## 1 Introduction  
Diabetes mellitus (DM) is a chronic disease showing an increased sugar level in blood over a prolonged period. Without proper treatment, diabetes can lead to acute complications, such as diabetic ketoacidosis or death due to a hyperosmalor state [1]. Chronic complications are cardiovascular disease, kidney failure, neuropathy, and diabetic feet [2]. There has been a long-standing concern about the association between diabetes and bone health. DM is also associated with bone health. This issue was first suggested nearly a century ago by studying the radiological feature of decelerated bone development and bone atrophy in type 1 diabetes children [3]. The reduction in bone formation during skeletal development is typical in diabetes patients, whereas in adults, hyperglycemia results in the loss of bone by increased bone resorption [4]. Delays in bone union or increases in healing time are features that are most commonly observed when comparing diabetic subjects with matched controls, in clinical studies [5].  
In animals with a streptozotocinocin (STZ)-induced diabetic condition, long-bone fractures show signs of impaired healing [6]. In diabetic animals, femur healing is delayed compared with normo-glycemic controls [7]. There is a double reduction in callus mechanical strength and size in genetic and STZ-induced diabetic animals [7]. Furthermore, the function of osteoblast during fracture healing is decreased in the STZ-induced diabetic condition compared to the control group [6]. Since bone healing is impaired in DM, attempts to improve bone healing have been undertaken. Platelet-rich plasma (PRP), which is thought to hold high levels of growth factors, has been considered for the treatment of diabetic fractures [8]. The administration of recombinant human bone morphogenetic protein-2 (rhBMP-2) increases the bone formation in diabetic rats via improving angiogenesis [9]. Diabetic animals show low levels of platelet-derived growth factor (PDGF) expression [10]. PDGF is also associated with angiogenesis [10; 11]. The administration of PDGF in diabetic animal models shows an increase in cell proliferation and bone formation [11].  
Sericin, a protein most commonly biosynthesized by mulberry (_Bombyx mori_) or non-mulberry silkworms (Antheraea mylitta), and also known as silk gum, has the role of enveloping the fibroin [12]. Sericin has a mostly uniform random coil structure with some \(\beta\)-sheet organized structures [13]. The amount of \(\beta\)-sheet structure is increased by stress, such as repeated moisture absorption and mechanical stretching [12; 13]. Sericin has many biological properties and has been investigated in tissue engineering [14]. Sericin induces bone-like hydroxyapatite nucleation and sericin-based biomaterials have been tested in bone tissue engineering [15]. High \(\beta\)-sheet content and molecular weight of sericin successfully induces hydroxyapatite nucleation [16]. Since sericin has low-profile mechanical properties, it has not been used for bone tissue engineering without a proper scaffold [17; 18].  
Based on sericin's property to influence bone regeneration, we hypothesized that the use of sericin would enhance new bone formation in a diabetic animal model. The purpose of this study was to evaluate the effect of sericin on bone regeneration of critical-sized defects in an STZ-induced type 1 diabetic animal model.