Characterization of the foreign body response to common surgical biomaterials in a murine model

Abstract

Background Implanted biomaterials are subject to a significant reaction from the host, known as the foreign body response (FBR). We quantified the FBR to five materials following subcutaneous implantation in mice. Materials and methods Polyvinyl alcohol (PVA) and silicone sheets are considered highly biocompatible biomaterials and were cut into 8mm-diameter disks. Expanded PTFE (ePTFE)and polypropylene are also widely used biocompatible biomaterials and were cut into 2cm-long cylinders. Cotton was selected as a negative control material that would invoke an intense FBR, was cut into disks and implanted. The implants were inserted subcutaneously into female C57BL/6 mice. On post-implantation days 14, 30, 60, 90 and 180, implants were retrieved. Cellularity was assessed with DAPI stain, collagen with Masson’s trichrome stain. mast cells with toluidine-blue, macrophages with F4/80 immunohistochemical-stain, and capsular thickness and foreign body giant cells with hematoxylin & eosin. Results DAPI revealed a significantly increased cellularity in both PVA andsilicone, and ePTFE had the lowest cell density. Silicone showed the lowest cellularity at d14 and d90 whereas ePTFE showed the lowest cellularity at days 30, 60, and 180. Masson’s trichrome staining demonstrated no apparent difference in collagen. Toluidine blue showed no differences in mast cells. There were, however, fewer macrophages associated with ePTFE. On d14, PVA had highest number of macrophages, whereas polypropylene had the highest number at all time points after d14. Giant cells increased earlier and gradually decreased later. On d90, PVA exhibited a significantly increased number of giant cells compared to polypropylene and silicone. Silicone consistently formed the thinnest capsule throughout all time points. On d14, cotton had formed the thickest capsule. On d30 polypropylenehas formed thickest capsule and on days 60, 90 and 180, PVA had formed thickest capsule. Conclusion These data reveal differences in capsule thickness and cellular response in an implant-related manor, indicating that fibrotic reactions to biomaterials are implant specific and should be carefully considered when performing studies on fibrosis when biomaterials are being used.

A new form of irritant rhinitis to filtering facepiece particle (FFP) masks (FFP2/N95/KN95 respirators) during COVID-19 pandemic

“…Mast cells are thought to be attracted by foreign body reactions and may attract macrophages through degranulation, maintaining and priming the inflammatory response in previous animal models. 16 Further studies are needed to investigate these mechanisms in patients with face mask-related IR.…”

Ligature-Induced Experimental Peri-Implantitis—A Systematic Review

“…Cotton on the other hand, has been shown to induce intense FBRs and also produced the most vertical MBL in the present review. Even though cotton is generally avoided in vivo, it has sometimes been used as a negative control in studies that compared the FBR to different biomaterials [32]. From reports on iatrogenic injuries following surgery, it is known that retained sterile cotton sponges can cause large lesions of foreign body type in both hard and soft tissues, sometimes referred to as “cottonballomas”.…”

Immunomodulatory Contribution of Mast Cells to the Regenerative Biomaterial Microenvironment

“…In vitro culture of human mast cell lines has demonstrated that interaction in the decellularized extracellular matrix (ECM) microenvironment promotes mast cell differentiation, maturation, and viability compared to collagen controls ( 9 ). However, in vivo studies have mainly just evaluated shifts in mast cell numbers associated with biomaterial deployment, though their general low numbers in tissue make it difficult to determine conclusive results from this approach ( 10, 11 ). Early studies with synthetic materials have focused on their functional role and mainly produced results characteristic of a classical mast cell phenotype highlighting contributions to early acute inflammatory cell infiltration ( 2 ), and fibrous capsule formation ( 12 ).…”

“…Although this immunomodulatory influence associated with improved tissue outcomes has been rigorously evaluated with macrophage 5,6 and T cell populations 7,8 , potential contribution of mast cells to the immunomodulatory effect of naturally derived biomaterials has been largely ignored. Studies have mainly just evaluated shifts in mast cell numbers associated with biomaterial deployment, though their general low numbers in tissue make it difficult to determine conclusive results from this approach 9,10 . Early studies with synthetic materials have focused on their functional role and mainly produced results characteristic of a classical mast cell phenotype highlighting contributions to early acute inflammatory cell infiltration 2 , and fibrous capsule formation 11 .…”