Tuning hydrogel properties with sequence-defined, non-natural peptoid crosslinkers

Morton, Logan D; Hillsley, Alexander; Austin, Mariah J.; Rosales, Adrianne M.

doi:10.1039/d0tb00683a

Cited by 8 publications

(10 citation statements)

References 49 publications

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“…Rosales et al synthesized a series of helical peptoid oligomers as crosslinkers in poly(ethylene glycol) (PEG) hydrogels. 277 The matrix stiffness of peptoid-cross-linked hydrogels increased with longer peptoid lengths, which indicated the effect of peptoid chain rigidity on bulk properties. Most importantly, the peptoid cross-linkers conferred enhanced stability in response to proteolysis compared with peptoid-cross-linked hydrogels.…”

Section: Tissue Engineering and Cell Culturementioning

confidence: 96%

“…Additionally, peptoids could also serve as cross-linkers for tuning hydrogel properties. Rosales et al synthesized a series of helical peptoid oligomers as cross-linkers in poly(ethylene glycol) (PEG) hydrogels . The matrix stiffness of peptoid-cross-linked hydrogels increased with longer peptoid lengths, which indicated the effect of peptoid chain rigidity on bulk properties.…”

Section: Applications Of Hierarchical Materials Assembled From Sequen...mentioning

confidence: 99%

“…Given the enormous diversity of potential sequential structures of the self-assembling sequence-defined synthetic polymers, the hierarchical self-assembly of those molecules will open a credible and broad route to reaching the robust hierarchical materials with advanced properties for various applications. For example, while some peptoid sequences have exhibited great potential for applications including 3D cell culture, disease modeling, and heavy metal extraction/remediation, − and self-assembled peptoid nanomaterials have shown some distinct advantages, including high surface area, robustness in water and organic solvents, and high biocompatibility, a combination of these functional peptoids with self-assembling blocks for hierarchical self-assembly will open new opportunities for the development of bioinspired materials for biomedical and environmental applications. The development of scalable and efficient synthetic methods for sequence-defined polymers is crucial to the large-scale assembly and applications of the resulting assembled nanomaterials to fulfill the high demand of functional materials in the future.…”

Section: Summary and Outlookmentioning

confidence: 99%

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Hierarchical Nanomaterials Assembled from Peptoids and Other Sequence-Defined Synthetic Polymers

Cai

Yang

et al. 2021

Chem. Rev.

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In nature, the self-assembly of sequence-specific biopolymers into hierarchical structures plays an essential role in the construction of functional biomaterials. To develop synthetic materials that can mimic and surpass the function of these natural counterparts, various sequence-defined bio- and biomimetic polymers have been developed and exploited as building blocks for hierarchical self-assembly. This review summarizes the recent advances in the molecular self-assembly of hierarchical nanomaterials based on peptoids (or poly-N-substituted glycines) and other sequence-defined synthetic polymers. Modern techniques to monitor the assembly mechanisms and characterize the physicochemical properties of these self-assembly systems are highlighted. In addition, discussions about their potential applications in biomedical sciences and renewable energy are also included. This review aims to highlight essential features of sequence-defined synthetic polymers (e.g., high stability and protein-like high-information content) and how these unique features enable the construction of robust biomimetic functional materials with high programmability and predictability, with an emphasis on peptoids and their self-assembled nanomaterials.

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Section: Tissue Engineering and Cell Culturementioning

confidence: 96%

Section: Applications Of Hierarchical Materials Assembled From Sequen...mentioning

confidence: 99%

Section: Summary and Outlookmentioning

confidence: 99%

See 1 more Smart Citation

Hierarchical Nanomaterials Assembled from Peptoids and Other Sequence-Defined Synthetic Polymers

Cai

Yang

et al. 2021

Chem. Rev.

