Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation

G. Marchioli, L. van Gurp, P.P. van Krieken, Dimitrios Stamatialis, M. Engelse, Clemens van Blitterswijk, Hermanus Bernardus Johannes Karperien, E. de Koning, J. Alblas, Lorenzo Moroni, Aart A. van Apeldoorn

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Abstract

In clinical islet transplantation, allogeneic islets of Langerhans are transplanted into the portal vein of patients with type 1 diabetes, enabling the restoration of normoglycemia. After intra-hepatic transplantation several factors are involved in the decay in islet mass and function mainly caused by an immediate blood mediated inflammatory response, lack of vascularization, and allo- and autoimmunity. Bioengineered scaffolds can potentially provide an alternative extra-hepatic transplantation site for islets by improving nutrient diffusion and blood supply to the scaffold. This would ultimately result in enhanced islet viability and functionality compared to conventional intra portal transplantation. In this regard, the biomaterial choice, the three-dimensional (3D) shape and scaffold porosity are key parameters for an optimal construct design and, ultimately, transplantation outcome. We used 3D bioplotting for the fabrication of a 3D alginate-based porous scaffold as an extra-hepatic islet delivery system. In 3D-plotted alginate scaffolds the surface to volume ratio, and thus oxygen and nutrient transport, is increased compared to conventional bulk hydrogels. Several alginate mixtures have been tested for INS1E β-cell viability. Alginate/gelatin mixtures resulted in high plotting performances, and satisfactory handling properties. INS1E β-cells, human and mouse islets were successfully embedded in 3D-plotted constructs without affecting their morphology and viability, while preventing their aggregation. 3D plotted scaffolds could help in creating an alternative extra-hepatic transplantation site. In contrast to microcapsule embedding, in 3D plotted scaffold islets are confined in one location and blood vessels can grow into the pores of the construct, in closer contact to the embedded tissue. Once revascularization has occurred, the functionality is fully restored upon degradation of the scaffold.

Original languageEnglish
Article number025009
Number of pages18
JournalBiofabrication
Volume7
Issue number2
DOIs
Publication statusPublished - 1 Jun 2015

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Islets of Langerhans Transplantation
Hydrogel
Hydrogels
Scaffolds
Liver Transplantation
Fabrication
Alginate
Transplantation
Food
Porosity
Biocompatible Materials
Gelatin
Nutrients
Portal Vein
Autoimmunity
Type 1 Diabetes Mellitus
Islets of Langerhans
Blood
Capsules
Blood Vessels

Keywords

  • IR-97122
  • METIS-311631

Cite this

Marchioli, G., van Gurp, L., van Krieken, P. P., Stamatialis, D., Engelse, M., van Blitterswijk, C., ... van Apeldoorn, A. A. (2015). Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation. Biofabrication, 7(2), [025009]. https://doi.org/10.1088/1758-5090/7/2/025009
Marchioli, G. ; van Gurp, L. ; van Krieken, P.P. ; Stamatialis, Dimitrios ; Engelse, M. ; van Blitterswijk, Clemens ; Karperien, Hermanus Bernardus Johannes ; de Koning, E. ; Alblas, J. ; Moroni, Lorenzo ; van Apeldoorn, Aart A. / Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation. In: Biofabrication. 2015 ; Vol. 7, No. 2.
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abstract = "In clinical islet transplantation, allogeneic islets of Langerhans are transplanted into the portal vein of patients with type 1 diabetes, enabling the restoration of normoglycemia. After intra-hepatic transplantation several factors are involved in the decay in islet mass and function mainly caused by an immediate blood mediated inflammatory response, lack of vascularization, and allo- and autoimmunity. Bioengineered scaffolds can potentially provide an alternative extra-hepatic transplantation site for islets by improving nutrient diffusion and blood supply to the scaffold. This would ultimately result in enhanced islet viability and functionality compared to conventional intra portal transplantation. In this regard, the biomaterial choice, the three-dimensional (3D) shape and scaffold porosity are key parameters for an optimal construct design and, ultimately, transplantation outcome. We used 3D bioplotting for the fabrication of a 3D alginate-based porous scaffold as an extra-hepatic islet delivery system. In 3D-plotted alginate scaffolds the surface to volume ratio, and thus oxygen and nutrient transport, is increased compared to conventional bulk hydrogels. Several alginate mixtures have been tested for INS1E β-cell viability. Alginate/gelatin mixtures resulted in high plotting performances, and satisfactory handling properties. INS1E β-cells, human and mouse islets were successfully embedded in 3D-plotted constructs without affecting their morphology and viability, while preventing their aggregation. 3D plotted scaffolds could help in creating an alternative extra-hepatic transplantation site. In contrast to microcapsule embedding, in 3D plotted scaffold islets are confined in one location and blood vessels can grow into the pores of the construct, in closer contact to the embedded tissue. Once revascularization has occurred, the functionality is fully restored upon degradation of the scaffold.",
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Marchioli, G, van Gurp, L, van Krieken, PP, Stamatialis, D, Engelse, M, van Blitterswijk, C, Karperien, HBJ, de Koning, E, Alblas, J, Moroni, L & van Apeldoorn, AA 2015, 'Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation' Biofabrication, vol. 7, no. 2, 025009. https://doi.org/10.1088/1758-5090/7/2/025009

Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation. / Marchioli, G.; van Gurp, L.; van Krieken, P.P.; Stamatialis, Dimitrios; Engelse, M.; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes; de Koning, E.; Alblas, J.; Moroni, Lorenzo; van Apeldoorn, Aart A.

In: Biofabrication, Vol. 7, No. 2, 025009, 01.06.2015.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation

AU - Marchioli, G.

AU - van Gurp, L.

AU - van Krieken, P.P.

AU - Stamatialis, Dimitrios

AU - Engelse, M.

AU - van Blitterswijk, Clemens

AU - Karperien, Hermanus Bernardus Johannes

AU - de Koning, E.

AU - Alblas, J.

AU - Moroni, Lorenzo

AU - van Apeldoorn, Aart A.

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N2 - In clinical islet transplantation, allogeneic islets of Langerhans are transplanted into the portal vein of patients with type 1 diabetes, enabling the restoration of normoglycemia. After intra-hepatic transplantation several factors are involved in the decay in islet mass and function mainly caused by an immediate blood mediated inflammatory response, lack of vascularization, and allo- and autoimmunity. Bioengineered scaffolds can potentially provide an alternative extra-hepatic transplantation site for islets by improving nutrient diffusion and blood supply to the scaffold. This would ultimately result in enhanced islet viability and functionality compared to conventional intra portal transplantation. In this regard, the biomaterial choice, the three-dimensional (3D) shape and scaffold porosity are key parameters for an optimal construct design and, ultimately, transplantation outcome. We used 3D bioplotting for the fabrication of a 3D alginate-based porous scaffold as an extra-hepatic islet delivery system. In 3D-plotted alginate scaffolds the surface to volume ratio, and thus oxygen and nutrient transport, is increased compared to conventional bulk hydrogels. Several alginate mixtures have been tested for INS1E β-cell viability. Alginate/gelatin mixtures resulted in high plotting performances, and satisfactory handling properties. INS1E β-cells, human and mouse islets were successfully embedded in 3D-plotted constructs without affecting their morphology and viability, while preventing their aggregation. 3D plotted scaffolds could help in creating an alternative extra-hepatic transplantation site. In contrast to microcapsule embedding, in 3D plotted scaffold islets are confined in one location and blood vessels can grow into the pores of the construct, in closer contact to the embedded tissue. Once revascularization has occurred, the functionality is fully restored upon degradation of the scaffold.

AB - In clinical islet transplantation, allogeneic islets of Langerhans are transplanted into the portal vein of patients with type 1 diabetes, enabling the restoration of normoglycemia. After intra-hepatic transplantation several factors are involved in the decay in islet mass and function mainly caused by an immediate blood mediated inflammatory response, lack of vascularization, and allo- and autoimmunity. Bioengineered scaffolds can potentially provide an alternative extra-hepatic transplantation site for islets by improving nutrient diffusion and blood supply to the scaffold. This would ultimately result in enhanced islet viability and functionality compared to conventional intra portal transplantation. In this regard, the biomaterial choice, the three-dimensional (3D) shape and scaffold porosity are key parameters for an optimal construct design and, ultimately, transplantation outcome. We used 3D bioplotting for the fabrication of a 3D alginate-based porous scaffold as an extra-hepatic islet delivery system. In 3D-plotted alginate scaffolds the surface to volume ratio, and thus oxygen and nutrient transport, is increased compared to conventional bulk hydrogels. Several alginate mixtures have been tested for INS1E β-cell viability. Alginate/gelatin mixtures resulted in high plotting performances, and satisfactory handling properties. INS1E β-cells, human and mouse islets were successfully embedded in 3D-plotted constructs without affecting their morphology and viability, while preventing their aggregation. 3D plotted scaffolds could help in creating an alternative extra-hepatic transplantation site. In contrast to microcapsule embedding, in 3D plotted scaffold islets are confined in one location and blood vessels can grow into the pores of the construct, in closer contact to the embedded tissue. Once revascularization has occurred, the functionality is fully restored upon degradation of the scaffold.

KW - IR-97122

KW - METIS-311631

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U2 - 10.1088/1758-5090/7/2/025009

DO - 10.1088/1758-5090/7/2/025009

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VL - 7

JO - Biofabrication

JF - Biofabrication

SN - 1758-5082

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