Visible light-initiated interfacial thiol-norbornene photopolymerization for forming an islet surface conformal coating

Han, Song; Mirmira, Raghavendra G.; Lin, Chien‐Chi

doi:10.1039/c4tb01593b

Cited by 24 publications

(25 citation statements)

References 55 publications

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“…The concentration of photoinitiator was fixed at 0.1 m M for either cleavage‐type initiator LAP [Figure (C)] or noncleavage‐type initiator EY [Figure (D)]. Typically, noncleavage (type II) photoinitiator EY was used with visible light‐mediated crosslinking, whereas cleavage‐type (type I) photoinitiator LAP was used in conjunction with UV light‐mediated crosslinking [Figure (E)]. Figure (F) shows a comparison of the resulting hydrogel moduli between gelation initiated by visible light or UV light.…”

Section: Resultsmentioning

confidence: 99%

“…While type I (cleavage‐type) photoinitiator by itself is sufficient in initiating photopolymerization, most of the type II photoinitiators (noncleavage type) require a coinitiator to achieve reasonable gelation kinetics. We have shown that it is possible to initiate thiol‐norbornene gelation using visible light and type II initiator eosin‐Y (EY) without using a coinitiator . Specifically, the thiol moiety is deprotonated by visible light excited EY, thus forming thiyl radicals capable of reacting with the norbornene group to form orthogonal thiol‐ether bond.…”

Section: Introductionmentioning

confidence: 99%

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Comparative study of visible light polymerized gelatin hydrogels for 3D culture of hepatic progenitor cells

Greene

Lin

Andrisani

et al. 2016

J of Applied Polymer Sci

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative study of visible light polymerized gelatin hydrogels for 3D culture of hepatic progenitor cells

Greene

Lin

Andrisani

et al. 2016

J of Applied Polymer Sci

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“…9 We have also utilized this unique and simple gelation system to form multi-layer hydrogels, 8 microgels, 15 and islet surface conformal coating. 16 This gelation system was also used to prepare visible light cured thiol-norbornene hydrogels capable of undergoing UV-light-mediated photodegradation. 17 …”

Section: Introductionmentioning

confidence: 99%

Modular and Adaptable Tumor Niche Prepared from Visible Light Initiated Thiol-Norbornene Photopolymerization

et al. 2016

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Photopolymerized biomimetic hydrogels with adaptable properties have been widely used for cell and tissue engineering applications. As a widely adopted gel crosslinking method, photopolymerization provides experimenters on-demand and spatial-temporal controls in gelation kinetics. Long wavelength ultraviolet (UV) light initiated photopolymerization is among the most popular methods in the fabrication of cell-laden hydrogels owing to its rapid and relatively mild gelation conditions. The use of UV light, however, still causes concerns regarding its potential negative impacts on cells. Alternatively, visible light based photopolymerization can be used to crosslink cell-laden hydrogels. The majority of visible light based gelation schemes involve photoinitiator, co-initiator, and co-monomer. This multi-component initiation system creates added challenges for optimizing hydrogel formulations. Here, we report a co-initiator/co-monomer-free visible light initiated thiol-norbornene photopolymerization scheme to prepare modular biomimetic hydrogels suitable for in situ cell encapsulation. Eosin-Y was used as the sole initiator to initiate modular gelation between synthetic macromers (e.g., thiolated poly(vinyl alcohol) or poly(ethylene glycol)) and functionalized extracellular matrices (ECM), including norbornene-functionalized gelatin (GelNB) and/or thiolated hyaluronic acid (THA). These components are modularly crosslinked to afford bio-inert (i.e., purely synthetic), bioactive (i.e., using gelatin), and biomimetic (i.e., using gelatin and hyaluronic acid) hydrogels. The stiffness of the hydrogels can be easily tuned without affecting the contents of the bioactive components. Furthermore, the use of naturally-derived biomacromolecules (e.g., gelatin and HA) renders these hydrogels susceptible to enzyme-mediated degradation. In addition to demonstrating efficient and tunable visible light mediated gelation, we also utilized this biomimetic modular gelation system to formulate artificial tumor niche and to study the effects of cell density and gel modulus on the formation of pancreatic ductal adenocarcinoma (PDAC) spheroids.

