Tunable, bioactive protein conjugated hyaluronic acid hydrogel for neural engineering applications

Shendi, Dalia; Dede, Ana; Yin, Yuan; Wang, Chaoming; Valmikinathan, Chandra M.; Jain, Aditya

doi:10.1039/c5tb02235e

Cited by 23 publications

(14 citation statements)

References 65 publications

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“…Therefore, the anti‐Fas HA microsphere gels did not elicit a pro‐death response in the NSCs. These results are consistent with our previously published studies in bulk anti‐Fas HA hydrogel . The cell viability percentage obtained is similar to NSCs encapsulated in microsphere gels fabricated using other techniques, such as emulsion based .…”

Section: Resultssupporting

confidence: 92%

“…The hydrogel precursor solutions were fabricated using our previously published methodology . Briefly, 1% HA was dissolved in 0.1 M NaOH and modified using divinyl sulfone (DVS) at 3 M excess to form VS‐HA, followed by dialysis and lyophilization for storage.…”

Section: Methodsmentioning

confidence: 99%

“…It has been demonstrated that Fas receptor (FasR)/Fas ligand (FasL)‐mediated signaling pathway provides neuroprotection, thus enhancing the survivability of NSCs . Anti‐Fas, antibody to FasR, conjugated hydrogels have also been shown to induce apoptosis in immune and inflammatory cells, such as central nervous system (CNS) resident microglia and T‐cells due to the high FasR expression on the cell surface …”

Section: Introductionmentioning

confidence: 99%

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Anti‐Fas conjugated hyaluronic acid microsphere gels for neural stem cell delivery

Shendi

Albrecht

Jain

2016

J Biomedical Materials Res

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Central nervous system (CNS) injuries and diseases result in neuronal damage and loss of function. Transplantation of neural stem cells (NSCs) has been shown to improve locomotor function after transplantation. However, due to the immune and inflammatory response at the injury site, the survival rate of the engrafted cells is low. Engrafted cell viability has been shown to increase when transplanted within a hydrogel. Hyaluronic acid (HA) hydrogels have natural anti-inflammatory properties and the backbone can be modified to introduce bioactive agents, such as anti-Fas, which we have previously shown to promote NSC survival while suppressing immune cell activity in bulk hydrogels in vitro. Although bulk HA hydrogels have shown to promote stem cell survival, microsphere gels for NSC encapsulation and delivery may have additional advantages. In this study, a flow-focusing microfluidic device was used to fabricate either vinyl sulfone-modified HA (VS-HA) or anti-Fas-conjugated HA (anti-Fas HA) microsphere gels encapsulated with NSCs. The majority of encapsulated NSCs remained viable for at least 24 h in the VS-HA and anti-Fas HA microsphere gels. Moreover, T-cells cultured in suspension with the anti-Fas HA microsphere gels had reduced viability after contact with the microsphere gels compared to the media control and soluble anti-Fas conditions. This approach can be adapted to encapsulate various cell types for therapeutic strategies in other physiological systems in order to increase survival by reducing the immune response. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 608-618, 2017.

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Section: Resultssupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti‐Fas conjugated hyaluronic acid microsphere gels for neural stem cell delivery

Shendi

Albrecht

Jain

2016

J Biomedical Materials Res

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“…The water‐swollen 3D network with biocompatibility and non‐immunogenicity structurally mimics extracellular matrix‐like biophysical properties . The degradation rates and mechanical properties of injectable hydrogels can be finely tuned through the choice of polymer, cross‐linking density, and concentration . Furthermore, the cell adhesive property of the injectable hydrogels can be modulated by the covalent conjugation of cell adhesion ligands to the hydrogel precursor .…”

Section: Introductionmentioning

confidence: 99%

Tunable Engineering of Heparinized Injectable Hydrogels for Affinity‐Based Sustained Delivery of Bioactive Factors

Kim

Thambi

Lym

et al. 2019

Macro Materials & Eng

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Here, the design of an in situ‐forming injectable hydrogel is reported based on pH‐ and temperature‐responsive copolymers finely engineered with heparin for the sustained delivery of bioactive factors. In order to develop such heparinized injectable hydrogels, pH‐ and temperature‐responsive copolymers based on poly(ethylene glycol) and poly(urethane sulfamethazine) (PEG‐PUSSM) are synthesized and acrylated, and subsequently coupled with thiolated heparin through Michael‐addition reaction. The content of heparin in the bioconjugates (Hep‐PUSSM) is finely tuned to control the release of heparin‐binding bioactive factors. The free‐flowing bioconjugate sols at room temperature transform to stable viscoelastic gel in physiological conditions, indicating that heparin modification does not affect the sol–gel transition. The subcutaneous administration of bioconjugate sols to the dorsal‐region of Sprague‐Dawley rats forms a hydrogel depot and shows controlled degradation. The bioconjugates effectively bind with bioactive factors (VEGF) through simple mixing, and the release is controlled over a period of 4 weeks without an initial burst. As a result, the implantation of VEGF‐loaded bioconjugate gel induces angiogenesis throughout the hydrogel network. The tunable engineering of the injectable hydrogel by heparinization with independent controllable physical properties sustains the release of bioactive factors, indicating that it may be a promising platform for the delivery of bioactive factors.

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“…Synthetic hydrogels are excellent modular platforms for use as sensors [1], drug delivery vehicles [2], and biomimetic scaffolds for tissue engineering applications [3,4]. Synthetic polymers such as poly(ethylene glycol) (PEG) are easily functionalized with a variety of reactive functionalities to provide a bioinert base for the creation of well-defined network architectures with high water content and controlled physical and biochemical properties [5].…”

Section: Introductionmentioning

confidence: 99%

Bio-orthogonal conjugation and enzymatically triggered release of proteins within multi-layered hydrogels

et al. 2017

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Tunable, bioactive protein conjugated hyaluronic acid hydrogel for neural engineering applications

Abstract: A one-step Michael addition click chemistry reaction is used to fabricate a bioactive conjugated hyaluronic acid (HA) scaffold for neural engineering applications.

Cited by 23 publications

References 65 publications

Anti‐Fas conjugated hyaluronic acid microsphere gels for neural stem cell delivery

Anti‐Fas conjugated hyaluronic acid microsphere gels for neural stem cell delivery

Tunable Engineering of Heparinized Injectable Hydrogels for Affinity‐Based Sustained Delivery of Bioactive Factors

Bio-orthogonal conjugation and enzymatically triggered release of proteins within multi-layered hydrogels

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