Dataset Information

Silk Nanofiber Hydrogels with Tunable Modulus to Regulate Nerve Stem Cell Fate.

ABSTRACT: Reconstruction of damaged nerves remains a significant unmet challenge in clinical medicine. To foster improvements, the control of neural stem cell (NSC) behaviors, including migration, proliferation and differentiation are critical factors to consider. Topographical and mechanical stimulation based on the control of biomaterial features is a promising approach, which are usually studied separately. The synergy between topography and mechanical rigidity could offer new insights into the control of neural cell fate if they could be utilized concurrently in studies. To achieve this need, silk fibroin self-assembled nanofibers with a beta-sheet-enriched structure are formed into hydrogels. Stiffness is tuned using different annealing processes to enable mechanical control without impacting the nanofiber topography. Compared with nonannealed nanofibers, NSCs on methanol annealed nanofibers with stiffness similar to nerve tissues differentiate into neurons with the restraint of glial differentiation, without the influence of specific differentiation biochemical factors. These results demonstrate that combining topographic and mechanical cues provides the control of nerve cell behaviors, with potential for neurogenerative repair strategies.

SUBMITTER: Bai S

PROVIDER: S-EPMC4269376 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Silk Nanofiber Hydrogels with Tunable Modulus to Regulate Nerve Stem Cell Fate.

Bai ShuMeng S Zhang WenMin W Lu Qiang Q Ma QuanHong Q Kaplan David L DL Zhu HeSun H

Journal of materials chemistry. B 20141001 38

Reconstruction of damaged nerves remains a significant unmet challenge in clinical medicine. To foster improvements, the control of neural stem cell (NSC) behaviors, including migration, proliferation and differentiation are critical factors to consider. Topographical and mechanical stimulation based on the control of biomaterial features is a promising approach, which are usually studied separately. The synergy between topography and mechanical rigidity could offer new insights into the control ...[more]

PMID: 25530851

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Project description:Background:Hydrogels with tuneable mechanical properties are an attractive material platform for 3D bioprinting. Thus far, numerous studies have confirmed that the biophysical cues of hydrogels, such as stiffness, are known to have a profound impact on mesenchymal stem cell (MSC) differentiation; however, their differentiation potential within 3D-bioprinted hydrogels is not completely understood. Here, we propose a protocol for the exploration of how the stiffness of alginate-gelatin (Alg-Gel) composite hydrogels (the widely used bioink) affects the differentiation of MSCs in the presence or absence of differentiation inducing factors. Methods:Two types of Alg-Gel composite hydrogels (Young's modulus: 50 kPa vs. 225 kPa) were bioprinted independently of porosity. Then, stiffness-induced biases towards adipogenic and osteogenic differentiation of the embedded MSCs were analysed by co-staining with alkaline phosphatase (ALP) and oil red O. The expression of specific markers at the gene level was detected after a 3-day culture. Results:Confocal microscopy indicated that all tested hydrogels supported MSC growth and viability during the culture period. Higher expression of adipogenic and osteogenic markers (ALP and lipoprotein lipase (LPL)) in stiffer 3D-bioprinted matrices demonstrated a more significant response of MSCs to stiffer hydrogels with respect to differentiation, which was more robust in differentiation-inducing medium. However, the LPL expression in stiffer 3D-bioprinted constructs was reduced at day 3 regardless of the presence of differentiation-inducing factors. Although MSCs embedded in softer hydrogels to some extent proceeded toward adipogenic and osteogenic lineages within a few days, their differentiation seemed to be slower and more limited. Interestingly, the hydrogel itself (without differentiation-inducing factors) exhibited a slight effect on whether MSCs differentiated towards an adipogenic or an osteogenic fate. Considering that the mechano-regulated protein Yes-associated protein (YAP) is involved in MSC fate decisions, we further found that inhibition of YAP significantly downregulated the expression of ALP and LPL in MSCs in stiffer constructs regardless of the induced growth factors present. Conclusions:These results demonstrate that the differentiation of MSCs in 3D-bioprinted matrices is dependent on hydrogel stiffness, which emphasizes the importance of biophysical cues as a determinant of cellular behaviour.

Dataset Information

Silk Nanofiber Hydrogels with Tunable Modulus to Regulate Nerve Stem Cell Fate.

Publications

Silk Nanofiber Hydrogels with Tunable Modulus to Regulate Nerve Stem Cell Fate.

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