Multiple‐Level Porous Polymer Monoliths with Interconnected Cellular Topology Prepared by Combining Hard Sphere and Emulsion Templating for Use in Bone Tissue Engineering

Paljevac, Muzafera; Gradišnik, Lidija; Lipovšek, Saška; Maver, Uroš; Kotek, Jiřı́; Krajnc, Peter

doi:10.1002/mabi.201700306

Cited by 25 publications

(21 citation statements)

References 27 publications

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“…In addition, as cellular penetration also depends on pore size and monolith thickness[ 51 , 52 ], ingrowth can be further improved by introducing larger macropores as shown here. Importantly, our findings showing that an increased macroporosity increases cell infiltration agree with those of Paljevac et al , which demonstrates its value in tissue engineering and 3D cell culture[ 50 ].…”

Section: Discussionsupporting

confidence: 91%

“…This approach first sintered poly(methyl methacrylate) (PMMA) beads for 24 h to fuse them together to create a sacrificial mold, then HIPE was poured over these sintered beads and polymerized. Subsequently, the PMMA was dissolved by ethyl acetate leaving a polyHIPE with ~100 μm macropores from the PMMA beads[ 50 ]. While this approach successfully generated multiscale porosity polyHIPEs, it is complex and time consuming.…”

Section: Discussionmentioning

confidence: 99%

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Combined Porogen Leaching and Emulsion Templating to produce Bone Tissue Engineering Scaffolds

Owen¹,

Sherborne²,

Evans³

et al. 2020

IJB

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Bone has a hierarchy of porosity that is often overlooked when creating tissue engineering scaffolds where pore sizes are typically confined to a single order of magnitude. High internal phase emulsion (HIPE) templating produces polymerized HIPEs (polyHIPEs): highly interconnected porous polymers which have two length scales of porosity covering the 1–100 µm range. However, additional larger scales of porosity cannot be introduced in the standard emulsion formulation. Researchers have previously overcome this by additively manufacturing emulsions; fabricating highly microporous struts into complex macroporous geometries. This is time consuming and expensive; therefore, here we assessed the feasibility of combining porogen leaching with emulsion templating to introduce additional macroporosity. Alginate beads between 275 and 780 µm were incorporated into the emulsion at 0, 50, and 100 wt%. Once polymerized, alginate was dissolved leaving highly porous polyHIPE scaffolds with added macroporosity. The compressive modulus of the scaffolds decreased as alginate porogen content increased. Cellular performance was assessed using MLO-A5 post-osteoblasts. Seeding efficiency was significantly higher and mineralized matrix deposition was more uniformly deposited throughout porogen leached scaffolds compared to plain polyHIPEs. Deep cell infiltration only occurred in porogen leached scaffolds as detected by histology and lightsheet microscopy. This study reveals a quick, low cost and simple method of producing multiscale porosity scaffolds for tissue engineering.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Combined Porogen Leaching and Emulsion Templating to produce Bone Tissue Engineering Scaffolds

Owen¹,

Sherborne²,

Evans³

et al. 2020

IJB

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“…Inactivation of microorganism on PolyHIPE scaffolds was commonly reported by using ethanol (Hayman et al, 2005;Caldwell et al, 2012;Moglia et al, 2014c;Eissa et al, 2018). There are also several studies that reported the use of UV irradiation (Moglia et al, 2011;Oh et al, 2015), gamma-irradiation (Yang et al, 2017), electron-beam irradiation (Hu et al, 2019), and autoclave (Naranda et al, 2016;Paljevac et al, 2018). Future studies investigating the effect of sterilisation methods on physical, chemical, and mechanical properties of emulsion templated scaffolds are needed to establish a greater degree of understanding of this matter.…”

Section: Washingmentioning

confidence: 99%

“…Casting enables the manufacturing of scaffolds in a wide range of shapes and sizes, depending on the mould design ( Paljevac et al, 2018 ; Diez-Ahedo et al, 2020 ; Dikici et al, 2020a ; Owen et al, 2020 ). Recently, Dikici et al (2020a) reported the fabrication of the PolyHIPEs in tubular form by designing a re-usable tubular silicone mould system that, HIPE can be injected into, polymerised, and recovered easily ( Figure 10Ab ).…”

Section: Development Of the Emulsion Templated Scaffoldsmentioning

confidence: 99%

Basic Principles of Emulsion Templating and Its Use as an Emerging Manufacturing Method of Tissue Engineering Scaffolds

Dikici

Claeyssens

2020

Front. Bioeng. Biotechnol.

