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- Abadpour, Shadab, et al.
(author)
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Adipose-Derived Stromal Cells Preserve Pancreatic Islet Function in a Transplantable 3D Bioprinted Scaffold
- 2023
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In: Advanced healthcare materials. - 2192-2640 .- 2192-2659. ; 12:32
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Journal article (peer-reviewed)abstract
- Intra-portal islet transplantation is currently the only clinically approved beta cell replacement therapy, but its outcome is hindered by limited cell survival due to a multifactorial reaction against the allogeneic tissue in liver. Adipose-derived stromal cells (ASCs) can potentially improve the islet micro-environment by their immunomodulatory action. The challenge is to combine both islets and ASCs in a relatively easy and consistent long-term manner in a deliverable scaffold. Manufacturing the 3D bioprinted double-layered scaffolds with primary islets and ASCs using a mix of alginate/nanofibrillated cellulose (NFC) bioink is reported. The diffusion properties of the bioink and the supportive effect of human ASCs on islet viability, glucose sensing, insulin secretion, and reducing the secretion of pro-inflammatory cytokines are demonstrated. Diabetic mice transplanted with islet-ASC scaffolds reach normoglycemia seven days post-transplantation with no significant difference between this group and the group received islets under the kidney capsules. In addition, animals transplanted with islet-ASC scaffolds stay normoglycemic and show elevated levels of C-peptide compared to mice transplanted with islet-only scaffolds. The data present a functional 3D bioprinted scaffold for islets and ASCs transplanted to the extrahepatic site and suggest a possible role of ASCs on improving the islet micro-environment.
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- Oskarsdotter, Kristin, 1995, et al.
(author)
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Autologous endothelialisation by the stromal vascular fraction on laminin-bioconjugated nanocellulose-alginate scaffolds
- 2023
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In: Biomedical Materials (Bristol). - 1748-605X .- 1748-6041. ; 18:4
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Journal article (peer-reviewed)abstract
- Establishing a vascular network in biofabricated tissue grafts is essential for ensuring graft survival. Such networks are dependent on the ability of the scaffold material to facilitate endothelial cell adhesion; however, the clinical translation potential of tissue-engineered scaffolds is hindered by the lack of available autologous sources of vascular cells. Here, we present a novel approach to achieving autologous endothelialisation in nanocellulose-based scaffolds by using adipose tissue-derived vascular cells on nanocellulose-based scaffolds. We used sodium periodate-mediated bioconjugation to covalently bind laminin to the scaffold surface and isolated the stromal vascular fraction and endothelial progenitor cells (EPCs; CD31+CD45−) from human lipoaspirate. Additionally, we assessed the adhesive capacity of scaffold bioconjugation in vitro using both adipose tissue-derived cell populations and human umbilical vein endothelial cells. The results showed that the bioconjugated scaffold exhibited remarkably higher cell viability and scaffold surface coverage by adhesion regardless of cell type, whereas control groups comprising cells on non-bioconjugated scaffolds exhibited minimal cell adhesion across all cell types. Furthermore, on culture day 3, EPCs seeded on laminin-bioconjugated scaffolds showed positive immunofluorescence staining for the endothelial markers CD31 and CD34, suggesting that the scaffolds promoted progenitor differentiation into mature endothelial cells. These findings present a possible strategy for generating autologous vasculature and thereby increase the clinical relevance of 3D-bioprinted nanocellulose-based constructs.
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- Sämfors, Sanna, 1987, et al.
(author)
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Design and biofabrication of a leaf-inspired vascularized cell-delivery device
- 2022
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In: Bioprinting. - : Elsevier BV. - 2405-8866. ; 26
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Journal article (peer-reviewed)abstract
- We designed and biofabricated a channeled construct as a possible cell-delivery device that can be endothelialized to overcome size limitations due to oxygen diffusion. The channeled device mimicking a leaf was designed using computer-aided design software, with fluid flow through the channels visualized using simulation studies. The device was fabricated either by form casting using a custom 3D-printed plastic mold or by 3D-bioprinting using Pluronic F-127 as sacrificial ink to print the channels. The actual leaf was cast or bioprinted using hydrogel made from a mixture of tunicate cellulose nanofibers and alginate that was cross-linked in calcium chloride solution to allow a stable device. The resulting device was a 20 × 8 × 3 mm or 35 × 18 × 3 mm (length × width × height) leaf with one main channel connected to several side channels. Surface modification using periodate oxidation, followed by laminin bioconjugation, was performed to enhance endothelial cell adhesion in the channels. We subsequently used human umbilical vein endothelial cells to demonstrate the efficacy of the device for promoting endothelialization. These results indicated that the biofabricated device has great potential for use in tissue-engineering for various applications associated with the need of perfusable vasculature.
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