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Cutaneous wound healing is an intricate orchestration of three overlapping phases of repair that encompass numerous cell types, signalling cascades, and microenvironment modifications to reach a successful resolution. Disruption of any of these steps will create an abnormal healing response resulting in either ulceration or excessive scarring. It has become evident that the extracellular matrix and its associated components are key orchestrators during this process. One of these essential matrix proteins is decorin, a small leucine‐rich proteoglycan (SLRP) that acts as a regulator of collagen fibrillogenesis and a non‐competitive inhibitor of multiple growth factors signalling cascades. Decorin is a necessary shut‐off switch for the pro‐reparative mechanism of the tissue replacement phase and limits the occurrence of hypertrophic scarring by preventing excessive repair. We investigated the use of decorin as a therapeutic by administering the matrix protein anchored in a slow‐release coacervate in a hypertrophic scarring mouse model. The results show that early wound healing phase measurements exhibit little difference in performance compared to our coacervate‐only baseline or HB‐EGF‐treated control mice. However, during the resolution phase of wound healing, the decorin‐treatment significantly reduces cutaneous thickness, enhances collagen alignment, and improves overall wound scoring in the mice. Thus, mice treated with decorin display better healing outcomes and could limit the hypertrophic scarring phenotype in the coacervate only, and HB‐EGF controls. These results suggest that decorin may be a promising tool and alternative therapy for patients who suffer from over‐exuberant matrix deposition during wound healing. [ABSTRACT FROM AUTHOR]

The aberrant glycosylation profile on the surface of cancer cells has been recognized for its potential diagnostic value towards assessing tumor progression. In this study, we initially investigate N-glycan profiles on the surface of normal (HPDE) and cancerous (Capan-1, Panc-1, and MIA PaCa-2) pancreatic cell lines, which are from different sites of pancreatic tumor. The enzymatically deglycosylated total N-glycans are permethylated via a quantitative solid-phase method and then analyzed by using MALDI-TOF MS and MALDI-QIT-TOF MS. We demonstrate that the level of high-mannose type glycans is higher among Capan-1 cells—pancreatic cancer cells that have metastasized to the liver—than that observed among Panc-1 and MIA PaCa-2 cells—pancreatic cancer cells from the pancreas duct head and tail regions, respectively. Furthermore, the relative abundance of highly-branched sialyted N-glycans is significantly up-regulated on Panc-1 and MIA PaCa-2 pancreatic cancer cells compared to that of normal HPDE pancreas cells. Taken together, these results indicate that specific N-glycosylation profile changes in pancreatic cancer cells can be used to not only distinguish between normal and cancerous cells but also provide more information on their location and metastatic potential. [ABSTRACT FROM AUTHOR]

• Successful optimization and scale-up of a cationic polyester, PEAD. • PEAD/heparin coacervate is used for protein delivery to extend the half lives. • New synthesis route improves the production safety and yield, and reduces the cost. • The successful scale-up makes it easier to commercialize this polycation. • This work may also inform scale-up efforts of similar polymers. Here we report optimization and scale-up of a biodegradable polycation, poly(ethylene argininylaspartate diglyceride) (PEAD) for the purpose of clinical translation. This polycation complexes heparin to form a coacervate. The resultant complex coacervate acts as a vehicle for controlled delivery of therapeutic proteins and through the bioactivity of heparin, greatly increases the half lives of many therapeutic proteins. In an effort to translate this drug delivery platform commercially and clinically, it is necessary to consider the scale of the synthesis, the environmental impact and the cost of the production. Therefore, we substituted the more expensive and hazardous solvents in the reactions, optimized the reaction parameters for a higher yield, scaled up the synthesis capacity up to hundreds of grams per batch and reduced the polymer cost by nearly 90%. The resultant PEAD bears more positive charges than the counterpart made using our previous method, and thus less polymer is needed to complex heparin for coacervation. The material demonstrated good cytocompatibility with human umbilical vein endothelial cells at concentrations up to 5 mg/ml, nearly 500-times more cytocompatible than the commercially resourced polyethyleneimine. Basic fibroblast growth factor was loaded in the coacervate with loading efficiency above 99%. The cargo steadily released approximately 1% over 37 days in vitro without an initial burst, indicating a highly stable coacervate for sustained release. This study paves the way for the translation of this delivery platform and may inform the scale-up of similar polymers. [ABSTRACT FROM AUTHOR]

Although the use of reactive oxygen species (ROS) has been extensively studied, current systems employ external stimuli such as light or electrical energy to produce ROS, which limits their practical usage. In this report, biocompatible metals were used to construct a novel electrochemical system that can spontaneously generate H2O2 without any external light or voltage. The corrosion of Mg transfers electrons to Au-decorated oxidized Ti in an energetically favorable process, and the spontaneous generation of H2O2 in an oxygen reduction reaction was revealed to occur at titanium by combined spectroscopic and electrochemical analyses. The controlled release of H2O2 noticeably enhanced in vitro angiogenesis even in the absence of growth factors. Finally, a new titanium implant prototype was developed by Mg incorporation, and its potential for promoting angiogenesis was demonstrated. [ABSTRACT FROM AUTHOR]

Although the use of reactive oxygen species (ROS) has been extensively studied, current systems employ external stimuli such as light or electrical energy to produce ROS, which limits their practical usage. In this report, biocompatible metals were used to construct a novel electrochemical system that can spontaneously generate H2O2 without any external light or voltage. The corrosion of Mg transfers electrons to Audecorated oxidized Ti in an energetically favorable process, and the spontaneous generation of H2O2 in an oxygen reduction reaction was revealed to occur at titanium by combined spectroscopic and electrochemical analyses. The controlled release of H2O2 noticeably enhanced in vitro angiogenesis even in the absence of growth factors. Finally, a new titanium implant prototype was developed by Mg incorporation, and its potential for promoting angiogenesis was demonstrated. [ABSTRACT FROM AUTHOR]