Microscopic local stiffening in a supramolecular hydrogel network expedites stem cell mechanosensing in 3D and bone regeneration

Yuan, Weihao; Wang, Shuangfeng; Fang, Chao; Yang, Yongkang; Xia, Xin; Yang, Boguang; Lin, Yuan; Li, Gang; Bian, Liming

doi:10.1039/d1mh00244a

Cited by 67 publications

(44 citation statements)

References 61 publications

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“…In contrast, hMSCs without osteogenic medium showed significantly low levels of ALP and RUNX2 on MeHA hydrogel, indicating that undifferentiated hMSCs expressed very low basal expression levels of these two markers (Figure S6). These results are consistent with the previous findings that the activation of the mechanotransduction pathway (YAP) is positively associated with the osteogenic differentiation of stem cells [31,32]. More importantly, our findings illustrate that the implementation of the nanostructure re-arranges the spatial distribution of cell-adhesive peptides to reinforce stem cell adhesion and differentiation on soft matrix.…”

Section: Local Rgd Clustering Supports Stem Cell Osteogenic Differentiation On Soft Matrixsupporting

confidence: 93%

Integrating Soft Hydrogel with Nanostructures Reinforces Stem Cell Adhesion and Differentiation

Yin

Yang

2022

J. Compos. Sci.

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Biophysical cues can regulate stem cell behaviours and have been considered as critical parameters of synthetic biomaterials for tissue engineering. In particular, hydrogels have been utilized as promising biomimetic and biocompatible materials to emulate the microenvironment. Therefore, well-defined mechanical properties of a hydrogel are important to direct desirable phenotypes of cells. Yet, limited research pays attention to engineering soft hydrogel with improved cell adhesive property, which is crucial for stem cell differentiation. Herein, we introduce silica nanoparticles (SiO2 NPs) onto the surface of methacrylated hyaluronic (MeHA) hydrogel to manipulate the presentation of cell adhesive ligands (RGD) clusters, while remaining similar bulk mechanical properties (2.79 ± 0.31 kPa) to that of MeHA hydrogel (3.08 ± 0.68 kPa). RGD peptides are either randomly decorated in the MeHA hydrogel network or on the immobilized SiO2 NPs (forming MeHA–SiO2). Our results showed that human mesenchymal stem cells exhibited a ~1.3-fold increase in the percentage of initial cell attachment, a ~2-fold increase in cell spreading area, and enhanced expressions of early-stage osteogenic markers (RUNX2 and alkaline phosphatase) for cells undergoing osteogenic differentiation with the osteogenic medium on MeHA–SiO2 hydrogel, compared to those cultured on MeHA hydrogel. Importantly, the cells cultivated on MeHA–SiO2 expressed a ~5-fold increase in nuclear localization ratio of the yes-associated protein, which is known to be mechanosensory in stem cells, compared to the cells cultured on MeHA hydrogel, thereby promoting osteogenic differentiation of stem cells. These findings demonstrate the potential use of nanomaterials into a soft polymeric matrix for enhanced cell adhesion and provide valuable guidance for the rational design of biomaterials for implantation.

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Section: Local Rgd Clustering Supports Stem Cell Osteogenic Differentiation On Soft Matrixsupporting

confidence: 93%

Integrating Soft Hydrogel with Nanostructures Reinforces Stem Cell Adhesion and Differentiation

Yin

Yang

2022

J. Compos. Sci.

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“…137 A following work from the same group also demonstrated that the mechanosensing and subsequent osteogenic differentiation of encapsulated MSCs could be further enhanced by chemical incorporation of acryloyl nanoparticles into the dynamic hydrogels, which created regionally stiff network structures. 398 Similarity, Wei et al described the assembly of a two-component host−guest hydrogel with Ada-grafted HA and in situ photopolymerized acryloyl-β-CD. These hydrogels exhibited reinforced mechanical properties, retained the desirable dynamic features, enabled chondrogenesis of the encapsulated human MSCs with greater collagen deposition, and promoted in vivo cartilage regeneration compared to covalently cross-linked MeHA hydrogels (Figure 24a).…”

Section: Stem Cells and Regenerative Medicinementioning

confidence: 99%

Structurally Dynamic Hydrogels for Biomedical Applications: Pursuing a Fine Balance between Macroscopic Stability and Microscopic Dynamics

et al. 2021

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Owing to their unique chemical and physical properties, hydrogels are attracting increasing attention in both basic and translational biomedical studies. Although the classical hydrogels with static networks have been widely reported for decades, a growing number of recent studies have shown that structurally dynamic hydrogels can better mimic the dynamics and functions of natural extracellular matrix (ECM) in soft tissues. These synthetic materials with defined compositions can recapitulate key chemical and biophysical properties of living tissues, providing an important means to understanding the mechanisms by which cells sense and remodel their surrounding microenvironments. This review begins with the overall expectation and design principles of dynamic hydrogels. We then highlight recent progress in the fabrication strategies of dynamic hydrogels including both degradation-dependent and degradation-independent approaches, followed by their unique properties and use in biomedical applications such as regenerative medicine, drug delivery, and 3D culture. Finally, challenges and emerging trends in the development and application of dynamic hydrogels are discussed.

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“…Yuan and colleagues reported a dynamic supramolecular hydrogel realizing the stiffening of a regional network with the addition of bioinert silica nanoparticles. 237 The silica nanoparticles were modified with methacryloyl groups (AcNPs) to photocrosslink with acryloyl β-cyclodextrin (Ac-β-CD) in gelatin host–guest hydrogels (GHG hydrogels) realizing the regional stiffen of hydrogel network. 237 Recently, microfluidic technology has been a conventional method for fabricating hydrogels with heterogeneous mechanical properties.…”

Section: The Development and Potential Applications Of 3d Msc Culture...mentioning

confidence: 99%

“…237 The silica nanoparticles were modified with methacryloyl groups (AcNPs) to photocrosslink with acryloyl β-cyclodextrin (Ac-β-CD) in gelatin host–guest hydrogels (GHG hydrogels) realizing the regional stiffen of hydrogel network. 237 Recently, microfluidic technology has been a conventional method for fabricating hydrogels with heterogeneous mechanical properties. The degradation of hydrogels will change the mechanical properties of hydrogels which have been made use of by the designers to manufacture dynamic 3D MSC culture systems.…”

Section: The Development and Potential Applications Of 3d Msc Culture...mentioning

confidence: 99%

Recent advances in 3D hydrogel culture systems for mesenchymal stem cell-based therapy and cell behavior regulation

Xia

Cai

2022

J. Mater. Chem. B

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Microscopic local stiffening in a supramolecular hydrogel network expedites stem cell mechanosensing in 3D and bone regeneration

Abstract: A cell-adaptable hydrogel containing microscopically local stiffening structures shows a heterogeneous and hierarchical hydrogel network topology, thereby facilitating the 3D stellate spreading of stem cells and promoting the bone regeneration.

Cited by 67 publications

References 61 publications

Integrating Soft Hydrogel with Nanostructures Reinforces Stem Cell Adhesion and Differentiation

Integrating Soft Hydrogel with Nanostructures Reinforces Stem Cell Adhesion and Differentiation

Structurally Dynamic Hydrogels for Biomedical Applications: Pursuing a Fine Balance between Macroscopic Stability and Microscopic Dynamics

Recent advances in 3D hydrogel culture systems for mesenchymal stem cell-based therapy and cell behavior regulation

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