Publications by authors named "T Vermonden"

82 Publications

Topographic Guidance in Melt-Electrowritten Tubular Scaffolds Enhances Engineered Kidney Tubule Performance.

Front Bioeng Biotechnol 2020 18;8:617364. Epub 2021 Jan 18.

Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

To date, tubular tissue engineering relies on large, non-porous tubular scaffolds (Ø > 2 mm) for mechanical self-support, or smaller (Ø 150-500 μm) tubes within bulk hydrogels for studying renal transport phenomena. To advance the engineering of kidney tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported kidney proximal tubules with enhanced properties. A custom-built melt-electrowriting (MEW) device was used to fabricate tubular fibrous scaffolds with small diameter sizes (Ø = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the tubular scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Tubular fibrous scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 1 mm and pore sizes of 0.2 mm were achieved and used for subsequent cell experiments. While HUVEC were unable to bridge the pores, ciPTEC formed tight monolayers in all scaffold microarchitectures tested. Well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). Here, we present smaller diameter engineered kidney tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
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http://dx.doi.org/10.3389/fbioe.2020.617364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848123PMC
January 2021

LCST polymers with UCST behavior.

Soft Matter 2021 Mar;17(8):2132-2141

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Science for Life, Faculty of Science, Utrecht University, P. O. Box 80082, 3508 TB Utrecht, The Netherlands.

In this study, temperature dependent behavior of dense dispersions of core crosslinked flower-like micelles is investigated. Micelles were prepared by mixing aqueous solutions of two ABA block copolymers with PEG B-blocks and thermosensitive A-blocks containing PNIPAM and crosslinkable moieties. At a temperature above the lower critical solution temperature (LCST), self-assembly of the polymers resulted in the formation of flower-like micelles with a hydrophilic PEG shell and a hydrophobic core. The micellar core was stabilized by native chemical ligation (NCL). Above the LCST, micelles displayed a radius of ∼35 nm, while a radius of ∼48 nm was found below the LCST due to hydration of the PNIPAM core. Concentrated dispersions of these micelles (≥7.5 wt%) showed glassy state behavior below a critical temperature (Tc: 28 °C) which is close to the LCST of the polymers. Below this Tc, the increase in the micelle volume resulted in compression of micelles together above a certain concentration and formation of a glass. We quantified and compared micelle packing at different concentrations and temperatures. The storage moduli (G') of the dispersions showed a universal dependence on the effective volume fraction, which increased substantially above a certain effective volume fraction of φ = 1.2. Furthermore, a disordered lattice model describing this behavior fitted the experimental data and revealed a critical volume fraction of φc = 1.31 close to the experimental value of φ = 1.2. The findings reported provide insights for the molecular design of novel thermosensitive PNIPAM nanoparticles with tunable structural and mechanical properties.
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http://dx.doi.org/10.1039/d0sm01505aDOI Listing
March 2021

Spinach and Chive for Kidney Tubule Engineering: the Limitations of Decellularized Plant Scaffolds and Vasculature.

AAPS J 2020 12 28;23(1):11. Epub 2020 Dec 28.

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

Tissue decellularization yields complex scaffolds with retained composition and structure, and plants offer an inexhaustible natural source of numerous shapes. Plant tissue could be a solution for regenerative organ replacement strategies and advanced in vitro modeling, as biofunctionalization of decellularized tissue allows adhesion of various kinds of human cells that can grow into functional tissue. Here, we investigated the potential of spinach leaf vasculature and chive stems for kidney tubule engineering to apply in tubular transport studies. We successfully decellularized both plant tissues and confirmed general scaffold suitability for topical recellularization with renal cells. However, due to anatomical restrictions, we believe that spinach and chive vasculature themselves cannot be recellularized by current methods. Moreover, gradual tissue disintegration and deficient diffusion capacity make decellularized plant scaffolds unsuitable for kidney tubule engineering, which relies on transepithelial solute exchange between two compartments. We conclude that plant-derived structures and biomaterials need to be carefully considered and possibly integrated with other tissue engineering technologies for enhanced capabilities.
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http://dx.doi.org/10.1208/s12248-020-00550-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769781PMC
December 2020

Hyaluronic acid and chondroitin sulfate (meth)acrylate-based hydrogels for tissue engineering: Synthesis, characteristics and pre-clinical evaluation.

Biomaterials 2021 01 22;268:120602. Epub 2020 Dec 22.

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Science for Life, Utrecht University, 3508 TB, Utrecht, the Netherlands. Electronic address:

Hydrogels based on photocrosslinkable Hyaluronic Acid Methacrylate (HAMA) and Chondroitin Sulfate Methacrylate (CSMA) are presently under investigation for tissue engineering applications. HAMA and CSMA gels offer tunable characteristics such as tailorable mechanical properties, swelling characteristics, and enzymatic degradability. This review gives an overview of the scientific literature published regarding the pre-clinical development of covalently crosslinked hydrogels that (partially) are based on HAMA and/or CSMA. Throughout the review, recommendations for the next steps in clinical translation of hydrogels based on HAMA or CSMA are made and potential pitfalls are defined. Specifically, a myriad of different synthetic routes to obtain polymerizable hyaluronic acid and chondroitin sulfate derivatives are described. The effects of important parameters such as degree of (meth)acrylation and molecular weight of the synthesized polymers on the formed hydrogels are discussed and useful analytical techniques for their characterization are summarized. Furthermore, the characteristics of the formed hydrogels including their enzymatic degradability are discussed. Finally, a summary of several recent applications of these hydrogels in applied fields such as cartilage and cardiac regeneration and advanced tissue modelling is presented.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120602DOI Listing
January 2021

Toward Antibacterial Coatings for Personalized Implants.

ACS Biomater Sci Eng 2020 10 10;6(10):5486-5492. Epub 2020 Sep 10.

Department of Orthopedics, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands.

The complex reconstructive surgeries for which patient-specific orthopedic, maxillofacial, or dental implants are used often necessitate wounds that are open for a considerable amount of time. Unsurprisingly, this allows bacteria to establish implant-associated infection, despite the scrupulous sterilization efforts made during surgery. Here, we developed a prophylactic bactericidal coating via electrophoretic deposition technology for two 3D-printed porous titanium implant designs. The surface characteristics, antibiotic release behavior, antibacterial properties, and impact on osteoblast cell proliferation of the optimized coatings were investigated. The results unequivocally confirmed the biofunctionality of the implants in vitro. This study reveals a new avenue for future antibacterial patient-specific implants.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00683DOI Listing
October 2020