Particle-Only gECM Wafers Enable Cohesive, ECM-Rich Scaffolds Without Secondary Polymers

Granular extracellular matrix (gECM)-based biomaterials commonly contain polymer components to improve scaffold cohesion and handling during fabrication and use. However, these polymer hydrogel components may dilute ECM content and increase fabrication and regulatory complexity. This study evaluated whether particle-only gECM wafers could serve as a simplified alternative to hydrogel-based gECM scaffolds while maintaining structural, mechanical, and biological performance. Decellularized human cartilage and skin tissues were processed and fabricated into three scaffold formats: gECM hydrogels, freeze-dried gECM hydrogel wafers, and freeze-dried particle-only gECM wafers. Across fabrication methods, scaffold swelling, volume fraction, and stiffness were strongly influenced by both tissue type and fabrication approach. gECM hydrogels exhibited the greatest swelling and lowest stiffness, while gECM wafers displayed higher volume fractions and greater mechanical stiffness. Notably, gECM particle-only wafers achieved performance comparable to gECM hydrogel wafers despite the absence of a secondary polymer network. Particle-only wafers also maintained swelling behavior and structural properties over 3 months of dry storage at room temperature, with only modest decreases in stiffness. In vitro studies showed sustained cell viability over 14 days on particle-only wafers, with chondrocytes infiltrating cartilage wafers and fibroblasts remaining primarily surface-localized on skin wafers. In addition, particle-only wafers remained cohesive during implantation into a bovine cartilage defect model. These findings demonstrate that particle-only gECM wafers can achieve structural integrity, mechanical performance, and cytocompatibility without the need for an additional polymer network, highlighting a simplified and ECM-rich biomaterial platform. By eliminating polymer carriers and enabling dry storage with preserved function, this approach supports the development of off-the-shelf, translationally accessible gECM particle-only wafers for tissue engineering applications.