Injectable shear-thinning hydrogels engineered with a self-assembling Dock-and-Lock mechanism

Lu, Hoang D.; Charati, Manoj B.; Kim, Iris L.; Burdick, Jason A.

doi:10.1016/j.biomaterials.2011.11.076

Cited by 177 publications

(166 citation statements)

References 43 publications

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“…Using this robust assembling strategy, a wide range of protein hydrogels have been engineered, ranging from random coil sequence-based hydrogels, to hydrogels encompassing folded globular domains with diverse functions. [6][7][8][9][10][11][12][13][14] Other methodologies toward constructing hydrogels have been subsequently developed, including those based on heterodimeric molecular recognition between protein motifs, [ 5 ] including growth factor mediated hydrogels, [ 15 ] "Dock-and-Lock" hydrogels, [ 16,17 ] and mixing-induced two-component hydrogels. [ 18 ] Despite these progresses, strategies to construct self-assembling protein hydrogels remain rather limited, limiting the possibility toward the systematic engineering of protein hydrogel properties.…”

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confidence: 99%

Protein Fragment Reconstitution as a Driving Force for Self‐Assembling Reversible Protein Hydrogels

Kong

2015

Adv Funct Materials

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Due to their potential biomedical applications, protein-based hydrogels have attracted considerable interest. Although various methods have been developed to engineer self-assembling, physically-crosslinked protein hydrogels, exploring novel driving forces to engineer such hydrogels remains challenging. Protein fragment reconstitution, also known as fragment complementation, is a self-assembling mechanism by which protein fragments can reconstitute the folded conformation of the native protein when split into two halves. Although it has been used in biophysical studies and bioassays, fragment reconstitution has not been explored for hydrogel construction. Using a small protein GL5 as a model, which is capable of fragment reconstitution to reconstitute the folded GL5 spontaneously when split into two halves, GN and GC, we demonstrate that protein fragment reconstitution is a novel driving force for engineering self-assembling reversible protein hydrogels. Fragment reconstitution between GN and GC crosslinks GN and GC-containing proteins into self-assembling reversible protein hydrogels. These novel hydrogels show temperature-dependent reversible sol-gel transition, and excellent property against erosion in water. Since many proteins can undergo fragment reconstitution, we anticipate that such fragment reconstitution may offer a general driving force for engineering protein hydrogels from a variety of proteins, and thus signifi cantly expanding the 'toolbox' currently available in the fi eld of biomaterials. DOI IntroductionProtein hydrogels have attracted considerable interest over the last two decades due to their potential applications in a wide range of biomedical applications, including drug delivery, as artifi cial extracellular matricies and regenerative medicines. [1][2][3] Among engineered protein hydrogels, self-assembling hydrogels are of particular interest. [ 2,4,5 ] Inspired by the pioneering work of Tirrell and co-workers, [ 6 ] researchers have been developing novel strategies for engineering self-assembling protein hydrogels [4][5][6][7][8] Adv. Funct explored in engineering self-assembling protein hydrogels or supramolecular protein polymers. For the two split fragments A and B that can undergo fragment reconstitution to reconstitute the native folded structure, it should be feasible to crosslink multifunctional polymers (S-A) n and (S-B) m into a polymer network and form a hydrogel, where S represents spacers, A and B are the two fragments capable of reconstituting, and m and n represent the number of repeating units (Figure 1 B). Using fragments from a loop elongation variant of GB1 as a model system, we demonstrate the proof-of-principle of using protein fragment reconstitution as a driving force to engineer self-assembling protein hydrogels. Using different protein designs, we demonstrate both two-component as well as singlecomponent approaches to engineer protein fragment reconstitution-driven protein hydrogels.

