title: 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: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China. Electronic address: wqinno8751@gmail.com.
authors: Qi
authors: Q
authors: Wang
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.
authors: Hao
authors: H
authors: Li
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.
authors: Yu
authors: Y
authors: Xiao
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.
authors: Shuan
authors: S
authors: Li
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.
authors: Bo
authors: B
authors: Li
authors: State Key Laboratory of Polymer Materials Engineering Poly Research Institute of Sichuan University, Chengdu 610065, PR China.
authors: Xiaowen
authors: X
authors: Zhao
authors: State Key Laboratory of Polymer Materials Engineering Poly Research Institute of Sichuan University, Chengdu 610065, PR China.
authors: Lin
authors: L
authors: Ye
authors: Department of Stomatology of People's Liberation Army General Hospital, Beijing 100853, PR China.
authors: Bin
authors: B
authors: Guo
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China; Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.
authors: Xinmin
authors: X
authors: Chen
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China. Electronic address: yiding2000@126.com.
authors: Yi
authors: Y
authors: Ding
authors: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.
authors: Chongyun
authors: C
authors: Bao
mesh_terms: D016301:Alveolar Bone Loss / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D001861:Bone Regeneration; D002478:Cells, Cultured; D048271:Chitosan / Q000031:analogs & derivatives*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D048909:Diabetes Complications / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016503:Drug Delivery Systems; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D017208:Rats, Wistar; D054457:Tissue Scaffolds / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000906:Antibodies; D003692:Delayed-Action Preparations; D014409:Tumor Necrosis Factor-alpha; D048271:Chitosan
keywords: Alveolar bone defect; Diabetes; Glucose-sensitive drug delivery; Scaffold; TNFα antibody