RESUMO
Volumetric muscle loss (VML) frequently results from traumatic incidents and can lead to severe functional disabilities. Hydrogels have been widely employed for VML tissue regeneration, which are unfortunately ineffective because of the lack of intimate contact with injured tissue for structural and mechanical support. Adhesive hydrogels allow for strong tissue connections for wound closure. Nevertheless, conventional adhesive hydrogels exhibit poor tissue adhesion in moist, bleeding wounds due to the hydration layer at the tissue-hydrogel interfaces, resulting in insufficient performance. In this study, we developed a novel, biocompatible, wet tissue adhesive powder hydrogel consisting of dextran-aldehyde (dex-ald) and gelatin for the regeneration of VML. This powder absorbs the interfacial tissue fluid and buffer solution on the tissue, spontaneously forms a hydrogel, and strongly adheres to the tissue via various molecular interactions, including the Schiff base reaction. In particular, the powder composition with a 1:4 ratio of dex-ald to gelatin exhibited optimal characteristics with an appropriate gelation time (258 s), strong tissue adhesion (14.5 kPa), and stability. Dex-ald/gelatin powder hydrogels presented strong adhesion to various organs and excellent hemostasis compared to other wet hydrogels and fibrin glue. A mouse VML injury model revealed that the dex-ald/gelatin powder hydrogel significantly improved muscle regeneration, reduced fibrosis, enhanced vascularization, and decreased inflammation. Consequently, our wet-adhesive powder hydrogel can serve as an effective platform for repairing various tissues, including the heart, muscle, and nerve tissues.
RESUMO
Background: Ex vivo lung perfusion (EVLP) is a useful technique for evaluating and repairing donor lungs for transplantation. However, studies examining the effects of perfusate temperature on graft function are limited. Thus, this study aimed to examine these effects during EVLP on ischemic-reperfusion injury in the donor lung. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups, as follows: no treatment (sham group, n=5), normothermic EVLP (37 °C, n=5), and subnormothermic EVLP (30 °C, n=5). Lung function analyses, including oxygen capacity (OC), compliance, and pulmonary vascular resistance (PVR), were performed hourly during EVLP. Further, after 4 h of EVLP, histological evaluation of the right lobe was performed using the lung injury severity (LIS) scale. The expression levels of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-18 were evaluated. Metabolomic analysis of left lung tissues was conducted using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) after 4 h of EVLP in the EVLP groups and after 1 h of cold preservation in the sham group. Results: Compared with those in the normothermic group, in the subnormothermic group, functional parameters during EVLP and subsequent histologic results were significantly superior, expression levels of inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and IL-18 were significantly lower, and glycolytic activity was significantly decreased. Furthermore, expression levels of mammalian target of rapamycin complex (mTORC), hypoxia-inducible factor (HIF) 1α, and nucleotide-binding domain, leucine-rich-containing family pyrin domain containing 3 (NLRP3) and its effector caspase-1 were significantly lower in the subnormothermic group than in the normothermic group. Conclusions: EVLP with subnormothermic perfusion improves lung graft function by reducing the expression of pro-inflammatory cytokines and glycolytic activity during EVLP. Additionally, EVLP can be a useful target for the improvement of graft function after transplantation.
