Locally controlled delivery of TNFα antibody from a novel glucose-sensitive scaffold enhances alveolar bone healing in diabetic conditions.

Abstract

Diabetic patients are often accompanied with severe alveolar bone destruction and an increased local TNFα level. Bone repair is a major challenge in those with poor glycemic control. Herein, we report a glucose-sensitive TNFα-antibody-delivery system based on quaternized chitosan and collagen for local long-term control of inflammation and improving osteogenesis in diabetes. We demonstrated that the glucose-sensitive delivery system was a honeycomb-shaped scaffold with pores suitable for bone regeneration. It was capable of attenuating inflammatory response of bone marrow stromal cells under the condition of hyperglucose and TNFα. Additionally, a special diabetic rat model with fluctuation of blood glucose level was established to investigate biological effects of the scaffold. Our results showed that this TNFα-antibody-delivery strategy effectively reduced inflammation by decreasing expression of local TNFα and inflammatory factors. More importantly, with the enhancement of osteogenesis-associated proteins, promoted alveolar bone healing was achieved in the diabetic rat model. The data indicate that such a delivery system possibly provides a potential therapeutic strategy for diabetic patients with severe alveolar bone defects.

• Authors: Qi Wang, Hao Li, Yu Xiao, Shuan Li, Bo Li, Xiaowen Zhao, Lin Ye, Bin Guo, Xinmin Chen, Yi Ding, Chongyun Bao
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 206 Pg. 232-42 (May 28 2015) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 25796348 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies
• Delayed-Action Preparations
• Tumor Necrosis Factor-alpha
• Chitosan

Topics

• Alveolar Bone Loss (complications, immunology, pathology, therapy)
• Animals
• Antibodies (administration & dosage, immunology, therapeutic use)
• Bone Regeneration
• Cells, Cultured
• Chitosan (analogs & derivatives)
• Delayed-Action Preparations (chemistry)
• Diabetes Complications (complications, immunology, pathology, therapy)
• Drug Delivery Systems
• Male
• Mesenchymal Stem Cells (cytology)
• Rats, Wistar
• Tissue Scaffolds (chemistry)
• Tumor Necrosis Factor-alpha (immunology)