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Eindhoven, Netherlands

Dankers P.Y.W.,TU Eindhoven | van Luyn M.J.A.,University of Groningen | Huizinga-van der Vlag A.,University of Groningen | Petersen A.H.,University of Groningen | And 3 more authors.
European Polymer Journal | Year: 2015

The development of local, intrarenal drug delivery therapies is imperative to induce a therapeutic effect without the requirement of high concentrations of drugs, thereby diminishing systemic side effects. Hydrogels are eminently suitable as drug delivery carriers in soft tissues. Here, we show that a supramolecular hydrogel carrier based on ureido-pyrimidinone (UPy) modified poly(ethylene glycol) can be easily formulated and conveniently be applied to deliver anti-inflammatory and anti-fibrotic growth factor protein BMP7 to the kidney. Short-term, immediate modulation of renal inflammation and extracellular matrix remodelling is shown in a rat model of acute kidney injury. Induction of ischemia/reperfusion injury was followed by renal subcapsular implantation of pristine and BMP7-loaded supramolecular hydrogels. The cortical area under the site of implantation was studied after 3 and 7. days. Subcapsular delivery of only 0.30. μg BMP7 from these supramolecular hydrogels led to a significant reduction in interstitial inflammatory and myofibroblast cell numbers at the site of implantation. These findings show that local, intrarenal delivery of an anti-inflammatory and anti-fibrotic drug from a supramolecular hydrogel carrier can be effective in the reduction of acute inflammation and incipient fibrosis. © 2015 Elsevier Ltd.

Klerk L.A.,FOM Institute for Atomic and Molecular Physics | Dankers P.Y.W.,TU Eindhoven | Dankers P.Y.W.,University of Groningen | Popa E.R.,University of Groningen | And 4 more authors.
Analytical Chemistry | Year: 2010

Supramolecular polymeric materials are of increasing interest for the use as drug delivery carriers. A thorough insight in the biocompatibility and the degradation of these materials in vivo are of fundamental importance to further their development and application in medical practice. Molecular imaging techniques are powerful tools that enable the elucidation of molecular distributions in and around such polymer implants. A supramolecular polymeric hydrogel was implanted under the renal capsule to study its biocompatibility with TOF-SIMS. This results in a molecular cartography of the polymer implant combined with the cellular signature of the implantation environment. In this experiment, molecular signals are observed from cells that are involved in the biological response to the implant, e.g., macrophages. These molecular signatures are compared with macrophage standards cultured in different polarization environments. On the basis of this comparison, information can be acquired on the various macrophage differentiations that are connected to different stages in the foreign body response. Mass spectrometric imaging techniques offer the opportunity to visualize different histological phenomena in a single experiment without the need for specific immunohistochemical markers. Cellular infiltration into the polymer is visualized, offering a clear view on both biological and polymer features in a single imaging experiment. © 2010 American Chemical Society.

Dankers P.Y.W.,TU Eindhoven | Dankers P.Y.W.,University of Groningen | Hermans T.M.,TU Eindhoven | Baughman T.W.,TU Eindhoven | And 11 more authors.
Advanced Materials | Year: 2012

A modular one-component supramolecular transient network in water, based on poly(ethylene glycol) and end-capped with four-fold hydrogen bonding units, is reported. Due to its nonlinear structural formation, this system allows active proteins to be added to the hydrogel during formation. Once implanted in vivo it releases the protein by erosion of both the protein and polymer via dissolution. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dankers P.Y.W.,University of Groningen | Dankers P.Y.W.,TU Eindhoven | Boomker J.M.,University of Groningen | Huizinga-van der Vlag A.,University of Groningen | And 7 more authors.
Biomaterials | Year: 2011

Maintenance of polarisation of epithelial cells and preservation of their specialized phenotype are great challenges for bioengineering of epithelial tissues. Mimicking the basement membrane and underlying extracellular matrix (ECM) with respect to its hierarchical fiber-like morphology and display of bioactive signals is prerequisite for optimal epithelial cell function in vitro. We report here on a bottom-up approach based on hydrogen-bonded supramolecular polymers and ECM-peptides to make an electro-spun, bioactive supramolecular mesh which can be applied as synthetic basement membrane. The supramolecular polymers used, self-assembled into nano-meter scale fibers, while at micro-meter scale fibers were formed by electro-spinning. We introduced bioactivity into these nano-fibers by intercalation of different ECM-peptides designed for stable binding. Living kidney membranes were shown to be bioengineered through culture of primary human renal tubular epithelial cells on these bioactive meshes. Even after a long-term culturing period of 19 days, we found that the cells on bioactive membranes formed tight monolayers, while cells on non-active membranes lost their monolayer integrity. Furthermore, the bioactive membranes helped to support and maintain renal epithelial phenotype and function. Thus, incorporation of ECM-peptides into electro-spun meshes via a hierarchical, supramolecular method is a promising approach to engineer bioactive synthetic membranes with an unprecedented structure. This approach may in future be applied to produce living bioactive membranes for a bio-artificial kidney. © 2010 Elsevier Ltd.

Dankers P.Y.W.,University of Groningen | Dankers P.Y.W.,TU Eindhoven | van Luyn M.J.A.,University of Groningen | Huizinga-van der Vlag A.,University of Groningen | And 6 more authors.
Biomaterials | Year: 2012

Intrarenal drug delivery from a hydrogel carrier implanted under the kidney capsule is an innovative way to induce kidney tissue regeneration and/or prevent kidney inflammation or fibrosis. We report here on the development of supramolecular hydrogels for this application. We have synthesized two types of supramolecular hydrogelators by connecting the hydrogen bonding moieties to poly(ethylene glycols) in two different ways in order to obtain hydrogels with different physico-chemical properties. Chain-extended hydrogelators containing hydrogen bonding units in the main chain, and bifunctional hydrogelators end-functionalized with hydrogen bonding moieties, were made. The influence of these hydrogels on the renal cortex when implanted under the kidney capsule was studied. The overall tissue response to these hydrogels was found to be mild, and minimal damage to the cortex was observed, using the infiltration of macrophages, formation of myofibroblasts, and the deposition of collagen III as relevant read-out parameters. Differences in tissue response to these hydrogels could be related to the different physico-chemical properties of the three hydrogels. The strong, flexible and slow eroding chain-extended hydrogels are proposed to be suitable for long-term intrarenal delivery of organic drugs, while the weaker, soft and fast eroding bifunctional hydrogel is eminently suitable for short-term, fast delivery of protein drugs to the kidney cortex. The favourable biological behaviour of the supramolecular hydrogels makes them exquisite candidates for subcapsular drug delivery, and paves the way to various opportunities for intrarenal therapy. © 2012 Elsevier Ltd.

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