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.

Keywords: Alveolar bone defect; Diabetes; Glucose-sensitive drug delivery; Scaffold; TNFα antibody.