Electrospining Machine: TPG-functionalized PLGA/PCL nanofibrous membranes regulate macrophage polarization and promote periodontal tissue regeneration by inhibiting PI3K/AKT and NF-κB signaling pathways

Background

Periodontitis is a common chronic inflammatory disease characterized by the destruction and resorption of periodontal tissue. Gingival inflammation, periodontal pocket formation, and periodontal tissue resorption are noteworthy symptoms and clinical pathological features of periodontitis. Studies have shown that effective periodontal treatment can significantly improve oral and systemic health. The main goal of periodontitis treatment is to regenerate damaged tissue and restore the function of damaged teeth. The regeneration of alveolar bone and cementum is considered a challenge in clinical practice.

The main point of this paper

Guided tissue regeneration technology:

The development of this technology has brought broad prospects for the regenerative treatment of periodontitis. The fiber membrane plays a vital role in preventing epithelial cells and fibroblasts from entering the alveolar bone regeneration space

Polymer membrane materials:

Common materials include poly (δ-caprolactone) (PCL) and poly (lactic-co-glycolic acid) (PLGA), which have been approved by the FDA for in vivo implantation.

Material limitations:

Polymer membrane materials have weak surface hydrophilicity, poor cell response, limited bone conduction potential, and insufficient immune microenvironment regulation

Graphene oxide and reduced graphene oxide:

Graphene oxide (GO) is well known for its excellent mechanical and biological properties, but due to its high cytotoxicity, reduced graphene oxide (rGO) has been more widely used

Tea polyphenols functionalized graphene oxide (TPG):

Graphene oxide is reduced and functionalized with tea polyphenols (TPs). TPG has better biocompatibility and is suitable for further application in modified PLGA/PCL fibers Membrane materials

Electrospun nanofibers:

With large specific surface area and porosity, it has great prospects for application in biomedical fields such as tissue engineering

nTPG/PLGA/PCL nanofiber membranes:

A new type of nanomaterial, nTPG/PLGA/PCL, was synthesized by electrospinning, which has excellent hydrophilicity, mechanical properties and biocompatibility

Macrophage polarization:

Plays a vital role in bone immunity and tissue regeneration. Proinflammatory cytokines produced by M1 macrophages stimulate bone resorption, and cytokines released by M2 macrophages promote bone regeneration

NTPG/PLGA/PCL Nanofiber Membrane: A novel immunomodulatory and tissue engineering material for regenerative treatment of periodontitis

Development of new Nanofiber Membrane:

The nTPG/PLGA/PCL Nanofiber Membrane was prepared by electrospinning, which has excellent hydrophilicity, mechanical properties and biocompatibility

Immunomodulatory effect:

nTPG/PLGA/PCL Nanofiber Membrane can regulate macrophage polarization and inhibit RAW by inhibiting PI3K/AKT and NF-κB signaling pathways. 264.7 polarizes to the M1 phenotype and promotes M2 polarization, thereby alleviating inflammation-induced damage and promoting periodontal tissue regeneration

Promoting periodontal tissue regeneration:

The material can directly promote the osteogenesis of periodontal ligament stem cells (hPDLSCs), indirectly promote the differentiation of colloid cells and osteoblasts, and upregulate the expression of colloid cell differentiation markers (cemp1 and CAP) and osteoblast differentiation markers (ALP, RUNX2, COL-1 and OCN)

In vivo and in vitro study results:

After implantation into the rat periodontal bone defect model, histological evaluation showed that 0.5% TPG/PLGA/PCL membrane could regenerate oriented collagen fibers and structurally intact epithelium

The expression of Micro-CT (BV/TV) and immunohistochemical markers (OCN, RUNX-2, COL-1 and BMP-2) showed satisfactory regeneration of alveolar bone and periodontal ligament

Clinical application prospects:

These findings provide new perspectives for the development of periodontal tissue regeneration materials and provide a new perspective for the future TPG-based polymer Nanofiber The clinical application of membrane lays a theoretical foundation

Summarize

In summary, we constructed nTPG/PLGA/PCL fibrous membranes to modulate the immune microenvironment of periodontitis, aiming to optimize periodontal regeneration. The addition of TPG improved the physical and mechanical properties of the fibrous membranes. These membranes showed good cytocompatibility and promoted cell adhesion and growth. Notably, under inflammatory conditions, 0.5% TPG/PLGA/PCL fibrous membranes had a stronger osteogenic effect on hPDLSCs compared with PLGA/PCL membranes. In addition, our results suggest that the immunomodulatory effect of 0.5% TPG/PLGA/PCL may be through the inhibition of RAW 264.7 M1 polarization by suppressing the PI3K/AKT and NF-κB signaling pathways. This study is expected to lay a theoretical foundation for the future clinical application of TPG-based polymer fibrous membranes.