Micro-structured, spontaneously eroding hydrogels accelerate endothelialization through presentation of conjugated growth factors

Jensen, Bettina E. B.; Edlund, Katrine; Zelikin, Alexander N.

doi:10.1016/j.biomaterials.2015.01.036

Cited by 19 publications

(28 citation statements)

References 55 publications

(64 reference statements)

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“…Finally, the prepared specimen can be directly used as substrates for adhesion and proliferation of mammalian cells toward characterization of hydrogels as biomaterials. 17 Microstructured hydrogels were prepared using elastomeric poly(dimethylsiloxane) stamps obtained from silicon wafers with a nominated surface topography (in this work, 10 μm wide circles with a 20 μm intercenter spacing). Solutions of PVA (varied polymer molar mass and solids content) were placed between the stamp and a glass coverslip to fill the stamp cavities and clamped at finger-tight pressure for 24 h. During this time, PVA undergoes partial dehydration, and upon removal of clamps, PVA microstructures remain on the glass coverslip.…”

Section: Resultsmentioning

confidence: 99%

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Poly(vinyl alcohol) Physical Hydrogels: Matrix-Mediated Drug Delivery Using Spontaneously Eroding Substrate

2016

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Poly(vinyl alcohol) hydrogels have a long and successful history of applications in biomedicine. Historically, these matrices were developed to be nondegradable—limiting their utility to applications as permanent implants. For tissue engineering and drug delivery, herein we develop spontaneously eroding physical hydrogels based on PVA. We characterize in detail a mild, noncryogenic method of producing PVA physical hydrogels using poly(ethylene glycol) as a gelating agent, and investigate PVA molar mass as a means to define the kinetics of erosion of these biomaterials. PVA hydrogels are characterized for associated inflammatory response in adhering macrophages, antiproliferative effects mediated through delivery of cytotoxic drugs to myoblasts, and pro-proliferative activity achieved via presentation of conjugated growth factors to endothelial cells. Together, these data present a multiangle characterization of these novel multifunctional matrices for applications in tissue engineering and drug delivery mediated by implantable biomaterials.

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Section: Resultsmentioning

confidence: 99%

“…Water extraction and ensuing hydrogelation of PVA chains could also be achieved using liquid, oligomeric samples of PEG. 17 The latter approach is potentially more friendly toward immobilized biological cargo such as proteins. However, detailed investigation of this method of PVA hydrogelation is missing.…”

Section: Introductionmentioning

confidence: 99%

Poly(vinyl alcohol) Physical Hydrogels: Matrix-Mediated Drug Delivery Using Spontaneously Eroding Substrate

2016

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“…[5,26] A variety of conjugation strategies and reactions can be used for this purpose, which have been reviewed in detail elsewhere. [26,73] Some of the most recent reports on the subject have successfully bound GFs on several polymeric biomaterials, including stem cell factor (SCF), [74] transforming growth factor beta 1 (TGF-β1), [72,75] EGF, [76][77][78][79] FGF-2, [76] nerve growth factor (NGF), [80] or VEGF. [81] Modification of gelatin with methacryloyl moieties, known as GelMA, allows the application of mild photopolymerization techniques for crosslinking.…”

Section: Materials With Covalently Bound Gfsmentioning

confidence: 99%

“…[83] In a somewhat different approach, poly(vinyl alcohol) (PVA) hydrogels were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, with terminal thiol groups being activated toward disulfide exchange. [76] A commercial protein cocktail containing mainly EGF and FGF-2 could then be successfully coupled to these moieties. GF-containing gels could communicate to adherent cells, and specifically enhanced proliferation of cells with the corresponding receptors (human umbilical vein endothelial cells, HUVECs), while exerting no specific effects on other cell types (myoblasts).…”

Section: Materials With Covalently Bound Gfsmentioning

confidence: 99%

“…GF-containing gels could communicate to adherent cells, and specifically enhanced proliferation of cells with the corresponding receptors (human umbilical vein endothelial cells, HUVECs), while exerting no specific effects on other cell types (myoblasts). [76] Another highly biocompatible conjugation alternative is the use of click chemistry, particularly copper-free reactions. For example, strain-promoted azide-alkyne cycloaddition (SPAAC) has been used to couple azide-modified EGF to primary amines in collagen, by means of dibenzo cyclooctyne (DBCO)-sulfo-N-hydroxysuccinimide (NHS) ester.…”

Section: Materials With Covalently Bound Gfsmentioning

confidence: 99%

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Biomaterials for Sequestration of Growth Factors and Modulation of Cell Behavior

Teixeira

Domingues

Shevchuk

et al. 2020

Adv Funct Materials

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Growth factors (GFs) are proteins secreted by cells that regulate a variety of biological processes. Although they have long been proposed as potent therapeutic agents, their administration in a soluble form has proven costly and ineffective due to their short half-lives in biological environments. Biomaterial-based approaches are increasingly sought as alternatives to improve the efficacy or, ideally, replace the need for exogenous administration of GFs in regenerative medicine strategies. The means by which these systems evolve from biomaterials for conventional controlled release of GFs to the recent extracellular matrix (ECM)-inspired approaches for sequestering these labile molecules and regulating their spatiotemporal activity and presentation are reviewed. Focus is placed on biomaterials functionalized either with ECM components, which show promiscuous GF binding, or with targeted GF ligands (antibodies, aptamers, or peptides). The potential of synthetic platforms with abiotic affinity as cost-effective alternatives to the current biological ligands is also discussed. Overall, the various GF sequestering systems developed so far have remarkably improved the activity of GFs at reduced doses and, in some cases, completely avoided the need for their exogenous administration to guide cell fates. These bioinspired concepts thus enable the rational exploration of the full therapeutic potential of GFs in regenerative medicine.

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Methods for producing microstructured hydrogels for targeted applications in biology

Garcia

Kiick

2019

Acta Biomaterialia

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Hydrogels have been broadly studied for applications in clinically motivated fields such as tissue regeneration, drug delivery, and wound healing, as well as in a wide variety of consumer and industry uses. While the control of mechanical properties and network structures are important in all of these applications, for regenerative medicine applications in particular, matching the chemical, topographical and mechanical properties for the target use/tissue is critical. There have been multiple alternatives developed for fabricating materials with microstructures with goals of controlling the spatial location, phenotypic evolution, and signaling of cells. The commonly employed polymers such as poly(ethylene glycol) (PEG), polypeptides, and polysaccharides (as well as others) can be processed by various methods in order to control material heterogeneity and microscale structures. We review here the more commonly used polymers, chemistries, and methods for generating microstructures in biomaterials, highlighting the range of possible morphologies that can be produced, and the limitations of each method. With a focus in liquidliquid phase separation, methods and chemistries well suited for stabilizing the interface and arresting the phase separation are covered. As the microstructures can affect cell behavior, examples of such effects are reviewed as well.

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Micro-structured, spontaneously eroding hydrogels accelerate endothelialization through presentation of conjugated growth factors

Cited by 19 publications

References 55 publications

Poly(vinyl alcohol) Physical Hydrogels: Matrix-Mediated Drug Delivery Using Spontaneously Eroding Substrate

Poly(vinyl alcohol) Physical Hydrogels: Matrix-Mediated Drug Delivery Using Spontaneously Eroding Substrate

Biomaterials for Sequestration of Growth Factors and Modulation of Cell Behavior

Methods for producing microstructured hydrogels for targeted applications in biology

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