ENGINEERING CELLULAR SELF‐ORGANISATION BY CONTROLLING THE IMMUNO-MECHANICAL INTERPLAY

Introduction

Both scar formation and restitutio ad integrum during bone regeneration rely on cellular self-organisation that involves cell contraction and fibronectin/collagen formation. This early stage of cellular self-organization is later followed by angiogenesis and mineralisation.

Immune-Mechanical Coupling

Scar-free regeneration of physiological tissue homeostasis requires balanced downregulation of early inflammation; however, little is understood of the immune-mechanical coupling involved. We aim to lay the foundation for reducing patient suffering resulting from scarring by combining two distinct scientific worlds, for which we have been a major driving force: the distinct regulation of local inflammation and the mechano-biology during regeneration.

Project Goals

By combining both of our areas of expertise, we aim to harvest the potential of the novel cross-disciplinary field Immuno-Mechanics. This ambitious project concentrates first on identifying the different mechanical niches that immune cells experience early in successful healing and non-healing.

1. Identifying Mechanical Niches: Focus on the different mechanical environments immune cells encounter during healing.
2. Engineering Synthetic Niches: We will engineer synthetic niches to control fibroblasts and fibroblast-immune cell interactions to steer cell self-organisation and matrix formation in vitro.
3. Verifying Effects in Vivo: We plan to verify that these synthetic niches reprogram hematoma composition and can thus reduce later scarring in vivo.

Experimental Challenges

The proposed experiments are challenging as they have never been done this way before, but are feasible since they capitalise on our strengths in osteo-immunology and mechano-biology.

Innovative Approaches

Novel technologies will be combined in a unique way to engineer the immune-mechanical cell niche, to passivate activated immune cells, and to reprogram cell fate. This will allow us to substantially advance the basic understanding of the interplay between immune cells and their mechanical niche during early regeneration.

Future Implications

By harnessing the mechanisms of the immune-mechanics interplay, we will lay the foundation for advancing immune-modulatory therapies to reduce harmful scarring.