In vitro degradation, swelling, and bioactivity performances of in situ forming injectable chitosan-matrixed hydrogels for bone regeneration and drug delivery.

Injectable, tissue mimetic, bioactive, and biodegradable hydrogels offer less invasive regeneration and repair of tissues. The monitoring swelling and in vitro degradation capacities of hydrogels are highly important for drug delivery and tissue regeneration processes. Bioactivity of bone tissue engineered constructs in terms of mineralized apatite formation capacity is also pivotal. We have previously reported in situ forming chitosan-based injectable hydrogels integrated with hydroxyapatite and heparin for bone regeneration, promoting angiogenesis. These hydrogels were functionalized by glycerol and pH to improve their mechano-structural properties. In the present study, functionalized hybrid hydrogels were investigated for their swelling, in vitro degradation, and bioactivity performances. Hydrogels have degraded gradually in phosphate-buffered saline (PBS) with and without lysozyme enzyme. The percentage weight loss of hydrogels and their morphological and chemical properties, and pH of media were analyzed. The swelling ratio of hydrogels (55%-68%(wt), 6 h of equilibrium) indicated a high degree of cross-linking, can be suitable for controlled drug release. Hydrogels have gradually degraded reaching to 60%-70% (wt%) in 42 days in the presence and absence of lysozyme, respectively. Simulated body fluid (SBF)-treated hydrogels containing hydroxyapatite-induced needle-like carbonated-apatite mineralization was further enhanced by heparin content significantly.

Hydroxyapatite-Integrated, Heparin- and Glycerol-Functionalized Chitosan-Based Injectable Hydrogels with Improved Mechanical and Proangiogenic Performance.

The investigation of natural bioactive injectable composites to induce angiogenesis during bone regeneration has been a part of recent minimally invasive regenerative medicine strategies. Our previous study involved the development of in situ-forming injectable composite hydrogels (Chitosan/Hydroxyapatite/Heparin) for bone regeneration. These hydrogels offered facile rheology, injectability, and gelation at 37 °C, as well as promising pro-angiogenic abilities. In the current study, these hydrogels were modified using glycerol as an additive and a pre-sterile production strategy to enhance their mechanical strength. These modifications allowed a further pH increment during neutralisation with maintained solution homogeneity. The synergetic effect of the pH increment and further hydrogen bonding due to the added glycerol improved the strength of the hydrogels substantially. SEM analyses showed highly cross-linked hydrogels (from high-pH solutions) with a hierarchical interlocking pore morphology. Hydrogel solutions showed more elastic flow properties and incipient gelation times decreased to just 2 to 3 min at 37 °C. Toluidine blue assay and SEM analyses showed that heparin formed a coating at the top layer of the hydrogels which contributed anionic bioactive surface features. The chick chorioallantoic membrane (CAM) assay confirmed significant enhancement of angiogenesis with chitosan-matrixed hydrogels comprising hydroxyapatite and small quantities of heparin (33 µg/mL) compared to basic chitosan hydrogels.

Bioactive Composite for Orbital Floor Repair and Regeneration.

In the maxillofacial area, specifically the orbital floor, injuries can cause bone deformities in the head and face that are difficult to repair or regenerate. Treatment methodologies include use of polymers, metal, ceramics on their own and in combinations mainly for repair purposes, but little attention has been paid to identify suitable materials for orbital floor regeneration. Polyurethane (PU) and hydroxyapatite (HA) micro- or nano- sized with different percentages (25%, 40% & 60%) were used to fabricate bioactive tissue engineering (TE) scaffolds using solvent casting and particulate leaching methods. Mechanical and physical characterisation of TE scaffolds was investigated by tensile tests and SEM respectively. Chemical and structural properties of PU and PU/HA scaffolds were evaluated by infrared (IR) spectroscopy and Surface properties of the bioactive scaffold were analysed using attenuated total reflectance (ATR) sampling accessory coupled with IR. Cell viability, collagen formed, VEGF protein amount and vascularisation of bioactive TE scaffold were studied. IR characterisation confirmed the integration of HA in composite scaffolds, while ATR confirmed the significant amount of HA present at the top surface of the scaffold, which was a primary objective. The SEM images confirmed the pores' interconnectivity. Increasing the content of HA up to 40% led to an improvement in mechanical properties, and the incorporation of nano-HA was more promising than that of micro-HA. Cell viability assays (using MG63) confirmed biocompatibility and CAM assays confirmed vascularization, demonstrating that HA enhances vascularization. These properties make the resulting biomaterials very useful for orbital floor repair and regeneration.

