Comparison of the compressive mechanical properties of auricular and costal cartilage from patients with microtia.

Children born with a small or absent ears undergo surgical reconstruction to restore their auricle. Currently, rib (costal) cartilage is used to carve the auricle. However as alternative, tissue engineered and synthetic materials are being developed to restore the auricle shape to overcome donor site morbidity and limited availability of rib cartilage. However, to date there is limited knowledge regarding the mechanical properties of the auricular and costal cartilage to optimise the required compressive properties of the graft. The remnant auricular and costal cartilage from 20 patients undergoing stage-1 microtia surgery was harvested. On the day of surgery, the cartilage was evaluated in compression, with each sample loaded to 300 g at 1 mm/s. RESULTS: The costal cartilage was observed to have a significantly higher Young's Elastic Modulus than auricular cartilage (average costal cartilage 11.43 MPa vs average auricular cartilage 2 MPa, p < 0.0001). The auricular cartilage showed a significantly higher relaxation rate than costal cartilage (average costal cartilage 0.72 MPa10-4 vs average auricular cartilage 1.93 MPa10-4, p < 0.05). The final absolute relaxation was significantly lower for elastic cartilage than costal cartilage (average costal cartilage 3.35 MPa vs average auricular cartilage 0.2 MPa, p < 0.0001). Alloplastic cartilage replacements used as alternatives for reconstruction were also evaluated. Silicone, Gore-Tex and Medpor were observed to have significantly higher Young's Elastic Modulus than costal and auricular cartilage. Costal cartilage has a higher Young's Elastic Modulus in compression compared to auricular cartilage. Current synthetic materials used to replace synthetic cartilage do not mimic costal cartilage, which should be addressed in the future.

Adipose derived stem cells and platelet rich plasma improve the tissue integration and angiogenesis of biodegradable scaffolds for soft tissue regeneration.

Current surgical reconstruction for soft tissue replacement involves lipotransfer to restore soft tissue replacements but is limited by survival and longevity of the fat tissue. Alternative approaches to overcome these limitations include using biodegradable scaffolds with stem cells with growth factors to generate soft tissue. Adipose derived stem cells (ADSCs) offer great potential to differentiate into adipose, and can be delivered using biodegradable scaffolds. However, the optimal scaffold to maximise this approach is unknown. This study investigates the biocompatibility of nanocomposite scaffolds (POSS-PCL) to deliver ADSCs with and without the addition of growth factors using platelet rich plasma (PRP) in vivo. Rat ADSCs were isolated and then seeded on biodegradable scaffolds (POSS-PCL). In addition, donor rats were used to isolate PRP to modify the scaffolds. The implants were then subcutaneously implanted for 3-months to assess the effect of PRP and ADSC on POSS-PCL scaffolds biocompatibility. Histology after explanation was examined to assess tissue integration (H&E) and collagen production (Massons Trichome). Immunohistochemistry was used to assess angiogenesis (CD3, α-SMA), immune response (CD45, CD68) and adipose formation (PPAR-γ). At 3-months PRP-ADSC-POSS-PCL scaffolds demonstrated significantly increased tissue integration and angiogenesis compared to PRP, ADSC and unmodified scaffolds (p < 0.05). In addition, PRP-ADSC-POSS-PCL scaffolds showed similar levels of CD45 and CD68 staining compared to unmodified scaffolds. Furthermore, there was increased PPAR-γ staining demonstrated at 3-months with PRP-ADSC-POSS-PCL scaffolds (p < 0.05). POSS-PCL nanocomposite scaffolds provide an effective delivery system for ADSCs. PRP and ADSC work synergistically to enhance the biocompatibility of POSS-PCL scaffolds and provide a platform technology for soft tissue regeneration.

Argon plasma surface modification promotes the therapeutic angiogenesis and tissue formation of tissue-engineered scaffolds in vivo by adipose-derived stem cells.

