Regeneration potential of decellularized periodontal ligament cell sheets combined with 15-deoxy-Δ^12,14-prostaglandin J₂ nanoparticles in a rat periodontal defect

Abstract

Periodontitis is a chronic inflammatory disease characterized by loss of attachment and destruction of the periodontium. Decellularized sheet, as an advanced tissue regeneration engineering biomaterial, has been researched and applied in many fields, but its effects on periodontal regeneration remain unclear. In this study, the biological properties of decellularized human periodontal ligament cell (dHPDLC) sheets were evaluated in vitro. Polycaprolactone/gelatin (PCL/GE) nanofibers were fabricated as a carrier to enhance the mechanical strength of the dHPDLC sheet. 15-deoxy- Δ 12 , 14 -prostaglandin J2 (15d-PGJ2) nanoparticles were added for anti-inflammation and regeneration improvement. For in vivo analysis, dHPDLC sheets combined with 15d-PGJ2 nanoparticles, with or without PCL/GE, were implanted into rat periodontal defects. The periodontal regeneration effects were identified by microcomputed tomography (micro-CT) and histological staining, and immunohistochemistry. The results revealed that DNA content was reduced by 96.6%. The hepatocyte growth factor, vascular endothelial growth factor, and basic fibroblast growth factor were preserved but reduced. The expressions or distribution of collagen I and fibronectin were similar in dHPDLC and nondecellularized cell sheets. The dHPDLC sheets maintained the intact structure of the extracellular matrix. It could be recellularized by allogeneic human periodontal stem ligament cells and retain osteoinductive potential. Newly formed bone, cementum, and PDL were observed in dHPDLC sheets combined with 15d-PGJ2 groups, with or without PCL/GE nanofibers, for four weeks post-operation in vivo. Bringing together all these points, this new construct of dHPDLC sheets can be a potential candidate for periodontal regeneration in an inflammatory environment of the oral cavity.

Cell-derived ECM loaded electrospun Polycaprolactone/Chitosan nanofibrous scaffolds for periodontal regeneration

“…Regarding immunocytochemistry analysis, PDLSCs expressed collagen I, fibronectin, laminin, asporin, osteopontin and osteocalcin. Interestingly, the decellularization process did not affect the expression of these proteins, which is in accordance with previous works [26,34]. Type I collagen and fibronectin are two of the predominant proteins present in the native PDL tissue [8].…”

Decellularized matrix could affect the proliferation and differentiation of periodontal ligament stem cells in vitro

“…DCM derived from periodontal ligament cells (PDLCs) has been studied as a promising biomaterial for periodontal regeneration 29,30 . Our preliminary study has confirmed that PDLC‐DCM could promote the formation of new bone, cementum, and periodontal ligament in the rat periodontal defect model, which supported the efficacy of PDLC‐DCM in periodontal regeneration 31 . However, the application of PDLC‐DCM might be limited owing to a lack of tissue source and difficulty in cell culture.…”

Advances Focusing on the Application of Decellularized Extracellular Matrix in Periodontal Regeneration

“…Moreover, decellularized membrane sheets combined with cytokines or new materials to achieve better tissue regeneration effects have been used in many tissue regeneration processes, such as dental tissue regeneration [ 7 ], bone regeneration [ 8 ], vascular reconstruction [ 9 ], nerve regeneration [ 10 ], and corneal regeneration [ 11 ]. Specifically, the common C-dECM sources for periodontal regeneration are the periodontal ligament stem cell sheet (PDLSC sheet) [ 12 ], the bone marrow mesenchymal stem cell sheet (BMSC sheet) [ 6 ], the human urogenic mesenchymal stem cell sheet (hUMSC sheet), and others such as dental folicle stem cells and L929 sheet-derived dECM can also be considered.…”

“…The biological properties of human periodontal membranes were evaluated in vitro by Jiang et al [ 7 ]. Decellularized PDLC sheets maintain an intact extracellular matrix structure, and the expression or distribution of type I collagen and fibronectin was similar in decellularized PDLC sheets and natural PDLC sheets, which contributes to the recellularization procedures and retaining the osteogenic potential of allogeneic human periodontal ligament stem cells.…”