Browsing by Subject "Click chemistry"

Now showing 1 - 3 of 3
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    Heparinized Gelatin-Based Hydrogels for Differentiation of Induced Pluripotent Stem Cells
    (American Chemical Society, 2022) Arkenberg, Matthew R.; Koehler, Karl; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and Technology
    Chemically defined hydrogels are increasingly utilized to define the effects of extracellular matrix (ECM) components on cellular fate determination of human embryonic and induced pluripotent stem cell (hESC and hiPSCs). In particular, hydrogels cross-linked by orthogonal click chemistry, including thiol-norbornene photopolymerization and inverse electron demand Diels-Alder (iEDDA) reactions, are explored for 3D culture of hESC/hiPSCs owing to the specificity, efficiency, cytocompatibility, and modularity of the cross-linking reactions. In this work, we exploited the modularity of thiol-norbornene photopolymerization to create a biomimetic hydrogel platform for 3D culture and differentiation of hiPSCs. A cell-adhesive, protease-labile, and cross-linkable gelatin derivative, gelatin-norbornene (GelNB), was used as the backbone polymer for constructing hiPSC-laden biomimetic hydrogels. GelNB was further heparinized via the iEDDA click reaction using tetrazine-modified heparin (HepTz), creating GelNB-Hep. GelNB or GelNB-Hep was modularly cross-linked with either inert macromer poly(ethylene glycol)-tetra-thiol (PEG4SH) or another bioactive macromer-thiolated hyaluronic acid (THA). The formulations of these hydrogels were modularly tuned to afford biomimetic matrices with similar elastic moduli but varying bioactive components, enabling the understanding of each bioactive component on supporting hiPSC growth and ectodermal, mesodermal, and endodermal fate commitment under identical soluble differentiation cues.
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    Photo-click hydrogels prepared from functionalized cyclodextrin and poly(ethylene glycol) for drug delivery and in situ cell encapsulation
    (ACS Publications, 2015-07-13) Shih, Han; Lin, Chien-Chi; Department of Biomedical Engineering, School of Engineering and Technology
    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 photoclick 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 photoclick reactions. Specifically, thiol-allylether hydrogels were formed by reacting multiarm PEGSH and βCD-AE, and thiol-norbornene hydrogels were formed by cross-linking βCD-SH and multiarm 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 photoclick reaction formed hydrogels with faster gelation kinetics at equivalent macromer contents. Using curcumin, an anti-inflammatory and anticancer hydrophobic molecule, we demonstrated that CD-cross-linked PEG-based hydrogels, when compared with pure PEG-based hydrogels, afforded higher drug loading efficiency and prolonged delivery in vitro. Cytocompatibility of these CD-cross-linked hydrogels were evaluated by in situ encapsulation of radical sensitive pancreatic MIN6 β-cells. All formulations and cross-linking conditions tested were cytocompatible for cell encapsulation. Furthermore, hydrogels cross-linked by βCD-SH showed enhanced cell proliferation and insulin secretion as compared to gels cross-linked by either dithiothreitol (DTT) or βCD-AE, suggesting the profound impact of both macromer compositions and gelation chemistry on cell fate in chemically cross-linked hydrogels.
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    Recent advances in bio-orthogonal and dynamic crosslinking of biomimetic hydrogels
    (Royal Society of Chemistry, 2020-09-21) Arkenberg, Matthew R.; Nguyen, Han D.; Lin, Chien-Chi; Biomedical Engineering, School of Engineering and Technology
    In recent years, dynamic, 'click' hydrogels have been applied in numerous biomedical applications. Owing to the mild, cytocompatible, and highly specific reaction kinetics, a multitude of orthogonal handles have been developed for fabricating dynamic hydrogels to facilitate '4D' cell culture. The high degree of tunability in crosslinking reactions of orthogonal 'click' chemistry has enabled a bottom-up approach to install specific biomimicry in an artificial extracellular matrix. In addition to click chemistry, highly specific enzymatic reactions are also increasingly used for network crosslinking and for spatiotemporal control of hydrogel properties. On the other hand, covalent adaptable chemistry has been used to recapitulate the viscoelastic component of biological tissues and for formulating self-healing and shear-thinning hydrogels. The common feature of these three classes of chemistry (i.e., orthogonal click chemistry, enzymatic reactions, and covalent adaptable chemistry) is that they can be carried out under ambient and aqueous conditions, a prerequisite for maintaining cell viability for in situ cell encapsulation and post-gelation modification of network properties. Due to their orthogonality, different chemistries can also be applied sequentially to provide additional biochemical and mechanical control to guide cell behavior. Herein, we review recent advances in the use of orthogonal click chemistry, enzymatic reactions, and covalent adaptable chemistry for the development of dynamically tunable and biomimetic hydrogels.