The application of engineered biomaterials for wound healing has been pursued since the beginning of tissue engineering. Here, we attempt to apply functionalized lignosulfonates to confer antioxidation to tissue microenvironments and to deliver oxygen to accelerate vascularization and healing responses without causing inflammatory responses. The results from fibrosis array shows that thiolated lignosulfonate in methacrylated gelatin can effectively attenuate fibrotic responses of human dermal fibroblasts. Elemental analysis of oxygen releasing nanoparticles shows the positive incorporation of calcium peroxide. Composites including nanoparticles of lignosulfonate and calcium peroxide release around 0.05% oxygen per day at least for 7 days. Stiffness can be precisely modulated to avoid adverse inflammatory responses. Injection of lignin composites with oxygen generation nanoparticles enhanced the formation of blood vessels and promoted infiltration of alpha-smooth muscle actin+ fibroblasts over 7 days. At 30 days after surgery, the lignin composite with oxygen generating nanoparticles remodels the collagen architecture resembling to the reticular pattern of normal collagen and leave minimal scars. Thus, our study shows the potential of functionalized lignosulfonate for wound healing applications requiring balanced antioxidation and controlled release of oxygen.
The Radiological Research Accelerator Facility has modified a decommissioned Varian Clinac to deliver ultra-high dose rates: operating in 9 MeV electron mode (FLASH mode), samples can be irradiated at a Source-Surface Distance (SSD) of 20 cm at average dose rates of up to 600 Gy/s (3.3 Gy per 0.13 µs pulse, 180 pulses per second). In this mode multiple pulses are required for most irradiations. By modulating pulse repetition rate and irradiating at SSD = 171 cm, dose rates below 1 Gy/min can be achieved, allowing comparison of FLASH and conventional irradiations with the same beam. Operating in 6 MV photon mode, with the conversion target removed (SuperFLASH mode), samples are irradiated at higher dose rates (0.2–150 Gy per 5 µs pulse, 360 pulses per second) and most irradiations can be performed with a single very high dose rate pulse. In both modes we have seen the expected inverse relation between dose rate and irradiated area, with the highest dose rates obtained for beams with a FWHM of about 2 cm and ± 10% uniformity over 1 cm diameter. As an example of operation of the ultra-high dose rate FLASH irradiator, we present dose rate dependence of dicentric chromosome yields.
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