BACKGROUND: Synthetic implants are being used to restore injured or damaged tissues following cancer resection and congenital diseases. However, the survival of large tissue implant replacements depends on their ability to support angiogenesis that if limited, causes extrusion and infection of the implant. This study assessed the beneficial effect of platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) on synthetic biomaterials in combination with argon plasma surface modification to enhance vascularisation of tissue-engineered constructs. METHODS: Non-biodegradable polyurethane scaffolds were manufactured and modified with plasma surface modification using argon gas (PM). Donor rats were then used to extract ADSCs and PRP to modify the scaffolds further. Scaffolds with and without PM were modified with and without ADSCs and PRP and subcutaneously implanted in the dorsum of rats for 3 months. After 12 weeks, the scaffolds were excised and the degree of tissue integration using H&E staining and Masson's trichrome staining, angiogenesis by CD31 and immune response by CD45 and CD68 immunohistochemistry staining was examined. RESULTS: H&E and Masson's trichrome staining showed PM+PRP+ADSC and PM+ADSC scaffolds had the greatest tissue integration, but there was no significant difference between the two scaffolds (p < 0.05). The greatest vessel formation after 3 months was shown with PM+PRP+ADSC and PM+ADSC scaffolds using CD31 staining compared to all other scaffolds (p < 0.05). The CD45 and CD68 staining was similar between all scaffolds after 3 months showing the ADSCs or PRP had no effect on the immune response of the scaffolds. CONCLUSIONS: Argon plasma surface modification enhanced the effect of adipose-derived stem cells effect on angiogenesis and tissue integration of polyurethane scaffolds. The combination of ADSCs and argon plasma modification may improve the survival of large tissue implants for regenerative applications.

Morphometric characterisation of human tracheas: focus on cartilaginous ring variation.

PURPOSE: Details regarding tracheal anatomy are currently lacking, with existing literature focussing mainly on the cricoid-tracheal region or the carina. External gross anatomy and internal morphology throughout the entire trachea is important for normal physiological functioning and various clinical applications such as designs for tracheal implants or endotracheal devices. OBJECTIVE: To determine quantitative and qualitative characteristics of gross tracheal and individual tracheal ring anatomy. METHOD: 10 tracheas were harvested from formaldehyde-fixed cadavers. Tracheal length, height and inter-ring distance were measured from complete tracheas. Individual rings were excised and the following measurements were taken at three points on the ring: thickness, width, and antero-posterior (A-P) length. RESULTS: The average tracheal length was 10.38 ± 0.85 cm with a mean of 19 ± 3 rings per trachea. The average width and A-P diameter of tracheal lumens were 17.31 ± 2.57 and 17.27 ± 2.56 mm, with a width-AP ratio of 1.00 ('C' shaped ring). The A-P diameter shows a trend of narrowing slightly from the upper 1/3 to the lower 1/3 of the trachea. While majority of tracheal rings consisted of the expected 'C' shape, more than 41% of the 147 counted rings consisted of abnormally shaped rings which were further analysed. CONCLUSION: This study provides further details regarding tracheal anatomy which will be useful for implant design. Of interest for anatomists, is the marked variability in tracheal ring morphology which could be further characterised in larger studies.

Comparison of the mechanical properties of different skin sites for auricular and nasal reconstruction.

