Granular Nanofiber-Hydrogel Composite-Programmed Regenerative Inflammation and Adipose Tissue Formation

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Immunology

Background:

• Biomaterial properties critically influence host immune responses, dictating tissue restoration outcomes.
• Physicochemical characteristics of materials can steer immune cells towards pro-regenerative or pro-fibrotic pathways.
• Understanding immune cell signaling is key to engineering effective regenerative biomaterials.

Purpose of the Study:

• To design and construct an injectable nanofiber-hydrogel composite (NHC) microparticle system.
• To evaluate the NHC's ability to promote host cell infiltration, immune cell recruitment, and tissue remodeling.
• To demonstrate the NHC's potential as an off-the-shelf solution for soft tissue loss.

Main Methods:

• Fabrication of NHC microparticles from cross-linked collagen nanofiber fragments and hyaluronic acid hydrogel.
• Covalent conjugation of collagen nanofibers to the hydrogel network.
• Assessment of NHC mechanical properties, porosity, and biocompatibility following subcutaneous injection.
• Evaluation of immune cell infiltration, migration, spreading, and proangiogenic effects.

Main Results:

• NHC microparticles exhibited mechanical properties similar to native soft tissues with high porosity for cell infiltration.
• NHC promoted significant infiltration, migration, and spreading of macrophages/monocytes.
• Sustained cell recruitment and enhanced proangiogenic effects were observed, including recruitment of PDGFRα+ perivascular progenitor cells.
• Extensive adipose tissue remodeling was achieved, indicating successful tissue restoration.

Conclusions:

• The developed injectable NHC microparticles demonstrate significant regenerative potential.
• NHC effectively modulates the host immune response to promote tissue regeneration.
• This biomaterial offers a promising off-the-shelf solution for treating extensive soft tissue defects.