The ‘Translational Biophotonics: Diagnostics and Therapeutic’ sessions are part of the European Conferences on Biomedical Optics, providing a platform for translational research in biomedical optics and biophotonics. This paper complements our invited talk at the conference held in Munich, Germany, June 25-29, 2023. We briefly describe the Longfellow Project as a new model of innovation through collaboration across academia and industry that we have developed at Massachusetts General Hospital Research Institute, Boston, USA, since 2015. We illustrate the implementation of the model by sharing the translation journey of a novel concept in corneal refractive surgery. Invented and currently in development at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, USA, in collaboration with international academic institutions and industry partners in Luebeck, Jena, and Munich, Germany, the procedure consists of injecting a viscous filler into a femtosecond laser-created corneal pocket to increase the refractive power thereby minimally invasive treating hyperopia and presbyopia. Our intent is not to provide a full review of the work in the field but to show through one concrete example what it takes to move a discovery in the lab along the translational pathway to clinical practice.
Of the reported ~20,000 skin disease related deaths in 2013, 30% were attributed to cutaneous infections, ulcers, wounds, and burns. Wound healing is currently visually assessed by physicians and commonly requires multiple clinical visits for frequent dressing changes. These are often painful and can further compromise tissue health along with increasing infection risks. Clinical workflows for skin wounds often include oxygenation assessment to help guide the course of treatment. However, the low oxygen perfusion intrinsic to these conditions renders standard-of-care blood oxygen saturation tools inaccurate. Transcutaneous oxygen measurements can overcome this issue, albeit with further complications such as time-consuming bedside calibrations and potentially painful application/removal of electrodes.
We present a ‘SMART’ bandage approach that features clinically-validated oxygen sensing molecules embedded within a hydrogel for direct open wound oxygenation measurements. The hydrogel incorporates a phosphorescent red-emitting oxygen-sensing metalloporphyrin covalently attached to a green fluorescent reference dye. As phosphorescence is quenched via collisional energy exchange with molecular oxygen, phosphorescence intensity and lifetime can be used to quantify oxygenation. The emission is bright enough to be visualized by the naked eye, and its intensity was found to increase 10x in oxygen deprived environments (0 mmHg pO2) compared to room air (160 mmHg pO2). Additionally, the hydrogel is capable of swelling up to 400% of its original size in wound exudate while maintaining skin adhesion properties. Along with minimizing the time and materials required for re-dressing, this novel wound dressing has potential for mediating drug delivery and reducing unnecessary patient discomfort.
This erratum corrects an error in “Sensing, monitoring, and release of therapeutics: the translational journey of next generation bandages,” by Z. Li et al.
This article aims to be a progress report on the Sensing, Monitoring And Release of Therapeutics (SMART) bandage—one of the three technologies that received the inaugural SPIE Photonics West Translational Research Symposium Award in 2015. Invented and developed by Dr. Conor L. Evans and his research team at the Wellman Center for Photomedicine, Massachusetts General Hospital, the SMART bandage is a tool aiming to provide measurements of physiological parameters in the skin alongside the administration of therapeutics on-demand. Since the project began in 2012, the chemists, physicists, and biomedical engineers in the team have worked closely with partners from academia and industry to develop oxygen-sensing SMART bandage prototypes that are now in first-in-human clinical studies. This report gives perspectives on the genesis and translational journey of the technology with an emphasis on the challenges encountered, and the solutions innovated at each stage of development.
Despite widespread government and public interest, there are significant barriers to translating basic science discoveries into clinical practice. Biophotonics and biomedical optics technologies can be used to overcome many of these hurdles, due, in part, to offering new portable, bedside, and accessible devices. The current JBO special issue highlights promising activities and examples of translational biophotonics from leading laboratories around the world. We identify common essential features of successful clinical translation by examining the origins and activities of three major international academic affiliated centers with beginnings traceable to the mid-late 1970s: The Wellman Center for Photomedicine (Mass General Hospital, USA), the Beckman Laser Institute and Medical Clinic (University of California, Irvine, USA), and the Medical Laser Center Lübeck at the University of Lübeck, Germany. Major factors driving the success of these programs include visionary founders and leadership, multidisciplinary research and training activities in light-based therapies and diagnostics, diverse funding portfolios, and a thriving entrepreneurial culture that tolerates risk. We provide a brief review of how these three programs emerged and highlight critical phases and lessons learned. Based on these observations, we identify pathways for encouraging the growth and formation of similar programs in order to more rapidly and effectively expand the impact of biophotonics and biomedical optics on human health.
