Effects of Poly(β-Amino Ester) Networks on Macrophage Response In Vitro

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Immunology

Background:

• Poly(β-amino ester)-based polymer networks (PBAEs) are degradable biomaterials with potential for in vivo applications.
• Understanding how PBAE network chemistry and structure influence cellular responses, particularly macrophages, is crucial for their development.

Purpose of the Study:

• To investigate the impact of PBAE network chemistry and structure on macrophage activation and inflammatory response.
• To assess the degradability and hydrophilicity of different PBAE formulations.

Main Methods:

• Synthesis of PBAE-diacrylate (PBAE-dA) macromers (B6, α6, A6) via Aza-Michael reaction.
• Characterization of PBAE network properties including hydrophilicity and degradation rates.
• Culture of pre-activated RAW-Blue™ and primary murine macrophages on PBAE networks with and without pre-adsorbed plasma.
• Assessment of macrophage response via NF-κB activation, gene expression (Il1b, Tnfa, Nos2), and cytokine production (IL-6, TNF-α, IL-18).

Main Results:

• PBAE network hydrophilicity and degradation rates varied, with B6 being least hydrophilic/slowest degrading and A6 being most hydrophilic/fastest degrading.
• Macrophage NF-κB activation was elevated in α6 and A6 networks, but this did not lead to significant downstream pro-inflammatory cytokine release.
• Pre-adsorbed plasma reduced macrophage activation on B6 and α6 networks but not on A6.
• The most hydrophilic A6 PBAE showed a greater macrophage response compared to other PBAEs but less than polystyrene controls.

Conclusions:

• PBAE material properties and degradation rates are tunable.
• PBAEs exhibit minimal impact on macrophage inflammatory responses, supporting their suitability for in vivo applications.
• Further research can optimize PBAE formulations for specific biomedical needs based on their tunable characteristics.