Advancing Hematopoietic Stem Cell Research: The Impact of Bioengineered 3D Bone Marrow Niches.

Hematopoietic stem cells (HSCs) sustain lifelong blood and immune cell production through tightly regulated interactions with the bone marrow (BM) niche, a highly organised and dynamic three-dimensional(3D) microenvironment. Within this niche, cellular composition, extracellular matrix (ECM) architecture, biomechanical properties, and biochemical gradients together govern stem cell quiescence, self-renewal, and lineage commitment. Disruption of this regulatory landscape contributes to impaired haematopoiesis, compromised transplantation outcomes, and the development of haematological malignancies, highlighting the need for experimental models that more faithfully capture native niche biology. In this review, we integrate current understanding of BM organisation, with emphasis on endosteal and vascular microdomains and their molecular and mechanical regulation. We then examine the evolution of bioengineered niche platforms from early two-dimensional cultures to advanced 3D systems. We discuss how studies in the literature have used these platforms to enable increasingly refined interrogation of niche-HSC interactions, disease-associated niche remodelling, and therapeutic response, while recognising the complementary role of xenotransplantation approaches in validating engineered niches under systemic regulation. Together, this review integrates current experimental and conceptual advances to present a coherent framework for understanding bioengineered 3D BM niches and their relevance to both fundamental and translational hematopoietic stem cell research.