3D Printing of Stem Cell Responsive Ionically-Crosslinked Polyethylene Glycol Diacrylate/ Alginate Composite Hydrogels Loaded with Basic Fibroblast Growth Factor for Dental Pulp Tissue Engineering: A Preclinical Evaluation in Animal Model

Abstract

The main aim of this study was to develop a 3D printed stem cell-responsive polyethylene glycol diacrylate (PEGDA) and sodium alginate (SA) composite hydrogel system (PEGDA/SA) loaded with basic fibroblast growth factor (bFGF) suitable for dental pulp tissue engineering. The PEGDA/SA loaded with bFGF (PEGDA/SA-bFGF) at different concentration ratios were 3D printed via stereolithography (SLA) under optimal processing conditions, followed by ionic crosslinking. The morphological and porous structure of the 3D printed PEGDA/SA-bFGF constructs and release profile of the bFGF were analyzed. The cellular compatibility of the hydrogel constructs was evaluated using human dental pulp stem cells (hDPSCs)in vitro. Subsequently, biocompatibility and tissue regenerative potential of the hydrogel constructs were evaluated in immunodeficient mice model. The in vitro cell culture results of PEGDA/SA-bFGF constructs exhibited high cell compatibility and supported cell proliferation, irrespective of their concentration ratios. Thein vivo animal experiment results showed that the hDPSCs-laden PEGDA/SA (PEGDA/SA-hDPSCs) group failed to form a good pulp structure even at various concentration ratios. When the mass ratio of PEGDA/SA was 25:1, hDPSCs-laden PEGDA/SA-bFGF (PEGDA/SA-bFGF-hDPSCs) group also failed to form dental pulp-like tissue but a partial loose connective tissue formation was observed. However, when the mass ratio of PEGDA/SA reduces to 20:1 ~ 15:1, the PEGDA/SA-bFGF-hDPSCs group tends to form a well-organized pulp structure post 4 weeks implantation, thus highlighting the potential of this particular hydrogel scaffolding system for dental pulp tissue regenerative applications.