Two-component protein-engineered physical hydrogels for cell encapsulation

Foo, Cheryl T. S. Wong Po; Lee, Jiseok; Mulyasasmita, Widya; Parisi‐Amon, Andreina; Heilshorn, Sarah C.

doi:10.1073/pnas.0904851106

Cited by 293 publications

(263 citation statements)

References 64 publications

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“…In this case, molecular engineering allows for the precise introduction of a range of signal response mechanisms to control hydrogel properties (for example, via crosslinking) or cellular interactions (for example, via degradation sites) 61 . This area is likely to expand in upcoming years, as the need for the complexity found in native tissues is realized.…”

Section: Hydrogels That Degrade With Timementioning

confidence: 99%

Moving from static to dynamic complexity in hydrogel design

2012

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Hydrogels are water-swollen polymer networks that have found a range of applications from biological scaffolds to contact lenses. Historically, their design has consisted primarily of static systems and those that exhibit simple degradation. However, advances in polymer synthesis and processing have led to a new generation of dynamic systems that are capable of responding to artificial triggers and biological signals with spatial precision. These systems will open up new possibilities for the use of hydrogels as model biological structures and in tissue regeneration.H ydrogels are water-swollen polymer networks that have been used for many decades, with applications as varied as contact lenses and super-absorbant materials. As the field of biomedical engineering has developed, hydrogels have become a prime candidate for application as molecule delivery vehicles and as carriers for cells in tissue engineering, owing to their ability to mimic many aspects of the native cellular environment (for example, high water content, mechanical properties that match soft tissues). Traditional hydrogels, formed through the covalent and non-covalent crosslinking of polymer chains, were regarded as relatively inert materials, providing a simple biomimetic three-dimensional (3D) environment, either for tissue production by local resident cells or for positioning of cells delivered in vivo. However, the simplicity of these materials may have in fact hindered their application, restricting cellular interactions with the environment and preventing uniform extracellular matrix (ECM) production and proper tissue development. In addition, these materials were limited to modelling static environments and lacked the spatiotemporal dynamic properties relevant for complex tissue processes. Fortunately, during the last decade the concepts of hydrogel design and cellular interaction have evolved, shedding light on how they may control cell behaviour, particularly for tissue engineering applications.Hydrogels with a range of mechanical properties, and capable of incorporating a wide range of biologically relevant molecules, from individual functional groups to multidomain proteins, are currently in development 1 . In addition, hydrogels are being designed with spatial heterogeneity, to either replicate properties in native tissue structures or to produce constructs with distinct regionally specific cell behavior 2 . As a result, studies to date have clearly demonstrated the possibility of creating well-defined microenvironments with control over the 3D presentation of signals to cells 3 . However, recently there has been a focus on the concept of hydrogels that exhibit dynamic complexity. These materials should evolve with time and in response to

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Section: Hydrogels That Degrade With Timementioning

confidence: 99%

Moving from static to dynamic complexity in hydrogel design

2012

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“…Engineered scaffolds (e.g., Refs. [43][44][45] ) will enable investigation of the effect of scaffold properties in 2D and 3D culture in more detail.…”

Section: Figmentioning

confidence: 99%

Substrate Three-Dimensionality Induces Elemental Morphological Transformation of Sensory Neurons on a Physiologic Timescale

Ribeiro

Vargo

Powell

et al. 2012

Tissue Engineering Part A

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The natural environment of a neuron is the three-dimensional (3D) tissue. In vivo, embryonic sensory neurons transiently express a bipolar morphology with two opposing neurites before undergoing cytoplasmic and cytoskeletal rearrangement to a more mature pseudo-unipolar axonal arbor before birth. The unipolar morphology is crucial in the adult for correct information transmission from the periphery to the central nervous system. On two-dimensional (2D) substrates this transformation is delayed significantly or absent. We report that a 3D culture platform can invoke the characteristic transformation to the unipolar axonal arbor within a time frame similar to in vivo, overcoming the loss of this essential milestone in 2D substrates. Additionally, 3D substrates alone provided an environment that promoted axonal branching features that reflect morphological patterns observed in vivo. We have also analyzed the involvement of soluble cues in these morphogenic processes by culturing the neurons in the presence and absence of nerve growth factor (NGF), a molecule that plays distinct roles in the development of the peripheral and central nervous systems. Without NGF, both 2D and 3D cultures had significant decreases in the relative population of unipolar neurons as well as shorter neurite lengths and fewer branch points compared to cultures with NGF. Interestingly, branching features of neurons cultured in 3D without NGF resemble those of neurons cultured in 2D with NGF. Therefore, neurons cultured in 3D without NGF lost the ability to differentiate into unipolar neurons, suggesting that this morphological hallmark requires not only presentation of soluble cues like NGF, but also the surrounding 3D presentation of adhesive ligands to allow for realization of the innate morphogenic program. We propose that in a 3D environment, various matrix and soluble cues are presented toward all surfaces of the cell; this optimized milieu allows neurons to elaborate their genuine phenotype and follow programmed instructions that are intrinsic to the neuron, but disrupted when cells were dissected from the embryo. Thus, this study presents quantitative data supporting that 3D substrates are critical for sustaining the in vivo ontogeny of neurons and deciphering signaling mechanisms necessary for designing biomaterial scaffolds for nerve generation and repair.

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“…cartilage defect) [8]. Moreover, various potential therapeutic agents, such as drugs [9,10], cells [11,12] and growth factors [13,14], could also be incorporated into the matrix by pre-mixing.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of a Novel Injectable Hydrogel

Pan¹

2013

Adv Genet Eng

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Two-component protein-engineered physical hydrogels for cell encapsulation

Cited by 293 publications

References 64 publications

Moving from static to dynamic complexity in hydrogel design

Moving from static to dynamic complexity in hydrogel design

Substrate Three-Dimensionality Induces Elemental Morphological Transformation of Sensory Neurons on a Physiologic Timescale

Preparation and Characterization of a Novel Injectable Hydrogel

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