Constructing Three-Dimensional Microenvironments Using Engineered Biomaterials for Hematopoietic Stem Cell Expansion

In a native bone marrow tissue microenvironment, mesenchymal stem/stromal cells form an important constituent of the stem cell niche, which is composed of extracellular matrix (ECM), niche cells, biophysical cues, and growth factors. These microenvironmental elements play a major role in guiding stem cell behavior, such as growth, stemness, maintenance, and lineage differentiation. The rapid progress in biomaterials advancement and stem cell biology has opened new directions in stem cell therapy. Ideally, biomaterials intended for tissue regenerative medicine applications should perform the structural and biochemical functions of the native ECM, which provides cells with physical (structural/morphological), chemical, and mechanical cues through its three-dimensional (3D) architecture, until the cells' own ECM takes over. Advanced techniques related to material synthesis are significantly important for designing temporary tissue engineering scaffolds, which not only support cell growth but also facilitates 3D tissue formation. This review concisely describes the types of natural and synthetic polymeric biomaterials and the different approaches of designing and developing porous scaffolds for the expansion of hematopoietic stem cells (HSCs). It also illustrates the relationship between material science and tissue engineering and reviews the most frequently used materials and some exciting recent advancements in scaffold manufacture technologies. Furthermore, this review focuses on an introduction to existing HSC niche concepts and summarizes approaches to mimic them in vitro. Impact Statement This review discusses designing novel biomaterial-based hematopoietic stem cell (HSC) expansion strategies that would contribute to the field of hematopoiesis and also proposes possible approaches for HSC expansion using interpenetrating network hydrogels, emulsion templated polymers poly(HIPEs) (high internal phase emulsion templated polymers), and three-dimensional cell printing, which could provide optimal environment for HSC attachment, proliferation, and differentiation. These novel approaches could improve the efficacy of bone marrow transplantation and also offer new insights in the field of regenerative biology.