image: Figure 1 Phototherapy and the underlying mechanisms. a) Introduction of light. The electromagnetic spectrum illustrates the distribution of electromagnetic waves across various wavelengths. The enlarged section corresponds to the ultraviolet, visible, and infrared regions, which are the primary wavelengths used in phototherapy applications. b) Schematic representation of the main mechanisms involved in phototherapy, including optogenetics, photobiomodulation, photodynamic therapy, and blue light therapy. Optogenetics activates light-sensitive proteins, such as channelrhodopsin-2 (ChR2), allowing significant cation influx, particularly Na+, through ion channels, leading to depolarization and neuronal excitation. Photobiomodulation employs red and near infrared (NIR) light to activate cytochrome C oxidase (CCO) in the mitochondrial electron transport chain, enhancing ATP synthesis and reducing oxidative stress while upregulating signaling molecules such as nitric oxide (NO) and calcium ions (Ca2+). ATP, adenosine triphosphate. Photodynamic therapy uses light of specific wavelengths to activate photosensitizers (PSs), generating reactive oxygen species (•OH, •O2-, and 1O2) to eliminate cancers and pathogens. Blue light phototherapy enhances bilirubin absorption in the skin, converting it into water-soluble lumirubin, which is excreted from the body without hepatic metabolism. c) Representative applications of diseases treated with phototherapy.
Credit: Min Lu et al.
Phototherapy, as a treatment method, has a history spanning 3,500 years. As early as ancient Egypt, people used a combination of sunlight and medicinal plants to treat conditions such as vitiligo. In the late 19th century, it was discovered that sunlight had therapeutic effects on anthrax and rickets. In the early 20th century, Niels Ryberg Finsen utilized artificial light sources to treat cutaneous tuberculosis, earning the Nobel Prize in Physiology or Medicine in 1903. In 1960, Dr. Maiman invented the solid-state laser and performed the first retinal tumor surgery using laser technology. In 1983, Rox Anderson introduced the concept of selective photothermolysis, laying the foundation for the development of photomedicine.
With continuous advancements in technology, phototherapy has evolved from being an adjunct treatment to a widely applied therapeutic method in medicine (Figure 1). Today, phototherapy plays a critical role in treating neonatal jaundice, wound healing, pigmentary disorders, and vascular abnormalities, offering a low-cost and highly precise treatment option for various diseases. Despite its enormous potential, existing wearable and implantable phototherapy devices still face challenges related to portability, personalization, illumination uniformity, and compatibility with the mechanical and optical properties of target tissues.
In a review article published in Light: Science & Applications, Professor Min Lu from the Ruijin Hospital Orthopedics Research Institute, Shanghai Jiao Tong University, Professor Mei X Wu from Massachusetts General Hospital, and Professor Zhitao Zhang from the School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, provide an in-depth analysis of the broad applications of phototherapy devices in the medical field, from the perspective of clinical phototherapy applications. They summarize the key challenges encountered in the practical application of wearable and implantable phototherapy devices. The article incorporates the latest advancements in photomedicine, materials science, and soft electronics, proposing targeted strategies to address current challenges, and highlighting how interdisciplinary research is driving the future development of phototherapy devices. The article also explores the integration of phototherapy devices with artificial intelligence (AI) technology and flexible sensing modules, proposing the possibility of enhancing therapeutic outcomes through the design of closed-loop phototherapy monitoring systems.
In the fabrication process of phototherapy devices, several technologies are discussed that can effectively solve current issues (Figure 2). For instance, OLED/µLED technologies can improve illumination uniformity and promote device miniaturization through modular designs. Liquid metals and stretchable conductive polymers, as flexible materials, enable devices to better conform to complex anatomical surfaces. To fully realize the potential of these technologies, low-temperature manufacturing techniques are crucial, especially considering that conventional flexible active materials are often sensitive to high temperatures. Furthermore, hybrid organic-inorganic thin-film encapsulation and advanced wearable/implantable power solutions will further improve the biocompatibility of wearable/implantable phototherapy devices and accelerate the development of phototherapy technology.
Finally, based on current technological advancements, the authors provide design strategies for next-generation phototherapy devices (Figure 3). The integration of AI with phototherapy devices presents a significant opportunity for the development of photomedicine. By combining wearable and implantable flexible sensing technologies, AI has the potential to build closed-loop systems that tightly integrate diagnostic and therapeutic functions, allowing for real-time adjustments to clinical applications and improving medical outcomes. As these technologies continue to progress, the future of photomedicine looks even more promising, with an increasingly important role in precision medicine.
These interdisciplinary innovations not only provide new solutions for future smart cities, smart homes, human-device interfaces, as well as health monitoring and safety screening but also signal the growing significance of phototherapy devices in clinical practice.
Journal
Light Science & Applications
Article Title
Challenges and Opportunities in Next-Generation LED Therapeutic Devices