Nanofibrous insulin/vildagliptin core-shell PLGA scaffold promotes diabetic wound healing

Chen-Hung Lee; Dong-Yi Chen; Ming-Jer Hsieh; Kuo-Chun Hung; Shu-Chun Huang; Chia-Jung Cho; Shih-Jung Liu

doi:10.3389/fbioe.2023.1075720

Nanofibrous insulin/vildagliptin core-shell PLGA scaffold promotes diabetic wound healing

Front Bioeng Biotechnol. 2023 Apr 24:11:1075720. doi: 10.3389/fbioe.2023.1075720. eCollection 2023.

Authors

Chen-Hung Lee¹, Dong-Yi Chen¹, Ming-Jer Hsieh¹, Kuo-Chun Hung¹, Shu-Chun Huang^{2

3

4}, Chia-Jung Cho⁵, Shih-Jung Liu^{6

7}

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
² Department of Physical Medicine and Rehabilitation, New Taipei Municipal Tucheng Hospital, Chang Gung Memorial Hospital, New Taipei City, Taiwan.
³ Department of Physical Medicine & Rehabilitation, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁴ College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁵ Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan.
⁶ Department of Orthopedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan.
⁷ Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan.

Abstract

Introduction: Slow wound repair in diabetes is a serious adverse event that often results in loss of a limb or disability. An advanced and encouraging vehicle is wanted to enhance clinically applicable diabetic wound care. Nanofibrous insulin/vildagliptin core-shell biodegradable poly (lactic-co-glycolic acid) (PLGA) scaffolds to prolong the effective drug delivery of vildagliptin and insulin for the repair of diabetic wounds were prepared. Methods: To fabricate core-shell nanofibrous membranes, vildagliptin mixture with PLGA, and insulin solution were pumped via separate pumps into two differently sized capillary tubes that were coaxially electrospun. Results and Discussion: Nanofibrous core-shell scaffolds slowly released effective vildagliptin and insulin over 2 weeks in vitro migration assay and in vivo wound-healing models. Water contact angle (68.3 ± 8.5° vs. 121.4 ± 2.0°, p = 0.006) and peaked water absorbent capacity (376% ± 9% vs. 283% ± 24%, p = 0.003) of the insulin/vildagliptin core-shell nanofibrous membranes remarkably exceeded those of a control group. The insulin/vildagliptin-loaded core-shell nanofibers improved endothelial progenitor cells migration in vitro (762 ± 77 cells/mm² vs. 424.4 ± 23 cells/mm², p < 0.001), reduced the α-smooth muscle actin content in vivo (0.72 ± 0.23 vs. 2.07 ± 0.37, p < 0.001), and increased diabetic would recovery (1.9 ± 0.3 mm² vs. 8.0 ± 1.4 mm², p = 0.002). Core-shell insulin/vildagliptin-loaded nanofibers extend the drug delivery of insulin and vildagliptin and accelerate the repair of wounds associated with diabetes.

Keywords: core-shell nanofiber; diabetes; insulin; vildagliptin; wound.