Topical Application of TT-10 Ameliorates Impaired Wound Healing.

BACKGROUND: In recent decades, chronic wounds have become an increasingly significant clinical concern due to their increasing morbidity and socioeconomic toll. However, there is currently no product available on the market that specifically targets this intricate process. One clear indicator of delayed wound repair is the inhibition of re-epithelialization. Yes-associated protein (YAP), which is a potential focal point for tissue repair and regeneration, has been shown to be prominent in several studies. In this context, we have identified the pharmacological product TT-10, which is a YAP activator, as a potential candidate for the treatment of various forms of chronic wounds. METHODS: The role of TT-10 in regulating YAP activity and subcellular localization was determined by western blotting and immunofluorescence staining. The effect of TT-10 on the biological functions of keratinocytes was assessed by proliferation, wound healing, and apoptosis assays. The impairment of YAP activity in chronic wounds was measured in human and mouse tissues. The in vivo efficacy of TT-10 was examined by gross examination, H&E staining, and measuring wound areas and gaps in normal, diabetic, and ischemic wounds. RESULTS: Our findings suggest that TT-10 facilitates the nuclear transport of YAP, consequently increasing YAP activity, which in turn increases the proliferation and migration of keratinocytes. Moreover, we showed that intracutaneous injection of TT-10 along the wound periphery promoted re-epithelization via YAP activation in the epidermis, culminating in accelerated wound closure in several chronic wound healing models. CONCLUSIONS: Our research highlights the potential of TT-10 to treat chronic wounds, which is a persistent challenge in tissue repair.

Dopamine-Modified Alginate Hydrogel with Effectiveness and Safety for Preoperative Localization of Lung Nodules.

It is important to mark an early lung tumor manifested with small nodules during computed tomography-guided and minimally invasive surgery. The aim of this study is to develop an injectable hydrogel for clinical lung nodule localization. Dopamine, a typical catechol-containing compound, was used to modify alginate for better gel formation and performance needed for localization application. Through the addition of an adequate oxidant and catalase, the catechol-conjugated alginate (C-ALG) hydrogel showed rapid gelation for less than 5 min, similar mechanical properties to lung tissue, slight swelling degree, good cell compatibility, and enough tissue adhesion for localization around the lung tissue. In addition, the C-ALG hydrogel increased the bursting pressure of lung tissue up to 266 ± 15-385 ± 13 mm-H2O that could prevent hydrogel rupture and migration during localizing surgery, suggesting the injectable hydrogel with effectiveness and safety for clinical applications.

Enzymatic Time-Temperature Indicator Prototype Developed by Immobilizing Laccase on Electrospun Fibers to Predict Lactic Acid Bacterial Growth in Milk during Storage.

Laccase was immobilized on a chitosan/polyvinyl alcohol/tetraethylorthosilicate electrospun film (ceCPTL) and colored with guaiacol to obtain a laccase time-temperature indicator (TTI) prototype. The activation energy (Ea) of coloration of the prototype was 50.89-33.62 kJ/mol when 8-25 µg/cm2 laccase was immobilized on ceCPTL, and that of lactic acid bacteria (LAB) growth in milk was 73.32 kJ/mol. The Ea of coloration of the TTI prototype onto which 8-10 µg/cm2 laccase was immobilized was in the required range for predicting LAB growth in milk. The coloration endpoint of the TTI prototype onto which 10 µg/cm2 (0.01 U) laccase was immobilized could respond to the LAB count reaching 106 colony-forming units (CFU)/mL in milk during a static temperature response test, and the prediction error was discovered to be low. In dynamic temperature response experiments with intermittent temperature changes between 4 and 25 °C, the coloration rate of the laccase TTI prototype was consistent with LAB growth. The results of this study indicate that the laccase TTI prototype can be applied as a visual monitoring indicator to assist in evaluating milk quality in cold chains.

Bovine Serum Albumin (BSA)/polyacrylonitrile (PAN) biohybrid nanofibers coated with a biomineralized calcium deficient hydroxyapatite (HA) shell for wound dressing.

Here, for the first time, a nanofibrous (NF) wound dressing comprising biomineralized polyacrylonitrile (PAN) nanofibers is developed. In contrast to the majority of the currently available nanofibrous wound dressings that are based on natural polymers, PAN is a synthetic, industrial polymer, which has been rarely considered for this purpose. PAN NFs are first hydrolyzed to allow for tethering of biofunctional agents (here Bovine Serum Albumin (BSA)). Later, the biofunctionlized PAN NFs are biomineralized by immersion in simulated body fluid (SBF). As a result, core-shell, calcium deficient hydroxyapatite (HA)/BSA/PAN nanofibers form, that are mechanically stronger (elastic modulus; 8.5 vs. 6 MPa) compared to the untreated PAN NFs. The biomineralized PAN NFs showed promising bioactivity as reflected in the cell biology tests with fibroblast and keratinocyte cells. Hs68 fibroblasts and HaCat keratinocytes were found to be more viable in the presence of the biomineralized NFs than when they were co-cultured with the neat PAN NFs. Such mechanical and biological characteristics of the biomineralized PAN NFs are favorable for wound dressing applications.

An electroactive alginate hydrogel nanocomposite reinforced by functionalized graphite nanofilaments for neural tissue engineering.

To address the need to biodegradable, electroactive conduits accelerating nerve regeneration, here we develop a nanocomposite hydrogel made of alginate reinforced by citric acid functionalized graphite nanofilaments. The green, simple functionalization enhances the nanofillers distribution and their biocompatibility, as verified using mesenchymal stem cells in vitro. The uniformly distributed nanofilaments raise mechanical stability of the nanocomposite hydrogel versus the neat one up to three times. Also, the nanofilaments enable electrical contact and intercellular signaling thereby stimulating their biological activity. In vitro studies proved the biocompatibility of the nanocomposite hydrogel whereon PC12 cells proliferate and spread evidently. In vivo tests also supported applicability of the nanocomposite hydrogel for implantation within body, and the samples showed no adverse reaction and no inflammatory responses after 14 days. Conclusively, the results certify that the developed electroactive nanocomposite hydrogel is able to stimulate nerve generation and could be confidently used as a nerve conduit material.