In-Situ Forming pH and Thermosensitive Injectable Hydrogels to Stimulate Angiogenesis: Potential Candidates for Fast Bone Regeneration Applications.

Biomaterials that promote angiogenesis are required for repair and regeneration of bone. In-situ formed injectable hydrogels functionalised with bioactive agents, facilitating angiogenesis have high demand for bone regeneration. In this study, pH and thermosensitive hydrogels based on chitosan (CS) and hydroxyapatite (HA) composite materials loaded with heparin (Hep) were investigated for their pro-angiogenic potential. Hydrogel formulations with varying Hep concentrations were prepared by sol-gel technique for these homogeneous solutions were neutralised with sodium bicarbonate (NaHCO3) at 4 °C. Solutions (CS/HA/Hep) constituted hydrogels setting at 37 °C which was initiated from surface in 5-10 minutes. Hydrogels were characterised by performing injectability, gelation, rheology, morphology, chemical and biological analyses. Hydrogel solutions facilitated manual dropwise injection from 21 Gauge which is highly used for orthopaedic and dental administrations, and the maximum injection force measured through 19 G needle (17.191 ± 2.296N) was convenient for manual injections. Angiogenesis tests were performed by an ex-ovo chick chorioallantoic membrane (CAM) assay by applying injectable solutions on CAM, which produced in situ hydrogels. Hydrogels induced microvascularity in CAM assay this was confirmed by histology analyses. Hydrogels with lower concentration of Hep showed more efficiency in pro-angiogenic response. Thereof, novel injectable hydrogels inducing angiogenesis (CS/HA/Hep) are potential candidates for bone regeneration and drug delivery applications.

Auxetic oesophageal stents: structure and mechanical properties.

Oesophageal cancer is the ninth leading cause of malignant cancer death and its prognosis remains poor, ranking as the sixth most frequent cause of death in the world. This research work aims to adopt an Auxetic (rotating-squares) geometry device, that had previously been examined theoretically and analysed by Grima and Evans (J Mater Sci Lett 19(17):1563-1565, 2000), to produce a novel Auxetic oesophageal stent and stent-grafts relevant to the palliative treatment of oesophageal cancer and also for the prevention of dysphagia. This paper discusses the manufacture of a small diameter Auxetic oesophageal stent and stent-graft. The oral deployment of such an Auxetic stent would be simplest if a commercial balloon dilatational catheter was used as this obviates the need for an expensive dedicated delivery system. A novel manufacturing route was employed in this research to develop both Auxetic films and Auxetic oesophageal stents, which ranged from conventional subtractive techniques to a new additive manufacturing method. Polyurethane was selected as a material for the fabrication of Auxetic films and Auxetic oesophageal stents because of its good biocompatibility and non-toxicological properties. The Auxetic films were later used for the fabrication of seamed Auxetic oesophageal stents. The flexible polyurethane tubular grafts were also attached to the inner luminal side of the seamless Auxetic oesophageal stents, in order to prevent tumour in-growth. Scanning electron microscopy was used to conduct surface morphology study by using different Auxetic specimens developed from different conventional and new additive manufacturing techniques. Tensile testing of the Auxetic films was performed to characterise their mechanical properties. The stent expansion tests of the Auxetic stents were done to analyse the longitudinal extension and radial expansion of the Auxetic stent at a range of radial pressures applied by the balloon catheter, and to also identify the pressure values where the Auxetic stent fails. Finite element models of both Auxetic film and Auxetic stent were developed, and the results were compared with experimental results with a good agreement. The tensile testing of the Auxetic polyurethane films revealed that the Poisson's ratio of the sample ranged between -0.87 and -0.963 at different uniaxial tensile load values. From the stent expansion test, it was found that the Auxetic oesophageal stent radially expanded from 0.5 to 5.73 mm and longitudinally extended from 0.15 to 1.83 mm at a range of applied pressure increments (0.5-2.7 bar) from the balloon catheter.

Study of the Structure of Hyperbranched Polyglycerol Coatings and Their Antibiofouling and Antithrombotic Applications.

While blood-contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings. Herein, a novel but simple strategy is described for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma-grafting of an ultrathin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O─C─O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface. In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3 log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG-coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice shows no evidence of toxicity nor inflammation.

Advancing cervical cancer diagnosis and screening with spectroscopy and machine learning.

