Engineering of injectable hydrogels associate with Adipose-Derived stem cells delivery for anti-cardiac hypertrophy agents

Objectives Gelatin, a degraded collagen, has been widely used as a scaffolding material in tissue engineering applications. In this work, we aimed at the development of in situ, cross-linking, cytocompatible hydrogels by the use of transglutaminase as a cross-linker for potential application in the regeneration of tissues. Methods Hydrogels were prepared from gelatin of different concentrations and bloom degree (175 (G175) or 300 (G300) bloom gelatin) and cross-linked with various amounts of microbial transglutaminase (mTG) at 37°C. Mechanical properties and cross-linking degree were studied by rheology and swelling experiments. Four hydrogels with different stiffness were selected for studies with embedded human adipose-derived stem cells (hASCs). Results Hydrogels were obtained with storage modulus (G’) values between 11 (±1) Pa and 1,800 (±200) Pa with gelation times between 80 (±6) and 450 (±36) seconds. G300 cross-linked gelatin hydrogels displayed higher gel stiffness, lower swelling ratio and gelled more rapidly compared to the hydrogels prepared from G175. Stiffer hydrogels (50 and 200 Pa) showed greater ability to support the proliferation of hASCs than softer ones (11 and 30 Pa). The highest cell proliferation was observed with a hydrogel of 200 Pa modulus. Conclusions Overall, transglutaminase cross-linked gelatin hydrogels might be suitable as injectable hydrogels for the engineering of musculoskeletal and other types of connective tissues.

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Preparation and characterization of amnion hydrogel and its synergistic effect with adipose derived stem cells towards IL1β activated chondrocytes

Scientific Reports ◽

10.1038/s41598-020-75921-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Maumita Bhattacharjee ◽

Jorge L. Escobar Ivirico ◽

Ho-Man Kan ◽

Rosalie Bordett ◽

Rishikesh Pandey ◽

...

Keyword(s):

Stem Cells ◽

Synergistic Effect ◽

Signaling Pathway ◽

Therapeutic Agent ◽

Cartilage Degeneration ◽

Adipose Derived Stem Cells ◽

Injectable Hydrogels ◽

Paracrine Effects

Abstract Inflammation leads to chondrocyte senescence and cartilage degeneration, resulting in osteoarthritis (OA). Adipose‐derived stem cells (ADSCs) exert paracrine effects protecting chondrocytes from degenerative changes. However, the lack of optimum delivery systems for ADSCs limits its use in the clinic. The use of extracellular matrix based injectable hydrogels has gained increased attention due to their unique properties. In the present study, we developed hydrogels from amnion tissue as a delivery system for ADSCs. We investigated the potential of amnion hydrogel to maintain ADSC functions, the synergistic effect of AM with ADSC in preventing the catabolic responses of inflammation in stimulated chondrocytes. We also investigated the role of Wnt/β-catenin signaling pathway in IL-1β induced inflammation in chondrocytes and the ability of AM-ADSC to inhibit Wnt/β-catenin signaling. Our results showed that AM hydrogels supported cell viability, proliferation, and stemness. ADSCs, AM hydrogels and AM-ADSCs inhibited the catabolic responses of IL-1β and inhibited the Wnt/β-catenin signaling pathway, indicating possible involvement of Wnt/β-catenin signaling pathways in IL-1β induced inflammation. The results also showed that the synergistic effect of AM-ADSCs was more pronounced in preventing catabolic responses in activated chondrocytes. In conclusion, we showed that AM hydrogels can be used as a potential carrier for ADSCs, and can be developed as a potential therapeutic agent for treating OA.

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