Notoginsenoside R1 functionalized gelatin hydrogels to promote reparative dentinogenesis

Pulp-capping materials are commonly adopted in the clinic to form reparative dentin and thus protect dental pulp tissues from cases of deep caries, accidentally exposed pulps or partial pulpotomy. Some traditional pulp capping materials used in the clinic include calcium hydroxide and mineral trioxide aggregates. However, there are limitations to thin restorative dentin, and a long period of time is needed to cause degenerative changes in dental pulp. In this paper, injectable colloidal gels were developed to induce the formation of reparative dentin through a simple UV method from methacrylic acid functionalized gelatin loaded with notoginsenoside R1 (Gel-MA/NGR1). The results of the physicochemical property examinations showed that the prepared Gel-MA/NGR1 hydrogel possessed an appropriate interconnected porous microarchitecture with a pore size of 10.5 micrometres and suitable mechanical properties with a modulus of 50-60 kPa, enabling cell adhesion and proliferation. The hydrogel remained hydrophilic with sustained drug release performance. In addition, Gel-MA/NGR1 significantly enhanced the odontogenetic differentiation of mouse dental papilla cells by elevating the expression levels of the dentinogenic markers ALP and OCN and extracellular matrix mineralization. In vivo stimulation was carried out by injecting the precursors into the predrilled alveolar cavity of Sprague-Dawley rats followed by immediate in situ UV crosslinking. The results showed that Gel-MA/NGR1 has a strong capacity to promote reparative dentin formation. Haematoxylin& eosin, Masson, and immunohistochemical staining (DMP-1, DSPP, OCN and RUNX2) and micro-CT were employed to illustrate the effectiveness of dentinogenesis, and the relative volumes of calcification were found to have increased similar to 175-fold. All of the results showed that the Gel-MA/NGR1 hydrogel promoted reparative dentin formation, which suggests that this hydrogel provides great potential as a pulp-capping material to induce dentin formation. Statement of significance Pulp capping therapy is required to treat deep dental caries and accidentally exposed pulp. However, there are limitations to thin restorative dentin and a long period of time is needed to cause degenerative changes in dental pulp for traditional pulp capping materials. In this paper, we report an unexpected, acute pulp capping material for inducing the formation of reparative dentin through a simple UV method from methacrylic acid (MA) functionalized gelatin loaded with NGR1 (Gel-MA/NGR1). The results showed that the Gel-MA/NGR1 has a strong capacity to promote reparative dentin formation (the relative volumes of calcification increased similar to 175 fold). Our work provides another potential choice for clinical application. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

Injectable colloidal gels loaded with notoginsenoside R1 were developed to induce reparative dentin formation through a simple UV method. Physicochemical examinations showed appropriate microarchitecture and mechanical properties of the Gel-MA/NGR1 hydrogel. In vivo stimulation demonstrated a significant increase in dentin formation, suggesting the potential of Gel-MA/NGR1 as a pulp-capping material.