Towards brain-tissue-like biomaterials

Axpe, Eneko; Orive, Gorka; Franze, Kristian; Appel, Eric A.

doi:10.1038/s41467-020-17245-x

Cited by 86 publications

(57 citation statements)

References 39 publications

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“…The functional properties of a hydrogel originate from its structure at multiple length scales ( 4 ), with mounting evidence for the importance of physical properties in controlling biological behavior ( 5 – 7 ). Atomic-scale chemical structure of the polymeric repeating units and pendant functional groups control most of the hydrogel’s chemical properties, and larger-scale features such as nanoscale mesh size, microscopic pores, and the overall polymer concentration primarily affect physical properties such as stiffness and solute transport ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Precise control of synthetic hydrogel network structure via linear, independent synthesis-swelling relationships

et al. 2021

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Hydrogel physical properties are tuned by altering synthesis conditions such as initial polymer concentration and polymer–cross-linker stoichiometric ratios. Traditionally, differences in hydrogel synthesis schemes, such as end-linked poly(ethylene glycol) diacrylate hydrogels and cross-linked poly(vinyl alcohol) hydrogels, limit structural comparison between hydrogels. In this study, we use generalized synthesis variables for hydrogels that emphasize how changes in formulation affect the resulting network structure. We identify two independent linear correlations between these synthesis variables and swelling behavior. Analysis through recently updated swollen polymer network models suggests that synthesis-swelling correlations can be used to make a priori predictions of the stiffness and solute diffusivity characteristics of synthetic hydrogels. The same experiments and analyses performed on methacrylamide-modified gelatin hydrogels demonstrate that complex biopolymer structures disrupt the linear synthesis-swelling correlations. These studies provide insight into the control of hydrogel physical properties through structural design and can be used to implement and optimize biomedically relevant hydrogels.

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Section: Introductionmentioning

confidence: 99%

Precise control of synthetic hydrogel network structure via linear, independent synthesis-swelling relationships

et al. 2021

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“…and Axpe et al.). [ 69,74 ] We suggest that the quick stress relaxation of our gel blends supports growth and migration of neural cultures, even in stiffer gels.…”

Section: Discussionmentioning

confidence: 96%

“…[ 31,32 ] Thus, mimicking the brains ECM in vitro is highly challenging. [ 69 ] Hydrogels feature advantageous properties for the 3D cultivation of neural models, such as the high water content (>90%), potential for functionalization, as well as chemical and physical tunability. [ 28 ] Studies demonstrated that soft hydrogels (<1.5 kPa) support neurite outgrowth [ 39 ] whereas stiffer hydrogels promote astrocyte differentiation.…”

Section: Discussionmentioning

confidence: 99%

Human Induced Pluripotent Stem Cell‐Derived Neural Progenitor Cells Produce Distinct Neural 3D In Vitro Models Depending on Alginate/Gellan Gum/Laminin Hydrogel Blend Properties

Kapr

Petersilie

Distler

et al. 2021

Adv Healthcare Materials

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Stable and predictive neural cell culture models are a necessary premise for many research fields. However, conventional 2D models lack 3D cell‐material/‐cell interactions and hence do not reflect the complexity of the in vivo situation properly. Here two alginate/gellan gum/laminin (ALG/GG/LAM) hydrogel blends are presented for the fabrication of human induced pluripotent stem cell (hiPSC)‐based 3D neural models. For hydrogel embedding, hiPSC‐derived neural progenitor cells (hiNPCs) are used either directly or after 3D neural pre‐differentiation. It is shown that stiffness and stress relaxation of the gel blends, as well as the cell differentiation strategy influence 3D model development. The embedded hiNPCs differentiate into neurons and astrocytes within the gel blends and display spontaneous intracellular calcium signals. Two fit‐for‐purpose models valuable for i) applications requiring a high degree of complexity, but less throughput, such as disease modeling and long‐term exposure studies and ii) higher throughput applications, such as acute exposures or substance screenings are proposed. Due to their wide range of applications, adjustability, and printing capabilities, the ALG/GG/LAM based 3D neural models are of great potential for 3D neural modeling in the future.

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“…However, a few drawbacks prevent GLIADEL wafers from fulfilling clinical expectations. For instance, the solid wafers suffer from a mechanical mismatch with brain tissue, which incurs risks of neuroinflammatory and neurodegenerative response [9][10][11]. In addition, the solid wafers cannot fully cover the irregular cavity wall and might be easily detached [4].…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Printing of Curcumin-Loaded Biodegradable and Flexible Scaffold for Intracranial Therapy of Glioblastoma Multiforme

Song

Fouladian

et al. 2021

Pharmaceutics

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A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable flexible porous scaffolds were developed via Fused Deposition Modelling (FDM) three-dimensional (3D) printing technology for the local delivery of curcumin. The flexible porous scaffolds were 3D printed with various geometries containing 1, 3, 5, and 7% (w/w) of curcumin, respectively, using curcumin-loaded polycaprolactone (PCL) filaments. The scaffolds were characterised by a series of characterisation studies and in vitro studies were also performed including drug release study, scaffold degradation study, and cytotoxicity study. The curcumin-loaded PCL scaffolds displayed versatile spatiotemporal characteristics. The polymeric scaffolds obtained great mechanical flexibility with a low tensile modulus of less than 2 MPa, and 4 to 7-fold ultimate tensile strain, which can avoid the mechanical mismatch problem of commercially available GLIADEL wafer with a further improvement in surgical margin coverage. In vitro release profiles have demonstrated the sustained release patterns of curcumin with adjustable release amounts and durations up to 77 h. MTT study has demonstrated the great cytotoxic effect of curcumin-loaded scaffolds against the U87 human GBM cell line. Therefore, 3D printed curcumin-loaded scaffold has great promise to provide better GBM treatment options with its mechanical flexibility and customisability to match individual needs, preventing post-surgery GBM recurrence and eventually prolonging the life expectancy of GBM patients.

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Towards brain-tissue-like biomaterials

Cited by 86 publications

References 39 publications

Precise control of synthetic hydrogel network structure via linear, independent synthesis-swelling relationships

Precise control of synthetic hydrogel network structure via linear, independent synthesis-swelling relationships

Human Induced Pluripotent Stem Cell‐Derived Neural Progenitor Cells Produce Distinct Neural 3D In Vitro Models Depending on Alginate/Gellan Gum/Laminin Hydrogel Blend Properties

Three-Dimensional Printing of Curcumin-Loaded Biodegradable and Flexible Scaffold for Intracranial Therapy of Glioblastoma Multiforme

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