BACKGROUND: Autologous and synthetic nasal and auricular frameworks require skin coverage. The surgeon's decides on the appropriate skin coverage for reconstruction based on colour matching, subcutaneous tissue thickness, expertise and experience. One of the major complications of placing subcutaneous implants is the risk of extrusion (migration through the skin) and infection. However, knowledge of lessening the differential between the soft tissue and the framework can have important implications for extrusion. This study compared the mechanical properties of the skin commonly used as skin sites for the coverage in auricular and nasal reconstruction. METHODS: Using ten fresh human cadavers, the tensile Young's Modulus of the skin from the forehead, forearm, temporoparietal, post-auricular and submandibular neck was assessed. The relaxation rate and absolute relaxation level was also assessed after 90 min of relaxation. RESULTS: The submandibular skin showed the greatest Young's elastic modulus in tension of all regions (1.28 MPa ±0.06) and forearm showed the lowest (1.03 MPa ±0.06). The forehead demonstrated greater relaxation rates among the different skin regions (7.8 MPa-07 ± 0.1). The forearm showed the lowest rate of relaxation (4.74 MPa-07 ± 0.1). The forearm (0.04 MPa ±0.004) and submandibular neck skin (0.04 MPa ±0.005) showed similar absolute levels of relaxation, which were significantly greater than the other skin regions (p < 0.05). CONCLUSIONS: This study provides an understanding into the biomechanical properties of the skin of different sites allowing surgeons to consider this parameter when trying to identify the optimal skin coverage in nasal and auricular reconstruction.

Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages.

Human adipose derived stem cells (ADSCs) are being explored for the repair of craniofacial defects due to their multi-differentiation potential and ease of isolation and expansion. Crucial to using ADSCs for craniofacial repair is the availability of materials with appropriate biomechanical properties that can support their differentiation into bone and cartilage. We tested the hypothesis that different modifications of chemical groups on the surface of a nanocomposite polymer could increase human ADSC adhesion and selectively enhance their osteogenic and chondrogenic differentiation. We show that the COOH modification significantly promoted initial cell adhesion and proliferation over 14days compared to NH2 surfaces. Expression of focal adhesion kinase and vinculin was enhanced after plasma surface polymerisation at 24h. The COOH modification significantly enhanced chondrogenic differentiation as indicated by up-regulation of aggrecan and collagen II transcripts. In contrast, NH2 group functionalised scaffolds promoted osteogenic differentiation with significantly enhanced expression of collagen I, alkaline phosphatase and osteocalcin both at the gene and protein level. Finally, chorioallantoic membrane grafting demonstrated that both NH2 and COOH functionalised scaffolds seeded with ADSCs were biocompatible and supported vessel ingrowth apparently to a greater degree than unmodified scaffolds. In summary, our study shows the ability to direct ADSC chondrogenic and osteogenic differentiation by deposition of different chemical groups through plasma surface polymerisation. Hence this approach could be used to selectively enhance bone or cartilage formation before implantation in vivo to repair skeletal defects. STATEMENT OF SIGNIFICANCE: Human adipose derived stem cells (hADSCs) are an exciting stem cell source for regenerative medicine due to their plentiful supply and ease of isolation. However, the optimal environmental cues to direct stem cells towards certain lineages change have to has not been identified. We have shown that by modifying the surface of the scaffold with specific chemical groups using plasma surface polymerisation techniques we can control ADSCs differentiation. This study shows that ADSCs can be differentiated towards osteogenic and chondrogenic lineages on amine (NH2) and carboxyl (COOH) modified scaffolds respectively. Plasma polymerisation can be easily applied to other biomaterial surfaces to direct stem cell differentiation for the regeneration of bone and cartilage.

Biomechanical Characterisation of the Human Auricular Cartilages; Implications for Tissue Engineering.

Currently, autologous cartilage provides the gold standard for auricular reconstruction. However, synthetic biomaterials offer a number of advantages for ear reconstruction including decreased donor site morbidity and earlier surgery. Critical to implant success is the material's mechanical properties as this affects biocompatibility and extrusion. The aim of this study was to determine the biomechanical properties of human auricular cartilage. Auricular cartilage from fifteen cadavers was indented with displacement of 1 mm/s and load of 300 g to obtain a Young's modulus in compression. Histological analysis of the auricle was conducted according to glycoprotein, collagen, and elastin content. The compression modulus was calculated for each part of the auricle with the tragus at 1.67 ± 0.61 MPa, antitragus 1.79 ± 0.56 MPa, concha 2.08 ± 0.70 MPa, antihelix 1.71 ± 0.63 MPa, and helix 1.41 ± 0.67 MPa. The concha showed to have a significantly greater Young's Elastic Modulus than the helix in compression (p < 0.05). The histological analysis demonstrated that the auricle has a homogenous structure in terms of chondrocyte morphology, extracellular matrix and elastin content. This study provides new information on the compressive mechanical properties and histological analysis of the human auricular cartilage, allowing surgeons to have a better understanding of suitable replacements. This study has provided a reference, by which cartilage replacements should be developed for auricular reconstruction.

