Porous Implants Modulate Healing and Induce Shifts in Local Macrophage Polarization in the Foreign Body Reaction

• Published in: Annals of biomedical engineering Vol. 42; no. 7; pp. 1508 - 1516
• Main Authors: Sussman, Eric M., Halpin, Michelle C., Muster, Jeanot, Moon, Randall T., Ratner, Buddy D.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.07.2014; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Biophysics; Classical Mechanics; Foreign-Body Reaction - immunology; Foreign-Body Reaction - pathology; Macrophages - immunology; Macrophages - pathology; Medical equipment; Mice; Polarization; Pores; Porosity; Prostheses and Implants - adverse effects; Wound Healing - immunology; Sphere-templated porous scaffolds; M1; M2; Foreign body capsule; Vascularization
• ISSN: 0090-6964; 1573-9686
• DOI: 10.1007/s10439-013-0933-0

The foreign body reaction (FBR) to implanted materials is of critical importance when medical devices require biological integration and vascularization to support their proper function (e.g., transcutaneous devices, implanted drug delivery systems, tissue replacements, and sensors). One class of materials that improves FBR outcomes is made by sphere-templating, resulting in porous structures with uniform, interconnected 34  μ m pores. With these materials we observe reduced fibrosis and increased vascularization. We hypothesized that improved healing is a result of a shift in macrophage polarization, often measured as the ratio of M1 pro-inflammatory cells to M2 pro-healing cells. In this study, macrophage polarity of 34  μ m porous implants was compared to non-porous and 160  μ m porous implants in subcutaneous mouse tissue. Immunohistochemistry revealed that macrophages in implant pores displayed a shift towards an M1 phenotype compared to externalized cells. Macrophages in 34  μ m porous implants had up to 63% greater expression of M1 markers and up to 85% reduction in M2 marker expression ( p  < 0.05). Macrophages immediately outside the porous structure, in contrast, showed a significant enrichment in M2 phenotypic cells. This study supports a role for macrophage polarization in driving the FBR to implanted materials.