Role of Berberine Thermosensitive Hydrogel in Periodontitis via PI3K/AKT Pathway In Vitro

Abstract

Periodontitis is a long-term inflammatory illness and a leading contributor to tooth loss in humans. Due to the influence of the anatomic parameters of teeth, such as root bifurcation lesions and the depth of the periodontal pocket, basic periodontal treatment on its own often does not completely obliterate flora microorganisms. As a consequence, topical medication has become a significant supplement in the treatment of chronic periodontitis. Berberine (BBR) has various pharmacological effects, such as hypoglycemic, antitumor, antiarrhythmic, anti-inflammatory, etc. The target of our project is to develop a safe and non-toxic carrier that can effectively release berberine, which can significantly reduce periodontal tissue inflammation, and to investigate whether berberine thermosensitive hydrogel can exert anti-inflammatory and osteogenic effects by modulating phosphatifylinositol-3-kinase/Protein Kinase B (PI3K/AKT) signaling pathway. Consequently, firstly berberine temperature-sensitive hydrogel was prepared, and its characterizations showed that the mixed solution gelated within 3 min under 37 °C with a hole diameter of 10–130 µm, and the accumulation of berberine release amounted to 89.99% at 21 days. CCK-8 and live-dead cell staining results indicated that this hydrogel was not biotoxic, and it is also presumed that the optimum concentration of berberine is 5 µM, which was selected for subsequent experiments. Real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB)results demonstrated that inflammatory factors, as well as protein levels, were significantly reduced in the berberine-loaded hydrogel group, and LY294002 (PI3K inhibitor) could enhance this effect (p < 0.05). In the berberine-loaded hydrogel group, osteogenesis-related factor levels and protein profiles were visibly increased, along with an increase in alkaline phosphatase expression, which was inhibited by LY294002 (p < 0.05). Therefore, berberine thermosensitive hydrogel may be an effective treatment for periodontitis, and it may exert anti-inflammatory and osteogenic effects through the PI3K/AKT signaling pathway.

Comparative study on the effects of different polishing methods on tooth surface microstructure and roughness following initial periodontal treatment

“…Some scholars have shown that the strips could be used to polish the surfaces of adjacent fillings, and the surface roughness and patient comfort would significantly improve (Ozdemir et al, 2022). (Wang et al, 2023). Therefore, it would be more suitable in clinical practice to limit the range of tooth surface detection from 5 mm in the crown to 5 mm in the root with the cemento-enamel junction as the midline, which has a certain reference value.…”

“…Because of the existence of root furcation in premolars and molars, basic treatment and polishing are insufficient once the furcation area is pathologically involved. Therefore, the average height of the root bifurcation limits the scope of periodontal treatment and polishing (Wang et al, 2023 ). Therefore, it would be more suitable in clinical practice to limit the range of tooth surface detection from 5 mm in the crown to 5 mm in the root with the cemento–enamel junction as the midline, which has a certain reference value.…”

Hydrogels promote periodontal regeneration

“…Thermosensitive hydrogels, for example, are in liquid form at low temperatures but gelate at higher temperatures, a property crucial for effective drug delivery. Wang et al (2023) developed a berberine heat-sensitive hydrogel that gels rapidly at body temperature (37 °C) within approximately 3 min, demonstrating efficacy in treating periodontal inflammatory bone conditions by modulating the PI3K/AKT signaling pathway and offering anti-inflammatory and osteogenic benefits. Xu et al (2019) created an injectable thermosensitive hydrogel that continuously released aspirin and erythropoietin, facilitating the healing of inflammation and alveolar bone repair.…”

Hydrogel Tissue Bioengineered Scaffolds in Bone Repair: A Review

“…In addition, to enhance the bioactivity of hydrogel scaffolds, β-GP matrix temperature-sensitive hydrogels are often used in combination with chitosan [116]. Wang et al [117] used chitosan in combination with β-GP to prepare a temperature-sensitive hydrogel for the promotion of periodontitis repair and bone regeneration, and their research found that berberine thermosensitive hydrogel may be an effective treatment for periodontitis, which can exert anti-inflammatory and osteogenic effects through the PI3K/AKT signaling pathway. Lu et al [118] prepared a thermosensitive hybridized hydrogel scaffold using collagen I (Col-I) In a word, photocurable hydrogel may become an excellent scaffold for bone repair, but the demand for photoinitiators limits its application in some fields, and the selection of photoinitiators becomes a key factor in determining the polymerization efficiency and the required light wavelength.…”