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Protein polymer hydrogels: effects of endotoxin on biocompatibility.

ABSTRACT: Protein polymer-based hydrogels have shown potential for tissue engineering applications, but require biocompatibility testing for in vivo use. Enzymatically crosslinked protein polymer-based hydrogels were tested in vitro and in vivo to evaluate their biocompatibility. Endotoxins present in the hydrogel were removed by Trition X-114 phase separation. The reduction of endotoxins decreased TNF-α production by a macrophage cell line in vitro; however, significant inflammatory response was still present compared to collagen control gels. A branched PEG molecule and dexamethasone were added to the hydrogel to reduce the response. In vitro testing showed a decrease in the TNF-α levels with the addition of dexamethasone. In vivo implantations into the epididymal fat pad of C57/BL6 mice, however, indicated a decreased inflammatory mediated immune response with a hydrogel treated with both PEGylation and endotoxin reduction. This study demonstrates the importance of endotoxin testing and removal in determining the biocompatibility of biomaterials.

SUBMITTER: Beenken-Rothkopf LN

PROVIDER: S-EPMC9070080 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Protein polymer hydrogels: effects of endotoxin on biocompatibility.

Beenken-Rothkopf Liese N LN Karfeld-Sulzer Lindsay S LS Zhang Xiaomin X Kissler Hermann H Michie Sara A SA Kaufman Dixon B DB Fontaine Magali J MJ Barron Annelise E AE

Journal of biomaterials applications 20120724 3

Protein polymer-based hydrogels have shown potential for tissue engineering applications, but require biocompatibility testing for in vivo use. Enzymatically crosslinked protein polymer-based hydrogels were tested in vitro and in vivo to evaluate their biocompatibility. Endotoxins present in the hydrogel were removed by Trition X-114 phase separation. The reduction of endotoxins decreased TNF-α production by a macrophage cell line in vitro; however, significant inflammatory response was still pr ...[more]

PMID: 22832218

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Project description:Foams made with polymer hydrogels can be used in a variety of applications, such as scaffolds for biomedical applications or decontamination processes. However, from a practical point of view, it is difficult to introduce bubbles into viscous or viscoelastic fluids and to produce large volumes of hydrogel foams. In the present article, we investigate the foaming process of poly(vinyl alcohol) (PVA)/borax transient hydrogels, where PVA chains reversibly bind to borax molecules. In a previous article, we showed that foams obtained with PVA/borax mixtures are highly stable because of both high interfacial and bulk viscosities and can be used to quickly absorb liquids, which make them suitable for detergency or decontamination processes. To produce these foams, we use a two-step foaming process which consists in first shearing a PVA solution to obtain a PVA foam and second adding borax to the PVA foam under continuous shearing. The obtained PVA/borax foams are stable for weeks. In this study, we observe a shear-induced collapse of the foams for formulations containing a low borax/PVA ratio, whereas they remain stable under shear for high PVA/borax ratios. Using scaling arguments, we find that the shear-induced collapse of the foams and bubbles is obtained below a critical ratio, N E/N B = 15, of the number of entanglements per chain, N E, and the number of borax per chain, N B. Rheology measurements show that the samples present a shear-thickening behavior that increases with the borax concentration. We suggest that during the foaming process when the shearing rate is of the order of 100 s-1, the viscosity of these samples diverges, leading to a viscous to fragile transition. To mimic the fast stretching of the PVA/borax thin films during the foaming process, we study the stretching of individual PVA/borax catenoid-shaped thin films at high stretching rates. We observe that the films containing low PVA/borax ratios do not minimize their surface area unlike what is theoretically expected for standard surfactant films. Moreover, the films tend to be unstable and fracture because the PVA/borax network does not have time to rearrange and relax stresses for high stretching rates.

Dataset Information

Protein polymer hydrogels: effects of endotoxin on biocompatibility.

Publications

Protein polymer hydrogels: effects of endotoxin on biocompatibility.

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