Three-Dimensional Biochemical Patterning of Click-Based Composite Hydrogels via Thiolene Photopolymerization

Abstract

Hydrogels formed from (meth)acrylated poly(ethylene glycol) precursors are commonly used in a variety of biomedical applications ranging from tissue engineering to biosensors. While this approach has proven quite diverse, a major limitation to this approach is the heterogeneities and nonidealities that arise in the gels from the chain polymerization process, which increases the difficulty in relating the network structure to the final physical properties of the gel. Here we have exploited the specificity and fidelity of the [3+2] cycloaddition reaction to synthesize hydrogels with controlled architectures and improved mechanical properties. Moreover, we demonstrate a general approach toward the integration of multifunctional photoreactive polypeptide sequences into the network structure that provides a facile way to independently tune the 3D chemical and physical properties of the gel. Standard photolithographic techniques were used to generate a variety of two- and three-dimensional patterns as well as controlled biochemical gradients within existing preformed hydrogels.

Diels−Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering

“…Anseth and co-workers developed a sequential click protocol relevant to both hydrogel synthesis and post-gelation modification 38,39,124 . Click cross-linked PEG hydrogels were first formed via CuAAC, as an extension of the method taken by Malkock et al 27 .…”

“…Click cross-linked PEG hydrogels were first formed via CuAAC, as an extension of the method taken by Malkock et al 27 . To enable photopatterning of their PEG hydrogels, multifunctional photoreactive polypeptide sequences were included within the network structure by incorporating the non-natural amino acid, Fmoc-Lys(alloc)-OH 124 . The allyloxycarbonyl (alloc) protecting group contains a vinyl functional group capable of reacting with any thiol-containing compound, such as cysteine.…”

Emerging Ideas: Engineering the Periosteum: Revitalizing Allografts by Mimicking Autograft Healing

“…Furthermore, by altering PEG degradation kinetics or hydrogel MSC densities we believe we can exercise temporal control over the initiation of remodeling and thereby increase early matrix production and ossification [45,48]. Moreover, our approach may be further enhanced through chemical modification of PEG macromers to alter degradation parameters [30,31], include controlled release of soluble factors (eg, statins, b-catenin agonists, growth factors) to increase MSC paracrine factor release, proliferation, differentiation, and/or matrix production [1-5, 7, 33, 35, 42], or use photopatterning strategies to achieve localized network modification and enable cell stratification in specific areas of hydrogels, as seen in native tissue [11,28]. Such alterations may provide further instructional cues for cells in the periosteum mimetic and synergistic healing may result using appropriate combinatorial strategies.…”

Hydrogel-Based Platforms for the Regeneration of Osteochondral Tissue and Intervertebral Disc

“…Indeed PEG hydrogels recently approved by the FDA for cosmetics, personal care products and pharmaceuticals, show peculiar properties, such as good biocompatibility, non-immunogenity, and resistance to protein adsorption which make their use satisfactory for different biomedical applications including surface modification, bio-conjugation, drug delivery and tissue engineering [47,48]. Three major crosslinking methods have been used to make PEG hydrogels, including radiation of linear or branched PEG polymers [49,50], free radical polymerization (FRP) of PEG acrylates [51], and specific chemical reactions, such as condensation [52], Michael-type additions [53,54], Click chemistry [55], and enzymatic reactions [56]. The most common approach to make PEG hydrogels is photo-polymerization, which utilizes light to convert liquid PEG macromer solutions into solid hydrogels at physiological temperature and pH.…”