Wavelength-Dependent Effects of Photobiomodulation for Wound Care in Diabetic Wounds.

Photobiomodulation, showing positive effects on wound healing processes, has been performed mainly with lasers in the red/infrared spectrum. Light of shorter wavelengths can significantly influence biological systems. This study aimed to evaluate and compare the therapeutic effects of pulsed LED light of different wavelengths on wound healing in a diabetic (db/db) mouse excision wound model. LED therapy by Repuls was applied at either 470 nm (blue), 540 nm (green) or 635 nm (red), at 40 mW/cm2 each. Wound size and wound perfusion were assessed and correlated to wound temperature and light absorption in the tissue. Red and trend-wise green light positively stimulated wound healing, while blue light was ineffective. Light absorption was wavelength-dependent and was associated with significantly increased wound perfusion as measured by laser Doppler imaging. Shorter wavelengths ranging from green to blue significantly increased wound surface temperature, while red light, which penetrates deeper into tissue, led to a significant increase in core body temperature. In summary, wound treatment with pulsed red or green light resulted in improved wound healing in diabetic mice. Since impeded wound healing in diabetic patients poses an ever-increasing socio-economic problem, LED therapy may be an effective, easily applied and cost-efficient supportive treatment for diabetic wound therapy.

Muscle-Specific Micro-Ribonucleic Acids miR-1-3p, miR-133a-3p, and miR-133b Reflect Muscle Regeneration After Single-Dose Zoledronic Acid Following Rotator Cuff Repair in a Rodent Chronic Defect Model.

BACKGROUND: Zoledronic acid improves bone microarchitecture and biomechanical properties after chronic rotator cuff repair (RCR) in rats. Besides the positive effects of zoledronic acid on bone mineral density and bone microarchitecture, bisphosphonates have positive effects on skeletal muscle function. PURPOSES/HYPOTHESIS: The purposes of this study were to (1) longitudinally evaluate circulating bone- and muscle-specific serum micro-ribonucleic acids (miRNAs) and (2) investigate supraspinatus muscle tissue after tenotomy and delayed RCR in a rat model. It was hypothesized that zoledronic acid would improve muscle regeneration after chronic RCR in rats. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 34 male Sprague-Dawley rats underwent unilateral (left) supraspinatus tenotomy (time point 1) with delayed transosseous RCR after 3 weeks (time point 2). All rats were sacrificed 8 weeks after RCR (time point 3). Animals were randomly assigned to 2 groups. One day after RCR, the control group was given 1 mL of subcutaneous saline solution, and the intervention group was treated with a subcutaneous single-dose of 100 µg/kg body weight of zoledronic acid. All 34 study animals underwent miRNA analysis at all 3 time points. In 4 animals of each group, histological analyses as well as gene expression analyses were conducted. RESULTS: Circulating miRNAs showed significantly different expressions between both study groups. In the control group, a significant downregulation was observed for muscle-specific miR-1-3p (P = .004), miR-133a-3p (P < .001), and miR-133b (P < .001). Histological analyses showed significantly higher rates of regenerating myofibers on the operated side (left) of both study groups compared with the nonoperated side (right; P = .002). On the nonoperated side, significantly higher rates of regenerating myofibers were observed in the intervention group compared with the control group (P = .031). The myofiber cross-sectional area revealed significantly smaller myofibers on both sides within the intervention group compared with both sides of the control group (P < .001). Within the intervention group, significantly higher expression levels of muscle development/regeneration marker genes embryonal Myosin heavy chain (P = .017) and neonatal Myosin heavy chain (P = .016) were observed on the nonoperated side compared with the operated side. CONCLUSION: An adjuvant single-dose of zoledronic acid after RCR in a chronic defect model in rats led to significant differences in bone- and muscle-specific miRNA levels. Therefore, miR-1-3p, miR-133a-3p, and miR-133b might be used as biomarkers for muscle regeneration after RCR. CLINICAL RELEVANCE: Adjuvant treatment with zoledronic acid may improve muscle regeneration after chronic RCR in humans, thus counteracting fatty muscle infiltration and atrophy.

A Microfluidic Multisize Spheroid Array for Multiparametric Screening of Anticancer Drugs and Blood-Brain Barrier Transport Properties.

Physiological-relevant in vitro tissue models with their promise of better predictability have the potential to improve drug screening outcomes in preclinical studies. Despite the advances of spheroid models in pharmaceutical screening applications, variations in spheroid size and consequential altered cell responses often lead to nonreproducible and unpredictable results. Here, a microfluidic multisize spheroid array is established and characterized using liver, lung, colon, and skin cells as well as a triple-culture model of the blood-brain barrier (BBB) to assess the effects of spheroid size on (a) anticancer drug toxicity and (b) compound penetration across an advanced BBB model. The reproducible on-chip generation of 360 spheroids of five dimensions on a well-plate format using an integrated microlens technology is demonstrated. While spheroid size-related IC50 values vary up to 160% using the anticancer drugs cisplatin (CIS) or doxorubicin (DOX), reduced CIS:DOX drug dose combinations eliminate all lung microtumors independent of their sizes. A further application includes optimizing cell seeding ratios and size-dependent compound uptake studies in a perfused BBB model. Generally, smaller BBB-spheroids reveal an 80% higher compound penetration than larger spheroids while verifying the BBB opening effect of mannitol and a spheroid size-related modulation on paracellular transport properties.

Antimicrobial photodynamic therapy fighting polymicrobial infections - a journey from in vitro to in vivo.

Rapidly evolving multidrug resistance renders conventional antimicrobial strategies increasingly inefficient. This urges the exploration of alternative strategies with a lower potential of resistance development to control microbial infections. A promising option is antimicrobial photodynamic therapy (aPDT), especially in the setting of wound infections. In this study its effectiveness was tested as a treatment option for polymicrobially infected wounds in both in vitro and in vivo models. First, aPDT was applied to wound-relevant Gram-positive and Gram-negative bacteria in planktonic culture as the standard in vitro test system and compared different media to show a possible dependency of the therapy on the surrounding environment. In a second step, aPDT was investigated in an in vitro model mimicking the wound bed conditions using fibrin-coated culture plates. Finally, we tested aPDT in vivo in a polymicrobial infected wound healing model in immunocompromised BALB/c mice. In vitro, it was shown that the bactericidal effectiveness of aPDT was strongly dependent on the surrounding environment of the phototoxic reaction. In vivo, the significant delay in wound healing induced by polymicrobial infection was drastically diminished by a two-times application of aPDT using 100 µM methylene blue (generally regarded as safe for topical application on human skin) and 24 J cm-2 pulsed red LED light. Our experiments suggest that aPDT is capable of significantly improving wound healing also in complicated polymicrobially infected wound situations.