A novel gelatin/carboxymethyl chitosan/nano-hydroxyapatite/ß-tricalcium phosphate biomimetic nanocomposite scaffold for bone tissue engineering applications.

Hydroxyapatite (HA) and tricalcium phosphate (TCP) constitute 60% of the content of the bone, and their combination has a better effect on bone tissue engineering than either single element. This study demonstrates a new degradable gelatin/carboxymethyl chitosan (CMC) bone scaffold loaded with both nano-HA and ß-TCP (hereinafter referred to as HCP), and freeze drying combined with stir foaming was used to obtain highly connected macropores. Only a few studies have used these components to synthesize a four-component osteogenic scaffold. The aim of this study was to comprehensively assess the biocompatibility and osteoinductivity of the nanocomposites. Three HCP/CMC/gelatin scaffolds were made with different HCP contents: group A (10 wt% HCP), group B (30 wt% HCP), and group C (50 wt% HCP) (the ratio of nano-HA and ß-TCP was fixed at 3:2). The scaffolds were macroporous with a high porosity and pore connectivity, as observed by morphological analysis by scanning electron microscopy. Additionally, the pore size of groups A and B was more homogeneous than that of group C. There were no significant differences in physicochemical characterization among the three groups. The Fourier-transform infrared (FTIR) spectroscopy test indicated that the scaffold contained active groups, such as hydroxyl, amino, or peptide bonds, corresponding to gelatin and CMC. The XRD results showed that the phase structures of HA and ß-TCP did not change in the nanocomposite. The scaffolds had biodegradation potential and an appreciable swelling ratio, as demonstrated with the in vitro test. The scaffolds were cultured in vitro with MC3T3-E1 cells, showing that osteoinduction and osteoconduction increased with the HCP content. None of the scaffolds showed cytotoxicity. However, cell adhesion and growth in group B were better than those in group A and group C. Therefore, freeze drying combined with a stir foaming method may have a solid component limit. This study demonstrates a novel four-component scaffold via a simple manufacturing process. Group B (30% HCP) had the best characteristics for bone scaffold materials.

In vivo terahertz imaging to evaluate scar treatment strategies: silicone gel sheeting.

Silicone gel sheeting (SGS) is widely used for scar treatment; however, studies showing its interaction with skin and efficacy of scar treatment are still lacking. THz light is non-ionizing and highly sensitive to changes in water content and thus skin hydration. In this work, we use in-vivo THz imaging to monitor how SGS affects the THz response of human skin during occlusion, and the associated THz reflectivity and refractive index changes are presented. We find that SGS effectively hydrates the skin beneath it, with minimal lateral effects beyond the sheeting. Our work demonstrates that THz imaging is able to detect the subtle hydration changes on the surface of human skin caused by SGS, and it has the potential to be used to evaluate different scar treatment strategies.

Design and fabrication of 3-D printed conductive polymer structures for THz polarization control.

In this paper, we numerically and experimentally demonstrate the inverse polarization effect in three-dimensional (3-D) printed polarizers for the frequency range of 0.5 - 2.7 THz. The polarizers simply consist of 3-D printed strip lines of conductive polylactic acid (CPLA, Proto-Pasta) and do not require a substrate or any further metallic deposition. The experimental and numerical results show that the proposed structure acts as a broadband polarizer between the range of 0.3 THz to 2.7 THz, in which the inverse polarization effect is clearly seen for frequencies above 0.5 THz. In the inverse polarization effect, the transmission of the transverse electric (TE) component exceeds that of the TM component, in contrast to the behavior of a typical wire-grid polarizer. We show how the performance of the polarizers depends on the spacing and thickness of the CPLA structure; extinction ratios higher than 20 dB are achieved. This is the first report using CPLA to fabricate THz polarizers, demonstrating the potential of using conductive polymers to design THz components efficiently and robustly.

Utilizing multilayer structures to enhance terahertz characterization of thin films ranging from aqueous solutions to histology slides.

