## 1 Introduction  
Bone defects, which can occur in the setting of trauma and fracture, can lead to local disorders and serious problems for public health [1; 2]. Autografts are the unsurpassable method in the treatment of bone defects owing to their osteoconductive, osteoinductive, and osteogenic properties. Allografts with osteoconductive and osteoinductive properties have been used in other bone grafts. However, such allografts have restrictions due to the limited supply, the morbidity at the graft donor sites, blood loss, and disease transmission [3; 4; 5].  
Cyclodext (CDs) are classified as macrocyclic oligosaccharides composed of \(\alpha\)-(1\(\rightarrow\)4) linked D-glucopyranose units [6]. Three common CDs such as \(\alpha\), \(\beta\), and \(\gamma\)-CDs are composed of 6, 7, and 8 glucose units, respectively. CDs are potential candidates in the treatment of bone defects because they can be used as functional carrier materials in complex pharmaceutical formulations [7; 8]. CDs have been broadly applied in pharmaceutical manufacturing since the first pharmaceutical formulation of prostaglandin E2/\(\beta\)-CD manufactured in Japan in 1976 [9]. CDs are able to incorporate suitable guest molecules (small molecules, ions, proteins, and oligonucleotides), inside their hydrophobic cavity resulting in better stability, higher water solubility, and increased bioavailability [10; 11; 12; 13; 14]. Recently, a new drug delivery system has emerged that combines different carriers with herbal molecules. This system improves the bioavailability and therapeutic potency of bioactive substances, which are physiological targets, without losing integrity or bioactivity [15].  
_Epimedii Herba_ (YinYangHou in Chinese) has been used to treat heart disease, osteoporosis, and rheumatism [16; 17]. Icarini (ICA) extracted from _Epimedii Herba_ is a major active flavonoid glycoside and has anti-oxidant, anti-inflammatory, and lipid-modulatory efficacies [16; 17]. In particular, it has been extensively shown to promote bone healing, such as in postmenopausal osteoporosis. Previous studies reported that ICA not only stimulated the proliferation of rat bone marrow-derived mesenchymal stem cells (MSCs) through ERK and MAPK signaling, but also promoted osteogenic differentiation of rat MSCs via vitalizing the PI3K-AKT-cGMP-PKG pathway [18; 19]. [PERSON] et al. recently revealed that ICA induced the proliferation and osteogenic differentiation of rat adipose-derived stem cells via the activation of RhoA-TAZ pathway [16]. Furthermore, [PERSON] et al. showed that ICA-imobilized poly(L-lactide) fibrous membranes enhanced osteogenic activity on MC3T3-E1 cells [17]. Recently, accumulating evidence has showed that ICA plays critical roles in bone regeneration. However, its short half-life, toxic adverse effects, and poor biocompatibility are of concern with regard to its clinical relevance for bone repair [20].  
Alginate (ALG) has been developed as a platform for drug delivery systems due to its good cytocompatibility, biodegradation, and biocompatibility [21]. In addition, owing to its chemical versatility, it can be further modified with various molecules via chemical conjugation [22]. In the current study, we developed a controlled delivery system for ICA using a \(\beta\)-CD-conjugated alginate (\(\beta\)-CD-ALG) nanocarrier to overcome the limitations of ICA. Moreover, we investigated the in vitro osteogenic potency of ICA/\(\beta\)-CD-ALG nanocarrier by analyzing alkaline phosphatase (ALP) levels, the amount of calcium deposits, and the levels of osteogenesis markers of MC3T3-E1 cells.