Notoginsenoside R1 Functionalized Gelatin Hydrogels to Promote Reparative Dentinogenesis

Abstract

Pulp capping therapy is required to treat deep dental caries and accidental exposed pulp. Some traditional pulp capping materials such as calcium hydroxide, trioxide mineral agglomerates are commonly used in clinic. However, limitations of the thin restorative dentin and long time needed prone to cause degenerative changes in dental pulp. In this paper, injectable colloidal gels are developed for inducing the formation of reparative dentin through a simple UV method from methacrylic acid (MA) functionalized gelatin loaded with NGR1 (Gel-MA/NGR1). Results of the physicochemical properties examinations showed that the prepared Gel-MA/NGR1 hydrogel possessed appropriate interconnected porous microarchitecture with pore size of 10.5 micrometers and mechanical properties with the modulus of 50-60KPa, enabling cell adhesion and proliferation. The hydrogel remained hydrophilic with sustained drug release performance. In addition, the Gel-MA/NGR1 significantly enhances the osteogenic differentiation of mouse dental papilla cells by elevating the expression levels of dentinogenic markers ALP and OCN and extracellular matrix mineralization. In-vivo stimulatory was carried out via injecting the precursors into the predrilled alveolar cavity of Sprague-Dawley Rats followed by immediately in situ UV crosslinking. The results showed that the Gel-MA/NGR1 gifted a delectable promotion capacity of reparative dentin formation. Hematoxylin & eosin, Masson, and immunohistochemical staining (DMP-1, DSPP, OCN and RUNX2) and micro-CT (the relative volumes of calcification increased ~175 folds) were employed to illustrate the effectiveness of dentinogenesis. All the results show that the Gel-MA/NGR1 hydrogel promoted reparative dentin formation, which suggested that such hydrogel provided great potential for pulp-capping materials to induce dentin formation.