Neotherix (United Kingdom)

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.

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.

Endometrial stromal and epithelial cell function is typically studied in vitro using standard two-dimensional monocultures, but these cultures fail to reflect the complex three-dimensional (3D) architecture of tissue. A 3D model of bovine endometrium that reflects the architectural arrangement of in vivo tissue would beneficially assist the study of tissue function. An electrospun polyglycolide (PGA) scaffold was selected to grow a 3D model of primary bovine endometrial epithelial and stromal cells, that reflects the architecture of the endometrium for the study of pathophysiology. Electrospun scaffolds were seeded with stromal and epithelial cells, and growth was assessed using histological techniques. Prostaglandin E2 and prostaglandin F2α responsiveness of endometrial scaffold constructs was tested using oxytocin plus arachidonic acid (OT + AA) or lipopolysaccharide (LPS). Stromal and epithelial cells growing on the electrospun scaffold had an architectural arrangement that mimicked whole tissue, deposited fibronectin, had appropriate expression of vimentin and cytokeratin and were responsive to OT + AA and LPS, as measured by prostaglandin accumulation. In conclusion, a functional 3D model of stromal and epithelial cells was developed using a PGA electrospun scaffold which may be used to study endometrial pathophysiology.