INTRODUCTION: In the UK alone, the incidence of cervical cancer is increasing, hence an urgent need for early and rapid detection of cancer before it develops. Spectroscopy in conjunction with machine learning offers a disruptive technology that promises to pick up cancer early as compared to the current diagnostic techniques used. AREAS COVERED: This review article explores the different spectroscopy techniques that have been used for the analysis of cervical cancer. Along with the extensive description of spectroscopic techniques, the various machine learning techniques are also described as well as the applications that have been explored in the diagnosis of cervical cancer. This review delimits the literature specifically associated with cervical cancer studies performed solely with the use of a spectroscopy technique, and machine learning. EXPERT OPINION: Although there are several methods and techniques to detect cervical cancer, the clinical sector requires to introduce new diagnostic technologies that help improve the quality of life of patients. These innovative technologies involve spectroscopy as a qualitative method and machine learning as a quantitative method. In this article, both the techniques and methodologies that allow and promise to be a new screening tool for the detection of cervical cancer are covered.

Investigating the chemical pathway to the formation of a single biofilm using infrared spectroscopy.

Diagnosing biofilm infections has remained a constant challenge for the last 50 years. Existing diagnostic methods struggle to identify the biofilm phenotype. Moreover, most methods of biofilm analysis destroy the biofilm making the resultant data interpretation difficult. In this study we introduce Fourier Transform Infra-Red (FTIR) spectroscopy as a label-free, non-destructive approach to monitoring biofilm progression. We have utilised FTIR in a novel application to evaluate the chemical composition of bacterial biofilms without disrupting the biofilm architecture. S. epidermidis (RP62A) was grown onto calcium fluoride slides for periods of 30 min-96 h, before semi-drying samples for analysis. We report the discovery of a chemical marker to distinguish between planktonic and biofilm samples. The appearance of new proteins in biofilm samples of varying maturity is exemplified in the spectroscopic data, highlighting the potential of FTIR for identifying the presence and developmental stage of a single biofilm.

Global serum profiling: an opportunity for earlier cancer detection.

The advances in cancer research achieved in the last 50 years have been remarkable and have provided a deeper knowledge of this disease in many of its conceptual and biochemical aspects. From viewing a tumor as a 'simple' aggregate of mutant cells and focusing on detecting key cell changes leading to the tumorigenesis, the understanding of cancer has broadened to consider it as a complex organ interacting with its close and far surroundings through tumor and non-tumor cells, metabolic mechanisms, and immune processes. Metabolism and the immune system have been linked to tumorigenesis and malignancy progression along with cancer-specific genetic mutations. However, most technologies developed to overcome the barriers to earlier detection are focused solely on genetic information. The concept of cancer as a complex organ has led to research on other analytical techniques, with the quest of finding a more sensitive and cost-effective comprehensive approach. Furthermore, artificial intelligence has gained broader consensus in the oncology community as a powerful tool with the potential to revolutionize cancer diagnosis for physicians. We herein explore the relevance of the concept of cancer as a complex organ interacting with the bodily surroundings, and focus on promising emerging technologies seeking to diagnose cancer earlier, such as liquid biopsies. We highlight the importance of a comprehensive approach to encompass all the tumor and non-tumor derived information salient to earlier cancer detection.

Infrared Spectroscopy of Urine for the Non-Invasive Detection of Endometrial Cancer.

Current triage for women with post-menopausal bleeding (PMB) to diagnose endometrial cancer rely on specialist referral for intimate tests to sequentially image, visualise and sample the endometrium. A point-of-care non-invasive triage tool with an instant readout could provide immediate reassurance for low-risk symptomatic women, whilst fast-tracking high-risk women for urgent intrauterine investigations. This study assessed the potential for infrared (IR) spectroscopy and attenuated total reflection (ATR) technology coupled with chemometric analysis of the resulting spectra for endometrial cancer detection in urine samples. Standardised urine collection and processing protocols were developed to ensure spectroscopic differences between cases and controls reflected cancer status. Urine spectroscopy distinguished endometrial cancer (n = 109) from benign gynaecological conditions (n = 110) with a sensitivity of 98% and specificity of 97%. If confirmed in subsequent low prevalence studies embedded in PMB clinics, this novel endometrial cancer detection tool could transform clinical practice by accurately selecting women with malignant pathology for urgent diagnostic work up whilst safely reassuring those without.

Dietary flavonoids inhibit the anticancer effects of the proteasome inhibitor bortezomib.

