constructs for tissue regeneration
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