Hypertrophic scars (HTS) and keloids are challenging problems. Their pathogenesis results from an overproduction of fibroblasts and excessive deposition of collagen. Studies suggest a possible anti-scarring effect of basic fibroblast growth factor (bFGF) during wound healing, but the precise mechanisms of bFGF are still unclear. In view of this, we investigated the therapeutic effects of bFGF on HTS animal model as well as human scar fibroblasts (HSF) model. We show that bFGF promoted wound healing and reduced the area of flattened non-pathological scars in rat skin wounds and HTS in the rabbit ear. We provide evidence of a new therapeutic strategy: bFGF administration for the treatment of HTS. The scar elevation index (SEI) and epidermal thickness index (ETI) was also significantly reduced. Histological reveal that bFGF exhibited significant amelioration of the collagen tissue. bFGF regulated extracellular matrix (ECM) synthesis and degradation via interference in the collagen distribution, the α-smooth muscle actin (α-SMA) and transforming growth factor-1 (TGF-β1) expression. In addition, bFGF reduced scarring and promoted wound healing by inhibiting TGFβ1/SMAD-dependent pathway. The levels of fibronectin (FN), tissue inhibitor of metalloproteinase-1 (TIMP-1) collagen I, and collagen III were evidently decreased, and matrix metalloproteinase-1 (MMP-1) and apoptosis cells were markedly increased. These results suggest that bFGF possesses favorable therapeutic effects on hypertrophic scars in vitro and in vivo, which may be an effective cure for human hypertrophic scars.

Photoacoustic tomography (PAT) offers three-dimensional (3D) structural and functional imaging of living biological tissue with label-free, optical absorption contrast. These attributes lend PAT imaging to a wide variety of applications in clinical medicine and preclinical research. Despite advances in live animal imaging with PAT, there is still a need for 3D imaging at centimeter depths in real-time. We report the development of four dimensional (4D) PAT, which integrates time resolutions with 3D spatial resolution, obtained using spherical arrays of ultrasonic detectors. The 4D PAT technique generates motion pictures of imaged tissue, enabling real time tracking of dynamic physiological and pathological processes at hundred micrometer-millisecond resolutions. The 4D PAT technique is used here to image needle-based drug delivery and pharmacokinetics. We also use this technique to monitor 1) fast hemodynamic changes during inter-ictal epileptic seizures and 2) temperature variations during tumor thermal therapy.

In this study, we monitor the progress of vasculature in early tumor growth using photoacoustic imaging over a 20 day period after subcutaneous inoculation of breast cancer tumor cells in a mouse. With 532 nm laser pulses employed as an irradiation source, the photoacoustic images were obtained through the photoacoustic signals received by a hydrophone in orthogonal mode. The morphological characteristics of vasculature in tumor region are clearly resolved in the photoacoustic images, and the change in structure as well as the increase in density can be identified. Moreover, the average photoacoustic signal strength of vasculature in tumor region, which is highly correlated with the total hemoglobin concentration of blood, is enhanced during early tumor growth. These results indicate the feasibility of detecting early stage tumor and monitoring the progress of anti-angiogenic therapy by photoacoustic imaging.

Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction of β-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent.

Purpose:The feasibility of medical imaging using a medical linear accelerator to generate acoustic waves is investigated. This modality, x-ray acoustic computed tomography (XACT), has the potential to enable deeper tissue penetration in tissue than photoacoustic tomography via laser excitation. Methods: Short pulsed (μs-range) 10 MV x-ray beams with dose-rate of approximately 30 Gy/min were generated from a medical linear accelerator. The acoustic signals were collected with an ultrasound transducer (500 KHz central frequency) positioned around an object. The transducer, driven by a computer-controlled step motor to scan around the object, detected the resulting acoustic signals in the imaging plane at each scanning position. A pulse preamplifier, with a bandwidth of 20 KHz-2 MHz at −3 dB, and switchable gains of 40 and 60 dB, received the signals from the transducer and delivered the amplified signals to a secondary amplifier. The secondary amplifier had bandwidth of 20 KHz-30 MHz at −3 dB, and a gain range of 10-60 dB. Signals were recorded and averaged 128 times by an oscilloscope. A sampling rate of 100 MHz was used to record 2500 data points at each view angle. One set of data incorporated 200 positions as the receiver moved 360• . The x-ray generated acoustic image was then reconstructed with the filtered back projection algorithm. Results: The x-ray generated acoustic signals were detected from a lead rod embedded in a chicken breast tissue. The authors found that the acoustic signal was proportional to the x-ray dose deposition, with a correlation of 0.998. The two-dimensional XACT images of the lead rod embedded in chicken breast tissue were found to be in good agreement with the shape of the object. Conclusions:The first x-ray acoustic computed tomography image is presented. The new modality may be useful for a number of applications, such as providing the location of a fiducial, or monitoring x-ray dose distribution during radiation therapy. Although much work is needed to improve the image quality of XACT and to explore its performance in other irradiation energies, the benefits of this modality, as highlighted in this work, encourage further study.