Resilin‐Based Hybrid Hydrogels for Cardiovascular Tissue Engineering

McGann, Christopher L.; Levenson, Eric A.; Kiick, Kristi L.

doi:10.1002/macp.201200412

Cited by 94 publications

(141 citation statements)

References 94 publications

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“…[134][135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150] VS are typically attached to polymer chains via multiple-step reactions, for example, fi rst reacting mercaptoalkanoic acid to divinyl sulfone to yield a free carboxylic acid group and subsequently performing an esterifi cation with hydroxyl groups on a carbohydrate via carbodiimide chemistry. [ 148 ] Single-step functionalizations are also possible via direct reactions between a polymer-bound hydroxyl or amine group and VS in the presence of a strong base [ 138,145 ] or copolymerization of a ring opening monomer possessing VS functionality that provides direct chain functionalization with VS without the need for post-polymerization reactions.…”

Section: Tissue Interactionsmentioning

confidence: 99%

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

Patenaude

Smeets

Hoare

2014

Macromol. Rapid Commun.

165

125

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Hydrogels that can form spontaneously via covalent bond formation upon injection in vivo have recently attracted significant attention for their potential to address a variety of biomedical challenges. This review discusses the design rules for the effective engineering of such materials, and the major chemistries used to form injectable, in situ gelling hydrogels in the context of these design guidelines are outlined (with examples). Directions for future research in the area are addressed, noting the outstanding challenges associated with the use of this class of hydrogels in vivo.

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Section: Tissue Interactionsmentioning

confidence: 99%

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

Patenaude

Smeets

Hoare

2014

Macromol. Rapid Commun.

165

125

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“…In order to gain the benefits of proteins as biomaterial matrices, due to their diverse amino acid chemistries for functionalization and biodegradability, recent studies have explored blending with synthetic polymers or other readily available proteins or ECM components. For example, elastin was alloyed with silk, [26] collagen, [27] and poly(lactide-co-glycolide), [28] while resilin was mixed with poly(ethylene glycol) [29] in order to extend utility.…”

Section: Introductionmentioning

confidence: 99%

Highly Tunable Elastomeric Silk Biomaterials

Partlow

Hanna

Rnjak‐Kovacina

et al. 2014

Adv Funct Materials

365

443

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Elastomeric, fully degradable and biocompatible biomaterials are rare, with current options presenting significant limitations in terms of ease of functionalization and tunable mechanical and degradation properties. We report a new method for covalently crosslinking tyrosine residues in silk proteins, via horseradish peroxidase and hydrogen peroxide, to generate highly elastic hydrogels with tunable properties. The tunable mechanical properties, gelation kinetics and swelling properties of these new protein polymers, in addition to their ability to withstand shear strains on the order of 100%, compressive strains greater than 70% and display stiffness between 200 – 10,000 Pa, covering a significant portion of the properties of native soft tissues. Molecular weight and solvent composition allowed control of material mechanical properties over several orders of magnitude while maintaining high resilience and resistance to fatigue. Encapsulation of human bone marrow derived mesenchymal stem cells (hMSC) showed long term survival and exhibited cell-matrix interactions reflective of both silk concentration and gelation conditions. Further biocompatibility of these materials were demonstrated with in vivo evaluation. These new protein-based elastomeric and degradable hydrogels represent an exciting new biomaterials option, with a unique combination of properties, for tissue engineering and regenerative medicine.

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“…Recombinant protein polymers have been widely investigated as biomaterials for tissue engineering applications 1, 2 and elastomeric polypeptides represent a particularly exciting subset of materials designed for soft tissues that require flexible, reversible elasticity. 3–17 In these applications, hydrogel scaffolds serve as temporary substitutes while healthy tissue regenerates 18 and an ideal scaffold would be durable enough to withstand the repetitive mechanical forces experienced by some of these soft tissues. 19–21 For example, collagen and elastin serve as critical structural components of cardiovascular tissues, which experience cyclic hemodynamic forces over extended time scales, and desirable biomaterials for cardiovascular applications would replicate the elasticity conferred by those proteins.…”

Section: Introductionmentioning

confidence: 99%

“…13, 14, 28 More recently, hybrid hydrogels, composed of recombinant elastomeric protein and PEG, have yielded materials in which encapsulated cells spread and adopt a spindle-like morphology. 17, 29 In addition, protein-PEG hydrogels comprising other proteins such as collagen 30–32 or fibrinogen, 30, 33–36 have been shown to improve biocompatibility and cell-matrix interaction. 35 …”

Section: Introductionmentioning

confidence: 99%

Resilin-PEG Hybrid Hydrogels Yield Degradable Elastomeric Scaffolds with Heterogeneous Microstructure

McGann¹,

Akins

Kiick

2015

Biomacromolecules

Self Cite

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Hydrogels derived from resilin-like polypeptides (RLPs) have shown outstanding mechanical resilience and cytocompatibility, and expanding the versatility of RLP-based materials via conjugation with other polypeptides and polymers would offer great promise in the design of a range of materials. Here, we present an investigation of the biochemical and mechanical properties of hybrid hydrogels composed of a recombinant RLP and a multi-arm PEG macromer. These hybrid hydrogels can be rapidly cross-linked through a Michael-type addition reaction between the thiols of cysteine residues on the RLP and vinyl sulfone groups on the multi-arm PEG. Oscillatory rheology and tensile testing confirmed the formation of elastomeric hydrogels with mechanical resilience comparable to aortic elastin; hydrogel stiffness was easily modulated through the cross-linking ratio. Macromolecular phase separation of the RLP-PEG hydrogels offers the unique advantage of imparting a heterogeneous microstructure, which can be used to localize cells, through simple mixing and crosslinking. Assessment of degradation of the RLP by matrix metalloproteinases (MMPs) illustrated the specific proteolysis of the polypeptide in both its soluble form and when cross-linked into hydrogels. Finally, the successful encapsulation and viable three-dimensional culture of human mesenchymal stem cells (hMSCs) demonstrated the cytocompatibility of the RLP-PEG gels. Overall, the cytocompatibility, elastomeric mechanical properties, micro-heterogeneity, and degradability of the RLP-PEG hybrid hydrogels offer a suite of promising properties for the development of cell-instructive, structured tissue engineering scaffolds.

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Resilin‐Based Hybrid Hydrogels for Cardiovascular Tissue Engineering

Cited by 94 publications

References 94 publications

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

Designing Injectable, Covalently Cross‐Linked Hydrogels for Biomedical Applications

Highly Tunable Elastomeric Silk Biomaterials

Resilin-PEG Hybrid Hydrogels Yield Degradable Elastomeric Scaffolds with Heterogeneous Microstructure

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