The dentist's role within the multi-disciplinary team maintaining quality of life for oral cancer patients in light of recent advances in radiotherapy.

Every year in Ireland over 400 people are diagnosed with head and neck cancer. Oral cancer, a specific type of head and neck cancer, is usually treated with surgery and often requires radiotherapy (RT). However, side effects of RT treatment, which include mucositis, xerostomia, radiation caries, trismus and osteoradionecrosis, can seriously compromise a patient's quality of life. Treatment for oral cancer patients is managed in a multidisciplinary team. General dental practitioners (GDPs), consultant/specialist dentists and oral-maxillofacial surgeons play an important role in these patients' care. Recent advances in the delivery of RT have not only improved locoregional control and survival rates, but have also reduced the incidence and severity of RT-associated side effects; however, no mode of RT delivery has successfully eliminated side effects. The role of dentists is essential in maintaining oral health and all patients should be dentally screened prior to commencing RT. Recent reports have attempted to standardise the quality of care for the oral cancer patient and have highlighted the significance of the role of the GDP. Despite the advancements in RT delivery, the dental team is still faced with a number of challenges, including the high number of patients lost to follow-up dental care, lack of an effective treatment for xerostomia, poor patient compliance, and a lack of standardised guidelines and funding. Addressing these challenges will involve increased communication between all members of the multidisciplinary team and increased involvement of the GDP, thereby ensuring that dental care continues to evolve concurrently with new methods of RT delivery.

The effect of cholecyst-derived extracellular matrix on the phenotypic behaviour of valvular endothelial and valvular interstitial cells.

Cholecyst-derived extracellular matrix (CEM) is a novel, proteinaceous biomaterial, derived from the porcine cholecyst, which may have potential applications as a scaffold in the area of heart valve tissue engineering. In this study the potential of CEM to support the proliferation of valvular endothelial cells (VECs) and valvular interstitial cells (VICs), while maintaining their phenotypic mRNA synthesis, protein expression and morphology was assessed by biochemical assays, electron microscopy, immunostaining and reverse-transcriptase polymerase chain reaction. VICs and VECs were isolated from the porcine aortic valve and techniques were developed for the isolation of CEM for cell culture. VECs and VICs cultured on CEM adhered and proliferated, maintaining their phenotypic morphology. VECs synthesised von Willebrand factor mRNA and endothelial nitric oxide synthase (eNOS) mRNA and expressed eNOS and VICs synthesised alpha-smooth muscle actin (alphaSMA) mRNA and expressed alphaSMA. Cellular area fraction of VICs expressing alphaSMA was 87.7+/-6.8% and cellular area fraction of VECs expressing eNOS was 93.8+/-9.3%. Findings of this study support the hypothesis that CEM is a potential biomaterial for tissue engineered heart valve scaffold design.

Biaxial mechanical evaluation of cholecyst-derived extracellular matrix: a weakly anisotropic potential tissue engineered biomaterial.

A new acellular, natural, biodegradable matrix has been discovered in the cholecyst-derived extracellular matrix (CEM). This matrix is rich in collagen and contains several other macromolecules useful in tissue remodeling. In this study, the principal material axes, collagen fiber orientations, and biaxial mechanical properties in a physiological loading regime were characterized. Fiber direction was determined by polarized light microscopy, and the principal axes and degree of anisotropy were determined mechanically. Macroscopic equibiaxial strain tests were then conducted on preconditioned specimens. While 13% of the area of CEM contains collagen fibers oriented between 50 degrees and 60 degrees from the neck-fundus axis, the principal material axis was oriented 63 degrees +/- 13.7 degrees , with an aspect ratio of 0.11 +/- 0.06, indicating a weak anisotropy in that direction. Under biaxial loading, CEM exhibited a large toe region followed by an exponential rise in stress in both principal and perpendicular axis directions, similar to other materials currently under research. There was no significant difference between the biaxial stress-strain profile and the burst stress-strain profile. The results demonstrate that CEM is weakly anisotropic and it has the ability to support large strains across a physiological loading regime.

Approaches to heart valve tissue engineering scaffold design.

Heart valve disease is a significant cause of mortality worldwide. However, to date, a nonthrombogenic, noncalcific prosthetic, which maintains normal valve mechanical properties and hemodynamic flow, and exhibits sufficient fatigue properties has not been designed. Current prosthetic designs have not been optimized and are unsuitable treatment for congenital heart defects. Research is therefore moving towards the development of a tissue engineered heart valve equivalent. Two approaches may be used in the creation of a tissue engineered heart valve, the traditional approach, which involves seeding a scaffold in vitro, in the presence of specific signals prior to implantation, and the guided tissue regeneration approach, which relies on autologous reseeding in vivo. Regardless of the approach taken, the design of a scaffold capable of supporting the growth of cells and extracellular matrix generation and capable of withstanding the unrelenting cardiovascular environment while forming a tight seal during closure, is critical to the success of the tissue engineered construct. This paper focuses on the quest to design, such a scaffold.

Characterizing nanoscale topography of the aortic heart valve basement membrane for tissue engineering heart valve scaffold design.

A fully effective prosthetic heart valve has not yet been developed. A successful tissue-engineered valve prosthetic must contain a scaffold that fully supports valve endothelial cell function. Recently, topographic features of scaffolds have been shown to influence the behavior of a variety of cell types and should be considered in rational scaffold design and fabrication. The basement membrane of the aortic valve endothelium provides important parameters for tissue engineering scaffold design. This study presents a quantitative characterization of the topographic features of the native aortic valve endothelial basement membrane; topographical features were measured, and quantitative data were generated using scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and light microscopy. Optimal conditions for basement membrane isolation were established. Histological, immunohistochemical, and TEM analyses following decellularization confirmed basement membrane integrity. SEM and AFM photomicrographs of isolated basement membrane were captured and quantitatively analyzed. The basement membrane of the aortic valve has a rich, felt-like, 3-D nanoscale topography, consisting of pores, fibers, and elevations. All features measured were in the sub-100 nm range. No statistical difference was found between the fibrosal and ventricular surfaces of the cusp. These data provide a rational starting point for the design of extracellular scaffolds with nanoscale topographic features that mimic those found in the native aortic heart valve basement membrane.

Scaffold with a natural mesh-like architecture: isolation, structural, and in vitro characterization.

An intact extracellular matrix (ECM) with a mesh-like architecture has been identified in the peri-muscular sub-serosal connective tissue (PSCT) of cholecyst (gallbladder). The PSCT layer of cholecyst wall is isolated by mechanical delamination of other layers and decellularized with a treatment with peracetic acid and ethanol solution (PES) in water to obtain the final matrix, which is referred to as cholecyst-derived ECM (CEM). CEM is cross-linked with different concentrations of glutaraldehyde (GA) to demonstrate that the susceptibility of CEM to degradation can be controlled. Quantitative and qualitative macromolecular composition assessments revealed that collagen is the primary structural component of CEM. Elastin is also present. In addition, the ultra-structural studies on CEM reveal the presence of a three-dimensional fibrous mesh-like network structure with similar nanoscale architecture on both mucosal and serosal surfaces. In vitro cell culture studies show that CEM provides a supporting structure for the attachment and proliferation of murine fibroblasts (3T3) and human umbilical vein endothelial cells (HUVEC). CEM is also shown to support the attachment and differentiation of rat adrenal pheochromocytoma cells (PC12).