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“…In addition, thiol–ene PEG hydrogels exhibit high cytocompatibility, precise spatiotemporal control of gelation, tunable degradation, and versatile modulation of biophysical and biochemical properties. The versatility of these hydrogels is demonstrated through extensive applications, ranging from protein and drug delivery, cartilage development, osteogenic differentiation, endothelial tubulogenesis, brain tumor models, synthetic matrix mimics, 2D culture substrates, and islet and cell encapsulation . However, these applications have been exclusively conducted in vitro, yielding little insight into the in vivo behavior of these hydrogels.…”

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confidence: 99%

Linkage Groups within Thiol–Ene Photoclickable PEG Hydrogels Control In Vivo Stability

Hunckler

Medina

Coronel

et al. 2019

Adv Healthcare Materials

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step-growth photopolymerization based on the orthogonal reaction between thiol and norbornene has emerged as an attractive strategy for many biomedical applications. [7,8] These step-growth photoinitiated (thiol-ene) hydrogels have shown great promise in 2D and 3D cell culture and organoid development, due, in part, to the low radical concentration and physiological pH required for crosslinking. [9] In addition, thiol-ene PEG hydrogels exhibit high cytocompatibility, precise spatiotemporal control of gelation, tunable degradation, and versatile modulation of biophysical and biochemical properties. The versatility of these hydrogels is demonstrated through extensive applications, ranging from protein and drug delivery, [10][11][12][13][14][15][16][17] cartilage development, [18,19] osteogenic differentiation, [20,21] endothelial tubulogenesis, [22] brain tumor models, [23] synthetic matrix mimics, [8,[24][25][26][27][28][29][30][31][32] 2D culture substrates, [33][34][35] and islet and cell encapsulation. [36][37][38][39][40][41][42][43] However, these applications have been exclusively conducted in vitro, yielding little insight into the in vivo behavior of these hydrogels. Our initial exploratory studies with these widely used 4-arm, ester-linked, thiol-ene PEG (PEG-4eNB) hydrogels implanted into the intraperitoneal space of mice unexpectedly showed that the hydrogels undergo rapid degradation in vivo ( Figure S1, Supporting Information). Hypothesizing that the poor in vivo stability may result from the hydrolysis of the ester linkage between the PEG backbone and norbornene functional end group, we replaced this connection with a more hydrolytically stable amide linkage. Here, we describe the characterization and implementation of 4-arm, amide-linked, thiol-ene PEG (PEG-4aNB) hydrogels that retain long-term stability in both in vitro and in vivo environments. We demonstrate rapid (<24 h) in vivo degradation of PEG-4eNB and gradual (>35 days) in vitro degradation. Conversely, PEG-4aNB retains long-term in vitro and in vivo stability while maintaining high cytocompatibility, and this material can be utilized as an appropriate replacement in many biomedical applications.The ester linkage in PEG hydrogels has been reported to be hydrolytically labile over the course of many weeks in cell culture. [44] This feature has been exploited further by introducing ester-containing poly(caprolactone) linkage groups to accelerate in vitro degradation of PEG hydrogels to within a Thiol-norbornene (thiol-ene) photoclickable poly(ethylene glycol) (PEG) hydrogels are a versatile biomaterial for cell encapsulation, drug delivery, and regenerative medicine. Numerous in vitro studies with these 4-arm ester-linked PEG-norbornene (PEG-4eNB) hydrogels demonstrate robust cytocompatibility and ability to retain long-term integrity with nondegradable crosslinkers. However, when transplanted in vivo into the subcutaneous or intraperitoneal space, these PEG-4eNB hydrogels with nondegradable crosslinkers rapidly degrade within 24 h. This char...

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Visible light-initiated interfacial thiol-norbornene photopolymerization for forming an islet surface conformal coating

Cited by 24 publications

References 55 publications

Comparative study of visible light polymerized gelatin hydrogels for 3D culture of hepatic progenitor cells

Comparative study of visible light polymerized gelatin hydrogels for 3D culture of hepatic progenitor cells

Modular and Adaptable Tumor Niche Prepared from Visible Light Initiated Thiol-Norbornene Photopolymerization

Linkage Groups within Thiol–Ene Photoclickable PEG Hydrogels Control In Vivo Stability

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