Materials Direct Adipose Stem Cells Fate And Their Bioactivity In Angiogenesis

In tissue engineering and regenerative medicine, biomaterials are rapidly beingdeveloped as powerful artificial stem cell niches to display and deliverstem-cell-regulatory signals in a precise and near-physiological fashion. Advances inunderstanding of stem cell interactions with biomaterials are leading to the developmentof new materials as stem cell delivery vehicle in tissue regeneration, and also couldprovide approaches to understand stem cell behavior in vivo. Meanwhile, the keychallenge in materials-based stem cell therapy is the establishment of an efficientvascularization for stem cells guaranteeing long-term survival and function.Consequently, the focus of tissue engineering has change toward the understanding ofthe interaction between biomaterials and stem cells, and the angiogenesis ability of thebiomaterials.Human adipose stem cells (hASCs) serves as the adult stem cell model to study theadult stem cell fate controlled with bioactive materials in this study. Self-assembledmonolayers of alkanethiolates on gold were introduced as surface chemistry model todeconstruct stem cell niche to identify and assess the effects of individual nichechemistry signal on hASCs fate. Isotropic functionalized RADA16-I and anisotropicaligned fibrin nanofiber hydrogels prepared via self-assembling and electrospinningrespectively are aimed to reconstruct and realize the complexity of the natural niche.These two kinds of biomaterials compose of hydrated and crosslinked network, whichare highly mimicking the natural stem cell niches physically.The surface chemistry signals, including OH, COOH, NH2, Phenyl, SH, Br andCH3, were used to direct hASCs fate in without differentiation medium. Chemicalgroups exhibited regulation effects on hASCs behaviors including initial adhesion,long-term morphology, proliferation and differentiation. Therefore, factors responsiblefor hASCs should be defined in molecular terms of chemical groups.Functionalized self-assembling peptide nanofiber hydrogels, obtained by directingextension of RADA16-I with ECM proteins-mimicking peptides, were studied as in situ3D artificial microenvironment for hASCs. Functional peptide motifs could regulatehASCs behaviors including3D migration, in situ3D proliferation and growth factorssecretion. These studies indicate that functionalized RADA16-I peptide hydrogels could be a promising3D scaffold to deliver bioactive signals for stem cells in tissueengineering.The angiogenesis ability of functionalized peptide hydrogels were evaluated within vitro3D micro-beads assay and in vivo CAM assay. Functionalized peptide hydrogelsprovided satisfactory microenvironments for endothelial cells migration, and increasedthe responsivity of endothelial cells to VEGF for sprouting. CAM assay indicated thatthese peptide hydrogels had satisfactory in vivo biocompatibility and angiogenesisability.Cell/biomaterials in situ3D co-culture was firstly introduced with electrospinning.The strings of aligned fibrin hydrogel could be used to direct the orientation of hASCsvia “contact guidance”. The in vitro angiogenesis ability of aligned fibrin hydrogels wasassessed via co-culture with endothelia colony forming cells (ECFCs). Aligned fibrinhydrogels with VEGF could induce ECFCs differentiation toward mature endothelialcells and secrete ECM proteins like collagen I, collagen IV, laminin.