A Composite Hydrogel Scaffold Permits Self‐Organization and Matrix Deposition by Cocultured Human Glomerular Cells

Tuffin, Jack; Burke, Madeline; Richardson, Thomas; Johnson, Timothy S.; Saleem, Moin A.; Satchell, Simon C.; Welsh, Gavin I.; Perriman, Adam W.

doi:10.1002/adhm.201900698

Cited by 19 publications

(24 citation statements)

References 29 publications

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“…There are limitations with the GlomSphere model, including the lack of glomerular mesangial cells, which can contribute to the signalling milieu as well as mesangial derived matrix components, and structural support for capillaries 34 . The latter is unlikely to be adequately recreated unless flow is also provided, which is currently beyond the capabilities of this type of model, though it was interesting that primitive vascularisation is seen in GlomSpheres, indicating that enough soluble signals (e.g.…”

Section: Discussionmentioning

confidence: 99%

GlomSpheres as a 3D co-culture spheroid model of the kidney glomerulus for rapid drug-screening

et al. 2021

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The glomerulus is the filtration unit of the kidney. Injury to any component of this specialised structure leads to impaired filtration and eventually fibrosis and chronic kidney disease. Current two and three dimensional (2D and 3D) models that attempt to recreate structure and interplay between glomerular cells are imperfect. Most 2D models are simplistic and unrepresentative, and 3D organoid approaches are currently difficult to reproduce at scale and do not fit well with current industrial drug-screening approaches. Here we report a rapidly generated and highly reproducible 3D co-culture spheroid model (GlomSpheres), better demonstrating the specialised physical and molecular structure of a glomerulus. Co-cultured using a magnetic spheroid formation approach, conditionally immortalised (CI) human podocytes and glomerular endothelial cells (GEnCs) deposited mature, organized isoforms of collagen IV and Laminin. We demonstrate a dramatic upregulation of key podocyte (podocin, nephrin and podocalyxin) and GEnC (pecam-1) markers. Electron microscopy revealed podocyte foot process interdigitation and endothelial vessel formation. Incubation with pro-fibrotic agents (TGF-β1, Adriamycin) induced extracellular matrix (ECM) dysregulation and podocyte loss, which were attenuated by the anti-fibrotic agent Nintedanib. Incubation with plasma from patients with kidney disease induced acute podocyte loss and ECM dysregulation relative to patient matched remission plasma, and Nintedanib reduced podocyte loss. Finally, we developed a rapid imaging approach to demonstrate the model’s usefulness in higher throughput pharmaceutical screening. GlomSpheres therefore represent a robust, scalable, replacement for 2D in vitro glomerular disease models.

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Section: Discussionmentioning

confidence: 99%

GlomSpheres as a 3D co-culture spheroid model of the kidney glomerulus for rapid drug-screening

et al. 2021

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“…[ 162 ] A 90% porous melt electrospun microfiber mesh with cancellous bone structure is incorporated into the shell and loaded with hydrogel to provide two‐phase support and continuously release the BMP‐2 scaffolds, thereby promoting osteogenesis and angiogenesis. [ 163,164 ]…”

Section: D Composite Materialsmentioning

confidence: 99%

“…[162] A 90% porous melt electrospun microfiber mesh with cancellous bone structure is incorporated into the shell and loaded with hydrogel to provide two-phase support and continuously release the BMP-2 scaffolds, thereby promoting osteogenesis and angiogenesis. [163,164] In another contribution, alginate-coated TiO 2 scaffolds are taken as the matrix of osteoblast differentiation induced by a simvastatin (SIM) carrier. Sodium alginate hydrogel coated scaffolds have lower cytotoxicity and significantly enhance the secretion of VEGF and osteocalcin (OC) in osteoblasts cultured on the TiO 2 scaffolds.…”

Section: Metal Scaffoldmentioning

confidence: 99%

Hydrogel Composites with Different Dimensional Nanoparticles for Bone Regeneration

Yang

Fang

et al. 2021

Macromol. Rapid Commun.

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The treatment of large segmental bone defects and complex types of fractures caused by trauma, inflammation, or tumor resection is still a challenge in the field of orthopedics. Various natural or synthetic biological materials used in clinical applications cannot fully replicate the structure and performance of raw bone. This highlights how to endow materials with multiple functions and biological properties, which is a problem that needs to be solved in practical applications. Hydrogels with outstanding biocompatibility, for their casting into any shape, size, or form, are suitable for different forms of bone defects. Therefore, they have been used in regenerative medicine more widely. In this review, versatile hydrogels are compounded with nanoparticles of different dimensions, and many desirable features of these materials in bone regeneration are introduced, including drug delivery, cell factor vehicle, cell scaffolds, which have potential in bone regeneration applications. The combination of hydrogels and nanoparticles of different dimensions encourages better filling of bone defect areas and has higher adaptability. This is due to the minimally invasive properties of the material and ability to match irregular defects. These biological characteristics make composite hydrogels with different dimensional nanoparticles become one of the most attractive options for bone regeneration materials.

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“…Several works reported enhanced mechanical properties, and hence biofunctionality, of hydrogel-based systems incorporating different types of structures, including fibers [15,16,18,27,28,52,[59][60][61], particles [62][63][64][65], or by using interpenetrating/semi-interpenetrating networks [13]. In this specific case of structural reinforcement, the way that reinforcing structures interact with the network dictates the way that stress propagates within the structure.…”

Section: Structural Reinforcementmentioning

confidence: 99%

Leveling Up Hydrogels: Hybrid Systems in Tissue Engineering

Neves

Moroni

Barrias

et al. 2020

Trends in Biotechnology

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A Composite Hydrogel Scaffold Permits Self‐Organization and Matrix Deposition by Cocultured Human Glomerular Cells

Cited by 19 publications

References 29 publications

GlomSpheres as a 3D co-culture spheroid model of the kidney glomerulus for rapid drug-screening

GlomSpheres as a 3D co-culture spheroid model of the kidney glomerulus for rapid drug-screening

Hydrogel Composites with Different Dimensional Nanoparticles for Bone Regeneration

Leveling Up Hydrogels: Hybrid Systems in Tissue Engineering

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