Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Design and Development of a Synthetic POSS-Nanocomposite Implant for Auricular Reconstruction

Auricular reconstruction using sculpted autologous costal cartilage following congenital microtia, trauma and cancer is effective, but complex, time consuming and may incur donor site morbidity. Current conventional synthetic alternatives are associated with infection and extrusion. A novel nanocomposite polymer based on polyhedral oligomeric silsesquioxane (POSS) covalently bonded to poly(carbonate-urea-urethane) (PCU), has developed and patented in our laboratory and displayed promising clinical applications in first-in-human. POSS-PCU has been utilised to develop synthetic 3D auricle construct for use as auricular cartilage replacement, which aims to reduce extrusion rates by mimicking the mechanical properties of human ears and by encouraging desirable cellular interactions. Methods & Material: A novel custom-made ear-shaped 3D negative glass-mould was fabricated from positive 3D-printing ear model of a CT scan obtained from the external part of the human ear. This glass-mould was used to manufacture 3D auricular scaffolds using POSS-PCU materials. Two novel fabrication techniques solvent-evaporation/porogen-leaching (POSS-PCUs) and phase-separation/porogen-leaching (POSS-PCUc) were developed to produce nanocomposite scaffolds. The fabrication, physicochemical properties (including nanoscale topography) and in-vitro cellular interactions of these novel fabricated nanocomposites were extensively studied and compared to current commercially available synthetic material (Medpor®). Further cell-material interactions were completed on the optimized POSS-PCUs and Medpor® to examine the angiogenic and inflammatory responses to these materials using human fibroblasts and macrophages. Finally, POSS-PCUs scaffolds with two different pore sizes ranging from 50-100µm & 150-250µm were subcutaneously evaluated compared with Medpor® in-vivo in a rodent model for up-to 3 months. Results: The glass-mould design using 3D-printing technology allowed the manufacture of customised auricular POSS-PCU scaffolds that replicated the original human auricle. Two different polymeric fabrication methods resulted in the production of two types of nanocomposite scaffolds with same average pore size (150µm) but different porosity (63.47±1.35% in POSS-PCUs & 85.21±1.19% in POSS-PCUc). POSS-PCUs had similar elastic modulus (5.73±0.17 MPa) to human ear cartilage (5.02±0.17 MPa) compared with POSS-PCUc (0.58±0.12 MPa) and Medpor® (140.9±0.04 MPa) elastic modulus which were significantly different (P<0.001). Optimised POSS-PCUs nanocompoiste showed greater protein adsorption, and subsequently increased fibroblast adhesion, growth, and collagen production in vitro, compared to Medpor®. A higher volume fraction of fibrotic tissue ingrowth with negligible capsular formation was achieved in vivo in POSS-PCUs with pore-sizes of 150-250µm than Medpor®. No evidence of chronic inflammation was observed in the implanted scaffolds. Conclusion: These findings as well as other clinical studies in man suggest that POSS-PCUs nanocomposite can be a promising biomaterial for auricular reconstruction

A national follow-up survey of UK graduates opinion of undergraduate oral surgery teaching

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Introduction: A national follow-up survey was undertaken to determine whether dental graduates from 2009 perceived that their undergraduate oral surgery education had equipped them for general dental practice 4 years after graduating. Materials and Methods: Graduates from the same 13 United Kingdom dental schools who had taken part in the original survey were invited to take part in this follow-up online survey. Their contact details were identified via the general dental council register, social media and alumni groups. Results: In total, 161 responded (2009b) which represents 16% of the graduates of the original survey in 2009a. A similar percentage of these respondents perceived that the teaching in oral surgery had given them sufficient knowledge to undertake independent practice (83% and 79% in 2009a and 2009b, respectively). Most respondents (99% in both years) reported confidence in undertaking simple forceps exodontia. Confidence in surgical exodontia was poor in both surveys, but one area that appeared improved in the follow-up related to the sectioning of teeth (84% in 2009b compared with 49% in 2009a). Areas of weakness identified in 2009 were reported to be improved in the follow-up. Conclusion: This follow-up survey supports the findings of the original survey. Future longitudinal studies would allow institutions to identify possible weaknesses in their curriculum and to track the career development of their graduates and facilitate robust data collection.Link_to_subscribed_fulltex