We propose a multilayer geometry to characterize thin-film samples in reflection terahertz time domain spectroscopy. Theory indicates that this geometry has higher sensitivity compared to ordinary transmission or reflection geometries when characterizing both low- and high-absorption samples. Pure water and water-ethanol mixtures are measured to verify the characterization accuracy of the proposed geometry and its capability to measure trace liquids. Paraffin-embedded oral cancer tissue is imaged to further show how the proposed geometry enhances the sensitivity for solid low-absorptive films.

In vivo estimation of water diffusivity in occluded human skin using terahertz reflection spectroscopy.

Water diffusion and the concentration profile within the skin significantly affect the surrounding chemical absorption and molecular synthesis. Occluding the skin causes water to accumulate in the top layer of the skin (the stratum corneum [SC]) and also affects the water diffusivity. Scar treatments such as silicone gel and silicone sheets make use of occlusion to increase skin hydration. However with existing techniques, it is not possible to quantitatively measure the diffusivity of the water during occlusion: current methods determine water diffusivity by measuring the water evaporated through the skin and thus require the skin to breathe. In this work, we use the high sensitivity of terahertz light to water to study how the water content in the SC changes upon occlusion. From our measurements, we can solve the diffusion equations in the SC to deduce the water concentration profile in occluded skin and subsequently to determine the diffusivity. To our knowledge, this is the first work showing how the diffusivity of human skin can be measured during occlusion and we envisage this paper as being used as a guide for non-invasively determining the diffusivity of occluded human skin in vivo.

THz in vivo measurements: the effects of pressure on skin reflectivity.

Terahertz (THz) light is non-ionizing and highly sensitive to subtle changes in water concentration which can be indicative of disease. The short THz penetration depth in bio-samples restricts in vivo measurements to be in a reflection geometry and the sample is often placed onto an imaging window. Upon contacting the imaging window, occlusion and compression of the skin affect the THz response. If not appropriately controlled, this could cause misleading results. In this work, we investigate and quantify how the applied pressure affects the THz response of skin and employ a stratified model to help understand the mechanisms at play. This work will enable future THz studies to have a more rigorous experimental protocol, which in turn will facilitate research in various potential biomedical applications under investigation.

In vivo THz imaging of human skin: Accounting for occlusion effects.

In vivo terahertz (THz) imaging of human skin needs to be done in reflection geometry due to the high attenuation of THz light by water in the skin. To aid the measurement procedure, there is typically an imaging window onto which the patient places the area of interest. The window enables better pulse alignment and helps keep the patient correctly positioned during the measurement. In this paper, we demonstrate how the occlusion caused by the skin contact with the imaging window during the measurement affects the THz response. By studying both rapid point measurements and imaging over an area of a human volar forearm, we find that even 5 seconds of occlusion affects the THz response. As the occlusion time increases, the skin surface water content increases, resulting in the reduction of the amplitude of the reflected THz pulse, especially in the first 3 minutes. Furthermore, it was found that the refractive index of the volar forearm increased by 10% to 15% after 20 minutes of occlusion. In this work, we examine and propose a model for the occlusion effects due to the quartz window with a view to compensating for its influence.

Determination of terahertz permittivity of dehydrated biological samples.

A key step in transforming terahertz imaging to a practical medical imaging modality lies in understanding the interactions between terahertz (THz) waves and biological tissues. Most of the models in the literature use the permittivity of liquid water to simulate the THz-tissue interactions, but they often neglect contributions from the biological background such as proteins and lipids because dehydrated biological samples are experimentally difficult to prepare. In this work, we present a method to prepare thin and flat dehydrated samples which can be easily handled and measured in a transmission setup. Our results will provide fundamental parameters for modelling THz-tissue interactions.

Recent advances in terahertz technology for biomedical applications.

Terahertz instrumentation has improved significantly in recent years such that THz imaging systems have become more affordable and easier to use. THz systems can now be operated by non-THz experts greatly facilitating research into many potential applications. Due to the non-ionising nature of THz light and its high sensitivity to soft tissues, there is an increasing interest in biomedical applications including both in vivo and ex vivo studies. Additionally, research continues into understanding the origin of contrast and how to interpret terahertz biomedical images. This short review highlights some of the recent work in these areas and suggests some future research directions.