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Platform technology for scalable assembly of instantaneously functional mosaic tissues.

Zhang B, Montgomery M, Davenport-Huyer L, Korolj A, Radisic M - Sci Adv (2015)

Bottom Line: We invented Tissue-Velcro, a bio-scaffold with a microfabricated hook and loop system.The assembled cardiac 3D tissue constructs were immediately functional as measured by their ability to contract in response to electrical field stimulation.Facile, on-demand tissue disassembly was demonstrated while preserving the structure, physical integrity, and beating function of individual layers.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada. ; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.

ABSTRACT
Engineering mature tissues requires a guided assembly of cells into organized three-dimensional (3D) structures with multiple cell types. Guidance is usually achieved by microtopographical scaffold cues or by cell-gel compaction. The assembly of individual units into functional 3D tissues is often time-consuming, relying on cell ingrowth and matrix remodeling, whereas disassembly requires an invasive method that includes either matrix dissolution or mechanical cutting. We invented Tissue-Velcro, a bio-scaffold with a microfabricated hook and loop system. The assembly of Tissue-Velcro preserved the guided cell alignment realized by the topographical features in the 2D scaffold mesh and allowed for the instant establishment of coculture conditions by spatially defined stacking of cardiac cell layers or through endothelial cell coating. The assembled cardiac 3D tissue constructs were immediately functional as measured by their ability to contract in response to electrical field stimulation. Facile, on-demand tissue disassembly was demonstrated while preserving the structure, physical integrity, and beating function of individual layers.

No MeSH data available.


Related in: MedlinePlus

Mechanical properties of Tissue-Velcro.(A) Representative force curve from the mechanical pull-off test of the scaffold (n = 4). Inset scale bar, 5 mm. (B) Representative uniaxial tensile stress-strain plots of the scaffold in the x direction (xD) and y direction (yD) (n = 4). (C) Summary of the measured apparent modulus of the scaffold in the x direction (xD), y direction (yD), and the anisotropic ratio (xD/yD) (mean ± SD, n = 4). (D and E) Representative 3D renderings of profilometry data of the preassembled scaffold components. (D) Bottom mesh and post (n = 3); (E) top hook (n = 3). (F) Illustration of the cross-sectional view of an assembled scaffold labeled with measured heights (n = 3).
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Figure 2: Mechanical properties of Tissue-Velcro.(A) Representative force curve from the mechanical pull-off test of the scaffold (n = 4). Inset scale bar, 5 mm. (B) Representative uniaxial tensile stress-strain plots of the scaffold in the x direction (xD) and y direction (yD) (n = 4). (C) Summary of the measured apparent modulus of the scaffold in the x direction (xD), y direction (yD), and the anisotropic ratio (xD/yD) (mean ± SD, n = 4). (D and E) Representative 3D renderings of profilometry data of the preassembled scaffold components. (D) Bottom mesh and post (n = 3); (E) top hook (n = 3). (F) Illustration of the cross-sectional view of an assembled scaffold labeled with measured heights (n = 3).

Mentions: The microhooks of a single layer scaffold, which protrude through the void space of another scaffold mesh and anchor onto its struts, were imaged by scanning electron microscopy (SEM) (Fig. 1D). The SEM image of two tissues brought into contact shows the attachment mechanism whereby the hooks of the bottom scaffold protrude through the honeycomb mesh of the top scaffold and affix the two tissue meshes together (Fig. 1E). The maximum force recorded to pull off the scaffold was 6.2 ± 1.1 mN, or when divided by the area of the scaffold (2.5 × 5 mm), the pressure required was 0.5 ± 0.1 kPa. Typically 18 hooks (equivalent to 82% of total hooks) will successfully lock in place across the scaffolds when two 2.5 × 5–mm layers are brought into direct contact without offset. A 3D reconstruction from a confocal z-stack of an assembled two-layer scaffold construct shows the interlocking mechanism (movie S1). A representative plot of the pull-off test is shown in Fig. 2A (movie S2). The binding force between the two scaffolds is sufficiently strong to withstand manual manipulation such as stretching or compression (movie S3). The presence of cells on the scaffold or a short culture time between two layers (3 days) did not significantly affect the pull-off force (fig. S2). Thus, the hook and loop interlocking mechanism was primarily responsible for the mechanical stability of the assembled layers. The pull-off force was significantly higher when two scaffolds were overlaid by 100% (Fig. 2A, 6.2 ± 1.1 mN) in comparison to measurements in partially overlaid scaffolds (fig. S2B, 2.0 ± 0.9 mN, P = 0.001) as expected.


