International Journal of Nanomedicine (Jan 2022)
Study on the Local Anti-Osteoporosis Effect of Polaprezinc-Loaded Antioxidant Electrospun Membrane
Abstract
Xue Gao,1,* Mohammed A Al-Baadani,2,* Minjie Wu,1 Ningyang Tong,1 Xinkun Shen,2 Xi Ding,1 Jinsong Liu2 1Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325016, People’s Republic of China; 2School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinkun ShenSchool and Hospital of Stomatology, Wenzhou Medical University, 268# Xueyuan West Road, Lucheng District, Wenzhou City, 325000, People’s Republic of ChinaTel +86-577-88066010Email [email protected] DingDepartment of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou City, 325016, People’s Republic of ChinaTel +86-577-55579913Email [email protected]: Compared with the healthy condition, osteoporotic bone defects are often accompanied by poor osteogenesis and excessive reactive oxygen species (ROS), which pose serious challenges to bone augmentation and repair by normal resorbable guided bone regeneration (GBR) membrane.Purpose: Polaprezinc (PZ) was loaded into polycaprolactone/gelatin (PG) hybrid electrospun nanofibers to fabricate a GBR membrane with antioxidant and osteogenesis ability.Methods: A series of physicochemical characterization were performed by scanning electron microscopy, Fourier-transform infrared spectroscopy, and water contact angle measurement. In addition to membrane degradation and PZ release detection, membranes were tested for cell viability, differentiation, and protein expression in MC3T3-E1 cells by CCK8, alkaline phosphatase activity, mineralization, and Western blotting assays. The membrane osteogenic capacity in cranial bone defects was studied by micro-CT in vivo.Results: PZ was successfully doped into the PCL/GEL nanofibers to form a hydrophilic GBR membrane. The cumulative release of PZ was closely related to the membrane degradation behavior. PG/0.4%PZ membranes produced the best protective effect on cell proliferation/differentiation under oxidative stress microenvironment; however, the PG/0.8%PZ membrane was cytotoxic. Western blotting demonstrated that the PZ-loaded membrane upregulated the Nrf2/HO-1/SOD1 signaling molecules in a concentration-dependent manner. In addition, micro-CT results showed an abundant formation of new bones in the PG/0.4%PZ group compared to the PG group.Conclusion: PZ-loaded degradable PG membranes (especially PG/0.4%PZ) have great potential to accelerate bone regeneration in oxidative stress-related diseases.Keywords: electrospun membrane, polaprezinc, antioxidant, osteogenesis, osteoporosis