Abstract:Human embryonic stem cells (hESC) hold great promise as a cell source for tissue engineering since they possess the ability to differentiate into any cell type within the body. However, much work must still be done to control the differentiation of the hESC to the desired lineage. In this study, we examined the effects of the nano-fibrous (NF) architecture in both two dimensional (2-D) poly(Llactic acid) (PLLA) thin matrices and 3-D PLLA scaffolds in vitro to assess their affect on the osteogenic differentiati… Show more
“…This suggests cooperative enhancement of L1 signaling on subcellular scales of substrate geometry, a phenomenon that deserves further mechanistic analysis. Scaffold topography has been shown to influence and enhance cellular responses, [65][66][67] as the 3-D architecture better emulates in vivo conditions compared to 2-D thin films.…”
This article focuses on elucidating the key presentation features of neurotrophic ligands at polymer interfaces. Different biointerfacial configurations of the human neural cell adhesion molecule L1 were established on two-dimensional films and three-dimensional fibrous scaffolds of synthetic tyrosine-derived polycarbonate polymers and probed for surface concentrations, microscale organization, and effects on cultured primary neurons and neural stem cells. Underlying polymer substrates were modified with varying combinations of protein A and poly-d-lysine to modulate the immobilization and presentation of the Fc fusion fragment of the extracellular domain of L1 (L1-Fc). When presented as an oriented and multimeric configuration from protein A-pretreated polymers, L1-Fc significantly increased neurite outgrowth of rodent spinal cord neurons and cerebellar neurons as early as 24 h compared to the traditional presentation via adsorption onto surfaces treated with poly-d-lysine. Cultures of human neural progenitor cells screened on the L1-Fc/polymer biointerfaces showed significantly enhanced neuronal differentiation and neuritogenesis on all protein A oriented substrates. Notably, the highest degree of βIII-tubulin expression for cells in 3-D fibrous scaffolds were observed in protein A oriented substrates with PDL pretreatment, suggesting combined effects of cell attachment to polycationic charged substrates with subcellular topography along with L1-mediated adhesion mediating neuronal differentiation. Together, these findings highlight the promise of displays of multimeric neural adhesion ligands via biointerfacially engineered substrates to “cooperatively” enhance neuronal phenotypes on polymers of relevance to tissue engineering.
“…This suggests cooperative enhancement of L1 signaling on subcellular scales of substrate geometry, a phenomenon that deserves further mechanistic analysis. Scaffold topography has been shown to influence and enhance cellular responses, [65][66][67] as the 3-D architecture better emulates in vivo conditions compared to 2-D thin films.…”
This article focuses on elucidating the key presentation features of neurotrophic ligands at polymer interfaces. Different biointerfacial configurations of the human neural cell adhesion molecule L1 were established on two-dimensional films and three-dimensional fibrous scaffolds of synthetic tyrosine-derived polycarbonate polymers and probed for surface concentrations, microscale organization, and effects on cultured primary neurons and neural stem cells. Underlying polymer substrates were modified with varying combinations of protein A and poly-d-lysine to modulate the immobilization and presentation of the Fc fusion fragment of the extracellular domain of L1 (L1-Fc). When presented as an oriented and multimeric configuration from protein A-pretreated polymers, L1-Fc significantly increased neurite outgrowth of rodent spinal cord neurons and cerebellar neurons as early as 24 h compared to the traditional presentation via adsorption onto surfaces treated with poly-d-lysine. Cultures of human neural progenitor cells screened on the L1-Fc/polymer biointerfaces showed significantly enhanced neuronal differentiation and neuritogenesis on all protein A oriented substrates. Notably, the highest degree of βIII-tubulin expression for cells in 3-D fibrous scaffolds were observed in protein A oriented substrates with PDL pretreatment, suggesting combined effects of cell attachment to polycationic charged substrates with subcellular topography along with L1-mediated adhesion mediating neuronal differentiation. Together, these findings highlight the promise of displays of multimeric neural adhesion ligands via biointerfacially engineered substrates to “cooperatively” enhance neuronal phenotypes on polymers of relevance to tissue engineering.
“…Setting the joint site as an example, this site exhibits less host responses to implant, because more body fluids and faster fluid exchange are helpful for removing the acidic degradation products effectively. In fact, many positive results of tissue repairing using PLA or PLGA porous scaffolds have been reported [27][28][29][30]48,49]. Our group has recently revealed that the body fluid exchanged faster than we initially supposed, even at the subcutaneous site, for a block copolymer hydrogel composed of PLGA-PEG-PLGA with initial pH 4 became neutral just ten hours after a subcutaneous injection into SD rats [50].…”
Section: Is There Any Significant Difference Of Cytotoxicity Between mentioning
confidence: 93%
“…That is why polyesters have been studied for a long time [14][15][16][17][18][19][20]. A lot of efforts have been done on improving the biocompatibility of the polyester porous scaffolds [21][22][23][24][25][26][27][28], and examinations of their medical applications [27][28][29][30][31][32][33].…”
Poly(lactic acid) (PLA) and other aliphatic polyesters containing the unit of lactic acid are very popular biodegradable materials. While the degradation products, lactic acids, have been worried to bring with negative influence on biocompatibility, the focused experimental studies are less reported. This study is aimed at an in vitro examination of cytotoxicity of both L-lactic acid and D,L-lactic acid. Mesenchymal stem cells (MSCs) derived from rat bone marrow are employed to test the cytotoxicity of the lactic acids. Considering that the addition of lactic acids not only introduces lactate groups but also alters medium pH and ion strength, these three candidate effects are examined in a decoupled way by setting different comparison groups. The results confirm that the change of medium pH is the predominant factor. It has also been found that D-lactate is more cytotoxic than L-lactate at high concentrations. Yet, either L-or D,L-lactic acids seem acceptable in most of medical applications, because the cytotoxicity is significant only when the concentrations are as high as 20 mmol/L for both of them.
“…Similarly, another study demonstrated that mouse ES cells can be induced to differentiate into specific neural lineages, that is, neurons, oligodendrocytes, and astrocytes, when seeded onto electrospun fibrous scaffolds (Xie et al, 2009). In another study, the nanofibrous architecture of the substrate enhanced the osteogenic differentiation of human ES cells compared to a more traditional scaffolding architecture (Smith et al, 2010). Thus, surface engineering approaches that alter the topographical structure of the substrate surface can be used to modulate ES cell behavior and fate.…”
Section: Control Of Cells By Geometric Modificationmentioning
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