Dietary flavonoids have many health-promoting actions, including anticancer activity via proteasome inhibition. Bor-tezomib is a dipeptide boronate proteasome inhibitor that has activity in the treatment of multiple myeloma but is not effective in chronic lymphocytic leukemia (CLL). Although CLL cells are sensitive in vitro to bortezomib-induced apoptosis when cultured in medium, the killing activity was blocked when cultured in 50% fresh autologous plasma. Dietary flavonoids, quercetin and myricetin, which are abundant in plasma, inhibited bortezomib-induced apoptosis of primary CLL and malignant B-cell lines in a dose-dependent manner. This inhibitory effect was associated with chemical reactions between quercetin and the boronic acid group, -RB(OH)2, in bortezomib. The addition of boric acid diminished the inhibitory effect of both quercetin and plasma on bortezomib-induced apoptosis. The protective effect was also reduced when myeloma cell lines, but not B-cell lines, were preincubated with quercetin, indicating a direct effect of quercetin on myeloma cells. At high doses, quercetin itself induced tumor cell death. These data indicate that dietary flavonoids limit the efficacy of bortezomib, whereas supplemental inorganic boric acid is able to reverse this. The complex interactions between quercetin, tumor cells, and bortezomib mean caution is required when giving dietary advice to patients.

Role of artificial intelligence and vibrational spectroscopy in cancer diagnostics.

INTRODUCTION: Raman and Infrared spectroscopic techniques are being used for the analysis of different types of cancers and other biological molecules. It is possible to identify cancers from normal tissues both in fresh and fixed tissues. These techniques can be used not only for the early diagnosis of cancer but also for monitoring the progression of the disease. Furthermore, chemical pathways to the progression of the disease process can be understood and followed. AREAS COVERED: More recently, Artificial Intelligence (AI), Neural Network (NN), and Machine Learning are being combined with spectroscopy, which is making it easier to understand the chemical structural details of cancers and biological molecules more precisely and accurately. In this report, these aspects are being outlined by using breast cancer as a specific example. EXPERT OPINION: A pathway showing to combine vibrational spectroscopy with AI and ML has immense potential in predicting various stages of different disease processes, in particular, in cancer diagnosis, staging, and designing treatment. This will result in improved patient care pathways.

Synthesis and characterisation of enhanced barrier polyurethane for encapsulation of implantable medical devices.

Polymeric membranes have been used as interfaces between implantable devices and biological tissues to operate as a protective barrier from water exchanging and to enhance biocompatibility. Polyurethanes have been used as biocompatible membranes for decades. In this study, copolymers of polyether urethane (PEU) with polydimethylsiloxane (PDMS) were synthesised with the goal of creating materials with low water permeability and high elasticity. PDMS was incorporated into polymer backbone as a part of the soft segment during polyurethane synthesis and physical properties as well as water permeability of resulting copolymer were studied in regard to PDMS content. Increase in PDMS content led to increase of microphase separation of the copolymer and corresponding increase in elastic modulus. Surface energy of the polymer was decreased by incorporating PDMS compared to unmodified PEU. PDMS in copolymer formed a hydrophobic surface which caused reduction in water permeability and water uptake of the membranes. Thus, PDMS containing polyurethane with its potent water resistant properties demonstrated a great promise for use as an implantable encapsulation material.

Advancing cancer diagnostics with artificial intelligence and spectroscopy: identifying chemical changes associated with breast cancer.

Background: Artificial intelligence (AI) and machine learning (ML) approaches in combination with Raman spectroscopy (RS) to obtain accurate medical diagnosis and decision-making is a way forward for understanding not only the chemical pathway to the progression of disease, but also for tailor-made personalized medicine. These processes remove unwanted affects in the spectra such as noise, fluorescence and normalization, and help in the optimization of spectral data by employing chemometrics. Methods: In this study, breast cancer tissues have been analyzed by RS in conjunction with principal component (PCA) and linear discriminate (LDA) analyses. Tissue microarray (TMA) breast biopsies were investigated using RS and chemometric methods and classified breast biopsies into luminal A, luminal B, HER2, and triple negative subtypes. Results: Supervised and unsupervised algorithms were applied on biopsy data to explore intra and inter data set biochemical changes associated with lipids, collagen, and nucleic acid content. LDA predicted specificity accuracy of luminal A, luminal B, HER2, and triple negative subtypes were 70%, 100%, 90%, and 96.7%, respectively. Conclusion: It is envisaged that a combination of RS with AI and ML may create a precise and accurate real-time methodology for cancer diagnosis and monitoring.

