Gingipain-Responsive Thermosensitive Hydrogel Loaded with SDF-1 Facilitates In Situ Periodontal Tissue Regeneration

Abstract

Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and unsatisfied periodontal regeneration. In this study, a smart gingipain-responsive hydrogel (PEGPD@SDF-1) was synthesized as an environmentally sensitive carrier for on-demand drug delivery. The PEGPD@SDF-1 hydrogel was synthesized from polyethylene glycol diacrylate (PEG-DA) based scaffolds, dithiothreitol (DTT), and a novel designed functional peptide module (FPM) via Michael-type addition reaction, and the hydrogel was further loaded with stromal cell derived factor-1 (SDF-1). The FPM exhibiting a structure of anchor peptide−short antimicrobial peptide (SAMP)− anchor peptide could be cleaved by gingipain specifically, and the SAMP was released out of the hydrogel for antibacterial effect in response to gingipain. The hydrogel properties were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), swelling ratio analysis, degradation evaluation, and release curve description of the SAMP and SDF-1. Results in vitro indicated the PEGPD@SDF-1 hydrogel exhibited preferable biocompatibility and could promote the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Antibacterial testing demonstrated that the PEGPD@SDF-1 hydrogel released the SAMP stressfully in response to gingipain stimulation, thereby strongly inhibiting the growth of Porphyromonas gingivalis. Furthermore, the study in vivo indicated that the PEGPD@SDF-1 hydrogel inhibited P. gingivalis reproduction, created a low-inflammatory environment, facilitated the recruitment of CD90+/CD34− stromal cells, and induced osteogenesis. Taken together, these results suggest that the gingipain-responsive PEGPD@SDF-1 hydrogel could facilitate in situ periodontal tissue regeneration and is a promising candidate for the on-demand local drug delivery system for periodontitis.

Periodontal Bifunctional Biomaterials: Progress and Perspectives

“…It kills bacteria by changing their membrane permeability without increasing drug resistance [59]. As the result, the systems have antibacterial activity against many kinds of bacteria and nearly achieve complete bone regeneration [13].…”

“…However, effectively regenerating periodontal tissues remains a challenge [12]. The purpose of periodontal therapy is to realize periodontal tissue regeneration after controlling inflammation via infection clearance [13]. To reach this goal, bioactive materials with antibacterial and osteogenic properties are in constant evolution.…”

Elements of 3D Bioprinting in Periodontal Regeneration: Frontiers and Prospects

“…Due to its high plasticity, hydrogel is a good carrier of bioactive molecules and has good biocompatibility and cellular affinity. It becomes an important scaffold material in 3D bioprinting and has an important application in periodontal regeneration [52,56,57]. In the study by Premjit Arpornmaeklong et al, it was found that specific chitosan/collagen ratio in 3D bioprinting thermosensitive β-glycerophosphate (BGP) chitosan/collagen hydrogel could promote the release of natural flavonoids, thereby affecting the growth and bioactivity of human PDLSCs [56].…”

“…A study found exendin-4 together with SDF-1α could promote the cellular viability of PDLSCs [91]. In vivo, hydrogel loaded with SDF-1α can gather CD90+/CD34− stromal cells to achieve in situ periodontal tissue regeneration [57]. Researchers revealed the platelet-rich fibrin and treated dentin matrix could also attract PDLSCs and bone marrow mesenchymal stem cells and accelerate their cell proliferation rate [92].…”

Angelica sinensis polysaccharide promotes the proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs) by activating the wnt/β-catenin pathway

“…Pulp tissues are located in the pulp cavity of teeth. Human dental pulp stem cells (hDPSCs) are capable of forming mineralized nodules (Liu et al, 2021). The cells are fusiform, and can self-renew and multidirectionally differentiate (Luan et al, 2021b).…”