103

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Tissue engineering (TE) aims to regenerate critical size defects, which cannot heal naturally, by using highly porous matrices called TE scaffolds made of biocompatible and biodegradable materials. There are various manufacturing techniques commonly used to fabricate TE scaffolds. However, in most cases, they do not provide materials with a highly interconnected pore design. Thus, emulsion templating is a promising and convenient route for the fabrication of matrices with up to 99% porosity and high interconnectivity. These matrices have been used for various application areas for decades. Although this polymer structuring technique is older than TE itself, the use of polymerised internal phase emulsions (PolyHIPEs) in TE is relatively new compared to other scaffold manufacturing techniques. It is likely because it requires a multidisciplinary background including materials science, chemistry and TE although producing emulsion templated scaffolds is practically simple. To date, a number of excellent reviews on emulsion templating have been published by the pioneers in this field in order to explain the chemistry behind this technique and potential areas of use of the emulsion templated structures. This particular review focusses on the key points of how emulsion templated scaffolds can be fabricated for different TE applications. Accordingly, we first explain the basics of emulsion templating and characteristics of PolyHIPE scaffolds. Then, we discuss the role of each ingredient in the emulsion and the impact of the compositional changes and process conditions on the characteristics of PolyHIPEs. Afterward, current fabrication methods of biocompatible PolyHIPE scaffolds and polymerisation routes are detailed, and the functionalisation strategies that can be used to improve the biological activity of PolyHIPE scaffolds are discussed. Finally, the applications of PolyHIPEs on soft and hard TE as well as in vitro models and drug delivery in the literature are summarised.

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“…The suitability of this material to support the growth and proliferation of human osteoblast cells has been also shown. 7 Recently, degradable polyHIPE materials have been prepared by photochemical thiol-ene polymerisation employing commercially available monomers. 8 The resulting scaffolds are chemically similar to common biomaterials, such as polylactide and polycaprolactone, and degrade by similar mechanisms (ester hydrolysis).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Differentiation Potential of Primary Human Endometrial Cells Cultured on 3D Scaffolds

et al. 2018

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Novel approaches for culturing primary human cells in vitro are increasingly needed to study cell and tissue physiology and to grow replacement tissue for regenerative medicine. Conventional 2D monolayer cultures of endometrial epithelial and stromal cells fail to replicate the complex 3D architecture of tissue. A fully synthetic scaffold that mimics the microenvironment of the human endometrium can ultimately provide a robust platform for investigating tissue physiology and, hence, take significant steps toward tackling female infertility and IVF failure. In this work, emulsion-templated porous polymers (known as polyHIPEs) were investigated as scaffolds for the culture of primary human endometrial epithelial and stromal cells (HEECs and HESCs). Infiltration of HEECs and HESCs into cell-seeded polyHIPE scaffolds was assessed by histological studies, and phenotype was confirmed by immunostaining. Confocal microscopy revealed that the morphology of HEECs and HESCs is representative of that found in vivo. RNA sequencing was used to investigate transcriptome differences between cells grown on polyHIPE scaffolds and in monolayer cultures. The differentiation status of HEECs and HESCs grown in polyHIPE scaffolds and in monolayer cultures was further evaluated by monitoring the expression of endometrial marker genes. Our observations suggest that a 3D cell culture model that could approximate native human endometrial architecture and function can be developed using tailored polyHIPE scaffolds.

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Multiple‐Level Porous Polymer Monoliths with Interconnected Cellular Topology Prepared by Combining Hard Sphere and Emulsion Templating for Use in Bone Tissue Engineering

Cited by 25 publications

References 27 publications

Combined Porogen Leaching and Emulsion Templating to produce Bone Tissue Engineering Scaffolds

Combined Porogen Leaching and Emulsion Templating to produce Bone Tissue Engineering Scaffolds

Basic Principles of Emulsion Templating and Its Use as an Emerging Manufacturing Method of Tissue Engineering Scaffolds

Enhanced Differentiation Potential of Primary Human Endometrial Cells Cultured on 3D Scaffolds

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