ECM‐Inspired Chemical Cues: Biomimetic Molecules and Techniques of Immobilization

Tam, Roger Y.; Owen, Shawn C.; Shoichet, Molly S.

doi:10.1002/9781118843499.ch1

Cited by 3 publications

(7 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the continuing development of novel orthogonal functional groups 8,72 and photocages with different reactivities, 47,48 there is great opportunity to incorporate spatially defined chemical cues, temporal-controlled biomolecule activation, and spatiotemporal control of gel stiffness into a single scaffold. Design strategies that combine these aspects with hydrogels that are also responsive to cellular stimuli such as protease secretion and traction forces will enable the design of more complex, biomimetic systems to better study important biological questions in vitro.…”

Section: ■ Summary and Outlookmentioning

confidence: 99%

“…In contrast, the use of chemically defined polymers can overcome these limitations. The application of bioorthogonal “click” chemistry, which are high yielding chemical reactions with minimal toxic byproducts, to hydrogels has significantly advanced the ability to tune hydrogel properties to accommodate various cells types for diverse tissue engineering applications . This has allowed for both conjugation of bioactive molecules, and cross-linking reactions to produce bulk hydrogels with uniform and reproducible physicochemical properties.…”

Section: Introductionmentioning

confidence: 99%

“…The application of bioorthogonal "click" chemistry, which are high yielding chemical reactions with minimal toxic byproducts, to hydrogels has significantly advanced the ability to tune hydrogel properties to accommodate various cells types for diverse tissue engineering applications. 8 This has allowed for both conjugation of bioactive molecules, and cross-linking reactions to produce bulk hydrogels with uniform and reproducible physicochemical properties. However, while studies using gels that are bulkconjugated with biochemical ligands 9 and formulated with specific mechanical properties 10 have provided important insights into how cell−matrix interactions dictate cell proliferation and differentiation of various stem cell types, these in vitro models are often still overly simplified compared to the native ECM.…”

Section: ■ Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Engineering Cellular Microenvironments with Photo- and Enzymatically Responsive Hydrogels: Toward Biomimetic 3D Cell Culture Models

2017

Self Cite

View full text Add to dashboard Cite

Conventional cell culture techniques using 2D polystyrene or glass have provided great insight into key biochemical mechanisms responsible for cellular events such as cell proliferation, differentiation, and cell-cell interactions. However, the physical and chemical properties of 2D culture in vitro are dramatically different than those found in the native cellular microenvironment in vivo. Cells grown on 2D substrates differ significantly from those grown in vivo, and this explains, in part, why many promising drug candidates discovered through in vitro drug screening assays fail when they are translated to in vivo animal or human models. To overcome this obstacle, 3D cell culture using biomimetic hydrogels has emerged as an alternative strategy to recapitulate native cell growth in vitro. Hydrogels, which are water-swollen polymers, can be synthetic or naturally derived. Many methods have been developed to control the physical and chemical properties of the hydrogels to match those found in specific tissues. Compared to 2D culture, cells cultured in 3D gels with the appropriate physicochemical cues can behave more like they naturally do in vivo. While conventional hydrogels involve modifications to the bulk material to mimic the static aspects of the cellular microenvironment, recent progress has focused on using more dynamic hydrogels, the chemical and physical properties of which can be altered with external stimuli to better mimic the dynamics of the native cellular microenvironment found in vivo. In this Account, we describe our progress in designing stimuli-responsive, optically transparent hydrogels that can be used as biomimetic extracellular matrices (ECMs) to study cell differentiation and migration in the context of modeling the nervous system and cancer. Specifically, we developed photosensitive agarose and hyaluronic acid hydrogels that are activated by single or two-photon irradiation for biomolecule immobilization at specific volumes within the 3D hydrogel. By controlling the spatial location of protein immobilization, we created 3D patterns and protein concentration gradients within these gels. We used the latter to study the effect of VEGF-165 concentration gradients on the interactions between endothelial cells and retinal stem cells. Hyaluronic acid (HA) is particularly compelling as it is naturally found in the ECM of many tissues and the tumor microenvironment. We used Diels-Alder click chemistry and cryogelation to alter the chemical and physical properties of these hydrogels. We also designed HA hydrogels to study the invasion of breast cancer cells. HA gels were chemically cross-linked with matrix metalloproteinase (MMP)-degradable peptides that degrade in the presence of cancer cell-secreted MMPs, thus allowing cells to remodel their local microenvironment and invade into HA/MMP-degradable gels.

show abstract

Section: ■ Summary and Outlookmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Engineering Cellular Microenvironments with Photo- and Enzymatically Responsive Hydrogels: Toward Biomimetic 3D Cell Culture Models

