Fabrication of Kidney Proximal Tubule Grafts Using Biofunctionalized Electrospun Polymer Scaffolds

Jansen, Katja; Castilho, Miguel; Aarts, Sanne; Kaminski, Michael M.; Lienkamp, Soeren S.; Pichler, Roman; Malda, Jos; Vermonden, Tina; Jansen, Jitske; Masereeuw, Rosalinde

doi:10.1002/mabi.201800412

Cited by 24 publications

(39 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the same time, they can influence cellular functionality and ECM deposition through proper scaffold design. Fibrous scaffolds have shown to facilitate cell migration and functionality by providing physiologically relevant mechanical stimulation (Castilho et al, 2017 , 2019 ; Jansen et al, 2019 ). For instance, cell growth and growth directionality can be positively affected by microfibers when ordered along a preferential direction (Castilho et al, 2017 ; Kennedy et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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

Genderen

Jansen

Kristen

et al. 2021

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

Introduction: 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.Materials and Methods: 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.Results: 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).Discussion and Conclusion: 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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Genderen

Jansen

Kristen

et al. 2021

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…These sieve-like areas likely trap injected cells. Even if our epithelial cells came through, they would grow over the perforations and hence occlude the vasculature (17). Gershlak et al did not go into detail on the colonization of the inner surfaces with endothelial cells (10).…”

Section: Leaf Vasculature Appears To Have Anatomical Restrictions Formentioning

confidence: 98%

“…While adhesive coating was unnecessary for kidney tissue, decellularized plant samples were coated for 4 h with 2 mg/mL l-3,4dihydroxyphenylalanine (L-DOPA, Sigma Aldrich) dissolved in 10 mM Tris buffer at pH 8.5, which was pre-incubated at 37°C for 45 min and 0.2 μm filter-sterilized (15). After thorough sample washing with HBSS, 500.000 parent or tetramethylrhodamine-isothiocyanate (TRITC)-labeled conditionally immortalized proximal tubule epithelial cells (ciPTEC) were seeded onto a rat kidney slice in an ultralow attachment plate or injected into the spinach petiole or chive stem using a 22 gauge injection needle and ciPTEC medium composed as described earlier (7,16,17). The ciPTEC cell line was obtained as described by Wilmer et al with informed consent of the donor and in accordance with the approved guidelines of the Radboud Institutional Review Board.…”

Section: Scaffold Recellularizationmentioning

confidence: 99%

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

Jansen

Evangelopoulou

Casellas

et al. 2020

AAPS J

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Adherence of NCI-H292 cells; tuning mechanical properties of materials [177,178,248] bFGF and AA2P based PGA/PLA Improving cells adhesion and stimulates cells proliferation and differentiation [249] Kidney (Section 6.2) Mg(OH) 2 and acellular ECM PLGA Neutralization of the effects induced by degradation of PLGA products, suppression of inflammatory reactions [186] l-DOPA and collagen IV PCL Improving cells adhesion and proliferation [250] Liver (Section 6.3) ECM-molecules PLA Microenvironment manipulation; changes of gene expression, protein contents, and cell adherence [251] PCL [252] HGF based Gelatin Controlled release for enhancement of the in vivo therapeutic effects RGD and YIGSR based PCL and PLA Improved hepatocyte adhesion [196] Cardiac muscles (Section 7.1) bFGF based PLGA Neovascular formation [253] Laminin based PU Improving cells adhesion [254] Skeletal muscles (Section 7.2)…”

Section: Gelatin Based Pcl Pgamentioning

confidence: 99%

Polymer- and Hybrid-Based Biomaterials for Interstitial, Connective, Vascular, Nerve, Visceral and Musculoskeletal Tissue Engineering

2020

View full text Add to dashboard Cite

In this review, materials based on polymers and hybrids possessing both organic and inorganic contents for repairing or facilitating cell growth in tissue engineering are discussed. Pure polymer based biomaterials are predominantly used to target soft tissues. Stipulated by possibilities of tuning the composition and concentration of their inorganic content, hybrid materials allow to mimic properties of various types of harder tissues. That leads to the concept of "one-matches-all" referring to materials possessing the same polymeric base, but different inorganic content to enable tissue growth and repair, proliferation of cells, and the formation of the ECM (extra cellular matrix). Furthermore, adding drug delivery carriers to coatings and scaffolds designed with such materials brings additional functionality by encapsulating active molecules, antibacterial agents, and growth factors. We discuss here materials and methods of their assembly from a general perspective together with their applications in various tissue engineering sub-areas: interstitial, connective, vascular, nervous, visceral and musculoskeletal tissues. The overall aims of this review are two-fold: (a) to describe the needs and opportunities in the field of bio-medicine, which should be useful for material scientists, and (b) to present capabilities and resources available in the area of materials, which should be of interest for biologists and medical doctors.Polymers 2020, 12, 620 2 of 30 allows to tailor functionalize the coatings, where their responsiveness to external stimuli is one of their biggest advantages.Polymers stand out as a special class of materials due to the flexibility of design of their blocks and various functionalities, which is brought by their versatile assembly or by introducing additional side-groups or blocks, in the case of block-co-polymers. In this regard, both synthetic and biocompatible polymers are available, and polymer engineering represents a growing area tailoring the needs often driven by applications. With all advantages and the flexibility of the design, there is one significant weakness of polymers-the softness. In regard with tissue engineering, that translates to the fact that some materials can match predominantly soft tissue, but it is difficult to tune mechanical properties of polymers to match the hardness of bones, tendons, etc. And since mechanical properties of materials affect and even drive cell and tissue growth, enhancement of mechanical properties of polymers and biomaterials is essential. Chemical crosslinking can be applied to address these challenges, but that solves problems only partially.To solve these challenges the so-called hybrid materials [6] are used, which possess both inorganic and organic contents. Increasingly, hybrid materials are used in designing the extracellular matrix. The hybrid matrix design for various tissue engineering applications should meet bio-medical requirements. On the one hand, it needs to be biocompatible and biodegradable, which is achieved through the po...

show abstract

Fabrication of Kidney Proximal Tubule Grafts Using Biofunctionalized Electrospun Polymer Scaffolds

Cited by 24 publications

References 44 publications

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

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

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

Polymer- and Hybrid-Based Biomaterials for Interstitial, Connective, Vascular, Nerve, Visceral and Musculoskeletal Tissue Engineering

Contact Info

Product

Resources

About