Biomechanical characterisation of the human nasal cartilages; implications for tissue engineering.

Nasal reconstruction is currently performed using autologous grafts provides but is limited by donor site morbidity, tissue availability and potentially graft failure. Additionally, current alternative alloplastic materials are limited by their high extrusion and infection rates. Matching mechanical properties of synthetic materials to the native tissue they are replacing has shown to be important in the biocompatibility of implants. To date the mechanical properties of the human nasal cartilages has not been studied in depth to be able to create tissue-engineered replacements with similar mechanical properties to native tissue. The young's modulus was characterized in compression on fresh-frozen human cadaveric septal, alar, and lateral cartilage. Due to the functional differences experienced by the various aspects of the septal cartilage, 16 regions were evaluated with an average elastic modulus of 2.72 ± 0.63 MPa. Furthermore, the posterior septum was found to be significantly stiffer than the anterior septum (p < 0.01). The medial and lateral alar cartilages were tested at four points with an elastic modulus ranging from 2.09 ± 0.81 MPa, with no significant difference between the cartilages (p < 0.78). The lateral cartilage was tested once in all cadavers with an average elastic modulus of 0.98 ± 0.29 MPa. In conclusion, this study provides new information on the compressive mechanical properties of the human nasal cartilage, allowing surgeons to have a better understanding of the difference between the mechanical properties of the individual nasal cartilages. This study has provided a reference, by which tissue-engineered should be developed for effective cartilage replacements for nasal reconstruction.

Nanoscale Surface Modifications of Medical Implants for Cartilage Tissue Repair and Regeneration.

BACKGROUND: Natural cartilage regeneration is limited after trauma or degenerative processes. Due to the clinical challenge of reconstruction of articular cartilage, research into developing biomaterials to support cartilage regeneration have evolved. The structural architecture of composition of the cartilage extracellular matrix (ECM) is vital in guiding cell adhesion, migration and formation of cartilage. Current technologies have tried to mimic the cell's nanoscale microenvironment to improve implants to improve cartilage tissue repair. METHODS: This review evaluates nanoscale techniques used to modify the implant surface for cartilage regeneration. RESULTS: The surface of biomaterial is a vital parameter to guide cell adhesion and consequently allow for the formation of ECM and allow for tissue repair. By providing nanosized cues on the surface in the form of a nanotopography or nanosized molecules, allows for better control of cell behaviour and regeneration of cartilage. Chemical, physical and lithography techniques have all been explored for modifying the nanoscale surface of implants to promote chondrocyte adhesion and ECM formation. CONCLUSION: Future studies are needed to further establish the optimal nanoscale modification of implants for cartilage tissue regeneration.

An update on the Application of Nanotechnology in Bone Tissue Engineering.

BACKGROUND: Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. METHODS: This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. RESULTS: Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. CONCLUSION: Future studies to improve the application of nanomaterials for bone tissue engineering are needed.

Nanoscale Surface Modifications of Orthopaedic Implants: State of the Art and Perspectives.

BACKGROUND: Orthopaedic implants such as the total hip or total knee replacement are examples of surgical interventions with postoperative success rates of over 90% at 10 years. Implant failure is associated with wear particles and pain that requires surgical revision. Improving the implant - bone surface interface is a key area for biomaterial research for future clinical applications. Current implants utilise mechanical, chemical or physical methods for surface modification. METHODS: A review of all literature concerning the nanoscale surface modification of orthopaedic implant technology was conducted. RESULTS: The techniques and fabrication methods of nanoscale surface modifications are discussed in detail, including benefits and potential pitfalls. Future directions for nanoscale surface technology are explored. CONCLUSION: Future understanding of the role of mechanical cues and protein adsorption will enable greater flexibility in surface control. The aim of this review is to investigate and summarise the current concepts and future directions for controlling the implant nanosurface to improve interactions.

