Wound healing involves a complex series of biochemical events and has traditionally been managed with 'low tech' dressings and bandages. The concept that diagnostic and theranostic sensors can complement wound management is rapidly growing in popularity as there is tremendous potential to apply this technology to both acute and chronic wounds. Benefits in sensing the wound environment include reduction of hospitalization time, prevention of amputations and better understanding of the processes which impair healing. This review discusses the state-of-the-art in detection of markers associated with wound healing and infection, utilizing devices imbedded within dressings or as point-of-care techniques to allow for continual or rapid wound assessment and monitoring. Approaches include using biological or chemical sensors of wound exudates and volatiles to directly or indirectly detect bacteria, monitor pH, temperature, oxygen and enzymes. Spectroscopic and imaging techniques are also reviewed as advanced wound monitoring techniques. The review concludes with a discussion of the limitations of and future directions for this field.
A real‐time, sensitive, and selective detection device to monitor the healing status of chronic wounds at the point of care is urgently required to render the management of this disease more effective. The photonic properties of porous silicon resonant microcavity (pSiRM) afford an excellent opportunity to be developed as a highly sensitive optical biosensor to monitor the presence of specific biomarkers found in the wound exudate, such as matrix metalloproteinases (MMPs). In this study, the pSiRM is designed, fabricated, and functionalized using a fluorogenic MMP peptide substrate featuring both a fluorophore and a quencher. The peptide‐functionalized pSiRM is then employed as a fluorescence‐based optical biosensor for MMPs. Active MMPs recognize and cleave the peptide sequence of the substrate, producing an immobilized peptide fragment carrying the fluorophore. The fluorescence intensity of the fluorophore embedded within the pSiRM matrix is enhanced by the photonic structure of the pSiRM compared to other pSi photonic structures. This fluorescence enhancement translates into high sensitivity, enabling detection of MMP‐1 at a limit of detection as low as 7.5 × 10−19 m after only 15 min incubation time. Finally, the biosensor also allows the detection and quantification of the concentration of MMPs in human wound fluid.
International audienceIn this report, a polymer-filled porous silicon (pSi) structure is described that is able to detect changes in temperature around a critical value en route to developing a temperature sensor deployed in wounds dressings that signals inflammation or infection of the wound bed. Using surface-initiated atom transfer radical polymerization (SI-ATRP), thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) chains are grafted onto pSi layers with different porosity and pore size and the optical changes (effective optical thickness below and above the lower critical solution temperature (LCST)) are monitored via interferometric reflectance spectroscopy. Six etching conditions and three different surface functionalization conditions are explored in order to optimise the optical response to temperature change. Thermally oxidised pSi samples with the highest investigated porosity (80%) show the largest optical response and will be the target for developing optical sensors of wound temperature
Classical methods for characterizing supported artificial phospholipid bilayers include imaging techniques such as atomic force microscopy and fluorescence microscopy. The use in the past decade of surface-sensitive methods such as surface plasmon resonance and ellipsometry, and acoustic sensors such as the quartz crystal microbalance, coupled to the imaging methods, have expanded our understanding of the formation mechanisms of phospholipid bilayers. In the present work, reflective interferometric Fourier transform spectrocopy (RIFTS) is employed to monitor the formation of a planar phospholipid bilayer on an oxidized mesoporous Si (pSiO(2)) thin film. The pSiO(2) substrates are prepared as thin films (3 μm thick) with pore dimensions of a few nanometers in diameter by the electrochemical etching of crystalline silicon, and they are passivated with a thin thermal oxide layer. A thin film of mica is used as a control. Interferometric optical measurements are used to quantify the behavior of the phospholipids at the internal (pores) and external surfaces of the substrates. The optical measurements indicate that vesicles initially adsorb to the pSiO(2) surface as a monolayer, followed by vesicle fusion and conversion to a surface-adsorbed lipid bilayer. The timescale of the process is consistent with prior measurements of vesicle fusion onto mica surfaces. Reflectance spectra calculated using a simple double-layer Fabry-Perot interference model verify the experimental results. The method provides a simple, real-time, nondestructive approach to characterizing the growth and evolution of lipid vesicle layers on the surface of an optical thin film.
In this paper, the covalent immobilization and luminescence enhancement of a europium (Eu(III)) complex in a porous silicon (pSi) layer with a microcavity (pSiMC) structure are demonstrated. The alkyne-pendant arm of the Eu(III) complex was covalently immobilized on the azide-modified surface via ligand-assisted "click" chemistry. The design parameters of the microcavity were optimized to obtain an efficient luminescence-enhancing device. Luminescence enhancements by a factor of 9.5 and 3.0 were observed for Eu(III) complex bound inside the pSiMC as compared to a single layer and Bragg reflector of identical thickness, respectively, confirming the increased interaction between the immobilized molecules and the electric field in the spacer of the microcavity. When comparing pSiMCs with different resonance wavelength position, luminescence was enhanced when the resonance wavelength overlapped with the maximum emission wavelength of the Eu(III) complex at 614 nm, allowing for effective coupling between the confined light and the emitting molecules. The pSiMC also improved the spectral color purity of the Eu(III) complex luminescence. The ability of a pSiMC to act as an efficient Eu(III) luminescence enhancer, combined with the resulting sharp linelike emission, can be exploited for the development of ultrasensitive optical biosensors.
Matrix metalloproteinases (MMP) are proteolytic enzymes important to wound healing. In non-healing wounds, it has been suggested that MMP levels become dysfunctional, hence it is of great interest to develop sensors to detect MMP biomarkers. This study presents the development of a label-free optical MMP biosensor based on a functionalised porous silicon (pSi) thin film. The biosensor is fabricated by immobilising a peptidomimetic MMP inhibitor in the porous layer using hydrosilylation followed by amide coupling. The binding of MMP to the immobilised inhibitor translates into a change of effective optical thickness over time. We investigated the effect of surface functionalisation on the stability of the pSi surface and evaluated sensing performance. We successfully demonstrated MMP detection in buffer solution and human wound fluid at physiologically relevant concentrations. This biosensor may find application as a point-of-care device that is prognostic of the healing trajectory of chronic wounds.
Chronic wounds do not heal within 3 months, and during the lengthy healing process, the wound is invariably exposed to bacteria, which can colonize the wound bed and form biofilms. This alters the wound metabolism and brings about a change of pH. In this work, porous silicon photonic films were coated with the pH-responsive polymer poly(2-diethylaminoethyl acrylate). We demonstrated that the pH-responsive polymer deposited on the surface of the photonic film acts as a barrier to prevent water from penetrating inside the porous matrix at neutral pH. Moreover, the device demonstrated optical pH sensing capability visible by the unaided eye.
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