Platform technology for scalable assembly of instantaneously functional mosaic tissues.

Zhang B, Montgomery M, Davenport-Huyer L, Korolj A, Radisic M - Sci Adv (2015)

Mechanical properties of Tissue-Velcro.(A) Representative force curve from the mechanical pull-off test of the scaffold (n = 4). Inset scale bar, 5 mm. (B) Representative uniaxial tensile stress-strain plots of the scaffold in the x direction (xD) and y direction (yD) (n = 4). (C) Summary of the measured apparent modulus of the scaffold in the x direction (xD), y direction (yD), and the anisotropic ratio (xD/yD) (mean ± SD, n = 4). (D and E) Representative 3D renderings of profilometry data of the preassembled scaffold components. (D) Bottom mesh and post (n = 3); (E) top hook (n = 3). (F) Illustration of the cross-sectional view of an assembled scaffold labeled with measured heights (n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643798&req=5

Figure 2: Mechanical properties of Tissue-Velcro.(A) Representative force curve from the mechanical pull-off test of the scaffold (n = 4). Inset scale bar, 5 mm. (B) Representative uniaxial tensile stress-strain plots of the scaffold in the x direction (xD) and y direction (yD) (n = 4). (C) Summary of the measured apparent modulus of the scaffold in the x direction (xD), y direction (yD), and the anisotropic ratio (xD/yD) (mean ± SD, n = 4). (D and E) Representative 3D renderings of profilometry data of the preassembled scaffold components. (D) Bottom mesh and post (n = 3); (E) top hook (n = 3). (F) Illustration of the cross-sectional view of an assembled scaffold labeled with measured heights (n = 3).
Mentions: The microhooks of a single layer scaffold, which protrude through the void space of another scaffold mesh and anchor onto its struts, were imaged by scanning electron microscopy (SEM) (Fig. 1D). The SEM image of two tissues brought into contact shows the attachment mechanism whereby the hooks of the bottom scaffold protrude through the honeycomb mesh of the top scaffold and affix the two tissue meshes together (Fig. 1E). The maximum force recorded to pull off the scaffold was 6.2 ± 1.1 mN, or when divided by the area of the scaffold (2.5 × 5 mm), the pressure required was 0.5 ± 0.1 kPa. Typically 18 hooks (equivalent to 82% of total hooks) will successfully lock in place across the scaffolds when two 2.5 × 5–mm layers are brought into direct contact without offset. A 3D reconstruction from a confocal z-stack of an assembled two-layer scaffold construct shows the interlocking mechanism (movie S1). A representative plot of the pull-off test is shown in Fig. 2A (movie S2). The binding force between the two scaffolds is sufficiently strong to withstand manual manipulation such as stretching or compression (movie S3). The presence of cells on the scaffold or a short culture time between two layers (3 days) did not significantly affect the pull-off force (fig. S2). Thus, the hook and loop interlocking mechanism was primarily responsible for the mechanical stability of the assembled layers. The pull-off force was significantly higher when two scaffolds were overlaid by 100% (Fig. 2A, 6.2 ± 1.1 mN) in comparison to measurements in partially overlaid scaffolds (fig. S2B, 2.0 ± 0.9 mN, P = 0.001) as expected.

Bottom Line: We invented Tissue-Velcro, a bio-scaffold with a microfabricated hook and loop system.The assembled cardiac 3D tissue constructs were immediately functional as measured by their ability to contract in response to electrical field stimulation.Facile, on-demand tissue disassembly was demonstrated while preserving the structure, physical integrity, and beating function of individual layers.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada. ; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.

ABSTRACT
Engineering mature tissues requires a guided assembly of cells into organized three-dimensional (3D) structures with multiple cell types. Guidance is usually achieved by microtopographical scaffold cues or by cell-gel compaction. The assembly of individual units into functional 3D tissues is often time-consuming, relying on cell ingrowth and matrix remodeling, whereas disassembly requires an invasive method that includes either matrix dissolution or mechanical cutting. We invented Tissue-Velcro, a bio-scaffold with a microfabricated hook and loop system. The assembly of Tissue-Velcro preserved the guided cell alignment realized by the topographical features in the 2D scaffold mesh and allowed for the instant establishment of coculture conditions by spatially defined stacking of cardiac cell layers or through endothelial cell coating. The assembled cardiac 3D tissue constructs were immediately functional as measured by their ability to contract in response to electrical field stimulation. Facile, on-demand tissue disassembly was demonstrated while preserving the structure, physical integrity, and beating function of individual layers.

No MeSH data available.


Related in: MedlinePlus