Changes in macrophage function and morphology due to biomedical polyurethane surfaces undergoing biodegradation

Abstract

Monocytes are recruited to the material surface of an implanted biomedical device recognizing it as a foreign body. Differentiation into macrophages subsequently occurs followed by fusion to form foreign body giant cells (FBGCs). Consequently, implants can become degraded, cause chronic inflammation or become isolated by fibrous encapsulation. In this study, a relationship between material surface chemistry and the FBGC response was demonstrated by seeding mature monocyte-derived macrophages (MDMs) on polycarbonate-based polyurethanes that differed in their chemical structures (synthesized with poly(1,6-hexyl 1,2-ethyl carbonate) diol, and either (14)C-hexane diisocyanate and butanediol (BD) (referred to as HDI) or 4,4'-methylene bisphenyl diisocyanate and (14)C-BD (referred to as MDI)) and material degradation assessed. At 48 h of cell-material interaction, the FBGC attached to HDI were more multinucleated (73%) compared to MDI or the polystyrene (PS) control (21 and 36%, respectively). There was a fivefold increase in the synthesis and secretion of a protein with an approximate molecular weight of 48 kDa and a pI of 6.1 (determined by two-dimensional gel electrophoresis) only from cells seeded on HDI. Immunoprecipitation confirmed that MSE and CE were synthesized and secreted de novo. Immunoblotting also showed an increase in secreted monocyte-specific esterase (MSE) and cholesterol esterase (CE) from cells seeded on HDI relative to PS and MDI. Significantly more radiolabel ((14)C) release and esterase activity were elicited by MDMs on HDI than MDI (P < 0.05). The material that was more degradable (HDI), elicited greater protein synthesis and esterase secretion as well as more multinucleated MDMs than MDI, suggesting that the material surface chemistry modulates the function of MDM at the site of an inflammatory response to an implanted device.

The Effect of Mesenchymal Stromal Cell–Hyaluronic Acid Hydrogel Constructs on Immunophenotype of Macrophages

“…[28][29][30] In a similar manner, MSCs have been shown to modulate immune cell function through a variety of paracrine and juxtacrine effects, though these interactions are not completely understood. Over the past two decades there have been an increasing number of injectable fillers based on chemically modified biomaterials to use for soft tissue wound repair.…”

Role of protein kinase C in the monocyte‐derived macrophage‐mediated biodegradation of polycarbonate‐based polyurethanes

“…17 Briefly, 0.1% Hoescht Dye no. 33258 was diluted in 10% 10X buffer containing 0.10M Trizma base, 2.0M NaCl, and 0.01M EDTA [in deionized, distilled water (ddH 2 O), pH 7.4] on the day of analysis.…”

“…7,16 The total esterase activity, de novo esterase synthesis, and amount of both CE and MSE in MDMs differed depending on the material surface. 17 The above studies clearly indicated that macrophages respond to small changes in polymer chemistry depending on which PCNU is the seeding surface for the MDMs; however, the mechanism of macrophage activation by these different materials is still unknown. One of the first responses associated with MDMs that occurs with exposure to these materials is the respiratory burst, which is mediated to some extent by protein kinase C (PKC).…”

Evaluation of the Bone Repair Capacity and the Cytotoxic Properties of a Particular Xenograft: An Experimental Study in Rats

“…Both cell types develop from a common precursor. 29 Since foreign body giant cells (FBGC) are the fusion products of monocytic precursors, which are also the precursors to macrophages, 30,31 the presence of such leukocytes in the wound healing compartment may be of central importance in driving the tissue reaction to the material. These results are similar to a previous investigation.…”