Mechanical metamaterials constitute a nascent category of architected structures comprising arranged periodic components with tailored geometrical features. These materials are now being employed as advanced medical implants due to their extraordinary mechanical properties over traditional devices. Nevertheless, to achieve desired tissue integration and regeneration, it is critical to study how the microarchitecture affects interactions between metamaterial scaffolds and living biological tissues. Based on human induced pluripotent stem cell technology and multiphoton lithography, we report the establishment of an in vitro microtissue model to study the integration and remodeling of human mesenchymal tissues on metamaterial scaffolds with different unit geometries. Microtissues showed distinct tissue morphologies and cellular behaviors between architected octet-truss and bowtie structures. Under the active force generated from mesenchymal tissues, the octet-truss and bowtie metamaterial scaffolds demonstrated unique instability phenomena, significantly different from uniform loading using conventional mechanical testing.