PEG-fibrin conjugates: the PEG impact on the polymerization dynamics.

Fibrin and its modifications, particularly those with functionalized polyethylene glycol (PEG), remain highly attractive as a biomaterial in drug delivery and regenerative medicine. Despite the extensive knowledge of fibrinogenesis, there is little information on the processes occurring after its modification. Previously, we found structural differences between native fibrin and its conjugates with PEG that allows us to hypothesize that a combination of methods such as terahertz (THz) pulsed spectroscopy and rheology may contribute to the characterization of gelation and reveal the effect of PEG on the polymerization dynamics. Compared to native fibrin, PEGylated fibrins had a homogenously soft surface; PEGylation also led to a significant decrease in the gelation time: from 42.75 min for native fibrin to 31.26 min and 35.09 min for 5 : 1 and 10 : 1 PEGylated fibrin, respectively. It is worth noting that THz pulsed spectroscopy makes it possible to reliably investigate only the polymerization process itself, while it does not allow us to observe statistically significant differences between the distinct PEGylated fibrin gels. The polymerization time constant of native fibrin measured by THz pulsed spectroscopy was 14.4 ± 2.8 min. However, it could not be calculated for PEGylated fibrin because the structural changes were too rapid. These results, together with those previously reported, led us to speculate that PEG-fibrin conjugates formed homogenously distributed highly water-shelled aggregates without bundling compared to native fibrin, ensuring rapid gelation and stabilization of the system without increasing its complexity.

In situ terahertz monitoring of an ice ball formation during tissue cryosurgery: a feasibility test.

SIGNIFICANCE: Uncontrolled cryoablation of tissues is a strong reason limiting the wide application of cryosurgery and cryotherapy due to the certain risks of unpredicted damaging of healthy tissues. The existing guiding techniques are unable to be applied in situ or provide insufficient spatial resolution. Terahertz (THz) pulsed spectroscopy (TPS) based on sensitivity of THz time-domain signal to changes of tissue properties caused by freezing could form the basis of an instrument for observation of the ice ball formation. AIM: The ability of TPS for in situ monitoring of tissue freezing depth is studied experimentally. APPROACH: A THz pulsed spectrometer operated in reflection mode and equipped with a cooled sample holder and ex vivo samples of bovine visceral adipose tissue is applied. Signal spectrograms are used to analyze the changes of THz time-domain signals caused by the interface between frozen and unfrozen tissue parts. RESULTS: Experimental observation of TPS signals reflected from freezing tissue demonstrates the feasibility of TPS to detect ice ball formation up to 657-µm depth. CONCLUSIONS: TPS could become the promising instrument for in situ control of cryoablation, enabling observation of the freezing front propagation, which could find applications in various fields of oncology, regenerative medicine, and THz biophotonics.

Terahertz radiation and the skin: a review.

SIGNIFICANCE: Terahertz (THz) radiation has demonstrated a great potential in biomedical applications over the past three decades, mainly due to its non-invasive and label-free nature. Among all biological specimens, skin tissue is an optimal sample for the application of THz-based methods because it allows for overcoming some intrinsic limitations of the technique, such as a small penetration depth (0.1 to 0.3 mm for the skin, on average). AIM: We summarize the modern research results achieved when THz technology was applied to the skin, considering applications in both imaging/detection and treatment/modulation of the skin constituents. APPROACH: We perform a review of literature and analyze the recent research achievements in THz applications for skin diagnosis and investigation. RESULTS: The reviewed results demonstrate the possibilities of THz spectroscopy and imaging, both pulsed and continuous, for diagnosis of skin melanoma and non-melanoma cancer, dysplasia, scars, and diabetic condition, mainly based on the analysis of THz optical properties. The possibility of modulating cell activity and treatment of various diseases by THz-wave exposure is shown as well. CONCLUSIONS: The rapid development of THz technologies and the obtained research results for skin tissue highlight the potential of THz waves as a research and therapeutic instrument. The perspectives on the use of THz radiation are related to both non-invasive diagnostics and stimulation and control of different processes in a living skin tissue for regeneration and cancer treatment.

Optimal hyperosmotic agents for tissue immersion optical clearing in terahertz biophotonics.

In this work, a thorough analysis of hyperosmotic agents for the immersion optical clearing (IOC) in terahertz (THz) range was performed. It was aimed at the selection of agents for the efficient enhancement of penetration depth of THz waves into biological tissues. Pulsed spectroscopy in the frequency range of 0.1 to 2.5 THz was applied for investigation of the optical properties of common IOC agents. Using the collimated transmission spectroscopy in visible range, binary diffusion coefficients of tissue water and agent in ex vivo rat brain tissue were measured. IOC agents were objectively compared using two-dimensional nomogram, accounting for their THz-wave absorption coefficients and binary diffusion coefficients. The results of this study demonstrate an interplay between the penetration depth enhancement and the diffusion rate and allow for pointing out glycerol as an optimal agent among the considered ones for particular applications in THz biophotonics.