Hematopoietic stem cell (HSC) transplantation provides an effective platform for the treatment of hematological disorders. However, the donor shortage of HSCs and immune responses severely restrict the clinical applications of HSCs. Compared to allogeneic transplantation, autogenous transplantation poses less risk to the immune system, but the problem associated with insufficient HSCs remains a substantial challenge. A significant strategy for obtaining sufficient HSCs is to promote the expansion of HSCs. In vivo, a bone marrow microenvironment supports the survival and hematopoiesis of HSCs. Therefore, it is crucial to establish a platform that mimics the features of a bone marrow microenvironment for the in vitro expansion of HSCs. Three-dimensional (3D) scaffolds have emerged as the most powerful tools to mimic cellular microenvironments for the growth and proliferation of stem cells. Biomedical polymers have been widely utilized as cell scaffolds due to their advantageous features including favorable biocompatibility, biodegradability, as well as adjustable physical and chemical properties. This review focuses on recent advances in the study of biomedical polymer scaffolds that mimic bone marrow microenvironments for the in vitro expansion of HSCs. Bone marrow transplantation and microenvironments are first introduced. Then, biomedical polymer scaffolds for the expansion of HSCs and future prospects are summarized and discussed.