Characterization and drug release investigation of amorphous drug-hydroxypropyl methylcellulose composites made via supercritical carbon dioxide assisted impregnation.

Hydroxypropylmethyl cellulose (HPMC)-indomethacin (4:1, w/w) drug composites (DCs) were prepared via supercritical carbon dioxide (sc-CO(2)) assisted impregnation. The effect of processing temperature (at fixed pressures) on the physical and other properties of the resulting HPMC-indomethacin DCs was investigated using a range of analytical techniques, including differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and powder X-ray diffraction (XRD) methods. The data suggest that for a 4:1 (w/w) HPMC-indomethacin ratio prepared at 130 degrees C (17.2 MPa), the indomethacin exists entirely in an amorphous dispersion within the polymer matrix. The primary interaction between HPMC and indomethacin appears to be hydrogen bonding between the carboxylic acid carbonyl group of indomethacin and hydroxyl group of HPMC. The initial (first 15 min) and overall drug release behavior within a 5h timeframe for the HPMC-indomethacin DCs, was analyzed. For the HPMC-indomethacin drug composite processed at 130 degrees C/17.2 MPa, drug release behavior obeyed a n-power law (n=0.54).

Modification of conventional glass-ionomer cements with N-vinylpyrrolidone containing polyacids, nano-hydroxy and fluoroapatite to improve mechanical properties.

OBJECTIVE: The objective of this study was to enhance the mechanical strength of glass-ionomer cements, while preserving their unique clinical properties. METHODS: Copolymers incorporating several different segments including N-vinylpyrrolidone (NVP) in different molar ratios were synthesized. The synthesized polymers were copolymers of acrylic acid and NVP with side chains containing itaconic acid. In addition, nano-hydroxyapatite and fluoroapatite were synthesized using an ethanol-based sol-gel technique. The synthesized polymers were used in glass-ionomer cement formulations (Fuji II commercial GIC) and the synthesized nanoceramic particles (nano-hydroxy or fluoroapatite) were also incorporated into commercial glass-ionomer powder, respectively. The synthesized materials were characterized using FTIR and Raman spectroscopy and scanning electron microscopy. Compressive, diametral tensile and biaxial flexural strengths of the modified glass-ionomer cements were evaluated. RESULTS: After 24h setting, the NVP modified glass-ionomer cements exhibited higher compressive strength (163-167 MPa), higher diametral tensile strength (DTS) (13-17 MPa) and much higher biaxial flexural strength (23-26 MPa) in comparison to Fuji II GIC (160 MPa in CS, 12MPa in DTS and 15 MPa in biaxial flexural strength). The nano-hydroxyapatite/fluoroapatite added cements also exhibited higher CS (177-179 MPa), higher DTS (19-20 MPa) and much higher biaxial flexural strength (28-30 MPa) as compared to the control group. The highest values for CS, DTS and BFS were found for NVP-nanoceramic powder modified cements (184 MPa for CS, 22 MPa for DTS and 33 MPa for BFS) which were statistically higher than control group. CONCLUSION: It was concluded that, both NVP modified and nano-HA/FA added glass-ionomer cements are promising restorative dental materials with improved mechanical properties.

Synthesis of N-vinylpyrrolidone modified acrylic acid copolymer in supercritical fluids and its application in dental glass-ionomer cements.

Compressed fluids such as supercritical CO(2) offer marvellous opportunities for the synthesis of polymers, particularly in applications in medicine and dentistry. It has several advantages in comparison to conventional polymerisation solvents, such as enhanced kinetics and simplified solvent removal process. In this study, poly(acrylic acid-co-itaconic acid-co-N-vinylpyrrolidone) (PAA-IA-NVP), a modified glass-ionomer polymer, was synthesised in supercritical CO(2) (sc-CO(2)) and methanol as a co-solvent. The synthesised polymer was characterized by (1)H-NMR, Raman and FT-IR spectroscopy and viscometry. The molecular weight of the final product was also measured using static light scattering method. The synthesised polymers were subsequently used in several glass ionomer cement formulations (Fuji II commercial GIC) in which mechanical strength (compressive strength (CS), diametral tensile strength (DTS) and biaxial flexural strength (BFS)) and handling properties (working and setting time) of the resulting cements were evaluated. The polymerisation reaction in sc-CO(2)/methanol was significantly faster than the corresponding polymerisation reaction in water and the purification procedures were simpler for the former. Furthermore, glass ionomer cement samples made from the terpolymer prepared in sc-CO(2)/methanol exhibited higher CS and DTS and comparable BFS compared to the same polymer synthesised in water. The working properties of glass ionomer formulations made in sc-CO(2)/methanol were comparable and in selected cases better than the values of those made from polymers synthesised in water.

