Nanopatterned bulk metallic glass-based biomaterials modulate macrophage polarization

Area of Science:

• Biomaterials Science
• Immunology
• Materials Engineering

Background:

• Biomaterial implants trigger foreign body responses (FBR), influenced by macrophage polarization.
• Surface topography is known to affect macrophage polarization, but research is limited by material processing challenges.
• Nanoscale surface features on high-modulus materials are needed to fully understand topography's impact on macrophage behavior.

Purpose of the Study:

• To investigate the ability of nanopatterned bulk metallic glasses (BMGs) to modulate murine macrophage polarization.
• To assess the in vitro and in vivo effects of nanopatterned BMGs on macrophage function and the host response.
• To explore nanopatterning as a technique for controlling macrophage polarization and FBR.

Main Methods:

• Fabrication of bulk metallic glasses (BMGs) with 55 nm nanorod arrays (BMG-55).
• In vitro culture of macrophages on BMG-55 and analysis of cytokine/chemokine secretion (TNF-α, IL-1α, IL-12, CCL-2, CXCL1).
• In vitro assessment of macrophage phagocytic potential, cell area, and actin protrusions.
• In vivo subcutaneous implantation of BMG-55 in mice and analysis of host response after 2 weeks (macrophage polarization markers, fibrous capsule thickness, vascularization).

Main Results:

• BMG-55 significantly reduced secretion of key inflammatory cytokines/chemokines (TNF-α, IL-1α, IL-12, CCL-2, CXCL1) in vitro.
• Macrophages cultured on BMG-55 showed enhanced phagocytic potential and altered morphology (decreased cell area, increased actin protrusions).
• In vivo, BMG-55 implants led to an increased Arg-1/iNOS ratio in macrophages, reduced fibrous capsule thickness, decreased macrophage fusion, and increased blood vessel formation.

Conclusions:

• Nanopatterning of BMGs is a viable strategy to selectively polarize macrophages towards a pro-repair phenotype.
• This approach can effectively modulate the foreign body response, leading to reduced fibrosis and enhanced angiogenesis.
• Nanopattered BMGs offer a powerful tool for studying macrophage polarization mechanisms and developing advanced immunomodulatory biomaterials.