Physical continuity at biomaterial-ECM interfaces regulate fibroblast activation via NF-κB

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cell Biology

Background:

• Fibrotic responses at biomaterial-tissue interfaces impede implant integration and regenerative healing.
• The role of biomaterial-extracellular matrix (ECM) interactions in regulating fibroblast activation is not well understood.
• Scaffold architecture, specifically microporous annealed particle (MAP) scaffolds, has shown potential in reducing fibrosis compared to other hydrogels.

Purpose of the Study:

• To investigate how biomaterial architecture influences ECM integration and fibroblast activation.
• To determine the impact of physical continuity between biomaterials and collagen on fibrotic signaling.

Main Methods:

• Developed a reductionist in vitro model integrating collagen type I with either MAP scaffolds or bulk hydrogels.
• Compared the effects of physically continuous composites versus collagen-excluding hydrogels on fibroblast behavior.
• Assessed collagen architecture, matrix compaction, fibroblast contractility, myofibroblast transition, and NF-κB signaling.

Main Results:

• Physical integration of collagen with MAP scaffolds stabilized collagen architecture and limited fibroblast-mediated matrix compaction.
• Mechanically integrated environments suppressed fibroblast contractility and attenuated myofibroblast differentiation.
• Fibroblasts in integrated environments showed reduced NF-κB expression and nuclear localization, favoring quiescent phenotypes.

Conclusions:

• Biomaterial-ECM physical continuity is a critical design principle for mitigating fibrotic signaling.
• MAP scaffolds facilitate collagen infiltration, leading to mechanically integrated composites that reduce fibrosis.
• Designing biomaterials for physical continuity with the ECM can enhance implant integration and regenerative healing.