3D-Printed Biohybrid Microstructures Enable Transplantation and Vascularization of Microtissues in the Anterior Chamber of the Eye

Hanie Kavand, Montse Visa, Martin Köhler, Wouter van der Wijngaart, Per-Olof Berggren, Anna Herland

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Abstract

Hybridizing biological cells with man-made sensors enable the detection of a wide range of weak physiological responses with high specificity. The anterior chamber of the eye (ACE) is an ideal transplantation site due to its ocular immune privilege and optical transparency, which enable superior noninvasive longitudinal analyses of cells and microtissues. Engraftment of biohybrid microstructures in the ACE may, however, be affected by the pupillary response and dynamics. Here, sutureless transplantation of biohybrid microstructures, 3D printed in IP-Visio photoresin, containing a precisely localized pancreatic islet to the ACE of mice is presented. The biohybrid microstructures allow mechanical fixation in the ACE, independent of iris dynamics. After transplantation, islets in the microstructures successfully sustain their functionality for over 20 weeks and become vascularized despite physical separation from the vessel source (iris) and immersion in a low-viscous liquid (aqueous humor) with continuous circulation and clearance. This approach opens new perspectives in biohybrid microtissue transplantation in the ACE, advancing monitoring of microtissue-host interactions, disease modeling, treatment outcomes, and vascularization in engineered tissues.

Original languageEnglish
Article numbere2306686
Number of pages10
JournalAdvanced Materials
Volume36
Issue number1
Early online date10 Oct 2023
DOIs
Publication statusPublished online - 10 Oct 2023

Bibliographical note

Funding Information:
This work was supported by the Swedish Foundation for Strategic Research (SSF Grant Project No. RMX18‐0066). P.‐O.B acknowledges funding support from Berth von Kantzow's Foundation, the European Research Council (Grant No. ERC‐2018‐AdG 834 860 EYELETS), the Family Erling‐Persson Foundation, Funds at Karolinska Institutet, the Jonas & Christina af Jochnick Foundation, the Swedish Diabetes Association, the Swedish Research Council, and the Novo Nordisk Foundation. H.K. acknowledges funding from the Wenner‐Gren foundation (UPD2021‐0185). A.H. acknowledges funding from Knut and Alice Wallenberg Stiftelse (2020.0206). A.H.’s work was supported by AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences (www.aimes.se), Karolinska Institutet (1‐249/2019), KTH Royal Institute of Technology (VF‐2019‐0110) and Getinge AB (4‐1599/2018). The authors would like to thank the SSF project partners and their team members for close collaboration and valuable discussions, including Prof. Göran Stemme, Assoc. Prof. Niclas Roxhed (KTH Royal Institute of Technology, Sweden), and Prof. Atila Alvandpour (Linköping Universty, Sweden). The authors would also like to thank the members of the Berggren group specially Dr. Ismael Valladolid Acebes and Dr. Noah Moruzzi (The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Sweden) and Prof. Helder André (St. Erik Eye Hospital, Karolinska Institutet, Sweden) for helpful discussions.

Publisher Copyright:
© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.

Keywords

  • anterior chamber of the eye
  • biohybrid
  • microstructures
  • microtissues
  • pancreatic islets
  • vascularization

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