Tissue engineering is a growing field with multidisciplinary players in cell biology, engineering, and medicine, aiming to maintain, restore, or enhance functions of tissues and organs. The extracellular matrix (ECM) plays fundamental roles in tissue development, maintenance, and repair, providing not only structural support, but also critical biochemical and biomechanical cues that regulate cell behavior and signaling. Although its specific composition varies across different tissue types and developmental stages, matrix molecules influence various cell functional properties in every tissue. Given the importance of ECM in morphogenesis, tissue homeostasis, and regeneration, ECM-based bioscaffolds, developed through tissue engineering approaches, have emerged as pivotal tools for recreating the native cellular microenvironment. The aim of this study is to present the main categories of these scaffolds (i.e., natural, synthetic, and hybrid), major fabrication techniques (i.e., tissue decellularization and multidimensional bioprinting), while highlighting the advantages and disadvantages of each category, focusing on biological activity and mechanical performance. Scaffold properties, such as mechanical strength, elasticity, biocompatibility, and biodegradability are essential to their function and integration into host tissues. Applications of ECM-based bioscaffolds span a range of engineering and regenerative strategies, including cartilage, bone, cardiac tissue engineering, and skin wound healing. Despite promising advances, challenges remain in standardization, scalability, and immune response modulation, with future directions directed towards improving ECM-mimetic platforms.

Hyaluronan (HA), a major extracellular matrix (ECM) glycosaminoglycan, plays a key role in breast cancer progression. Although native HA lacks sulfate groups, chemically modified sulfated hyaluronan (sHA) has demonstrated promising antitumor activity. Previous work from our group showed that sHA alters cellular functions and modulates ECM-related gene expression in triple-negative breast cancer (TNBC) cells. The aim of this study was to investigate the effects of low-molecular-weight HA (50 kDa) and its sulfated derivative of the same molecular weight, sHA, in MDA-MB-231 and MCF-7 breast cancer cells using advanced 3D cell culture models. Gene expression analyses focused on ECM components, including HA receptors and matrix metalloproteinases (MMPs) that were evaluated. The 3D cell morphology was examined using scanning electron microscopy (SEM). Spheroid growth and expression profiles linked to ECM remodeling and invasiveness were also assessed. Notably, sHA significantly inhibited 3D spheroid growth, reduced cell spreading in a cell line-dependent manner and influenced the expression of genes correlated with ECM remodeling and HA synthesis. These findings emphasize the importance of 3D models for studying ECM-driven breast cancer progression, further supporting sHA as a potential therapeutic modulator.