Electroresponsive hyaluronic acid-based hydrogel for wound healing with real-time monitoring of bacterial metabolism to prevent infection
(English) Chronic skin wounds represent a major healthcare and socioeconomic challenge due to their high prevalence, prolonged healing times, and elevated risk of complications, particularly in conditions such as diabetic foot ulcers and vascular ulcers. In this context, the development of advanced...
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| Formato: | tesis doctoral |
| Fecha de publicación: | 2026 |
| País: | España |
| Recursos: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/459248 |
| Acesso em linha: | https://hdl.handle.net/2117/459248 https://dx.doi.org/10.5821/dissertation-2117-459248 |
| Access Level: | acceso embargado |
| Palavra-chave: | Hyaluronic acid hydrogels Click chemistry Polyethylene glycol crosslinking Conducting polymers PEDOT-MeOH Electroresponsive hydrogels Wound healing Biomaterials Electrochemical sensing NADH detection 66 - Enginyeria, tecnologia i indústria química. Metal·lúrgia 616. 5 - Pell. Dermatologia clínica Àrees temàtiques de la UPC::Enginyeria química Àrees temàtiques de la UPC::Enginyeria biomèdica |
| Resumo: | (English) Chronic skin wounds represent a major healthcare and socioeconomic challenge due to their high prevalence, prolonged healing times, and elevated risk of complications, particularly in conditions such as diabetic foot ulcers and vascular ulcers. In this context, the development of advanced wound dressings capable of promoting tissue regeneration while simultaneously monitoring the wound status constitutes a critical clinical need. Hyaluronic acid (HA), as a natural component of the skin extracellular matrix, stands out as an ideal biomimetic platform for the design of hydrogels intended for cutaneous wound healing, owing to its excellent biocompatibility, high water-retention capacity, and regulatory role in the wound-healing process. In this thesis, HA-based hydrogels crosslinked via click chemistry are developed using a three-arm polyethylene glycol (PEG) as a crosslinking agent, enabling the formation of well-defined three-dimensional networks under mild and biocompatible conditions. These hydrogels (clickHA) are designed to maintain a favorable moist environment, absorb wound exudate, and promote autolytic debridement, thereby contributing to the removal of necrotic tissue and to the reduction of bacterial burden. The trifunctional architecture of PEG allows precise control over the crosslinking density and, consequently, over the mechanical and structural properties of the hydrogel, ensuring adequate mechanical compliance with skin tissue and ease of clinical handling. The incorporation of a semi-interpenetrating network of a conducting polymer, poly[3,4-ethylenedioxythiophene-2-yl methanol] (PEDOT-MeOH), obtained by chemical oxidative polymerization of EDOT-MeOH monomers infiltrated into the clickHA matrix, endows the system with electro-responsive properties without compromising its structural integrity or biocompatibility. The influence of the infiltrated monomer concentration is systematically analyzed, demonstrating a progressive increase in electroactivity and the onset of electronic percolation at an EDOT-MeOH concentration of 0.05 M, above which effective conductive connectivity and reproducible electrochemical responses are achieved. Molecular dynamics simulations provide a mechanistic understanding of the internal organization of the system, revealing that EDOT-MeOH monomers aggregate into domains stabilized by π–π interactions that act as nucleation sites for polymerization, resulting in a homogeneous distribution of the conducting polymer within the HA matrix without altering its global structure. Finally, the electrochemical stability of the system and its application as an electrochemical sensor for the detection of NADH, a relevant biomarker of bacterial infection, are evaluated. ClickHA/PEDOT-MeOH hydrogels exhibit stable and selective electrochemical responses in the presence of interferents, both in model solutions and in bacterial culture media, enabling the early detection of infections. Overall, this thesis validates the clickHA/PEDOT-MeOH system as a robust multifunctional platform that integrates skin regeneration and electrochemical diagnostics, with high potential for translation into advanced smart wound dressings. |
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