The effects of varying poly(ethylene glycol) hydrogel crosslinking density and the crosslinking mechanism on protein accumulation in three-dimensional hydrogels

Lee, Soah; Tong, Xinming; Yang, Fan

doi:10.1016/j.actbio.2014.05.023

Cited by 124 publications

(137 citation statements)

References 29 publications

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“…Previously, we have shown that varying the monomer molecular weight or concentration can differentially influence protein accumulation in the three-dimensional PEG hydrogel formed by different crosslinking mechanisms. 13 However, the effect of the crosslinking mechanism on protein release is still unknown because the hydrogel crosslinking process can be altered in the presence of encapsulated proteins or therapeutics. Therefore, the goal of the study was to investigate how chain-growth and step-growth polymerization influence the effect of varying the PEG molecular weight or concentration on the efficiency of encapsulated protein release and protein diffusivity.…”

Section: Introductionmentioning

confidence: 99%

Effects of the poly(ethylene glycol) hydrogel crosslinking mechanism on protein release

2016

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Poly(ethylene glycol) (PEG) hydrogels are widely used to deliver therapeutic biomolecules, due to high hydrophilicity, tunable physicochemical properties, and anti-fouling properties. Although different hydrogel crosslinking mechanisms are known to result in distinct network structures, it is still unknown how these various mechanisms influence biomolecule release. Here we compared the effects of chain-growth and step-growth polymerization for hydrogel crosslinking on the efficiency of protein release and diffusivity. For chain-growth-polymerized PEG hydrogels, while decreasing PEG concentration increased both the protein release efficiency and diffusivity, it was unexpected to find out that increasing PEG molecular weight did not significantly change either parameter. In contrast, for step-growth-polymerized PEG hydrogels, both decreasing PEG concentration and increasing PEG molecular weight resulted in an increase in the protein release efficiency and diffusivity. For step-growth-polymerized hydrogels, the protein release efficiency and diffusivity were further decreased by increasing crosslink functionality (4-arm to 8-arm) of the chosen monomer. Altogether, our results demonstrate that the crosslinking mechanism has a differential effect on controlling protein release, and this study provides valuable information for the rational design of hydrogels for sophisticated drug delivery.

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Section: Introductionmentioning

confidence: 99%

Effects of the poly(ethylene glycol) hydrogel crosslinking mechanism on protein release

2016

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“…The influence of stiffness has been carefully explored in the context of PEG-based artificial ECM, both in vitro and in vivo [10,15]. The degree of stiffness was found to both modulate the behaviour of cells with very soft gels being permissive for non-proteolytic migration and increased moduli resulting in a switch to proteolytic dependent invasion, and subsequent control over the extent of tissue invasion [16,17].…”

Section: Introductionmentioning

confidence: 99%

Regulation of tissue ingrowth into proteolytically degradable hydrogels

et al. 2015

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“…For example, increasing the crosslink density decreases the distance between crosslinks in the hydrogel (i.e., mesh size), often resulting in a decreased initial burst of cargo. 26-27 Yang and coworkers demonstrated mesh size-dependent release of the model protein bovine serum albumin (BSA) from PEG-based hydrogels with mesh sizes ranging from 4 nm to 14 nm. 26 For hydrogel compositions with a mesh size below 6 nm, only about ∼15% of encapsulated BSA was released.…”

Section: Introductionmentioning

confidence: 99%

“…26-27 Yang and coworkers demonstrated mesh size-dependent release of the model protein bovine serum albumin (BSA) from PEG-based hydrogels with mesh sizes ranging from 4 nm to 14 nm. 26 For hydrogel compositions with a mesh size below 6 nm, only about ∼15% of encapsulated BSA was released. In contrast, for the hydrogel with a mesh size of approximately 15 nm, ∼100% of encapsulated BSA was released within 2 hours.…”

Section: Introductionmentioning

confidence: 99%

Thiol–ene Click Hydrogels for Therapeutic Delivery

Kharkar

Rehmann

Skeens

et al. 2016

ACS Biomater. Sci. Eng.

189

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Hydrogels are of growing interest for the delivery of therapeutics to specific sites in the body. For use as a delivery vehicle, hydrophilic precursors are usually laden with bioactive moieties and then directly injected to the site of interest for in situ gel formation and controlled release dictated by precursor design. Hydrogels formed by thiol–ene click reactions are attractive for local controlled release of therapeutics owing to their rapid reaction rate and efficiency under mild aqueous conditions, enabling in situ formation of gels with tunable properties often responsive to environmental cues. Herein, we will review the wide range of applications for thiol–ene hydrogels, from the prolonged release of anti-inflammatory drugs in the spine to the release of protein-based therapeutics in response to cell-secreted enzymes, with a focus on their clinical relevance. We will also provide a brief overview of thiol–ene click chemistry and discuss the available alkene chemistries pertinent to macromolecule functionalization and hydrogel formation. These chemistries include functional groups susceptible to Michael type reactions relevant for injection and radically-mediated reactions for greater temporal control of formation at sites of interest using light. Additionally, mechanisms for the encapsulation and controlled release of therapeutic cargoes are reviewed, including i) tuning the mesh size of the hydrogel initially and temporally for cargo entrapment and release and ii) covalent tethering of the cargo with degradable linkers or affinity binding sequences to mediate release. Finally, myriad thiol–ene hydrogels and their specific applications also are discussed to give a sampling of the current and future utilization of this chemistry for delivery of therapeutics, such as small molecule drugs, peptides, and biologics.

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The effects of varying poly(ethylene glycol) hydrogel crosslinking density and the crosslinking mechanism on protein accumulation in three-dimensional hydrogels

Cited by 124 publications

References 29 publications

Effects of the poly(ethylene glycol) hydrogel crosslinking mechanism on protein release

Effects of the poly(ethylene glycol) hydrogel crosslinking mechanism on protein release

Regulation of tissue ingrowth into proteolytically degradable hydrogels

Thiol–ene Click Hydrogels for Therapeutic Delivery

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