Mechanobiological Approaches for Stimulating Chondrogenesis of Stem Cells

Volz, Mallory; Wyse-Sookoo, Kimberley R; Travascio, Francesco; Huang, Chun Yuh; Best, Thomas M.

doi:10.1089/scd.2022.0049

Cited by 9 publications

(11 citation statements)

References 153 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, Li et al applied compression and shear force on fibrin-polyurethane composite scaffolds cultured with human MSCs and observed increased gene expressions for Sox9, COL2A1, and ACAN and increased expression levels of the major compositions of the cartilage extracellular matrix (ECM), i.e., type II collagen, and glycosaminoglycan (GAG) . These studies demonstrated that the application of MS can promote the chondrogenic differentiation of stem cells. − The 3D scaffold design is also critical for successful cartilage tissue engineering. The scaffold should provide mechanical support while also facilitating nutrient exchange and waste removal.…”

Section: Introductionmentioning

confidence: 99%

Biophysical Electrical and Mechanical Stimulations for Promoting Chondrogenesis of Stem Cells on PEDOT:PSS Conductive Polymer Scaffolds

Liu

Lin

et al. 2023

Biomacromolecules

View full text Add to dashboard Cite

The investigation of the effects of electrical and mechanical stimulations on chondrogenesis in tissue engineering scaffolds is essential for realizing successful cartilage repair and regeneration. The aim of articular cartilage tissue engineering is to enhance the function of damaged or diseased articular cartilage, which has limited regenerative capacity. Studies have shown that electrical stimulation (ES) promotes mesenchymal stem cell (MSC) chondrogenesis, while mechanical stimulation (MS) enhances the chondrogenic differentiation capacity of MSCs. Therefore, understanding the impact of these stimuli on chondrogenesis is crucial for researchers to develop more effective tissue engineering strategies for cartilage repair and regeneration. This study focuses on the preparation of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conductive polymer (CP) scaffolds using the freeze-drying method. The scaffolds were fabricated with varying concentrations (0, 1, 3, and 10 wt %) of (3-glycidyloxypropyl) trimethoxysilane (GOPS) as a crosslinker and an additive to tailor the scaffold properties. To gain a comprehensive understanding of the material characteristics and the phase aggregation phenomenon of PEDOT:PSS scaffolds, the researchers performed theoretical calculations of solubility parameters and surface energies of PSS, PSS-GOPS, and PEDOT polymers, as well as conducted material analyses. Additionally, the study investigated the potential of promoting chondrogenic differentiation of human adipose stem cells by applying external ES or MS on a PEDOT:PSS CP scaffold. Compared to the group without stimulation, the group that underwent stimulation exhibited significantly up-regulated expression levels of chondrogenic characteristic genes, such as SOX9 and COL2A1. Moreover, the immunofluorescence staining images exhibited a more vigorous fluorescence intensity of SOX9 and COL II proteins that was consistent with the trend of the gene expression results. In the MS experiment, the strain excitation exerted on the scaffold was simulated and transformed into stress. The simulated stress response showed that the peak gradually decreased with time and approached a constant value, with the negative value of stress representing the generation of tensile stress. This stress response quantification could aid researchers in determining specific MS conditions for various materials in tissue engineering, and the applied stress conditions could be further optimized. Overall, these findings are significant contributions to future research on cartilage repair and biophysical ES/MS in tissue engineering.

show abstract

Section: Introductionmentioning

confidence: 99%

Biophysical Electrical and Mechanical Stimulations for Promoting Chondrogenesis of Stem Cells on PEDOT:PSS Conductive Polymer Scaffolds

Liu

Lin

et al. 2023

Biomacromolecules

View full text Add to dashboard Cite

show abstract

“…16 This is because substrates with low moduli (0.1-25 kPa) appear to mimic the developing limb bud and thus simulates the biomechanics of developing cartilage. 16,18 Studies have found that such substrates upregulate chondrogenic markers and ECM deposition. 16 However, future studies using the CA will need to be completed to confirm this.…”

Section: Discussionmentioning

confidence: 99%

“…However, Chondro‐Gide, the most commonly used AMIC technique has reported some complications in terms of poor defect filling, inadequate integration with the border zone as well as subchondral bone and lamina abnormalities which could be attributed to the use of collagen type I – a material not inherently chondro‐inductive and offers inferior chondrogenesis compared to collagen type II 13,14 . Studies have reported that BMSC chondrogenesis could be optimized, or even enhanced, under certain environmental conditions viz., a soft substrate (0.1–25 kPa), presence of both sulfated glycosaminoglycans (sGAGs) and collagen type II, as well as allowance for cell aggregation 15–18 . As such, one of our long‐term goals is to create a scaffold for AMIC that closely approximates the biochemistry of human hyaline cartilage while possessing a substrate stiffness that promotes BMSC aggregation and chondrogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…13,14 Studies have reported that BMSC chondrogenesis could be optimized, or even enhanced, under certain environmental conditions viz., a soft substrate (0.1-25 kPa), presence of both sulfated glycosaminoglycans (sGAGs) and collagen type II, as well as allowance for cell aggregation. [15][16][17][18] As such, one of our long-term goals is to create a scaffold for AMIC that closely approximates the biochemistry of human hyaline cartilage while possessing a substrate stiffness that promotes BMSC aggregation and chondrogenesis.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The development of a nucleus pulposus‐derived cartilage analog scaffold for chondral repair and regeneration

