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Recellularization and Integration of Dense Extracellular Matrix by Percolation of Tissue Microparticles
Author(s) -
Barthold Jeanne E.,
St. Martin Brittany M.,
Sridhar Shankar Lalitha,
Vernerey Franck,
Schneider Stephanie Ellyse,
Wacquez Alexis,
Ferguson Virginia L.,
Calve Sarah,
Neu Corey P.
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202103355
Subject(s) - extracellular matrix , materials science , decellularization , cartilage , self healing hydrogels , tissue engineering , biomedical engineering , scaffold , regeneration (biology) , hyaluronic acid , nanotechnology , microbiology and biotechnology , anatomy , biology , medicine , polymer chemistry
Cells embedded in the extracellular matrix of tissues play a critical role in maintaining homeostasis while promoting integration and regeneration following damage or disease. Emerging engineered biomaterials utilize decellularized extracellular matrix as a tissue‐specific support structure; however, many dense, structured biomaterials unfortunately demonstrate limited formability, fail to promote cell migration, and result in limited tissue repair. Here, a reinforced composite material of densely packed acellular extracellular matrix microparticles in a hydrogel, termed tissue clay, that can be molded and crosslinked to mimic native tissue architecture is developed. Hyaluronic acid‐based hydrogels are utilized, amorphously packed with acellular cartilage tissue particulated to ≈125–250 microns in diameter and defined a percolation threshold of 0.57 (v/v) beyond which the compressive modulus exceeded 300 kPa. Remarkably, primary chondrocytes recellularize particles within 48 h, a process driven by chemotaxis, exhibit distributed cellularity in large engineered composites, and express genes consistent with native cartilage repair. In addition, broad utility of tissue clays through recellularization and persistence of muscle, skin, and cartilage composites in an in vivo mouse model is demonstrated. The findings suggest optimal material architectures to balance concurrent demands for large‐scale mechanical properties while also supporting recellularization and integration of dense musculoskeletal and connective tissues.