Affiliations: [a] Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, School and Hospital of Stomatology, Shanxi Medical University, Taiyuan, China
Correspondence:
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Corresponding author: Bin Zhao, School and Hospital of Stomatology, Shanxi Medical University, No. 56 Xinjian Road, Yingze District, Taiyuan 030001, China. E-mail: sxmu0688@126.com
Abstract: BACKGROUND:Advances in bone tissue engineering offer novel options for the regeneration of bone tissue. In the current clinical treatment, the method of accelerating bone tissue regeneration rate by promoting early angiogenesis has been widely accepted. OBJECTIVE:This study aimed to develop a long-acting slow-release system using the pro-angiogenic drug tetramethylpyrazine (TMPZ) and pro-osteogenic drug icariin (ICA), which can be administered locally to achieve the sequential release of TMPZ and ICA for better clinically efficiency in the treatment of bone defects. METHODS:This study aimed to prepare microspheres with a core-shell structure using two polymers, poly lactic-co-glycolic acid and silk fibroin, by coaxial electrostatic spraying. Based on the therapeutic model for bone defects, the pro-angiogenic drug TMPZ and pro-osteogenic drug ICA were encapsulated in the shell and core layers of the microspheres, respectively. Subsequently, TMPZ and ICA were released sequentially to promote early angiogenesis and late osteogenesis, respectively, at the site of the bone defect. The optimal preparation parameters for preparing the drug-loaded microspheres were identified using the univariate controlled variable method. Additionally, microsphere morphology and core-shell structure, such as physical properties, drug-loading properties, in vitro degradation and drug release patterns, were characterised using scanning electron microscope and laser scanning confocal microscopy. RESULTS:The microspheres prepared in this study were well-defined and had a core-shell structure. The hydrophilicity of the drug-loaded microspheres changed compared to the no-load microspheres. Furthermore, in vitro results indicated that the drug-loaded microspheres with high encapsulation and loading efficiencies exhibited good biodegradability and cytocompatibility, slowly releasing the drug for up to three months. CONCLUSION:The development of the drug delivery system with a dual-step release mechanism has potential clinical applications and implications in the treatment of bone defects.
