Photocrosslinked alginate hydrogels with tunable biodegradation rates and mechanical properties

Jeon, Oju; Bouhadir, Kamal H.; Mansour, Joseph M.; Alsberg, Eben

doi:10.1016/j.biomaterials.2009.01.034

Cited by 519 publications

(477 citation statements)

References 48 publications

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“…While recent work has used similar click chemistry for localized drug delivery, this work presents the first use of the tetrazine-norbornene click reaction to covalently crosslink polysaccharides into hydrogels [29,38]. Crosslinking of alginate by different methods has been extensively explored to make covalently crosslinked hydrogels that are mechanically robust, but these chemistries lack the cytocompatibility inherent in the bioorthogonal click reaction reported here [19,21,39]. The simplicity of this crosslinking modality provides the opportunity to control the mechanical properties of the click alginate hydrogel by adjusting the ratio of the polymers, rather than changing the total concentration of polymers in the system.…”

Section: Discussionmentioning

confidence: 99%

“…Alginate hydrogels must display cell adhesive ligands in order for mammalian cells to attach, spread, and proliferate on the surface of the hydrogel. Without ligands such as RGD presented from the hydrogel surface, few cells will attach, and those that do will retain a spherical morphology and undergo apoptosis [21]. Unfortunately, the carbodiimide chemical reaction most commonly used to attach RGD peptides to the backbone of alginate is slow and requires lengthy purification and lyophillization time [40].…”

Section: Discussionmentioning

confidence: 99%

“…To overcome many of the challenges associated with ionic crosslinking, alternative covalent crosslinking strategies have been developed, though none are completely biologically inert [18][19][20][21]. Many of these covalent crosslinking strategies produce stable and uniform gels with mechanical properties that are controllable over a wider range compared to ionically crosslinked gels, but they may not be optimal for protein or cell encapsulation due to the cross-reactivity of the crosslinking chemistry with cells and proteins.…”

Section: Introductionmentioning

confidence: 99%

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Versatile click alginate hydrogels crosslinked via tetrazine–norbornene chemistry

et al. 2015

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Abstract:Alginate hydrogels are well-characterized, biologically inert materials that are used in many biomedical applications for the delivery of drugs, proteins, and cells. Unfortunately, canonical covalently crosslinked alginate hydrogels are formed using chemical strategies that can be biologically harmful due to their lack of chemoselectivity. In this work we introduce tetrazine and norbornene groups to alginate polymer chains and subsequently form covalently crosslinked click alginate hydrogels capable of encapsulating cells without damaging them. The rapid, bioorthogonal, and specific click reaction is irreversible and allows for easy incorporation of cells with high post-encapsulation viability. The swelling and mechanical properties of the click alginate hydrogel can be tuned via the total polymer concentration and the stoichiometric ratio of the complementary click functional groups. The click alginate hydrogel can be modified after gelation to display cell adhesion peptides for 2D cell culture using thiol-ene chemistry.Furthermore, click alginate hydrogels are minimally inflammatory, maintain structural integrity over several months, and reject cell infiltration when injected subcutaneously in mice. Click alginate hydrogels combine the numerous benefits of alginate hydrogels with powerful bioorthogonal click chemistry for use in tissue engineering applications involving the stable encapsulation or delivery of cells or bioactive molecules.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Versatile click alginate hydrogels crosslinked via tetrazine–norbornene chemistry

et al. 2015

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“…Tailoring the degradation characteristics of a hydrogel may therefore be of critical importance in promoting endochondral ossification of engineered grafts [47][48][49][50]. Alternatively, or perhaps in conjunction, inflammatory cytokines may be leveraged to direct more efficient resorption of a large cartilaginous template [51].…”

Section: Discussionmentioning

confidence: 99%

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

et al. 2015

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Cartilaginous tissues engineered using mesenchymal stem cells (MSCs) have been shown to generate bone in vivo by executing an endochondral program. This may hinder the use of MSCs for articular cartilage regeneration, but opens the possibility of using engineered cartilaginous tissues for large bone defect repair. Hydrogels may be an attractive tool in the scaling-up of such tissue engineered grafts for endochondral bone regeneration. In this study, we compared the capacity of different naturally derived hydrogels (alginate, chitosan, and fibrin) to support chondrogenesis and hypertrophy of MSCs in vitro and endochondral ossification in vivo. In vitro, alginate and chitosan constructs accumulated the highest levels of sGAG, with chitosan constructs synthesising the highest levels of collagen. Alginate and fibrin constructs supported the greatest degree of calcium accumulation, though only fibrin constructs calcified homogenously. In vivo, chitosan constructs facilitated neither vascularization nor endochondral ossification, and also retained the greatest amount of sGAG, suggesting it to be a more suitable material for the engineering of articular cartilage.Both alginate and fibrin constructs facilitated vascularization and endochondral bone formation as well as the development of a bone marrow environment. Alginate constructs accumulated significantly more mineral and supported greater bone formation in central regions of the engineered tissue. In conclusion, this study demonstrates the capacity of chitosan hydrogels to promote and better maintain a chondrogenic phenotype in MSCs and highlights the potential of utilizing alginate hydrogels for MSC-based endochondral bone tissue engineering applications.

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“…However, similar to hyaluronic acid, alginate can also be modified with polymerizable chemical groups such as (meth)acrylates. [26] The most widely used synthetic polymer for engineering tissue-mimetic hydrogels is poly(ethylene glycol) (PEG). PEG is considered to be a "blank slate" biomaterial due to its resistance to protein adsorption.…”

Section: Overview Of Tissue-mimetic Hydrogelsmentioning

confidence: 99%

Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics

2017

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Tissue engineering holds great promise for advancing cancer research and achieving the goals of the Cancer Moonshot by providing better models for basic research and testing novel therapeutics. This paper focuses on the use of hydrogel biomaterials due to their unique ability to entrap cells in three-dimensional (3D) matrix that mimics tissues and can be programmed with physical and chemical cues to recreate key aspects of tumor microenvironments. The chemistry of some commonly used hydrogel platforms is discussed, and important examples of their use in tissue engineering 3D cancer models are highlighted. Challenges and opportunities for future research are also discussed.

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Photocrosslinked alginate hydrogels with tunable biodegradation rates and mechanical properties

Cited by 519 publications

References 48 publications

Versatile click alginate hydrogels crosslinked via tetrazine–norbornene chemistry

Versatile click alginate hydrogels crosslinked via tetrazine–norbornene chemistry

Engineering cartilage or endochondral bone: A comparison of different naturally derived hydrogels

Shooting for the moon: using tissue-mimetic hydrogels to gain new insight on cancer biology and screen therapeutics

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