The complex surface topology and soft mechanics of the skin poses a considerable challenge to the development of wearable, conformal sensors. As a results, current clinical assessments of healing-related skin parameters often rely on bulky and expensive optical systems that are difficult to deploy at the point of care. Here, using a rapid-drying, liquid bandage containing oxygen-sensing molecules, we created a wearable sensor bandage that conforms the surface geometry of skin and wounds, and provides two-dimensional maps of cutaneous oxygenation in a non-disruptive fashion. Custom oxygen sensing phosphors have been developed in house that are at least five times brighter than the commercial sensing molecules, enabling the visualization of oxygen concentration using a simple color camera or even by eye under ambient lighting conditions. The oxygen-sensing bandage has been applied to monitor tissue ischemia, graft integration, as well as the progression of burn in animal models. Recent studies have demonstrated its ability to track and quantify skin inflammation induced by complete Freund’s adjuvant in an in vivo porcine model.
In most retinal laser treatments the therapeutic effect is initiated by a transient temperature increase at and around the
retinal pigment epithelium (RPE). Especially in long exposure time treatments like Transpupillary Thermotherapy (TTT)
choroidal perfusion has a strong influence on the realized temperature at the fundus. The fundus blood circulation and
therefore the heat dissipation is influenced by the intraocular pressure (IOP), which is investigated in the study presented
here. In order to reduce the choroidal perfusion, the IOP is increased by injection of physiological saline solution into the
eye of anaesthetized rabbits. The fundus is irradiated with 3.64 W/cm2 by means of a TTT-laser (λ = 810 nm) for t = 20 s
causing a retinal temperature increase. Realtime temperature determination at the irradiated spot is achieved by a non
invasive optoacoustic technique. Perfusion can be reduced by increasing IOP, which leads to different temperature
increases when irradiating the retina. This should be considered for long time laser treatments.
Tumor thermo treatment such as photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) deal with long term and large laser spot exposures. The induced temperature increase is not exactly known [1]. Under these conditions convective heat transfers due to the blood flow in the choroid and the choriocapillaris must be considered in addition to the usually calculated heat conduction. From an existing analytical model defining a unique convective term for the whole fundus irradiated with Gaussian irradiance distribution lasers [2], we developed a numerical one allowing a precise modelling of convection and calculating heating evolution and temperature profiles of the fundus of the eye. The aim of this study is to present the modelling and several comparisons between experimental results [3] and numerical ones concerning the convective heat transfers inside the fundus of the eye.
A 3-D finite element model of the human eye is developed to study the heat transfers induced by an argon laser absorbed on the iris tissue. The main objective is to explain the appearance of complications inherent to the iridectomy such as corneal burns and lens opacities. Contraction burn preceding the iris opening by photovaporization is studied. The iris temperature threshold fixed as onset for the tissue removal is 300 degrees Celsius. For closed angle glaucoma, the thermal history on the corneal endothelium and lens due to recurrent laser shots with pulse durations of 0.5 sec, 0.05 sec and 0.04 sec are presented and discussed. Typically, an overheating of the lens and cornea endothelium by the side of the iridectomy site is observed. This phenomena is important on the cornea endothelium where the temperature increases to 70 degrees Celsius in case of two recurrent laser pulses of 0.5 sec in duration, 0.43 W in power and 0.5 sec in relaxation time. For irradiation time of 0.05 sec this overheating is much less important and the temperature on the cornea endothelium doesn't exceed 47 degrees Celsius. These computations confirm that short laser pulses decrease the amount of adverse effects and agree well with experiments reported by ophthalmologists.
KEYWORDS: Argon ion lasers, 3D modeling, Finite element methods, Eye, Modeling and simulation, Iris, Tissues, Laser development, Convection, Objectives
A 3D finite element model is developed to study the conduction and convection heat transfer due to an argon laser iridectomy in the human eye. The objective is to explain the appearance of two important postoperative complications reported by ophthalmologists: corneal burns and lens opacities. Contraction burn is studied using simple shot of 1 s in duration, 0.5 mm in size, 0.4 W in power and double laser shot of 0.5 s in duration, 0.5 mm in size, 0.4 W in power and 0.5 s of relaxation time. Iris tissue pyrolisis temperature threshold is included as onset of tissue removal. Two laser spot positions on the iris circumference are considered. The phenomena of cornea and lens overheating for both normal and pathological human eyes are presented and discussed.
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