International Journal of Nanomedicine (Sep 2020)
RGD- and VEGF-Mimetic Peptide Epitope-Functionalized Self-Assembling Peptide Hydrogels Promote Dentin-Pulp Complex Regeneration
Abstract
Kun Xia,1,2,* Zhuo Chen,3,4,* Jie Chen,1 Huaxing Xu,1 Yunfei Xu,1 Ting Yang,1 Qi Zhang1 1Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, People’s Republic of China; 2Department of Preventive Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, People’s Republic of China; 3Department of Endodontics, The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou 310006, People’s Republic of China; 4Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou 310006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi ZhangDepartment of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai, Engineering Research Center of Tooth Restoration and Regeneration, Yanchang Road 399, Shanghai 200072, People’s Republic of ChinaTel +86-21-66311659Fax +86-21-66524025Email [email protected]: Cell-based tissue engineering is a promising method for dentin-pulp complex (DPC) regeneration. The challenges associated with DPC regeneration include the generation of a suitable microenvironment that facilitates the complete odontogenic differentiation of dental pulp stem cells (DPSCs) and the rapid induction of angiogenesis. Thus, the survival and subsequent differentiation of DPSCs are limited. Extracellular matrix (ECM)-like biomimetic hydrogels composed of self-assembling peptides (SAPs) were developed to provide an appropriate microenvironment for DPSCs. For functional DPC regeneration, the most important considerations are to provide an environment that promotes the adequate attachment of DPSCs and rapid vascularization of the regenerating pulp. Morphogenic signals in the form of growth factors (GFs) have been incorporated into SAPs to promote productive DPSC behaviors. However, the use of GFs has several drawbacks. We envision using a scaffold with SAPs coupled with long-term factors to increase DPSC attachment and vascularization as a method to address this challenge.Methods: In this study, we developed synthetic material for an SAP-based scaffold with RGD- and vascular endothelial growth factor (VEGF)-mimetic peptide epitopes with the dual functions of dentin and pulp regeneration. DPSCs and human umbilical vein endothelial cells (HUVECs) were used to evaluate the biological effects of SAP-based scaffolds. Furthermore, the pulpotomized molar rat model was employed to test the reparative and regenerative effects of SAP-based scaffolds.Results: This scaffold simultaneously presented RGD- and VEGF-mimetic peptide epitopes and provided a 3D microenvironment for DPSCs. DPSCs grown on this composite scaffold exhibited significantly improved survival and angiogenic and odontogenic differentiation in the multifunctionalized group in vitro. Histological and functional evaluations of a partially pulpotomized rat model revealed that the multifunctionalized scaffold was superior to other options with respect to stimulating pulp recovery and dentin regeneration in vivo.Conclusion: Based on our data obtained with the functionalized SAP scaffold, a 3D microenvironment that supports stem cell adhesion and angiogenesis was generated that has great potential for dental pulp tissue engineering and regeneration.Keywords: dentin-pulp complex regeneration, dental pulp stem cells, self-assembling peptides, cell adhesion, angiogenesis, multifunctionalization
