## 1 Introduction  
Successful bone regeneration requires close coordination of various factors, such as cells, marrow stroma microenvironment and vascular networks [1]. Specifically, the neovascularization process mediated by ECs is crucial, because it not only facilitates mass exchanges, but also recruits requisite cell sources (e.g., BMSCs) for skeletal regeneration [2; 3]. Besides, it is reported that osteogenic phenotype and paracrine of angiogenic factors from autologous BMSCs are also very important during bone defect repair [4], and thus transplantation of in vitro expanded BMSCs has attracted intense interests in bone regeneration field [5]. However, a growing body of evidence has revealed that after BMSC grafting in vivo, either in the form of cell suspension or in combination with biological scaffolds, they often undergo oxygen and nutrients deprivation, which impair their survival and functionality [6; 7]. This phenomenon could be mainly attributed to the impaired circulating networks in the topical damaged area of the host or the postponent neoangiogenesis in the scaffolds [1]. Therefore, the development of strategies which not only promote the osteogenic differentiation of BMSCs but also upregulate their angiogenic factors expressions to realize a rapid revascularization is urgently needed. Reportedly, the angiogenic activities of BMSCs and HUVECs are regulated by various signaling pathways, among which the HIF-1\(\alpha\) pathway is considered as a proximate control point [8; 9]. The HIF-1\(\alpha\) is the master regulator of oxygen homeostasis, associating with multiple physiological functions, such as glucose uptake, erythropoiesis, metabolism, cell proliferation, apoptosis regulation and angiogenesis [10]. Under normoxic conditions, HIF-1\(\alpha\) is very unstable and easily hydroxylated by prolyl hydroxylases (PHD); while under hypoxic conditions, prolyl hydroxylation of HIF-1\(\alpha\) is inhibited and nuclear HIF-1\(\alpha\) accumulation occurs. The HIF-1\(\alpha\) then heterodimerizes with the HIF-1\(\beta\) subunit to form an active HIF-complex and binds to the hypoxia-responsive element (HRE), which then induces transcription of multiple HIF-responsive genes, including those involved in angiogenesis, such as VEGF [11; 12]. DFO, firstly used as iron chelator to treat iron overload diseases, is also a hypoxia-mimetic agent which can activate the HIF-1\(\alpha\) signaling pathway under normoxic circumstances, and thereafter upregulate the production of various downstream angiogenesis-related factors including VEGF [11; 13]. In addition, DFO can also promote osteogenic phenotype of BMSCs via the Wnt/\(\beta\)-Catenin signaling pathway [14; 15]. Therefore, the application of DFO is expected to achieve angiogenic and osteogenic coupling effects which are essential for orthopaedics pharmacology. Nevertheless, DFO half-life is very short and it always demands repeated applications in large amounts, which is not suitable for practical use [16; 17]. To tackle this shortcoming, effective local release carriers are needed. Drug bolus, microspheres, micelles and NPs have long been studied in the domain of drug sustained release. In that regard, copolymer-based NPs are promising candidates and have been widely used because of their biocompatibility, biodegradability as well as convenient and minimally-invasive usage [18; 19]. For example, recently [PERSON] et al. prepared functionalized magnetic iron oxide/alginate core-shell nanoparticles for cancer therapy. These nanoparticles could selectively target the tumor tissue and efficiently realize a topical hyperthermia, in the existence of D-galactosamine and an AC magnetic field [20]. In another study, a macroporous scaffold derived from alginate was synthesized and showed good mineralization in cell-based bone tissue engineering applications; furthermore, hMSCs could positively attach and proliferate on this mineralized scaffold [21].