Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing  

作　　者：Wanyi Zhou Zhiguang Duan Jing Zhao Rongzhan Fu Chenhui Zhu Daidi Fan 

机构地区：[1]Shaanxi Key Laboratory of Degradable Biomedical Materials,School of Chemical Engineering,Northwest University,Xi’an,710069,Shaanxi,China [2]Shaanxi R&D Center of Biomaterials and Fermentation Engineering,School of Chemical Engineering,Northwest University,Xi’an,710069,Shaanxi,China [3]Biotech.&Biomed.Research Institute,Northwest University,Xi’an,710069,Shaanxi,China

出　　处：《Bioactive Materials》2022年第11期1-17,共17页生物活性材料（英文）

基　　金：This work was supported by the National key Research and devel-opment program of China(2019YFA0905200);the National Natural Science Foundation of China(21878247,21808184);Key Program of the National Natural Science Foundation of China(21838009).

摘　　要：Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres con-taining celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 ◦C) and solid-like elasticity (protect wounds against external forces, approximately 25 ◦C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/ GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.

关 键 词：Dual-responsive Temperature-sensitive Shape self-adaptive hydrogels Diabetic wound healing 

分 类 号：TQ427.26[化学工程] R587.1[医药卫生—内分泌]