Crosslinker structure modulates bulk mechanical properties and dictates hMSC behavior on hyaluronic acid hydrogels

Morton, Logan D; Castilla‐Casadiego, David A.; Palmer, Ajay C; Rosales, Adrianne M.

doi:10.1016/j.actbio.2022.11.027

Cited by 8 publications

(23 citation statements)

References 70 publications

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“…However, some articles report on peptoids' cytocompatibility and bioactivity toward mesenchymal stem cells. As an example, Morton et al exploited unstructured, helical, and non-helical peptoids to tune the biomechanical properties of hydrogels to realize 3D cultures of stem cells that did not report any toxic effect after seeding and cultivating in direct contact [ 51 ]. Statz et al were able to correlate the length and the surface density of peptoids on titanium substrates with their antifouling activity towards fibroblasts.…”

Section: Resultsmentioning

confidence: 99%

Nano-topography and functionalization with the synthetic peptoid GN2-Npm9 as a strategy for antibacterial and biocompatible titanium implants

Gamna,

Cochis,

Mojsoska

et al. 2024

Heliyon

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Section: Resultsmentioning

confidence: 99%

Nano-topography and functionalization with the synthetic peptoid GN2-Npm9 as a strategy for antibacterial and biocompatible titanium implants

Gamna,

Cochis,

Mojsoska

et al. 2024

Heliyon

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“…Although all tested hydrogels endowed embedded MSCs with enhanced expression of immunomodulatory IDO, the softer hydrogel seems to enhance IDO production to a certain degree. IFN-γ supplementation seems to have less effects on softer hydrogels [138] (Table 1).…”

Section: Viscoelasticitymentioning

confidence: 99%

Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells by Hydrogel Encapsulation

Cheng,

Anggelia,

Liu

et al. 2024

Cells

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Mesenchymal stromal cells (MSCs) showcase remarkable immunoregulatory capabilities in vitro, positioning them as promising candidates for cellular therapeutics. However, the process of administering MSCs and the dynamic in vivo environment may impact the cell–cell and cell–matrix interactions of MSCs, consequently influencing their survival, engraftment, and their immunomodulatory efficacy. Addressing these concerns, hydrogel encapsulation emerges as a promising solution to enhance the therapeutic effectiveness of MSCs in vivo. Hydrogel, a highly flexible crosslinked hydrophilic polymer with a substantial water content, serves as a versatile platform for MSC encapsulation. Demonstrating improved engraftment and heightened immunomodulatory functions in vivo, MSCs encapsulated by hydrogel are at the forefront of advancing therapeutic outcomes. This review delves into current advancements in the field, with a focus on tuning various hydrogel parameters to elucidate mechanistic insights and elevate functional outcomes. Explored parameters encompass hydrogel composition, involving monomer type, functional modification, and co-encapsulation, along with biomechanical and physical properties like stiffness, viscoelasticity, topology, and porosity. The impact of these parameters on MSC behaviors and immunomodulatory functions is examined. Additionally, we discuss potential future research directions, aiming to kindle sustained interest in the exploration of hydrogel-encapsulated MSCs in the realm of immunomodulation.

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“…[40] All hydrogels were prepared using photoinitiated thiol-ene cross-linking with a norbornene-functionalized hyaluronic acid, as described previously. [40] We have shown that the hydrogels resulting from these different cross-linkers span a swollen elastic moduli range from ≈1.5 to 12 kPa. [40] Fourier-transform infrared spectroscopy (FTIR) was used to assess the chemical composition of the cross-linked hydrogels.…”

Section: Cross-linker Structure Determines Hydrogel Propertiesmentioning

confidence: 99%

“…In general, a variety of hydrogel scaffolds have been found to enhance the immunomodulatory potential of licensed hMSCs, compared to cells cultured on plastic. [16,[39][40][41][42][43][44][45][46][47][48] However, there is debate as to the ideal stiffness range to promote beneficial immunomodulatory effects. [43] Abdeen et al found that hMSCs cultured on 2D polyacrylamide hydrogels showed increased vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 production on stiffer hydrogels (E ≈40 kPa) than on softer counterparts (E ≈500 Pa), [41] while Ogle et al showed that hMSCs cultured on 30 kPa polyethylene glycol (PEG) hydrogels showed significantly more secretion of many immunomodulatory factors than on stiffer 100 kPa hydrogels.…”

Section: Introductionmentioning

confidence: 99%

Peptoid‐Cross‐Linked Hydrogel Stiffness Modulates Human Mesenchymal Stromal Cell Immunoregulatory Potential in the Presence of Interferon‐Gamma

Castilla‐Casadiego,

Morton,

Loh

et al. 2024

Macromolecular Bioscience

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Human mesenchymal stromal cell (hMSC) manufacturing requires the production of large numbers of therapeutically potent cells. Licensing with soluble cytokines improves hMSC therapeutic potency by enhancing secretion of immunoactive factors but typically decreases proliferative ability. Soft hydrogels, however, have shown promise for boosting immunomodulatory potential, which may compensate for decreased proliferation. Here, hydrogels were crosslinked with peptoids of different secondary structures to generate substrates of various bulk stiffness but fixed network connectivity. Secretion of interleukin 6 (IL‐6), monocyte chemoattractive protein (MCP‐1), macrophage colony‐stimulating factor (MCS‐F), and vascular endothelial growth factor (VEGF) were shown to depend on hydrogel stiffness in the presence of interferon gamma (IFN‐γ) supplementation, with soft substrates further improving secretion. The immunological function of these secreted cytokines was then investigated via coculture of hMSCs seeded on hydrogels with Primary Peripheral Blood Mononuclear Cells (PBMCs) in the presence and absence of IFN‐γ. Co‐cultures with hMSCs seeded on softer hydrogels showed decreased PBMC proliferation with IFN‐γ. To probe possible signaling pathways, immunofluorescent studies probed the NF‐κB pathway and demonstrated that IFN‐γ supplementation and softer hydrogel mechanics led to higher activation of this pathway. Overall, these studies may allow for production of more efficacious therapeutic hMSCs in the presence of IFN‐γ.This article is protected by copyright. All rights reserved

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Crosslinker structure modulates bulk mechanical properties and dictates hMSC behavior on hyaluronic acid hydrogels

Cited by 8 publications

References 70 publications

Nano-topography and functionalization with the synthetic peptoid GN2-Npm9 as a strategy for antibacterial and biocompatible titanium implants

Nano-topography and functionalization with the synthetic peptoid GN2-Npm9 as a strategy for antibacterial and biocompatible titanium implants

Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells by Hydrogel Encapsulation

Peptoid‐Cross‐Linked Hydrogel Stiffness Modulates Human Mesenchymal Stromal Cell Immunoregulatory Potential in the Presence of Interferon‐Gamma

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