The osteoimmunomodulatory property of a barrier collagen membrane and its manipulation via coating nanometer-sized bioactive glass to improve guided bone regeneration

Abstract

A barrier membrane is a major component of guided bone regeneration (GBR), which is traditionally viewed as a physical barrier. Due to its "foreign body" nature, the implantation of a barrier membrane would inevitably modulate immune response and subsequently affect bone dynamics, which has long been neglected. To bridge this knowledge gap, we investigated the osteoimmunomodulatory effects of barrier collagen membranes. It is found that barrier collagen membranes elicit significant effects on modulating the osteoimmune response of macrophages, by upregulating the expression of pro-inflammatory cytokines (TNFα, IL-1β, IL-6, and IL-18) and osteogenic factors (BMP2/6, WNT10b, OSM). The modulated-osteoimmune environment was beneficial for the osteogenic differentiation of BMSCs, due to the activation of BMP, canonical WNT/β-catenin, and OSM signalling pathways. The membrane-mediated osteoimmunomodulation was further modulated to show whether osteogenesis could be enhanced via manipulating the membrane-mediated osteoimmunomodulation. The membrane-mediated osteoimmune response was successfully tuned through coating the collagen membranes with nanometer-sized bioactive glass Ca2ZnSi2O7 by pulsed laser deposition, which is indicated from the change in the expression profile of inflammatory cytokines and the upregulated expression of osteogenic factors. The modulated osteoimmune environment enhanced the osteogenic differentiation of BMSCs, suggesting that collagen membranes with nanometer-sized Ca2ZnSi2O7 coating can be promising for GBR applications. These results collectively imply that barrier membranes are bioactive barriers with an osteoimmunomodulatory effect and not just physical barriers. New generation barrier membranes should be designed with a favourable osteoimmunomodulatory property.

A Facile Flow-Casting Production of Bioactive Glass Coatings on Porous Titanium for Bone Tissue Engineering

“…Moreover, it was observed from the high magnification images that the cells on bare PT presented elongated morphology compared to the cells on BG-coated PT presenting tabular morphology at day 4 ( Figure 6 e–f). BG coatings have been reported to not only enhance osteoblastic proliferation, but also induce osteogenic differentiation [ 32 , 41 ]. In addition, it was reported that human mesenchymal stem cells (hMSCs) with elongated morphology exhibited lowered osteogenesis compared to polygonal-like hMSCs, which is positively correlated with down-expression of cell morphological indexes including integrin β1 and N-cadherin [ 42 ].…”

Immunomodulation‐Based Strategy for Improving Soft Tissue and Metal Implant Integration and Its Implications in the Development of Metal Soft Tissue Materials

“…[ 24 ] The expression of macrophage polarization related genes was detected by RT‐qPCR as previously described. [ 25 ] The primer sequences for the target genes are listed in the Supporting Information (Table S1, Supporting Information). The expression of macrophage polarization related proteins was evaluated by western blot (CCR7 1:10000, CD86 1:1000, iNOS 1:1000, CD206 1:1000, Arg‐1 1:1000) as previously described.…”

Macrophage phenotype in the epigallocatechin-3-gallate (EGCG)-modified collagen determines foreign body reaction

“…After anaesthetization by chloral hydrate, the surgical area on the back skin was shaved and aseptically prepared. Then three sagittal incisions of approximately 10 mm were made in the dorsal skin and subcutaneous pockets were created for membrane implantation (Chen et al, ). Then a pure collagen membrane and an EGCG‐modified collagen membrane were implanted into the pockets.…”