Thomas,

Buchweitz,

Baek

et al. 2023

J Biomedical Materials Res

View full text Add to dashboard Cite

Focal chondral defects (FCDs) significantly impede quality of life for patients and impose severe economic costs on society. One of the most promising treatment options—autologous matrix‐induced chondrogenesis (AMIC)—could benefit from a scaffold that contains both of the primary cartilage matrix components—sulfated glycosaminoglycans (sGAGs) and collagen type II. Here, 17 different protocols were evaluated to determine the most optimum strategy for decellularizing (decelling) the bovine nucleus pulposus (bNP) to yield a natural biomaterial with a cartilaginous constituency. The resulting scaffold was then characterized with respect to its biochemistry, biomechanics and cytocompatibility. Results indicated that the optimal decell protocol involved pre‐crosslinking the tissue prior to undergoing decell with trypsin and Triton X‐100. The residual DNA content of the scaffold was found to be 32.64 ± 9.26 ng/mg dry wt. of tissue with sGAG and hydroxyproline (HYP) contents of 72.53 ± 16.43. and 78.38 ± 8.46 μg/mg dry wt. respectively. The dynamic viscoelastic properties were found to be preserved (complex modulus: 17.92–16.62 kPa across a range of frequencies) while the equilibrium properties were found to have significantly decreased (aggregate modulus: 11.51 ± 9.19 kPa) compared to the non‐decelled fresh bNP tissue. Furthermore, the construct was also found to be cytocompatible with bone marrow stem cells (BMSCs). While it was not permissive of cellular infiltration, the BMSCs were still found to have lined the laser drilled channels in the scaffold. Taken together, the biomaterial developed herein could be a valuable addition to the AMIC family of scaffolds or serve as an off‐the‐shelf standalone option for cartilage repair.

show abstract

“…MSCs differentiation under proper mechanical stimulation already successfully generates quality cartilage, tendon, bone, and cardiomyogenic tissue (Gu et al, 2017;Kataoka et al, 2020;Liu et al, 2022a;Park et al, 2022;Volz et al, 2022). Recently, the frequency and intensity of mechanical stimulation have been optimized in several studies (Chan et al, 2011a;Lee et al, 2016;Elsaadany et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Mechanical stimulation promotes MSCs healing the lesion of intervertebral disc annulus fibrosus

Deng

Kang

Jin

et al. 2023

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) and scaffolds offer promising perspectives for annulus fibrosus (AF) repair. The repair effect was linked to features of the local mechanical environment related to the differentiation of MSCs. In this study, we established a Fibrinogen-Thrombin-Genipin (Fib-T-G) gel which is sticky and could transfer strain force from AF tissue to the human mesenchymal stem cells (hMSCs) embedded in the gel. After the Fib-T-G biological gel was injected into the AF fissures, the histology scores of intervertebral disc (IVD) and AF tissue showed that Fib-T-G gel could better repair the AF fissure in caudal IVD of rats, and increase the expression of AF-related proteins including Collagen 1 (COL1), Collagen 2 (COL2) as well as mechanotransduction-related proteins including RhoA and ROCK1. To clarify the mechanism that sticky Fib-T-G gel induces the healing of AF fissures and the differentiation of hMSCs, we further investigated the differentiation of hMSCs under mechanical strain in vitro. It was demonstrated that both AF-specific genes, including Mohawk and SOX-9, and ECM markers (COL1, COL2, aggrecan) of hMSCs were up-regulated in the environment of strain force. Moreover, RhoA/ROCK1 proteins were also found to be significantly up-regulated. In addition, we further -demonstrated that the fibrochondroinductive effect of the mechanical microenvironment process could be significantly blocked or up-regulated by inhibiting the RhoA/ROCK1 pathway or overexpressing RhoA in MSCs, respectively. Summarily, this study will provide a therapeutic alternative to repair AF tears and provide evidence that RhoA/ROCK1 is vital for hMSCs response to mechanical strain and AF-like differentiation.

show abstract

Mechanobiological Approaches for Stimulating Chondrogenesis of Stem Cells

Cited by 9 publications

References 153 publications

Biophysical Electrical and Mechanical Stimulations for Promoting Chondrogenesis of Stem Cells on PEDOT:PSS Conductive Polymer Scaffolds

Biophysical Electrical and Mechanical Stimulations for Promoting Chondrogenesis of Stem Cells on PEDOT:PSS Conductive Polymer Scaffolds

The development of a nucleus pulposus‐derived cartilage analog scaffold for chondral repair and regeneration

Mechanical stimulation promotes MSCs healing the lesion of intervertebral disc annulus fibrosus

Contact Info

Product

Resources

About