Sequential modes of crosslinking tune viscoelasticity of cell-instructive hydrogels

Vining, Kyle H.; Stafford, Alexander; Mooney, David J.

doi:10.1016/j.biomaterials.2018.10.013

Cited by 95 publications

(86 citation statements)

References 44 publications

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“…However, in response to licensing, encapsulates in purely alginate microgels displayed increased up-regulation of immunomodulatory genes compared with those in APA microgels. The additional cross-linking with PDL would likely have decreased substrate viscoelasticity, which has been linked to a more muted response to licensing in encapsulated MSCs (41). Nevertheless, the ability of MAPA mMSCs to broadly adopt an immunomodulatory phenotype upon licensing supports their usage to reduce dosing and increase efficacy.…”

Section: Discussionmentioning

confidence: 99%

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

Mao

Özkale

Shah

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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134

104

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Mesenchymal stem cell (MSC) therapies demonstrate particular promise in ameliorating diseases of immune dysregulation but are hampered by short in vivo cell persistence and inconsistencies in phenotype. Here, we demonstrate that biomaterial encapsulation into alginate using a microfluidic device could substantially increase in vivo MSC persistence after intravenous (i.v.) injection. A combination of cell cluster formation and subsequent cross-linking with polylysine led to an increase in injected MSC half-life by more than an order of magnitude. These modifications extended persistence even in the presence of innate and adaptive immunity-mediated clearance. Licensing of encapsulated MSCs with inflammatory cytokine pretransplantation increased expression of immunomodulatory-associated genes, and licensed encapsulates promoted repopulation of recipient blood and bone marrow with allogeneic donor cells after sublethal irradiation by a ∼2-fold increase. The ability of microgel encapsulation to sustain MSC survival and increase overall immunomodulatory capacity may be applicable for improving MSC therapies in general.

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Section: Discussionmentioning

confidence: 99%

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

Mao

Özkale

Shah

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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134

104

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“…The dECM hydrogels relaxed completely after compression, whereas tissues did not, irrespective of the underlying disease. The relaxation behavior of a sample is dictated, in part, by the topical arrangement of ECM in intact tissue or degree and type (e.g., ionic or covalent) of internal cross-linking in hydrogels (28,30). This may explain the higher degree of relaxation seen in the dECM hydrogels and the reduced degree of relaxation of IPF tissue compared with COPD GOLD IV and control tissue.…”

Section: L702mentioning

confidence: 99%

Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue

Hilster

Sharma²,

Jonker

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

109

115

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de Hilster RHJ, Sharma PK, Jonker MR, White ES, Gercama EA, Roobeek M, Timens W, Harmsen MC, Hylkema MN, Burgess JK. Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue. Chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are associated with changes in extracellular matrix (ECM) composition and abundance affecting the mechanical properties of the lung. This study aimed to generate ECM hydrogels from control, severe COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) IV], and fibrotic human lung tissue and evaluate whether their stiffness and viscoelastic properties were reflective of native tissue. For hydrogel generation, control, COPD GOLD IV, and fibrotic human lung tissues were decellularized, lyophilized, ground into powder, porcine pepsin solubilized, buffered with PBS, and gelled at 37°C. Rheological properties from tissues and hydrogels were assessed with a low-load compression tester measuring the stiffness and viscoelastic properties in terms of a generalized Maxwell model representing phases of viscoelastic relaxation. The ECM hydrogels had a greater stress relaxation than tissues. ECM hydrogels required three Maxwell elements with slightly faster relaxation times () than that of native tissue, which required four elements. The relative importance (R i) of the first Maxwell element contributed the most in ECM hydrogels, whereas for tissue the contribution was spread over all four elements. IPF tissue had a longer-lasting fourth element with a higher R i than the other tissues, and IPF ECM hydrogels did require a fourth Maxwell element, in contrast to all other ECM hydrogels. This study shows that hydrogels composed of native human lung ECM can be generated. Stiffness of ECM hydrogels resembled that of whole tissue, while viscoelasticity differed.

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“…[ 43,44 ] Moreover, the functional properties of adaptable networks with lower molecular weight biopolymers (such as oxLAM) as network‐crosslinking agents remain elusive to date. [ 29,62 ] Aldehyde‐functionalized oxLAM biopolymer can readily bind to amine‐containing biomaterials via Schiff base formation, which is convenient to install dynamic crosslinks with ECM‐mimetic gelatin ( Figure A). Gelatin's polypeptide backbone contains an appreciable number of amine‐terminated sidechains (e.g., lysine, hydroxylysine and arginine) that are available for establishing imine bonds with oxLAM.…”

Section: Resultsmentioning

confidence: 99%

Mechanochemical Patternable ECM‐Mimetic Hydrogels for Programmed Cell Orientation

Lavrador

Gaspar

Mano

2020

Adv Healthcare Materials

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Native human tissues are supported by a viscoelastic extracellular matrix (ECM) that can adapt its intricate network to dynamic mechanical stimuli. To recapitulate the unique ECM biofunctionality, hydrogel design is shifting from typical covalent crosslinks toward covalently adaptable networks. To pursue such properties, herein hybrid polysaccharide-polypeptide networks are designed based on dynamic covalent assembly inspired by natural ECM crosslinking processes. This is achieved through the synthesis of an amine-reactive oxidized-laminarin biopolymer that can readily crosslink with gelatin (oxLAM-Gelatin) and simultaneously allow cell encapsulation. Interestingly, the rational design of oxLAM-Gelatin hydrogels with varying aldehyde-to-amine ratios enables a refined control over crosslinking kinetics, viscoelastic properties, and degradability profile. The mechanochemical features of these hydrogels post-crosslinking offer an alternative route for imprinting any intended nano-or microtopography in ECM-mimetic matrices bearing inherent cell-adhesive motifs. Different patterns are easily paved in oxLAM-Gelatin under physiological conditions and complex topographical configurations are retained along time. Human adipose-derived mesenchymal stem cells contacting mechanically sculpted oxLAM-Gelatin hydrogels sense the underlying surface nanotopography and align parallel to the anisotropic nanoridge/nanogroove intercalating array. These findings demonstrate that covalently adaptable features in ECM-mimetic networks can be leveraged to combine surface topography and cell-adhesive motifs as they appear in natural matrices.

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Sequential modes of crosslinking tune viscoelasticity of cell-instructive hydrogels

Cited by 95 publications

References 44 publications

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation

Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue

Mechanochemical Patternable ECM‐Mimetic Hydrogels for Programmed Cell Orientation

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