2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…One has precise control over the biological signals incorporated within the hydrogel because peptides are significantly less complex, and generally more stable [76], than their native protein analogues, which often contain multiple signaling domains [77]. Many biologically active peptides have been developed for use in regenerative medicine [78]. Most commonly employed is the fibronectin-derived RGD peptide sequence.…”

Section: Strategies In Photochemical Patterning Of Biological Signalsmentioning

confidence: 99%

Thiol-ene and photo-cleavage chemistry for controlled presentation of biomolecules in hydrogels

Grim

Marozas

Anseth

2015

Journal of Controlled Release

109

View full text Add to dashboard Cite

Hydrogels have emerged as promising scaffolds in regenerative medicine for the delivery of biomolecules to promote healing. However, increasing evidence suggests that the context that biomolecules are presented to cells (e.g., as soluble verses tethered signals) can influence their bioactivity. A common approach to deliver biomolecules in hydrogels involves physically entrapping them within the network, such that they diffuse out over time to the surrounding tissues. While simple and versatile, the release profiles in such system are highly dependent on the molecular weight of the entrapped molecule relative to the network structure, and it can be difficult to control the release of two different signals at independent rates. In some cases, supraphysiologically high loadings are used to achieve therapeutic local concentrations, but uncontrolled release can then cause deleterious off-target side effects. In vivo, many growth factors and cytokines are stored in the extracellular matrix (ECM) and released on demand as needed during development, growth, and wound healing. Thus, emerging strategies in biomaterial chemistry have focused on ways to tether or sequester biological signals and engineer these bioactive scaffolds to signal to delivered cells or endogenous cells. While many strategies exist to achieve tethering of peptides, protein, and small molecules, this review focuses on photochemical methods, and their usefulness as a mild reaction that proceeds with fast kinetics in aqueous solutions and at physiological conditions. Photo-click and photo-caging methods are particularly useful because one can direct light to specific regions of the hydrogel to achieve spatial patterning. Recent methods have even demonstrated reversible introduction of biomolecules to mimic the dynamic changes of native ECM, enabling researchers to explore how the spatial and dynamic context of biomolecular signals influences important cell functions. This review will highlight how two photochemical methods have led to important advances in the tissue regeneration community, namely the thiol-ene photo-click reaction for bioconjugation and photocleavage reactions that allow for the removal of protecting groups. Specific examples will be highlighted where these methodologies have been used to engineer hydrogels that control and direct cell function with the aim of inspiring their use in regenerative medicine.

show abstract

“…Consequently, tissue engineers have begun to utilise and develop novel synthetic materials that do not possess the unpredictable variation associated with natural, decellularized scaffolds [ 49 ]. These synthetic materials can also be modified to mimic features of the native ECM in a bottom-up approach, where any scaffold is seen as a blank canvas on which scientists can add desirable features, such as motifs for adhesion or migration [ 51 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Extracellular Matrix (ECM) Adhesion Motifs in Functionalised Hydrogels

Morwood,

El-Karim,

Clarke

et al. 2023

Molecules

View full text Add to dashboard Cite

To create functional tissue engineering scaffolds, biomaterials should mimic the native extracellular matrix of the tissue to be regenerated. Simultaneously, the survival and functionality of stem cells should also be enhanced to promote tissue organisation and repair. Hydrogels, but in particular, peptide hydrogels, are an emerging class of biocompatible scaffolds which act as promising self-assembling biomaterials for tissue engineering and regenerative therapies, ranging from articular cartilage regeneration at joint defects, to regenerative spinal cord injury following trauma. To enhance hydrogel biocompatibility, it has become imperative to consider the native microenvironment of the site for regeneration, where the use of functionalised hydrogels with extracellular matrix adhesion motifs has become a novel, emerging theme. In this review, we will introduce hydrogels in the context of tissue engineering, provide insight into the complexity of the extracellular matrix, investigate specific adhesion motifs that have been used to generate functionalised hydrogels and outline their potential applications in a regenerative medicine setting. It is anticipated that by conducting this review, we will provide greater insight into functionalised hydrogels, which may help translate their use towards therapeutic roles.

show abstract

ECM‐Inspired Chemical Cues: Biomimetic Molecules and Techniques of Immobilization

Cited by 3 publications

References 115 publications

Engineering Cellular Microenvironments with Photo- and Enzymatically Responsive Hydrogels: Toward Biomimetic 3D Cell Culture Models

Engineering Cellular Microenvironments with Photo- and Enzymatically Responsive Hydrogels: Toward Biomimetic 3D Cell Culture Models

Thiol-ene and photo-cleavage chemistry for controlled presentation of biomolecules in hydrogels

The Role of Extracellular Matrix (ECM) Adhesion Motifs in Functionalised Hydrogels

Contact Info

Product

Resources

About