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confidence: 99%

Protein Fragment Reconstitution as a Driving Force for Self‐Assembling Reversible Protein Hydrogels

Kong

2015

Adv Funct Materials

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“…Heterodimeric associating pairs have included heparin oligomers and heparinbinding coiled-coils attached to the ends of four arm PEG, 60,75,76 WW domains and proline-rich domains incorporated along the backbone of engineered proteins, 59,77 and heterodimeric coiled-coils in the polymer backbone 78 or incorporated as side chains. 79,80 Mixing difunctional biotin proteins with streptavidin, which naturally tetramerizes to form network junctions 81 and a recently reported ''dock and lock'' mechanism based on homodimerizing RIIa subunits of c-AMP-dependent kinase A and A-kinase anchoring protein 58 further illustrate the versatility of two-component physical gels driven by selective protein associations.…”

Section: Physical Gels With Protein-associating Domainsmentioning

confidence: 95%

“…57 Shear thinning and rapid self-healing properties make the materials ideal for injectable biomedical hydrogels, and many investigations have demonstrated the utility of the materials for this purpose. [58][59][60] Besides affecting the responsive transitions of hydrogels, the associating group molecular weight 61 and coiled-coil sequence impact the mechanical properties of gels by controlling the structure of network junctions. Consistent with the theory of gelation, an association number of >2 is required for gelation of telechelic polymers.…”

Section: Physical Gels With Protein-associating Domainsmentioning

confidence: 99%

Physics of engineered protein hydrogels

Kim

Tang

Olsen

2013

J Polym Sci B Polym Phys

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Artificially engineered proteins and synthetic polypeptides have attracted widespread interest as building blocks for polymer hydrogels. The biophysical properties of the proteins, such as molecular recognition abilities, folded chain structures, and sequence-dependent thermodynamic behavior, enable advances in functional, responsive, and tunable gels. This review discusses the design of polymer hydrogels that incorporate protein domains, highlighting new challenges in polymer physics that are presented by this emerging class of materials. Five types of engineered protein hydrogels are discussed: (a) physically associating protein polymer gels, (b) amorphous artificially engineered protein networks, (c) engineered proteins with crystalline domains, (d) stretchable protein tertiary structures in gels, and (e) protein gels with biological recognition properties. The physics of the protein component and the physical properties of the resulting hydrogels are summarized, illustrating how advances in understanding these systems are leading to exciting novel biofunctional hydrogels.

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“…Most biomaterials do not exhibit favorable rheological properties for 3D printing so researchers have transformed the rheological properties of biomaterials by functionalizing them with moieties that form physical crosslinks (Lu et al, 2012a;Shepherd et al, 2012;Ouyang et al, 2016). An example of this involves supramolecular bonding of adamantane and β-cyclodextrin moieties, which assemble into a complex at low stress and disassemble when exposed to high stress (Ouyang et al, 2016).…”

Section: Strategies For Biomaterials Printingmentioning

confidence: 99%

Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior

Meco

Lampe

2018

Front. Mater.

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Biomaterial scaffolds mimic aspects of the native central nervous system (CNS) extracellular matrix (ECM) and have been extensively utilized to influence neural cell (NC) behavior in in vitro and in vivo settings. These biomimetic scaffolds support NC cultures, can direct the differentiation of NCs, and have recapitulated some native NC behavior in an in vitro setting. However, NC transplant therapies and treatments used in animal models of CNS disease and injury have not fully restored functionality. The observed lack of functional recovery occurs despite improvements in transplanted NC viability when incorporating biomaterial scaffolds and the potential of NC to replace damaged native cells. The behavior of NCs within biomaterial scaffolds must be directed in order to improve the efficacy of transplant therapies and treatments. Biomaterial scaffold topography and imbedded bioactive cues, designed at the microscale level, can alter NC phenotype, direct migration, and differentiation. Microscale patterning in biomaterial scaffolds for spatial control of NC behavior has enhanced the capabilities of in vitro models to capture properties of the native CNS tissue ECM. Patterning techniques such as lithography, electrospinning and three-dimensional (3D) bioprinting can be employed to design the microscale architecture of biomaterial scaffolds. Here, the progress and challenges of the prevalent biomaterial patterning techniques of lithography, electrospinning, and 3D bioprinting are reported. This review analyzes NC behavioral response to specific microscale topographical patterns and spatially organized bioactive cues.

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Injectable shear-thinning hydrogels engineered with a self-assembling Dock-and-Lock mechanism

Cited by 177 publications

References 43 publications

Protein Fragment Reconstitution as a Driving Force for Self‐Assembling Reversible Protein Hydrogels

Protein Fragment Reconstitution as a Driving Force for Self‐Assembling Reversible Protein Hydrogels

Physics of engineered protein hydrogels

Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior

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