TY - JOUR

T1 - Xeno-free in vitro cultivation and osteogenic differentiation of hAD-MSCs on resorbable 3D printed RESOMER®

AU - Kirsch, Marline

AU - Herder, Annabelle Christin

AU - Boudot, Cécile

AU - Karau, Andreas

AU - Rach, Jessica

AU - Handke, Wiebke

AU - Seltsam, Axel

AU - Scheper, Thomas

AU - Lavrentieva, Antonina

N1 - Funding information: Acknowledgments: The authors would like to acknowledge Annalea Brüggemann for data preparation support and Thorsten Strempel for material processing support. The publication of this article was funded by the Open Access fund of Leibniz Universität Hannover.

PY - 2020/7/31

Y1 - 2020/7/31

N2 - The development of alloplastic resorbable materials can revolutionize the field of implantation technology in regenerative medicine. Additional opportunities to colonize the three-dimensionally (3D) printed constructs with the patient's own cells prior to implantation can improve the regeneration process but requires optimization of cultivation protocols. Human platelet lysate (hPL) has already proven to be a suitable replacement for fetal calf serum (FCS) in 2D and 3D cell cultures. In this study, we investigated the in vitro biocompatibility of the printed RESOMER® Filament LG D1.75 materials as well as the osteogenic differentiation of human mesenchymal stem cells (hMSCs) cultivated on 3D printed constructs under the influence of different medium supplements (FCS, human serum (HS) and hPL). Additionally, the in vitro degradation of the material was studied over six months. We demonstrated that LG D1.75 is biocompatible and has no in vitro cytotoxic effects on hMSCs. Furthermore, hMSCs grown on the constructs could be differentiated into osteoblasts, especially supported by supplementation with hPL. Over six months under physiological in vitro conditions, a distinct degradation was observed, which, however, had no influence on the biocompatibility of the material. Thus, the overall suitability of the material LG D1.75 to produce 3D printed, resorbable bone implants and the promising use of hPL in the xeno-free cultivation of human MSCs on such implants for autologous transplantation have been demonstrated.

AB - The development of alloplastic resorbable materials can revolutionize the field of implantation technology in regenerative medicine. Additional opportunities to colonize the three-dimensionally (3D) printed constructs with the patient's own cells prior to implantation can improve the regeneration process but requires optimization of cultivation protocols. Human platelet lysate (hPL) has already proven to be a suitable replacement for fetal calf serum (FCS) in 2D and 3D cell cultures. In this study, we investigated the in vitro biocompatibility of the printed RESOMER® Filament LG D1.75 materials as well as the osteogenic differentiation of human mesenchymal stem cells (hMSCs) cultivated on 3D printed constructs under the influence of different medium supplements (FCS, human serum (HS) and hPL). Additionally, the in vitro degradation of the material was studied over six months. We demonstrated that LG D1.75 is biocompatible and has no in vitro cytotoxic effects on hMSCs. Furthermore, hMSCs grown on the constructs could be differentiated into osteoblasts, especially supported by supplementation with hPL. Over six months under physiological in vitro conditions, a distinct degradation was observed, which, however, had no influence on the biocompatibility of the material. Thus, the overall suitability of the material LG D1.75 to produce 3D printed, resorbable bone implants and the promising use of hPL in the xeno-free cultivation of human MSCs on such implants for autologous transplantation have been demonstrated.

KW - 3D printing

KW - Adipose tissue-derived mesenchymal stem cells (hAD-MSCs)

KW - Fetal calve serum

KW - Human platelet lysate

KW - Human serum

KW - In vitro biocompatibility

KW - In vitro degradation

KW - Osteogenic differentiation

KW - RESOMER®

KW - Resorbable polymers

UR - http://www.scopus.com/inward/record.url?scp=85089741025&partnerID=8YFLogxK

U2 - 10.3390/ma13153399

DO - 10.3390/ma13153399

M3 - Article

AN - SCOPUS:85089741025

VL - 13

JO - MATERIALS

JF - MATERIALS

SN - 1996-1944

IS - 15

M1 - 3399

ER -