Guiding macrophage temporal evolution via integrin targeting on peptide-functionalized titanium surfaces to optimize...

Area of Science:

• Biomaterials Science
• Immunology
• Tissue Engineering

Background:

• Titanium's bioinertness can cause fibrous encapsulation and inflammation, hindering implant integration.
• Modulating macrophage phenotype from pro-inflammatory to pro-repair is crucial for enhancing implant performance.

Purpose of the Study:

• To investigate how a functionalized titanium surface (TiBP-linker-RGD) dynamically regulates macrophage phenotype transition.
• To elucidate the role of the integrin signaling axis in this process.

Main Methods:

• Surface functionalization with TiBP-linker-RGD.
• Transcriptomic analysis to assess cellular responses.
• Integrin blockade experiments to confirm signaling pathways.
• In vitro co-culture and in vivo air pouch models to evaluate tissue response.

Main Results:

• The functionalized surface induced an early adhesion-dependent inflammatory state (Day 1) via the RGD-integrin αVβ3 axis.
• This state evolved into a pro-repair phenotype by Day 4, characterized by low ROS and high IL-10.
• Optimized collagen synthesis in fibroblasts and reduced inflammation in vivo were observed.

Conclusions:

• The TiBP-linker-RGD surface effectively primes immune responses and promotes tissue repair.
• This study provides a molecular understanding of immune modulation for designing advanced biomaterials.