Modular Multifunctional Poly(ethylene glycol) Hydrogels for Stem Cell Differentiation

Singh, Anirudha; Zhan, Junpeng; Ye, Zhaoyang; Elisseeff, Jennifer H.

doi:10.1002/adfm.201201902

Cited by 55 publications

(53 citation statements)

References 51 publications

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“…Another relevant work reported by Elisseeff and colleagues showed a tunable CD/PEG hybrid hydrogel crosslinked by chain-growth photopolymerization. It is worth noting that the functionalized βCD motifs were ‘threaded’ onto PEG-diacrylate after overnight incubation 34 . We believe that the threading of CD to PEG chains was minimal, if any, since we added βCD into the mixture right before photopolymerization in all experiments.…”

Section: Resultsmentioning

confidence: 99%

Photoclick Hydrogels Prepared from Functionalized Cyclodextrin and Poly(ethylene glycol) for Drug Delivery and in Situ Cell Encapsulation

Han

Lin

2015

Biomacromolecules

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Polymers or hydrogels containing modified cyclodextrin (CD) are highly useful in drug delivery applications as CD is a cytocompatible amphiphilic molecule that can complex with a variety of hydrophobic drugs. Here, we designed modular photo-click thiol-ene hydrogels from derivatives of βCD and poly(ethylene glycol) (PEG), including βCD-allylether (βCD-AE), βCD-thiol (βCD-SH), PEG-thiol (PEGSH), and PEG-norbornene (PEGNB). Two types of CD-PEG hybrid hydrogels were prepared using radical-mediated thiol-ene photo-click reactions. Specifically, thiol-allylether hydrogels were formed by reacting multi-arm PEGSH and βCD-AE, and thiol-norbornene hydrogels were formed by cross-linking βCD-SH and multi-arm PEGNB. We characterized the properties of these two types of thiol-ene hydrogels, including gelation kinetics, gel fractions, hydrolytic stability, and cytocompatibility. Compared with thiol-allylether hydrogels, thiol-norbornene photo-click reaction formed hydrogels with faster gelation kinetics at equivalent macromer contents. Using curcumin, an anti-inflammatory and anti-cancer hydrophobic molecule, we demonstrated that CD-crosslinked PEG-based hydrogels, when compared with pure PEG-based hydrogels, afforded higher drug loading efficiency and prolonged delivery in vitro. Cytocompatibility of these CD-crosslinked hydrogels were evaluated by in situ encapsulation of radical sensitive pancreatic MIN6 β-cells. All formulations and crosslinking conditions tested were cytocompatible for cell encapsulation. Furthermore, hydrogels crosslinked by βCD-SH showed enhanced cell proliferation and insulin secretion as compared to gels crosslinked by either dithiothreitol (DTT) or βCD-AE, suggesting the profound impact of both macromer compositions and gelation chemistry on cell fate in chemically crosslinked hydrogels.

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Section: Resultsmentioning

confidence: 99%

Photoclick Hydrogels Prepared from Functionalized Cyclodextrin and Poly(ethylene glycol) for Drug Delivery and in Situ Cell Encapsulation

Han

Lin

2015

Biomacromolecules

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“…Synthetic polymers can be tailored to achieve desirable degradation profiles or rates of growth factor delivery, but it has long been known that additional modifications are necessary to promote improved cell attachment 13,14 . While such approaches are being used to better understand and direct cell behavior 15–17 , degradation products of some synthetic materials have been associated with inflammatory and foreign body responses in certain conditions 18–20 . Some naturally-based materials such as the polysaccharide alginate can persist for long periods of time in vivo , but like synthetic polymers require modification in order to have tunable rates of degradation or present cell-binding motifs that cells would encounter in the three-dimensional environment 21,22 .…”

