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    Biomaterial scaffold architecture influences tissue healing. Physically integrating scaffolds with the extracellular matrix (ECM) reduces fibrosis by stabilizing collagen and suppressing fibroblast activation, promoting better implant integration.

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    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.