Abstract
Different bioinks have been used to produce cell-laden alginate-based hydrogel constructs for cell replacement therapy but some of these approaches suffer from issues with print quality, long-term mechanical instability, and bioincompatibility. In this study, new alginate-based bioinks were developed to produce cell-laden grid-shaped hydrogel constructs with stable integrity and immunomodulating capacity. Integrity and printability were improved by including the co-block-polymer Pluronic F127 in alginate solutions. To reduce inflammatory responses, pectin with a low degree of methylation was included and tested for inhibition of Toll-Like Receptor 2/1 (TLR2/1) dimerization and activation and tissue responses under the skin of mice. The viscoelastic properties of alginate-Pluronic constructs were unaffected by pectin incorporation. The tested pectin protected printed insulin-producing MIN6 cells from inflammatory stress as evidenced by higher numbers of surviving cells within the pectin-containing construct following exposure to a cocktail of the pro-inflammatory cytokines namely, IL-1β, IFN-γ, and TNF-α. The results suggested that the cell-laden construct bioprinted with pectin-alginate-Pluronic bioink reduced tissue responses via inhibiting TLR2/1 and support insulin-producing β-cell survival under inflammatory stress. Our study provides a potential novel strategy to improve long-term survival of pancreatic islet grafts for Type 1 Diabetes (T1D) treatment.
Highlights
Transplantation of 3D bioprinted cell-laden constructs is emerging as a novel therapeutic strategy to restore function of damaged organs or tissues [1]
To simultaneously increase the printability of the bioink and the flexibility of the constructs after crosslinking, Pluronic F127 was blended with the alginate solution to make a bioink consisting of 6% alginate-13% Pluronic F127 [11]
The degradation was likely caused by incomplete crosslinking between opposing guluronic acid sequences in the backbone of alginate [40] resulting from the presence of the block-co-polymer Pluronic F127 that increases the dis tance between alginate molecules [41]
Summary
Transplantation of 3D bioprinted cell-laden constructs is emerging as a novel therapeutic strategy to restore function of damaged organs or tissues [1]. Printability of alginate may be improved by inclusion of other polymers with more favorable printing properties into the bioink Such a printability enhancing poly mer is the block-co-polymer Pluronic F127 (Poloxamer 407). This tri block co-polymer is widely employed as a bioink component due to its low cytotoxicity, reliable printability and sol-gel transition at room temperature [10]. Another advantage of inclusion of Pluronic F127 is the generation of micropores with superior porosity and immunoiso lating properties [11,12]. Such micropores do not allow host immune cells to enter the construct while allowing diffusion of oxygen, glucose, nutrients, and insulin [11,13]
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