Immunological response of polysaccharide nanogel-incorporating PEG hydrogels in an in vivo diabetic model

Abstract

Cell-based therapies hold significant advantages in comparison with the traditional drug-based or injection-based treatments. However, for long-term functional cellular implants, immune acceptance must be established. To accomplish the acceptance of the implanted cells, various biomaterial systems have been studied. Nanogels have shown great potential for modulation of cellular microenvironments, acting as a physical barrier between the immune system and the implant. However, internalization of nano-scale materials by implanted cells is not desirable and is yet to be overcome. In this study, we incorporated acrylate modified cholesterol-bearing pullulan (CHPOA) nanogels into poly (ethylene glycol) diacrylate (PEGDA) hydrogels through covalent crosslinking, where we used visible light-induced photopolymerization. We characterized morphology and swelling properties of CHPOA incorporated PEG composite hydrogels using FE-SEM and gravimetric analysis. Also, we investigated the biocompatibility properties of composite hydrogels in vivo, where we used both healthy and diabetic mice. We induced diabetes in mice using a low dose streptozotocin (STZ) injections and implanted composite hydrogels in both diabetic and healthy mice through subcutaneous route. Immune cell infiltration of the retrieved tissue was examined through histological analysis, where we observed minimum immune response levels of 0–2 rareness, according to ISO standard of biological evaluation of medical devices. Our observation suggests that the composite hydrogel developed here can be used to introduce nanostructured domains into bulk hydrogels and that this system has potential to be used as immunologically acceptable composite material in cellular therapy without internalization of nanoparticles.

Keywords:

• Acrylate modified cholesterol-bearing pullulan (CHPOA)
• PEG hydrogel
• immune tolerance
• biocompatibility
• composite hydrogel
• cell therapy

Acknowledgements

We thank Dr. A. Cihan Taşkın, Ahmet Kocabay, Nihan Coşkun from the Koç University Animal Research Facility for in vivo experiments and Prof Dr. Hakan Örer about the discussions on in vivo diabetic mouse model. The authors gratefully acknowledge the use of services and facilities of the Koç University Surface Science Center, Koç University Research Center for Translational Medicine, funded by the Presidency of Turkey, Presidency of Strategy and Budget. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Presidency of Strategy and Budget.

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under 1001-Scientific and Technological Research Projects Funding Program (116S442, 113M232), 1002-Scientific and Technological Research Projects Funding Program (115M040) and Koc University Seed Fund SF.00028. Türkiye Bilimsel ve Teknolojik Araştirma Kurumu;Koç Üniversitesi;Türkiye Bilimsel ve Teknolojik Araştirma Kurumu; Türkiye Bilimsel ve Teknolojik Araştirma Kurumu.