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The effect of polyethylenglycol gel on the delivery and osteogenic differentiation of homologous tooth germ–derived stem cells in a porcine model

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Abstract

Objectives

The aim of this study was to investigate if bone regeneration can be promoted by homologous transplantation of STRO-1 sorted (STRO-1+) porcine tooth germ mesenchymal stem cells (TGSCs) with the combination of polyethylenglycol (PEG)-based hydrogel and biphasic calcium phosphate (BCP) scaffolds.

Material and methods

TGSCs were isolated from impacted third molars of domestic pigs. Nine critical-sized defects were created as (1) untreated defect; filled with (2) autogenous bone; (3) BCP + PEG; (4) BCP + PEG + unsorted TGSCs; (5) BCP + unsorted TGSCs; (6) BCP + PEG + STRO-1-sorted TGSCs; (7) BCP + STRO-1-sorted TGSCs; (8) BCP + PEG + osteogenic induced unsorted TGSCs; and (9) BCP + PEG + osteogenic induced STRO-1-sorted TGSCs in 20 domestic pigs. CM-DiI labelling was used to track cells in vivo. Histomorphometric assessment of new bone formation was achieved by toluidine blue O staining and microradiography after 1, 2, 4 and 12 weeks posttransplantation.

Results

Complete healing was achieved in all defects although defects with PEG hydrogel presented better bone formation while STRO-1+ and unsorted TGSCs showed similar ability to form new bone after 12 weeks. Transplanted cells were seen in defects where PEG hydrogel was used as carriers in contrast to defects treated with cells and only bone grafts.

Conclusions

PEG hydrogel is an efficient carrier for homologous stem cell transplantation. TGSCs are capable of promoting bone healing in critical-sized defects in combination with bone graft and PEG hydrogel.

Clinical relevance

This study provides information about the importance of the delivery vehicle for future translational stem cell delivery approaches.

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Acknowledgments

We would like to thank Aart Molenberg (Straumann Company) for supplying us with the PEG hydrogels and the ITI International Team for Implantology (750-2011) for granting our work. The animal studies were performed in cooperation with the Semmelweis-University, Budapest, Hungary. Specimen processing was undertaken in the laboratories of the Department of Oral and Maxillofacial Surgery, University of Erlangen-Nürnberg, Erlangen, Germany. The authors have no conflicts of interest. The work of Dr. Endre Felszeghy, Elke Diebel, and Andrea Schönherr is highly appreciated.

Funding

The work was supported by the ITI International Team for Implantology (750-2011).

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Authors and Affiliations

  1. Istanbul Universitesi Dis Hekimligi Fak., Faculty of Dentistry, Department of Oral Surgery, Istanbul University, Prof. Dr. Cavit Orhan Tütengil Sokak.No.4 Vezneciler-Fatih-, 34093, Istanbul, Turkey

    Mustafa Ramazanoglu

  2. Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Glueckstrasse 11, 91054, Erlangen, Germany

    Tobias Moest, Zacharias Polyviou, Katharina Herrmann, Rainer Lutz, Friedrich Wilhelm Neukam & Karl Andreas Schlegel

  3. Faculty of Dentistry, Department of Oral Surgery, Istanbul Altinbas University, 34217, Istanbul, Turkey

    Pınar Ercal

  4. Faculty of Electrical and Electronics Engineering, Department of Biomedical Engineering, Yıldız Technical University, 34349, Istanbul, Turkey

    Gorke Gurel Pekozer

  5. Institut Straumann AG, Peter Merian-Weg 12, 4002, Basel, Switzerland

    Aart Molenberg

  6. Faculty of Engineering, Department of Genetics and Bioengineering, Yeditepe University, 34755, Istanbul, Turkey

    Gamze Torun Kose

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  1. Mustafa Ramazanoglu
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Correspondence to Mustafa Ramazanoglu.

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This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This study was approved by Agricultural Administrative Office of the Capital and Country Pest, Food Chain Security Management, Department of Epidemic and Animal Welfare (approval no. 22.1/3879/003/2008). Animal care keeping and surgical procedures were performed in the European Animal Research Centre (“EARC”; 2053 Herceghalom, Hungary, Gesztenyes ut 1; Certified for “Biological evaluation of medical devices” (EN ISO 10993-2:2006).

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Supplementary Figure

Osteogenic, adipogenic and chondrogenic differentiation of pTGSCs; Microscopic observation of Alizarin Red (Scale bar 200 μm), Alcian Blue (Scale bar 50 μm), Oil Red O (Scale bar 50 μm) and von Kossa (Scale bar 100 μm) stained pTGSCs under bright field microscope after 21 days in differentiation medium. (PNG 27995 kb)

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Ramazanoglu, M., Moest, T., Ercal, P. et al. The effect of polyethylenglycol gel on the delivery and osteogenic differentiation of homologous tooth germ–derived stem cells in a porcine model. Clin Oral Invest 25, 3043–3057 (2021). https://doi.org/10.1007/s00784-020-03625-6

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