Role of Salivary Biomarkers in Oral Cancer Detection.

Oral cancers are the sixth most frequent cancer with a high mortality rate. Oral squamous cell carcinoma accounts for more than 90% of all oral cancers. Standard methods used to detect oral cancers remain comprehensive clinical examination, expensive biochemical investigations, and invasive biopsy. The identification of biomarkers from biological fluids (blood, urine, saliva) has the potential of early diagnosis. The use of saliva for early cancer detection in the search for new clinical markers is a promising approach because of its noninvasive sampling and easy collection methods. Human whole-mouth saliva contains proteins, peptides, electrolytes, organic, and inorganic salts secreted by salivary glands and complimentary contributions from gingival crevicular fluids and mucosal transudates. This diagnostic modality in the field of molecular biology has led to the discovery and potential of salivary biomarkers for the detection of oral cancers. Biomarkers are the molecular signatures and indicators of normal biological, pathological process, and pharmacological response to treatment hence may provide useful information for detection, diagnosis, and prognosis of the disease. Saliva's direct contact with oral cancer lesions makes it more specific and potentially sensitive screening tool, whereas more than 100 salivary biomarkers (DNA, RNA, mRNA, protein markers) have already been identified, including cytokines (IL-8, IL-1b, TNF-α), defensin-1, P53, Cyfra 21-1, tissue polypeptide-specific antigen, dual specificity phosphatase, spermidine/spermineN1-acetyltransferase , profilin, cofilin-1, transferrin, and many more. However, further research is still required for the reliability and validation of salivary biomarkers for clinical applications. This chapter provides the latest up-to-date list of known and emerging potential salivary biomarkers for early diagnosis of oral premalignant and cancerous lesions and monitoring of disease activity.

Raman spectroscopy can discriminate between normal, dysplastic and cancerous oral mucosa: a tissue-engineering approach.

Head and neck cancer (HNC) is the sixth most common malignancy worldwide. Squamous cell carcinoma, the primary cause of HNC, evolves from normal epithelium through dysplasia before invading the connective tissue to form a carcinoma. However, less than 18% of suspicious oral lesions progress to cancer, with diagnosis currently relying on histopathological evaluation, which is invasive and time consuming. A non-invasive, real-time, point-of-care method could overcome these problems and facilitate regular screening. Raman spectroscopy is a non-invasive optical technique with the ability to extract molecular level information to help determine the functional groups present in a tissue and the molecular conformations of tissue constituents. In the present study, Raman spectroscopy was assessed for its ability to discriminate between normal, dysplastic and HNC. Tissue engineered models of normal, dysplastic and HNC were constructed using normal oral keratinocytes, dysplastic and HNC cell lines, and their biochemical content predicted by interpretation of spectral characteristics. Spectral differences were evident in both the fingerprint (600/cm to 1800/cm) and high wave-number compartments (2800/cm to 3400/cm). Visible differences were seen in peaks relating to lipid content (2881/cm), protein structure (amide I, amide III), several amino acids and nucleic acids (600/cm to 1003/cm). Multivariate data analysis algorithms successfully identified subtypes of dysplasia and cancer, suggesting that Raman spectroscopy not only has the potential to differentiate between normal, pre-malignant and cancerous tissue models but could also be sensitive enough to detect subtypes of dysplasia or cancer on the basis of their subcellular differences. Copyright © 2016 John Wiley & Sons, Ltd.

Mapping Nanostructural Variations in Silk by Secondary Electron Hyperspectral Imaging.

Nanostructures underpin the excellent properties of silk. Although the bulk nanocomposition of silks is well studied, direct evidence of the spatial variation of nanocrystalline (ordered) and amorphous (disordered) structures remains elusive. Here, secondary electron hyperspectral imaging can be exploited for direct imaging of hierarchical structures in carbon-based materials, which cannot be revealed by any other standard characterization methods. Through applying this technique to silks from domesticated (Bombyx mori) and wild (Antheraea mylitta) silkworms, a variety of previously unseen features are reported, highlighting the local interplay between ordered and disordered structures. This technique is able to differentiate composition on the nanoscale and enables in-depth studies into the relationship between morphology and performance of these complex biopolymer systems.