Human adipose-derived stromal/stem cells (hASC) are widely used for in vitro modeling of physiologically relevant human adipose tissue. These models are useful for the development of tissue constructs for soft tissue regeneration and 3-dimensional (3D) microphysiological systems (MPS) for drug discovery. In this systematic review, we report on the current state of hASC culture and assessment methods for adipose tissue engineering using 3D MPS. Our search efforts resulted in the identification of 184 independent records, of which 27 were determined to be most relevant to the goals of the present review. Our results demonstrate a lack of consensus on methods for hASC culture and assessment for the production of physiologically relevant in vitro models of human adipose tissue. Few studies have assessed the impact of different 3D culture conditions on hASC adipogenesis. Additionally, there has been a limited use of assays for characterizing the functionality of adipose tissue in vitro. Results from this study suggest the need for more standardized culture methods and further analysis on in vitro tissue functionality. These will be necessary to validate the utility of 3D MPS as an in vitro model to reduce, refine, and replace in vivo experiments in the drug discovery regulatory process.

International regulatory agencies such as the Food and Drug Administration have mandated that the scientific community develop humanized microphysiological systems (MPS) as an in vitro alternative to animal models in the near future. While the breast cancer research community has long appreciated the importance of three-dimensional (3D) growth dynamics in their experimental models, there are remaining obstacles preventing a full conversion to humanized MPS for drug discovery and pathophysiological studies. This perspective evaluates the current status of human tissue-derived cells and scaffolds as building blocks for an “idealized” breast cancer MPS based on bioengineering design principles. It considers the utility of adipose tissue as a potential source of endothelial, lymphohematopoietic, and stromal cells for the support of breast cancer epithelial cells. The relative merits of potential MPS scaffolds derived from adipose tissue, blood components, and synthetic biomaterials is evaluated relative to the current “gold standard” material, Matrigel, a murine chondrosarcoma-derived basement membrane-enriched hydrogel. The advantages and limitations of a humanized breast cancer MPS are discussed in the context of in-process and destructive read-out assays.

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.