Publication practices of medical students at British medical schools: experience, attitudes and barriers to publish.

INTRODUCTION: With research playing a vital role in improving clinical practice, it is important that medical students understand the role of research and submitting articles for publication. Therefore, the aim of this study was to ascertain the experience, motivation and attitude of publishing of medical students. METHODS: A cross-sectional survey of British medical students from seven medical schools in the United Kingdom. RESULTS: Seventy-two of 515 had submitted an article for publication with a total of 124 articles being submitted. The main motivation to publish was for career progression. For the students that had not published, not having an opportunity to perform research was felt to be the main barrier. Only 49% of students had taken part in a research or audit project. Sixty-two percent of students stated they were not encouraged by the seniors to participate in research projects. From 515 medical students, only 88 students had submitted an article for a scientific meeting. CONCLUSIONS: Students have a positive attitude towards publishing and they feel it is important. However, it is clear that students require and would welcome education in writing papers and abstracts, skills that they will need in their postgraduate careers.

Epidemiology of neonatal respiratory failure in the United States: projections from California and New York.

We wanted to determine the incidence, cost, outcome, and patterns of care for neonates requiring mechanical ventilation (MV) in the United States. Using 1994 state hospital discharge data from California and New York, we conducted an observational study of all neonatal hospitalizations (n = 16,405) with MV, comparing outcomes at centers of different technological capability, and generating national projections using census and natality reports. The MV rate was 18 per 1,000 live births. Although the incidence was much higher in lower birth weight (BW) babies, one-third had normal BW. The incidence was higher in boys (20 versus 15.6 per 1,000) and in blacks (29 per 1,000). Hospital mortality was 11.1%, higher in minority groups, and associated with low BW, congenital anomalies, and major hemorrhage. Mean hospital length of stay and costs were 31.1 d and $51,700. Half of all deaths occurred at lower level centers. There are 80,000 cases per year in the United States with 8,500 deaths and total hospital costs of $4.4 billion. We conclude neonatal respiratory failure is common, expensive, and frequently fatal. There are a surprisingly large number of normal BW cases and there are large racial differences.

Quality-adjusted survival in the first year after the acute respiratory distress syndrome.

There is little information on long-term outcome after acute respiratory distress syndrome (ARDS). We measured quality-adjusted survival in the first year after ARDS in a prospective cohort (n = 200). All patients met traditional criteria for ARDS. Patients with sepsis and acute nonpulmonary organ dysfunction at presentation were excluded. The cohort was healthy before onset of ARDS as evidenced by high functional status (mean Karnofsky Performance Status index: 82.2/100 where >/= 80 = able to perform normal activities independently) and minimal comorbid illness (mean Charlson-Deyo comorbidity score: 0.32/17 where 0 = absence of chronic illness). We determined quality-adjusted life-years (QALYs) using the Quality of Well-being (QWB) scale (0 to 1 scale where 1 = optimal well-being), measured at 6 and 12 mo. Survival was 69.5 +/- 5.0% at 1 month, fell to 55.7 +/- 3.7% at 6 mo, and did not change at 12 mo, yielding a survival of 59 life-years in the first year per 100 patients with ARDS. QWB was low at 6 and 12 mo (0.59 +/- 0.015 and 0.60 +/- 0.015), yielding a quality-adjusted survival of 36 QALYs per 100 patients (sensitivity range: 21 to 46 QALYs). We conclude that ARDS developing in previously healthy patients is associated with poor quality-adjusted survival. These data are important for cost-effectiveness analyses and long-term care.