Abstract

In this work, a one-shot process for the simultaneous foaming of polycaprolactone (PCL) and impregnation of mesoglycan (MSG) into the porous structure was successfully attempted. Supercritical carbon dioxide plays the role of the foaming agent with respect to PCL and of the solvent with respect to MSG. The main objective is to produce an innovative topical device for application on skin lesions, promoting prolonged pro-resolving effects. The obtained device offers a protective barrier to ensure a favorable and sterilized environment for the wound healing process. The impregnation kinetics revealed that a pressure of 17 MPa, a temperature of 35 °C, and a time of impregnation of 24 h assured a proper foaming of PCL in addition to the impregnation of the maximum amount of MSG; i.e., 0.22 mgMSG/mgPCL. After a preliminary study conducted on PCL granules used as brought, the MSG impregnation was performed at the optimized process conditions also on a PCL film, produced by compression molding, with the final goal of producing medical patches. Comparing the dissolution profiles in phosphate buffered saline solution (PBS) of pure MSG and MSG impregnated on foamed PCL, it was demonstrated that the release of MSG was significantly prolonged up to 70 times. Next, we performed functional assays of in vitro wound healing, cell invasion, and angiogenesis to evaluate the biological effects of the PCL-derived MSG. Interestingly, we found the ability of this composite system to promote the activation of human keratinocytes, fibroblasts, and endothelial cells, as the main actors of tissue regeneration, confirming what we previously showed for the MSG alone.

Highlights

  • After a skin lesion, the wound healing proceeds as a dynamic process that involves several stages, mainly the inflammation, the re-epithelialization, and the tissue remodeling

  • Once we characterized the loading and the release of MSG from PCL film, we investigated its effects about the activation of human keratinocytes, fibroblasts, and endothelial cells as the main cell populations involved in skin wound repair

  • The challenge was to produce composite biopolymer/drug systems to be used as topical patches for the wound healing process

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Summary

Introduction

The wound healing proceeds as a dynamic process that involves several stages, mainly the inflammation, the re-epithelialization, and the tissue remodeling. The skin tissue repair occurs thanks to the interaction of different extracellular matrix (ECM) components, including glycosaminoglycans (GAGs) and proteoglycans (PGs), that play a significant role in each stage of the wound healing process [1]. In this ECM, several cell populations attend to the granulation, re-epithelialization, and tissue remodeling, following the initial haemostatic and inflammatory phases [2]. Fibroblasts become ready to differentiate in myofibroblasts, a key event in the granulation process of tissue repair [4]

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