Section: Introductionmentioning

confidence: 99%

Keratin hydrogel carrier system for simultaneous delivery of exogenous growth factors and muscle progenitor cells

et al. 2015

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Ideal material characteristics for tissue engineering or regenerative medicine approaches to volumetric muscle loss (VML) include the ability to deliver cells, growth factors and molecules that support tissue formation from a system with a tunable degradation profile. Two different types of human hair-derived keratins were tested as options to fulfill these VML design requirements: (1) oxidatively extracted keratin (keratose) characterized by a lack of covalent crosslinking between cysteine residues, and (2) reductively extracted keratin (kerateine) characterized by disulfide crosslinks. Human skeletal muscle myoblasts cultured on coatings of both types of keratin had increased numbers of multinucleated cells compared to collagen or Matrigel™ and adhesion levels greater than collagen. Rheology showed elastic moduli from 102 – 105 Pa and viscous moduli from 101 – 104 Pa depending on gel concentration and keratin type. Kerateine and keratose showed differing rates of degradation due to the presence or absence of disulfide crosslinks, which likely contributed to observed differences in release profiles of several growth factors. In vivo testing in a subcutaneous mouse model showed that keratose hydrogels can be used to deliver mouse muscle progenitor cells and growth factors. Histological assessment showed minimal inflammatory responses and an increase in markers of muscle formation.

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“…For example, Elisseeff and colleagues have developed α-CD-threaded PEGDA hydrogels for tuning the biophysical and biochemical properties of chain-growth PEG-based hydrogels. [102] Figure 9 illustrates how supramolecular polymers can serve as ‘carriers’ to impart multiple and orthogonal functionalities to a hydrogel network. The PEG ‘necklaces’ are decorated/threaded with functionalized αCD to produce hydrogels with tunable mechanics (by changing PEGDA concentration), adhesion (by adjusting the concentration of functionalized αCD but not PEGDA), or chemistry (by introducing αCD with different functional groups, e.g., -CH 3 or -PO 4− ).…”

Section: Hydrogels Formed From Supramolecular Assemblymentioning

confidence: 99%

“…The PEG ‘necklaces’ are decorated/threaded with functionalized αCD to produce hydrogels with tunable mechanics (by changing PEGDA concentration), adhesion (by adjusting the concentration of functionalized αCD but not PEGDA), or chemistry (by introducing αCD with different functional groups, e.g., -CH 3 or -PO 4− ). By manipulating the compositions of these supramolecules, multifunctional hydrogels were created for promoting adhesion, proliferation, and differentiation of hMSCs [102] or for studying the roles of matrix mechanics and functions on cancer cell invasion. [103] While not demonstrated in this publication, protease-sensitivity can be integrated into PEG-CD hydrogels by replacing PEGDA with diacrylated PEG-peptide macromers (Figure 1C).…”

Section: Hydrogels Formed From Supramolecular Assemblymentioning

confidence: 99%

Recent advances in crosslinking chemistry of biomimetic poly(ethylene glycol) hydrogels

Lin

2015

RSC Adv.

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The design and application of biomimetic hydrogels have become an important and integral part of modern tissue engineering and regenerative medicine. Many of these hydrogels are prepared from synthetic macromers (e.g., poly(ethylene glycol) or PEG) as they provide high degrees of tunability for matrix crosslinking, degradation, and modification. For a hydrogel to be considered biomimetic, it has to recapitulate key features that are found in the native extracellular matrix, such as the appropriate matrix mechanics and permeability, the ability to sequester and deliver drugs, proteins, and or nucleic acids, as well as the ability to provide receptor-mediated cell-matrix interactions and protease-mediated matrix cleavage. A variety of chemistries have been employed to impart these biomimetic features into hydrogel crosslinking. These chemistries, such as radical-mediated polymerizations, enzyme-mediated crosslinking, bio-orthogonal click reactions, and supramolecular assembly, may be different in their crosslinking mechanisms but are required to be efficient for gel crosslinking and ligand bioconjugation under aqueous reaction conditions. The prepared biomimetic hydrogels should display a diverse array of functionalities and should also be cytocompatible for in vitro cell culture and/or in situ cell encapsulation. The focus of this article is to review recent progress in the crosslinking chemistries of biomimetic hydrogels with a special emphasis on hydrogels crosslinked from poly(ethylene glycol)-based macromers.

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Modular Multifunctional Poly(ethylene glycol) Hydrogels for Stem Cell Differentiation

Cited by 55 publications

References 51 publications

Photoclick Hydrogels Prepared from Functionalized Cyclodextrin and Poly(ethylene glycol) for Drug Delivery and in Situ Cell Encapsulation

Photoclick Hydrogels Prepared from Functionalized Cyclodextrin and Poly(ethylene glycol) for Drug Delivery and in Situ Cell Encapsulation

Keratin hydrogel carrier system for simultaneous delivery of exogenous growth factors and muscle progenitor cells

Recent advances in crosslinking chemistry of biomimetic poly(ethylene glycol) hydrogels

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