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“…[4] On the other hand, synthetic materials like polyethylene glycol (PEG) offer well-defined, highly tunable systems, but they are bioinert and must be functionalized with bioactive molecules to permit cellular interaction. [5][6][7] Recombinant protein-based biomaterials offer an alternative that is reproducible, cell-interactive, and facilitates the independent tuning of biochemical and biomechanical properties, emerging as an advantageous 3D culture platform for a variety of cell types. [8][9][10] Elastin-like proteins (ELPs) are a class of mechanically tunable, protein-engineered materials well-suited for studying encapsulated cell response to matrix-derived signaling cues.…”

Section: Introductionmentioning

confidence: 99%

Tuning Polymer Hydrophilicity to Regulate Gel Mechanics and Encapsulated Cell Morphology

Huang

Roth

Hubka

et al. 2022

Adv Healthcare Materials

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Mechanically tunable hydrogels are attractive platforms for 3D cell culture, as hydrogel stiffness plays an important role in cell behavior. Traditionally, hydrogel stiffness has been controlled through altering either the polymer concentration or the stoichiometry between crosslinker reactive groups. Here, an alternative strategy based upon tuning the hydrophilicity of an elastin-like protein (ELP) is presented. ELPs undergo a phase transition that leads to protein aggregation at increasing temperatures. It is hypothesized that increasing this transition temperature through bioconjugation with azide-containing molecules of increasing hydrophilicity will allow direct control of the resulting gel stiffness by making the crosslinking groups more accessible. These azide-modified ELPs are crosslinked into hydrogels with bicyclononyne-modified hyaluronic acid (HA-BCN) using bioorthogonal, click chemistry, resulting in hydrogels with tunable storage moduli (100-1000 Pa). Human mesenchymal stromal cells (hMSCs), human umbilical vein endothelial cells (HUVECs), and human neural progenitor cells (hNPCs) are all observed to alter their cell morphology when encapsulated within hydrogels of varying stiffness. Taken together, the use of protein hydrophilicity as a lever to tune hydrogel mechanical properties is demonstrated. These hydrogels have tunable moduli over a stiffness range relevant to soft tissues, support the viability of encapsulated cells, and modify cell spreading as a consequence of gel stiffness.

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“…[25,30] In addition, we previously showed that increasing the length of helical peptoid crosslinkers increased the elastic moduli of PEG hydrogels, breaking the trend predicted by rubber elasticity theory for flexible polymer networks. [31] Thus, peptoids are an excellent model system for probing the effect of crosslinker chain structure on bulk mechanics for engineered ECM applications.…”

Section: Introductionmentioning

confidence: 99%

Crosslinker Structure Modulates Bulk Mechanical Properties and Dictates hMSC Behavior on Hyaluronic Acid Hydrogels

Morton

Castilla‐Casadiego

Palmer

et al. 2022

Preprint

Self Cite

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Synthetic hydrogels are attractive platforms due in part to their highly tunable mechanics, which impact cell behavior and secretory profile. These mechanics are often controlled by altering the number of crosslinks or the total polymer concentration in the gel, leading to structure-property relationships that inherently couple network connectivity to the overall modulus. In contrast, the native extracellular matrix (ECM) contains structured biopolymers that enable stiff gels even at low polymer content, facilitating 3D cell culture and permeability of soluble factors. To mimic the hierarchical order of natural ECM, this work describes a synthetic hydrogel system in which mechanics are tuned using the structure of sequence-defined peptoid crosslinkers, while fixing network connectivity. Peptoid crosslinkers with different secondary structures are investigated: 1) a helical, molecularly stiff peptoid, 2) a non-helical, less stiff peptoid, and 3) an unstructured, relatively flexible peptoid. Bulk hydrogel storage modulus increases when crosslinkers of higher chain stiffness are used. In-vitro studies assess the viability, proliferation, cell morphology, and immunomodulatory activity of human mesenchymal stem cells (hMSCs) on each hydrogel substrate. Matrix mechanics regulate the morphology of hMSCs on the developed substrates, and all of the hydrogels studied upregulate IDO production over culture on TCP. Softer substrates further this upregulation to a plateau. Overall, this system offers a biomimetic strategy for decoupling hydrogel storage modulus from network connectivity, enabling systematic study of biomaterial properties on hMSC behavior and enhancement of cellular functionality for therapeutic applications.

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Tuning hydrogel properties with sequence-defined, non-natural peptoid crosslinkers

Abstract: Helical peptoid crosslinkers confer tunable mechanical properties and enzymatic stability to hydrogels for cell culture.

Cited by 8 publications

References 49 publications

Hierarchical Nanomaterials Assembled from Peptoids and Other Sequence-Defined Synthetic Polymers

Hierarchical Nanomaterials Assembled from Peptoids and Other Sequence-Defined Synthetic Polymers

Tuning Polymer Hydrophilicity to Regulate Gel Mechanics and Encapsulated Cell Morphology

Crosslinker Structure Modulates Bulk Mechanical Properties and Dictates hMSC Behavior on Hyaluronic Acid Hydrogels

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