Photodegradable Macromers and Hydrogels for Live Cell Encapsulation and Release

Abstract

Hydrogel scaffolds are commonly used as 3D carriers for cells because their properties can be tailored to match natural extra-cellular matrix. Hydrogels may be used in tissue engineering and regenerative medicine to deliver therapeutic cells to injured or diseased tissue through controlled degradation. Hydrolysis and enzymolysis are the two most common mechanisms employed for hydrogel degradation, but neither allows sequential or staged release of cells. In contrast, photodegradation allows external real-time spatial and temporal control over hydrogel degradation, and allows for staged and sequential release of cells. We synthesized and characterized a series of macromers incorporating photodegradbale ortho-nitrobenzyl (o-NB) groups in the macromer backbone. We formed hydrogels from these macromers via redox polymerization and quantified the apparent rate constants of degradation (k app ) of each via photorheology at 370 nm, 10 mW/cm 2 . Decreasing the number of aryl ethers on the o-NB group increases k app , and changing the functionality from primary to seconday at the benzylic site dramatically increases k app . Human mesenchymal stem cells (hMSCs) survive encapsulation in the hydrogels (90% viability post-encapsulation). By exploiting the differences in reactivity of two different o-NB linkers, we quantitatively demonstrate the biased release of one stem cell population (green-fluroescent protein expressing hMSCs) over another (red-fluorescent protein expressing hMSCs).

Shape-Changing Photodegradable Hydrogels for Dynamic 3D Cell Culture

“…At a certain thickness, depending on the light dose, the light is attenuated sufficiently such that the gel is no longer degrading. 35 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 …”

“…We found cell viability is somewhat compromised following encapsulation due to the polymerization conditions, most likely due to the APS/TEMED radical initiator since the macromers and polymerization conditions do not affect cell viability as discussed in the Supporting Information, S4). In another study, we found > 90% viability using a similar encapsulation protocol for human mesenchymal stem cells, 35 but it is difficult to compare viabilities from one study to another due to differences in composition, and to potential differences in sensitivity for different cell types. Mironi-Harpaz et al compared crosslinking efficiency versus cytotoxicity to bovine aortic smooth muscle cells.…”

“…We directly visualized the depth of degradation by imaging the light yellow to orange-brown color change caused by the molar absorptivity increase of the degraded o-NB units under visible light. 35 The thickness of the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 19 degraded region was measured as the full-width-half-maximum (FWHM) of a cross-sectional intensity profile taken from the area with visible color change ( Figure S1). The volume change was evaluated by imaging the shift in fluorescent microbead locations at exposed sample surfaces compared to the non-exposed surface ( Figure S2).…”

Short Soluble Coumarin Crosslinkers for Light-Controlled Release of Cells and Proteins from Hydrogels

“…39 Light-Triggered Release of Iron Oxide Nanoparticles from Nanogels. Using the same chemistry, crosslinker 2 was also employed to synthesize light-degradable nanogels.…”

Synthesis, Characterization, and Application in HeLa Cells of an NIR Light Responsive Doxorubicin Delivery System Based on NaYF4:Yb,Tm@SiO2-PEG Nanoparticles

“…Initially, UV-Vis 11 light was used to trigger the release of drugs after inducing conformational changes 12,13 solubility variations 14 or the photodegradation of a specific group. 15,16 However, in-vitro studies demonstrated that the UV-Vis light can be toxic for living cells since it is widely absorbed by tissue, diminishing the light penetration to few microns. To solve these problems, NIR light has been used as external stimulus, which coupled with plasmonic systems provokes a local temperature increment that ends up with the drug release 17,18 .…”