Spermidine-Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ.
Qianqian WuRunjiao YangWenxuan FanLi WangJing ZhanTingting CaoQiming LiuXianshu PiaoYinghui ZhongWenxian ZhaoShuhan ZhangJiaao YuSong LiangThomas M RobertsBingdi WangZhen-Ning LiuPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN-SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non-dynamic photo-crosslinked bonds respectively. The single network hydrogel before photo-crosslinking exhibits excellent injectability and thus can be printed and photo-crosslinked in situ to form double network hydrogels. DN-SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an "operando" comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN-SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN-DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.
Keyphrases
- wound healing
- tissue engineering
- hyaluronic acid
- drug delivery
- inflammatory response
- oxidative stress
- liver failure
- reactive oxygen species
- stem cells
- physical activity
- drug induced
- mental health
- quantum dots
- clinical trial
- mesenchymal stem cells
- metabolic syndrome
- adipose tissue
- mass spectrometry
- intensive care unit
- insulin resistance
- high resolution
- hepatitis b virus
- toll like receptor
- bone marrow
- cystic fibrosis
- skeletal muscle
- lipopolysaccharide induced
- extracorporeal membrane oxygenation
- double blind
- network analysis
- extracellular matrix
- acute respiratory distress syndrome