Clinical and experimental applications of NIR-LED photobiomodulation.

This review presents current research on the use of far-red to near-infrared (NIR) light treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly referred to as "photobiomodulation," uses light in the far-red to near-infrared region of the spectrum (630-1000 nm) and modulates numerous cellular functions. Positive effects of NIR-light-emitting diode (LED) light treatment include acceleration of wound healing, improved recovery from ischemic injury of the heart, and attenuated degeneration of injured optic nerves by improving mitochondrial energy metabolism and production. Various in vitro and in vivo models of mitochondrial dysfunction were treated with a variety of wavelengths of NIR-LED light. These studies were performed to determine the effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production. NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction.

Effect of near-infrared light on in vitro cellular ATP production of osteoblasts and fibroblasts and on fracture healing with intramedullary fixation.

OBJECTIVE: Evaluate the effect of near-infrared light (NIR) on immediate production of ATP by osteoblasts and fibroblasts in vitro, and the healing process of rat femur fractures with intramedullary fixation. BACKGROUND: NIR is one potential treatment option for complications of fracture healing, which has shown to stimulate cellular proliferation and to enhance the healing process. METHODS: Cell culture - MC3T3-E1 and 3T3-A31 cells were subjected to NIR at 660 nm, 830 nm, or both combined. ATP was assayed at 5, 10, 20, and 45 min after exposure. Animal study - 18 rats had surgery with retrograde intramedullary pins inserted into their femurs, which then underwent closed, transverse femur fracture. Rats were randomly divided into 3 study groups of 6 each: nonirradiated controls, 660 nm, and 830 nm NIR. Healing process was assessed by a blinded radiologist, assigning a healing score of 1-6 for radiographs taken on days 0, 7, 14, and 21. RESULTS: Cell culture - All groups gave significant increase in ATP within 5-10 min, with decay to baseline by 45 min. 660 nm NIR was significantly more effective than 830 nm with fibroblasts or either wavelength with osteoblasts. Animal study - A significant increase in the fracture healing grade in the 660 nm group at day 14, but with no differences at day 21. CONCLUSION: The study demonstrated an immediate increase in ATP production in vitro and an initial acceleration of callus formation in the fracture healing process, in the presence of NIR.

Effect of NASA light-emitting diode irradiation on molecular changes for wound healing in diabetic mice.

OBJECTIVE: The purpose of this study was to assess the changes in gene expression of near-infrared light therapy in a model of impaired wound healing. BACKGROUND DATA: Light-Emitting Diodes (LED), originally developed for NASA plant growth experiments in space, show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper we present the effects of LED treatment on wounds in a genetically diabetic mouse model. MATERIALS AND METHODS: Polyvinyl acetal (PVA) sponges were subcutaneously implanted in the dorsum of BKS.Cg-m +/+ Lepr(db) mice. LED treatments were given once daily, and at the sacrifice day, the sponges, incision line and skin over the sponges were harvested and used for RNA extraction. The RNA was subsequently analyzed by cDNA array. RESULTS: Our studies have revealed certain tissue regenerating genes that were significantly upregulated upon LED treatment when compared to the untreated sample. Integrins, laminin, gap junction proteins, and kinesin superfamily motor proteins are some of the genes involved during regeneration process. These are some of the genes that were identified upon gene array experiments with RNA isolated from sponges from the wound site in mouse with LED treatment. CONCLUSION: We believe that the use of NASA light-emitting diodes (LED) for light therapy will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/illness level of activity. This work is supported and managed through the Defense Advanced Research Projects Agency (DARPA) and NASA Marshall Space Flight Center-SBIR Program.

NASA light-emitting diodes for the prevention of oral mucositis in pediatric bone marrow transplant patients.

OBJECTIVE: The purpose of this study was to determine the effects of prophylactic near-infrared light therapy from light-emitting diodes (LEDs) in pediatric bone marrow transplant (BMT) recipients. BACKGROUND DATA: Oral mucositis (OM) is a frequent side effect of chemotherapy that leads to increased morbidity. Near-infrared light has been shown to produce biostimulatory effects in tissues, and previous results using near-infrared lasers have shown improvement in OM indices. However, LEDs may hold greater potential for clinical applications. MATERIALS AND METHODS: We recruited 32 consecutive pediatric patients undergoing myeloablative therapy in preparation for BMT. Patients were examined by two of three pediatric dentists trained in assessing the Schubert oral mucositis index (OMI) for left and right buccal and lateral tongue mucosal surfaces, while the patients were asked to rate their current left and right mouth pain, left and right xerostomia, and throat pain. LED therapy consisted of daily treatment at a fluence of 4 J/cm(2) using a 670-nm LED array held to the left extraoral epithelium starting on the day of transplant, with a concurrent sham treatment on the right. Patients were assessed before BMT and every 2-3 days through posttransplant day 14. Outcomes included the percentage of patients with ulcerative oral mucositis (UOM) compared to historical epidemiological controls, the comparison of left and right buccal pain to throat pain, and the comparison between sides of the buccal and lateral tongue OMI and buccal pain. RESULTS: The incidence of UOM was 53%, compared to an expected rate of 70-90%. There was also a 48% and 39% reduction of treated left and right buccal pain, respectively, compared to untreated throat pain at about posttransplant day 7 (p < 0.05). There were no significant differences between sides in OMI or pain. CONCLUSION: Although more studies are needed, LED therapy appears useful in the prevention of OM in pediatric BMT patients.