PEG hydrogel degradation and the role of the surrounding tissue environment

Reid, Branden; Gibson, Matthew; Singh, Anirudha; Taube, Janis M.; Furlong, Cecilia; Murcia, Melissa; Elisseeff, Jennifer H.

doi:10.1002/term.1688

Cited by 116 publications

(93 citation statements)

References 16 publications

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“…The histological data we collected as part of this study showed that the increase in MTR values and macromolecular ratios are associated with the extent of infiltrating cells in the capsule region. These immune cells consist of macrophages, neutrophils or dendritic cells [52]. Although MRI currently is not able to identify these cells, a distinctive difference was observed in both MTR and macromolecular ratio between the immunosuppressed group and the non-immunosuppressed groups (Fig.…”

Section: Discussionmentioning

confidence: 99%

Magnetization transfer contrast MRI for non-invasive assessment of innate and adaptive immune responses against alginate-encapsulated cells

et al. 2014

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By means of physical isolation of cells inside semi-permeable hydrogels, encapsulation has been widely used to immunoprotect transplanted cells. While spherical alginate microcapsules are now being used clinically, there still is little known about the patient’s immune system response unless biopsies are obtained. We investigated the use of Magnetization Transfer (MT) imaging to non-invasively detect host immune responses against alginate capsules containing xenografted human hepatocytes in four groups of animals, including transplanted empty capsules (−Cells/−IS), capsules with live cells with (+LiveCells/+IS) and without immunosuppression (+LiveCells/−IS), and capsules with apoptotic cells in non-immunosuppressed animals (+DeadCells/−IS). The highest MT ratio (MTR) was found in +LiveCells/−IS, which increased from day 0 by 38% and 53% on days 7 and 14 after transplantation respectively, and corresponded to a distinctive increase in cell infiltration on histology. Furthermore, we show that macromolecular ratio maps based on MT data are more sensitive to cell infiltration and fibrosis than conventional MTR maps. Such maps showed a significant difference between +LiveCells/−IS (0.18±0.02) and +DeadCells/−IS (0.13±0.02) on day 7 (P<0.01) existed, which was not observed on MTR imaging. We conclude that MT imaging, which is clinically available, can be applied for non-invasive monitoring of the occurrence of a host immune response against encapsulated cells.

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Section: Discussionmentioning

confidence: 99%

Magnetization transfer contrast MRI for non-invasive assessment of innate and adaptive immune responses against alginate-encapsulated cells

et al. 2014

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“…In vivo degradation rates of polymers could be faster than in vitro; the higher in vivo degradation rate has been explained by the effects caused by cellular and enzymatic activities found in the body 16 . Traditionally, it is believed that PEG-based hydrogels degrade due to ester hydrolysis 17 and hydroxyl radicals 18 . The statistical results of the collagen assay showed the statistically significant difference between the 2 groups, but reepithelialization of PEG-based treatment was better than the Coloskin treatment after 14 d (Fig.…”

Section: Discussionmentioning

confidence: 99%

A PEG-based hydrogel for effective wound care management

Chen

Liao

et al. 2017

cell transplant

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It is extremely challenging to achieve strong adhesion in soft tissues while minimizing toxicity, tissue damage, and other side effects caused by wound sealing materials. In this study, flexible synthetic hydrogel sealants were prepared based on polyethylene glycol (PEG) materials. PEG is a synthetic material that is nontoxic and inert and, thus, suitable for use in medical products. We evaluated the in vitro biocompatibility tests of the dressings to assess cytotoxicity and irritation, sensitization, pyrogen toxicity, and systemic toxicity following the International Organization for Standardization 10993 standards and the in vivo effects of the hydrogel samples using Coloskin liquid bandages as control samples for potential in wound closure.

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“…[1, 15, 18] However, it is widely recognized that PEGDA hydrogels are susceptible to slow degradation in vivo and are therefore unsuitable for long-term implants. [1, 10, 19, 20]In current literature, the in vivo degradation of PEGDA hydrogels is typically attributed to hydrolysis of the endgroup acrylate esters that are introduced upon acrylation of PEG diol. However, until recently, the hydrolytic degradation profile of PEGDA hydrogels was poorly characterized, as the majority of reports on PEGDA hydrolysis referred to a study with tri(ethylene glycol) diacrylate (TEGDA).…”

Section: Introductionmentioning

confidence: 99%

“…[29] Thus, the observed degradation of PEGDA hydrogels could be a result of ester group cleavage via hydrolysis, ether cleavage via oxidation, or some combination of the two. [20, 24]…”

Section: Introductionmentioning

confidence: 99%

Determination of thein vivodegradation mechanism of PEGDA hydrogels

Browning

Cereceres

Luong

et al. 2014

J. Biomed. Mater. Res.

155

172

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Poly(ethylene glycol) (PEG) hydrogels are one of the most extensively utilized biomaterials systems due to their established biocompatibility and highly tunable properties. It is widely acknowledged that traditional acrylate-derivatized PEG (PEGDA) hydrogels are susceptible to slow degradation in vivo and are therefore unsuitable for long-term implantable applications. However, there is speculation whether the observed degradation is due to hydrolysis of endgroup acrylate esters or oxidation of the ether backbone both of which are possible in the foreign body response to implanted devices. PEG diacrylamide (PEGDAA) is a polyether-based hydrogel system with similar properties to PEGDA but with amide linkages in place of the acrylate esters. This provides a hydrolytically-stable control that can be used to isolate the relative contributions of hydrolysis and oxidation to the in vivo degradation of PEGDA. Here we show that PEGDAA hydrogels remained stable over 12 weeks of subcutaneous implantation in a rat model while PEGDA hydrogels underwent significant degradation as indicated by both increased swelling ratio and decreased modulus. As PEGDA and PEGDAA have similar susceptibility to oxidation, these results demonstrate for the first time that the primary in vivo degradation mechanism of PEGDA is hydrolysis of the endgroup acrylate ester. Additionally, the maintenance of PEGDAA hydrogel properties in vivo indicates their suitability for long-term implants. These studies serve to elucidate key information about a widely used biomaterial system to allow for better implantable device design and to provide a biostable replacement option for PEGDA in applications that require long-term stability.

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PEG hydrogel degradation and the role of the surrounding tissue environment

Cited by 116 publications

References 16 publications

Magnetization transfer contrast MRI for non-invasive assessment of innate and adaptive immune responses against alginate-encapsulated cells

Magnetization transfer contrast MRI for non-invasive assessment of innate and adaptive immune responses against alginate-encapsulated cells

A PEG-based hydrogel for effective wound care management

Determination of thein vivodegradation mechanism of PEGDA hydrogels

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