Nanophotonic and hydrogel-based diagnostic system for the monitoring of chronic wounds.

Chronic wounds present a major healthcare burden, yet most wounds are only assessed superficially, and treatment is rarely based on the analysis of wound biomarkers. This lack of analysis is based on the fact that sampling of wound biomarkers is typically invasive, leading to a disruption of the wound bed while biomarker detection and quantification is performed in a remote laboratory, away from the point of care. Here, we introduce the diagnostic element of a novel theranostic system that can non-invasively sample biomarkers without disrupting the wound and that can perform biomarker quantification at the point of care, on a short timescale. The system is based on a thermally switchable hydrogel scaffold that enhances wound healing through regeneration of the wound tissue and allows the extraction of wound biomarkers non-destructively. We demonstrate the detection of two major biomarkers of wound health, i.e., IL-6 and TNF-α, in human matrix absorbed into the hydrogel dressing. Quantification of the biomarkers directly in the hydrogel is achieved using a chirped guided mode resonant biosensor and we demonstrate biomarker detection within the clinically relevant range of pg/mL to µg/mL concentrations. We also demonstrate the detection of IL-6 and TNF-α at concentration 1 ng/mL in hydrogel dressing absorbed with clinical wound exudate samples. The high sensitivity and the wide dynamic range we demonstrate are both essential for the clinical relevance of our system. Our test makes a major contribution towards the development of a wound theranostic for guided treatment and management of chronic wounds.

Hydrolytic Degradability, Cell Tolerance and On-Demand Antibacterial Effect of Electrospun Photodynamically Active Fibres.

Photodynamically active fibres (PAFs) are a novel class of stimulus-sensitive systems capable of triggering antibiotic-free antibacterial effect on-demand when exposed to light. Despite their relevance in infection control, however, the broad clinical applicability of PAFs has not yet been fully realised due to the limited control in fibrous microstructure, cell tolerance and antibacterial activity in the physiologic environment. We addressed this challenge by creating semicrystalline electrospun fibres with varying content of poly[(l-lactide)-co-(glycolide)] (PLGA), poly(ε-caprolactone) (PCL) and methylene blue (MB), whereby the effect of polymer morphology, fibre composition and photosensitiser (PS) uptake on wet state fibre behaviour and functions was studied. The presence of crystalline domains and PS-polymer secondary interactions proved key to accomplishing long-lasting fibrous microstructure, controlled mass loss and controlled MB release profiles (37 °C, pH 7.4, 8 weeks). PAFs with equivalent PLGA:PCL weight ratio successfully promoted attachment and proliferation of L929 cells over a 7-day culture with and without light activation, while triggering up to 2.5 and 4 log reduction in E. coli and S. mutans viability, respectively. These results support the therapeutic applicability of PAFs for frequently encountered bacterial infections, opening up new opportunities in photodynamic fibrous systems with integrated wound healing and infection control capabilities.

Synthesis and Fabrication of Surface-Active Microparticles Using a Membrane Emulsion Technique and Conjugation of Model Protein via Strain-Promoted Azide-Alkyne Click Chemistry in Physiological Conditions.

The rapid surface immobilization of protein on monodispersed polyester microcarriers is reported. A model protein, functionalized with a dibenzocyclooctyne core, immobilizes on the surface of azide-terminal polycaprolactone microcarriers within 10 min compared to 12 h for other conjugation techniques, and it is conducted in physiological conditions and in the absence of coupling reagents.

Photodynamically Active Electrospun Fibers for Antibiotic-Free Infection Control.

Antimicrobial biomaterials are critical to aid in the regeneration of oral soft tissue and prevent or treat localized bacterial infections. With the rising trend in antibiotic resistance, there is a pressing clinical need for new antimicrobial chemistries and biomaterial design approaches enabling on-demand activation of antibiotic-free antimicrobial functionality following an infection that are environment-friendly, flexible and commercially viable. This study explores the feasibility of integrating a bioresorbable electrospun polymer scaffold with localized antimicrobial photodynamic therapy (aPDT) capability. To enable aPDT, we encapsulated a photosensitizer (PS) in polyester fibers in the PS inert state, so that the antibacterial function would be activated on-demand via a visible light source. Fibrous scaffolds were successfully electrospun from FDA-approved polyesters, either poly(ε-caprolactone (PCL) or poly[(rac-lactide)-co-glycolide] (PLGA), with encapsulated PS (either methylene blue (MB) or erythrosin B (ER)). These were prepared and characterized with regards to their loading efficiency (UV-vis spectroscopy), microarchitecture (SEM, porometry, and BET (Brunauer-Emmett-Teller) analysis), tensile properties, hydrolytic behavior (contact angle, dye release capability, degradability), and aPDT effect. The electrospun fibers achieved an ∼100 wt % loading efficiency of PS, which significantly increased their tensile modulus and reduced their average fiber diameter and pore size with respect to PS-free controls. In vitro, PS release varied between a burst release profile to limited release within 100 h, depending on the selected scaffold formulation, while PLGA scaffolds displayed significant macroscopic shrinkage and fiber merging, following incubation in phosphate buffered saline solution. Exposure of PS-encapsulated PCL fibers to visible light successfully led to at least a 1 log reduction in Escherichia coli viability after 60 min of light exposure, whereas PS-free electrospun controls did not inactive microbes. This study successfully demonstrates the significant potential of PS-encapsulated electrospun fibers as photodynamically active biomaterial for antibiotic-free infection control.