The use of tough hydrogels as biomaterials is limited as a consequence of time-consuming fabrication techniques, toxic starting materials, and large strain hysteresis under deformation. Herein, we report the simultaneous application of nucleophilic thiol-yne and inverse electron-demand Diels-Alder additions to independently create two interpenetrating networks in a simple one-step procedure. The resultant hydrogels display compressive stresses of 14-15 MPa at 98% compression without fracture or hysteresis upon repeated load. The hydrogel networks can be spatially and temporally postfunctionalized via radical thiylation and/or inverse electron-demand Diels-Alder addition to residual functional groups within the network. Furthermore, gelation occurs rapidly under physiological conditions, enabling encapsulation of human cells.
Stem cell injections for the treatment of articular cartilage damage are a promising approach to achieve tissue regeneration. However, this method is encumbered by high cell apoptosis rates, low retention in the cartilage lesion, and inefficient chondrogenesis. Here, we have used a facile, very low cost-based microfluidic technique to create visible light-cured microgels composed of gelatin norbornene (GelNB) and a poly(ethylene glycol) (PEG) cross-linker. In addition, we have demonstrated that the process enables the rapid in situ microencapsulation of human bone marrow-derived mesenchymal stem cells (hBMSCs) under biocompatible microfluidic-processing conditions for long-term maintenance. The hBMSCs exhibited an unusually high degree of chondrogenesis in the GelNB microgels with chondro-inductive media, specifically toward the hyaline cartilage structure, with significant upregulation in type II collagen expression compared to the bulk hydrogel and "gold standard" pellet culture. Overall, we have demonstrated that these protein-based microgels can be engineered as promising therapeutic candidates for articular cartilage regeneration, with additional potential to be used in a variety of other applications in regenerative medicine.
Reversible
photocycloaddition reactions have previously been employed
in chemical cross-linking for the preparation of biomaterial scaffolds.
However, the processes require activation by high-energy UV light,
rendering them unsuitable for modification in biological environments.
Here we demonstrate that the [2 + 2] photocycloaddition of styrylpyrene
can be activated by visible light at λ = 400–500 nm,
enabling rapid and effective conjugation and cross-linking of poly(ethylene
glycol) (PEG) in water and under mild irradiation conditions (I = 20 mW cm–2). Notably, the reversion
of the cycloaddition can be triggered by low-energy UV light at λ
= 340 nm, which allows for efficient cleavage of the dimer adduct.
Using this wavelength-gated reversible photochemical reaction we are
able to prepare PEG hydrogels and modulate their mechanical properties
in a bidirectional manner. We also demonstrate healing of the fractured
hydrogel by external light triggers. Furthermore, we show that human
mesenchymal stem cells can be encapsulated within the gels with high
viability post encapsulation. This photochemical approach is therefore
anticipated to be highly useful in studies of cell mechanotransduction,
with relevance to disease progression and tissue regeneration.
Predicting wavelength-dependent photochemical
reactivity is challenging.
Herein, we revive the well-established tool of measuring action spectra
and adapt the technique to map wavelength-resolved covalent bond formation
and cleavage in what we term “photochemical action plots”.
Underpinned by tunable lasers, which allow excitation of molecules
with near-perfect wavelength precision, the photoinduced reactivity
of several reaction classes have been mapped in detail. These include
photoinduced cycloadditions and bond formation based on photochemically
generated o-quinodimethanes and 1,3-dipoles such
as nitrile imines as well as radical photoinitiator cleavage. Organized
by reaction class, these data demonstrate that UV/vis spectra fail
to act as a predictor for photochemical reactivity at a given wavelength
in most of the examined reactions, with the photochemical reactivity
being strongly red shifted in comparison to the absorption spectrum.
We provide an encompassing perspective of the power of photochemical
action plots for bond-forming reactions and their emerging applications
in the design of wavelength-selective photoresists and photoresponsive
soft-matter materials.
Discerning Tastes: The regioselectivity of the nucleophilic addition of thiols to electron‐deficient alkynes is controlled by the choice of the solvent (i.e. the polarity of the reaction mixture) and the catalyst. Both thioalkenes and dithianes can be prepared in a rapid reaction that generates no by‐products (see scheme). In turn the utility of this reaction is shown for efficient end‐group modification of polymers.
Recent developments
in photochemistry have introduced new methods
to prepare hydrogels initiated by nonharmful light which is essential
for encapsulation of cells and bioactive components. However, bioorthogonal
photoclick reactions generally requires two components for cross-linking
and, in many cases, the formation of a reactive intermediate that
may cross-react with nucleophiles in biological media. Here we report
the utilization of a visible light triggered dimerization of electron-rich
anthracene for polymer cross-linking to form bulk hydrogels and microgels.
Incorporation of gelatin within the hydrogel enhanced cell attachment
and viability after 7 days of culture and spatiotemporal conjugation
of a bioactive component using photochemical dimerization of anthracene
was demonstrated. This work therefore introduces a simple yet powerful
tool for light modulated bioorthogonal polymer cross-linking, which
can be utilized in various bioengineering applications.
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