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Emerging engineered biomaterials utilize decellularized extracellular matrix as a tissue\u2010specific 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\u2010based hydrogels are utilized, amorphously packed with acellular cartilage tissue particulated to \u2248125\u2013250 microns in diameter and defined a percolation threshold of 0.57 (v\/v) beyond which the compressive modulus exceeded 300\u00a0kPa. 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\u2010scale mechanical properties while also supporting recellularization and integration of dense musculoskeletal and connective tissues.<\/jats:p>","DOI":"10.1002\/adfm.202103355","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T03:21:35Z","timestamp":1624418495000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Recellularization and Integration of Dense Extracellular Matrix by Percolation of Tissue Microparticles"],"prefix":"10.1002","volume":"31","author":[{"given":"Jeanne E.","family":"Barthold","sequence":"first","affiliation":[{"name":"Paul M. 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