Advances in the fields of tissue engineering and regenerative medicine require biomaterials that instruct, rather than simply permit, a desired cellular response. Yet tissues are hierarchical, vary in space and time, and can differ person-to person. I will describe efforts to create biomaterials that replicate the complex cellular and extracellular microenvironment found in the tissues and organs of our body. These include porous, hydrogel/granular, and composite biomaterials for musculoskeletal tissue regeneration, hematopoietic stem cell biomanufacturing, and as model systems to investigate endometrial pathologies and invasive brain cancer. I will describe convergence of materials science and generative manufacturing to create composite biomaterials to regenerate craniomaxillofacial tissues. I will also describe (granular) hydrogel models to study niche regulation of hematopoietic stem cells and patient-derived glioblastoma specimens. These tools enable study of dynamic processes such as remodeling and multicellular signaling that inform stem cell quiescence as well as brain cancer invasion and drug resistance. However, contemporary tissue engineering efforts must also consider patient heterogeneity, gender/sex, and social factors. Hence, I will also describe interdisciplinary efforts to account for sex differences in tissue engineering models as well as to create hierarchical models of the endometrial tissue microenvironment to investigate endometriosis. Interdisciplinary connections are essential for accelerating translation of scientific discoveries into innovations that improve our collective quality of life.