Background Hemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner. Results In this study, we constructed a hemostatic sponge OBNC-DFO by fermentation of Komagataeibacterxylinus combined with TEMPO oxidation to obtain oxidized bacterial nanocellulose (OBNC). Then angiogenetic drug desferrioxamine (DFO) was grafted through an amide bond, and it promoted clot formation and activated coagulation reaction by rapid blood absorption due to the high total pore area (approximately 42.429 m2/g measured by BET). The further release of DFO stimulated the secretion of HIF-1α and the reconstruction of blood flow, thus achieving rapid hemostasis and vascularization in damaged tissue. This new hemostatic sponge can absorb water at a rate of approximate 1.70 g/s, rapidly enhancing clot formation in the early stage of hemostasis. In vitro and in vivo coagulation experiments (in rat tail amputation model and liver trauma model) demonstrated superior pro-coagulation effects of OBNC and OBNC-DFO to clinically used collagen hemostatic sponges (COL). They promoted aggregation and activation of red blood cells and platelets with shorter whole blood clotting time, more robust activation of endogenous coagulation pathways and less blood loss. In vitro cellular assays showed that OBNC-DFO prevailed over OBNC by promoting the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the release of DFO enhanced the secretion of HIF-1α, further strengthening vascularization in damaged skin. In the rat skin injury model, 28 days after being treated with OBNC-DFO, skin appendages (e.g., hair follicles) became more intact, indicating the achievement of structural and functional regeneration of the skin. Conclusion This hemostatic and vascularization-promoting oxidized bacterial nanocellulose hemostatic sponge, which rapidly activates coagulation pathways and enables skin regeneration, is a highly promising hemostatic and pro-regenerative repair biomaterial. Graphical Abstract

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Breast cancer has a marked recurrence and metastatic trait and is one of the most prevalent malignancies affecting women’s health worldwide. Tumor initiation and progression begin after the cell goes from a quiescent to an activated state and requires different mechanisms to act in concert to regulate t a specific set of spectral genes for expression. Cancer stem cells (CSCs) have been proven to initiate and drive tumorigenesis due to their capability of self-renew and differentiate. In addition, CSCs are believed to be capable of causing resistance to anti-tumor drugs, recurrence and metastasis. Therefore, exploring the origin, regulatory mechanisms and ultimate fate decision of CSCs in breast cancer outcomes has far-reaching clinical implications for the development of breast cancer stem cell (BCSC)-targeted therapeutic strategies. In this review, we will highlight the contribution of BCSCs to breast cancer and explore the internal and external factors that regulate the fate of BCSCs.