Dynamic Manipulation of Hydrogels to Control Cell Behavior: A Review

Vats, Kanika; Benoit, Danielle S. W.

doi:10.1089/ten.teb.2012.0716

Cited by 61 publications

(46 citation statements)

References 129 publications

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“…ES alters the local electrical field [45], enhances the release of nerve growth factors from SCs [46], promotes the induction of neurotrophins release [15], and enhances the proliferation and functional activity of SCs in vitro. ES was shown to enhance the release of nerve growth factor and brain-derived neurotrophic factor from Schwann cells in a calcium-dependent mechanism [46].…”

Section: Discussionmentioning

confidence: 99%

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

et al. 2018

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Peripheral nerve injuries often lead to incomplete recovery and contribute to significant disability to approximately 360,000 people in the USA each year. Stem cell therapy holds significant promise for peripheral nerve regeneration, but maintenance of stem cell viability and differentiation potential in vivo are still major obstacles for translation. Using a made-in-house 96-well vertical electrical stimulation (ES) platform, we investigated the effects of different stimulating pulse frequency, duration and field direction on human neural crest stem cell (NCSC) differentiation. We observed dendritic morphology with enhanced neuronal differentiation for NCSCs cultured on cathodes subject to 20 Hz, 100μs pulse at a potential gradient of 200 mV/mm. We further evaluated the effect of a novel cell-based therapy featuring optimized pulsatile ES of NCSCs for in vivo transplantation following peripheral nerve regeneration. 15 mm critical-sized sciatic nerve injuries were generated with subsequent surgical repair in sixty athymic nude rats. Injured animals were randomly assigned into five groups (N = 12 per group): blank control, ES, NCSC, NCSC + ES, and autologous nerve graft. Optimized ES was applied immediately after surgical repair for 1 h in ES and NCSC + ES groups. Recovery was assessed by behavioral (CatWalk gait analysis), wet muscle-mass, histomorphometric, and immunohistochemical analyses at either 6 or 12 weeks after surgery (N = 6 per group). Gastrocnemius muscle wet mass measurements in ES + NCSC group were comparable to autologous nerve transplantation and significantly higher than other groups (p < 0.05). Quantitative histomorphometric analysis and catwalk gait analysis showed similar improvements by ES on NCSCs (p < 0.05). A higher number of viable NCSCs was shown via immunochemical analysis, with higher Schwann cell (SC) differentiation in the NCSC + ES group compared to the NCSC group (p < 0.05). Overall, ES on NCSC transplantation significantly enhanced nerve regeneration after injury and repair, and was comparable to autograft treatment. Thus, ES can be a potent alternative to biochemical and physical cues for modulating stem cell survival and differentiation. This novel cell-based intervention presents an effective and safe approach for improved outcomes after peripheral nerve repair.

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Section: Discussionmentioning

confidence: 99%

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

et al. 2018

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“…6 Taking the advantages from both classes of materials, recent work has focused on synthesizing hybrid hydrogels with both natural and synthetic components. 7-8 …”

Section: Introductionmentioning

confidence: 99%

Thiol–norbornene photoclick hydrogels for tissue engineering applications

Lin

Han

2014

J of Applied Polymer Sci

188

214

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Thiol-norbornene (thiol-ene) photo-click hydrogels have emerged as a diverse material system for tissue engineering applications. These hydrogels are cross-linked through light mediated orthogonal reactions between multi-functional norbornene-modified macromers (e.g., poly(ethylene glycol), hyaluronic acid, gelatin) and sulfhydryl-containing linkers (e.g., dithiothreitol, PEG-dithiol, bis-cysteine peptides) using low concentration of photoinitiator. The gelation of thiol-norbornene hydrogels can be initiated by long-wave UV light or visible light without additional co-initiator or co-monomer. The cross-linking and degradation behaviors of thiol-norbornene hydrogels are controlled through material selections, whereas the biophysical and biochemical properties of the gels are easily and independently tuned owing to the orthogonal reactivity between norbornene and thiol moieties. Uniquely, the cross-linking of step-growth thiol-norbornene hydrogels is not oxygen-inhibited, therefore the gelation is much faster and highly cytocompatible compared with chain-growth polymerized hydrogels using similar gelation conditions. These hydrogels have been prepared as tunable substrates for 2D cell culture, as microgels or bulk gels for affinity-based or protease-sensitive drug delivery, and as scaffolds for 3D cell culture. Reports from different laboratories have demonstrated the broad utility of thiol-norbornene hydrogels in tissue engineering and regenerative medicine applications, including valvular and vascular tissue engineering, liver and pancreas-related tissue engineering, neural regeneration, musculoskeletal (bone and cartilage) tissue regeneration, stem cell culture and differentiation, as well as cancer cell biology. This article provides an up-to-date overview on thiol-norbornene hydrogel cross-linking and degradation mechanisms, tunable material properties, as well as the use of thiol-norbornene hydrogels in drug delivery and tissue engineering applications.

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“…It is known that the cell response is affected by mechanical properties of the cell substrate . Cells probe the hydrogel surface as they attach, spread, and migrate and therefore, the resistance of the material to the applied stress, measured as the elasticity, can direct cell behavior . This was also observed by Pelham et al for epithelial cells and fibroblasts on polyacrylamide gels of varying stiffness .…”

Section: Resultsmentioning

confidence: 71%

Development of Gelatin‐Alginate Hydrogels for Burn Wound Treatment

Stubbe

Mignon

Declercq

et al. 2019

Macromolecular Bioscience

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Hydrogels are interesting as wound dressing for burn wounds to maintain a moist environment. Especially gelatin and alginate based wound dressings show strong potential. Both polymers are modified by introducing photocrosslinkable functionalities and combined to hydrogel films (gel‐MA/alg‐MA). In one protocol gel‐MA films are incubated in alg‐MA solutions and crosslinked afterward into double networks. Another protocol involves blending both and subsequent photocrosslinking. The introduction of alginate into the gelatin matrix results in phase separation with polysaccharide microdomains in a protein matrix. Addition of alg(‐MA) to gel‐MA leads to an increased swelling compared to 100% gelatin and similar to the commercial Aquacel Ag dressing. In vitro tests show better cell adhesion for films which have a lower alginate content and also have superior mechanical properties. The hydrogel dressings exhibit good biocompatibility with adaptable cell attachment properties. An adequate gelatin‐alginate ratio should allow application of the materials as wound dressings for several days without tissue ingrowth.

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Dynamic Manipulation of Hydrogels to Control Cell Behavior: A Review

Cited by 61 publications

References 129 publications

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

Optimal electrical stimulation boosts stem cell therapy in nerve regeneration

Thiol–norbornene photoclick hydrogels for tissue engineering applications

Development of Gelatin‐Alginate Hydrogels for Burn Wound Treatment

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