Female breast cancer accounts for 15.2% of all new cancer cases in the United States, with a continuing increase in incidence despite efforts to discover new targeted therapies. With an approximate failure rate of 85% for therapies in the early phases of clinical trials, there is a need for more translatable, new preclinical in vitro models that include cellular heterogeneity, extracellular matrix, and human-derived biomaterials. Specifically, adipose tissue and its resident cell populations have been identified as necessary attributes for current preclinical models. Adipose-derived stromal/stem cells (ASCs) and mature adipocytes are a normal part of the breast tissue composition and not only contribute to normal breast physiology but also play a significant role in breast cancer pathophysiology. Given the recognized pro-tumorigenic role of adipocytes in tumor progression, there remains a need to enhance the complexity of current models and account for the contribution of the components that exist within the adipose stromal environment to breast tumorigenesis. This review article captures the current landscape of preclinical breast cancer models with a focus on breast cancer microphysiological system (MPS) models and their counterpart patient-derived xenograft (PDX) models to capture patient diversity as they relate to adipose tissue.

Cellulose nanofibrils (CNFs) and TEMPO-oxidized cellulose nanofibrils (TOCNFs) are hydrated, high-aspect-ratio biomaterials with tunable physicochemical properties, whereas human-derived extracellular matrix (ECM) hydrogels provide matrix-associated biochemical cues. In this study, CNF- and TOCNF-based hybrid scaffolds incorporating human ECM hydrogel components were developed and evaluated in vitro as platforms relevant to cutaneous wound repair. Hybrid formulations gelled at physiological temperature and exhibited formulation-dependent shear-thinning behavior, elastic properties, protein release/leaching profiles, and porous fibrillar microstructures. Selected formulations supported cell-associated metabolic activity of human dermal fibroblasts and adipose-derived stromal/stem cells under two-dimensional and three-dimensional culture conditions. Additional exploratory studies demonstrated qualitative compatibility with adipogenic culture and condition-dependent changes in wound-gap width. In the absence of in vivo validation and confirmatory biological assays, these findings are interpreted as proof-of-concept rather than evidence of wound-healing efficacy. Overall, the results demonstrate the feasibility of combining CNF or TOCNF structural networks with human-derived ECM hydrogels to generate hybrid scaffolds with wound-relevant material properties and preliminary cytocompatibility, supporting further mechanistic and preclinical evaluation.