A fibroblast/macrophage co-culture model to evaluate the biocompatibility of an electrospun Dextran/PLGA scaffold and its potential to induce inflammatory responses

Abstract

Fibroblasts and macrophages are the two major types of cells responding to implanted biomaterials. They play crucial roles in inflammatory responses, host-material interactions and tissue remodeling. However, the synergistic interactions of these two cell types with biomaterials are not fully understood. In this investigation, an in vitro fibroblast/macrophage co-culture system was utilized to examine the biocompatibility and the potential to induce inflammatory responses of an electrospun Dextran/PLGA scaffold. The scaffold did not affect the morphologies, attachments, proliferations and viabilities of both the fibroblasts and macrophages, cultured separately or together. Moreover, it only activated a small subset of the macrophages implicating a low potential to induce either severe acute or chronic inflammatory response. Additionally, fibroblasts played a role in prolonging macrophage activation in the presence of the scaffolds. Using antibody arrays, IL-10, SDF-1, MIP-1 gamma and RANTES were found to be up-regulated when the cells were incubated with the scaffolds. The results of subdermal implantation of the Dextran/PLGA scaffolds confirmed its biocompatibility and low inflammatory potential.

Vitamin E acetate addition to poly(d,l)lactic acid modifies its mechanical behavior without affecting biocompatibility

“…Cell proliferation and differentiation onto implanted biomaterials surface are the major hallmark of material biocompatibility, which is the most fundamental and crucial concern for designing implantable biomaterials. 3,[38][39][40][41] As 10% Vit. E and Vit.…”

A macrophage/fibroblast co-culture system using a cell migration chamber to study inflammatory effects of biomaterials

“…Furthermore, these THP-1-derived macrophages can be further differentiated in a proinflammatory M1 phenotype by lipopolysaccharide (LPS) stimulation [7]. Since experimental models applying only one cell type can only identify a limited set of pro-inflammatory signals [16,17], cell co-culture systems involving two or more types of cells have been employed to mimic more accurately the complexity of the in vivo inflammatory situation [11,18,19]. So far, different in vitro macrophage/fibroblast co-culture models have been used to study inflammatory reactions [18,20,21].…”

“…Since experimental models applying only one cell type can only identify a limited set of pro-inflammatory signals [16,17], cell co-culture systems involving two or more types of cells have been employed to mimic more accurately the complexity of the in vivo inflammatory situation [11,18,19]. So far, different in vitro macrophage/fibroblast co-culture models have been used to study inflammatory reactions [18,20,21]. However, in most of the previous studies, different cell types were seeded on test materials as mixed cultures, resulting in immediate direct contact of cells [18].…”

“…So far, different in vitro macrophage/fibroblast co-culture models have been used to study inflammatory reactions [18,20,21]. However, in most of the previous studies, different cell types were seeded on test materials as mixed cultures, resulting in immediate direct contact of cells [18]. This does not resemble adequately the in vivo situation when a time-resolved arrival of cells on the implant surface occurs and a specific spatial and time-dependent release and exchange of signaling molecules occurs.…”

Towards an in vitro model mimicking the foreign body response: tailoring the surface properties of biomaterials to modulate extracellular matrix

“…Although numerous studies aim at surface modification of implants to reduce the host response212, tuning biomaterials surface properties to promote a suitable host response could be an appealing strategy to improve in situ tissue regeneration through an in vivo bioreactor approach. Furthermore, though various in vitro foreign body response (FBR) models have been proposed to study cell-cell signaling, correlation between cell activity followed by secretion of extracellular matrix (ECM) components with material properties is lacking131415. Here, we propose a new strategy to modulate the host response for tissue regeneration applications.…”