Oxygen plays a crucial role in wound healing and is involved in multiple wound healing processes [1,2]. The use of healing markers (e.g. oxygen, pH, temperature), biochemical cues from biocompatible matrices and materials, and their correlation with wound healing has the potential to generate valuable diagnostic, prognostic and therapeutic information [[3], [4], [5], [6]]. Noninvasive technologies that provide clinicians with the capability to diagnose and/or assess the response to treatment could greatly impact patient outcome and healthcare costs, especially in the treatment of acute and chronic wounds (i.e., burns, surgical wounds, pressure ulcers, diabetic foot ulcers). In the U.S., acute and chronic wounds affect millions of people and are associated with billions of dollars in healthcare costs [7].
There are numerous techniques available for physiological monitoring of tissue oxygenation [[8], [9], [10]]. Optical methods have emerged as a potential modality to be used in clinical practice, in part due to the introduction of the principle of quenching of phosphorescence by oxygen exhibited by certain classes of molecules [11,12]. Phosphorescence quenching provides a means to directly measure the partial oxygen pressure (pO2) in tissue. This measurement of dissolved tissue oxygen is distinctly different than the blood oxygen saturation (StO2) measurement via the calculation of the fraction of oxygenated relative to total hemoglobin in blood, which is currently the clinical standard-of-care. Phosphorescence-based oxygen sensing relies on specific types of triplet-state emitting molecules such as metallated porphyrins, a highly studied class of molecules. Their unique structural versatility has allowed the development of a large number of functionalized porphyrin molecules [[13], [14], [15], [16], [17], [18], [19]] resulting in the availability of oxygen sensors with spectral profiles and photophysical properties that can be synthetically tailored for a wide range of biomedical applications. The structural versatility of porphyrin-based oxygen sensors also provides surface functional group derivatization that enables the expansion of their structures to macromolecular constructs for embedding in biocompatible matrices and materials [20,21]. A group of oxygen-sensing porphyrin molecules recently developed by Roussakis et al. includes red-emitting metalloporphyrins with high phosphorescence quantum yields [22] that will further simplify optical systems that have already enabled pO2 measurements with oxygen-sensing formulations and consumer-grade camera equipment [[23], [24], [25]].
Biocompatible matrices and materials offer characteristics that have been exploited in wound healing. There are several materials that have displayed promising results such as keratin, dextran, collagen, chitosan, synthetic polymers such as poly (lactic co-glycolic acid) and poly (lactic acid) among others [[26], [27], [28], [29], [30], [31], [32]]. For example, dextran has the ability to regenerate healthy and scar-free tissue in burn wounds [27]. When included in a scaffold, collagen can stimulate the growth of new tissue, create a moist healing environment, and absorb large amounts of exudative fluids [33], which are all desired properties for wound healing platforms. The ability of collagen to form a variety of homogeneous composites with other water-soluble materials provides a novel approach to synthesize functional composite scaffolds whereby the wound healing characteristics of the individual components can be exploited. Additionally, the composite scaffold material's morphology and topography can be tailored to provide contact guidance cues to stimulate cell response (i.e., cell re-epithelialization, cell migration and proliferation), migration direction and speed to facilitate wound closure [34,35].
Theranostic materials integrate both therapeutic and diagnostic functionality into a single system. By synthesizing materials with specific functionality, morphology, topography and healing properties, theranostic materials can be used to image and target biomarkers to monitor wound healing while a scaffold material simultaneously provides an optimal healing environment. The scaffold material could also serve as a therapeutic vehicle to enhance healing. Current research has focused on the advancement of biological therapies (e.g. growth factors) [36,37]. At the same time, passive and active biocompatible materials strategies have been studied, however, the care system lacks of mechanisms to monitor the progression of wound healing [38,39]. Advanced wearable technologies are under development, however, these experience challenges related with re-absorbability, toxicity of the degradation products, and disruption of the wound bed during removal [39].
A collagen-dextran biocomposite is particularly promising due to its biocompatibility, biodegradability and its ability to promote definitive repair, release therapeutics and incorporate sensing molecules for theranostic applications. The objective is to use this approach as a theranostic platform to address and track the progression of wound healing, or deterioration, without removal or reapplication; thus avoiding disruption of the wound bed, promoting tissue regeneration, and monitor healing (i.e., by the incorporation of therapeutics and sensing molecules into an optimal wound healing material matrix). Herein, an oxygen-sensing collagen-dextran biocomposite scaffold membrane was developed as an approach to monitor tissue oxygenation during wound healing using in vivo whole animal optical imaging techniques. This work is the first demonstration of the applicability of our recently developed, brightly-emitting porphyrin molecule in in vivo oxygenation imaging. The strong, visible-wavelength phosphorescence exhibited by this molecule has enabled the use of standard, small animal imaging instrumentation.
https://www.sciencedirect.com/science/article/abs/pii/S0142961219302716