Constructing 3D Macroporous Microfibrous Scaffolds with a Featured Surface by Heat Welding and Embossing.

Three-dimensional (3D) microfibrous scaffolds hold great promise for biomedical applications due to their good mechanical properties and biomimetic structure similar to that of the fibrous natural extracellular matrix. However, the large diameter and smooth surface of microfibers provide limited cues for regulating cell activity and behaviors. In this work, we report a facile heat-welding-and-embossing strategy to develop 3D macroporous microfibrous scaffolds with a featured surface topography. Here, solid monosodium glutamate (MSG) particles with crystalline ridge-like surface features play a key role as templates in both the formation of scaffold pores and the surface embossing of scaffold fibers when short thermoplastic polypropylene microfibers were heat-welded. The embossing process can be programmed by adjusting heating temperatures and MSG/fiber ratios. Compared to traditional 3D microfibrous scaffolds, the as-welded 3D scaffolds show higher compressive strength and modulus. Taking mouse C2C12 myoblasts as a model cell line, the scaffolds with embossed surface features significantly promoted the growth of cells, interactions of cells and scaffolds, and formation of myotubes. The findings indicate that the as-prepared 3D scaffolds are a good platform for cell culture study. The facile strategy can be applied to fabricate different fibrous scaffolds by changing the combination of templates and thermoplastic polymer fibers with a melting temperature lower than that of the template. The obtained insights in this work could provide a guide and inspiration for the design and fabrication of functional 3D fibrous scaffolds.

Changes in pelvic organ prolapse mesh mechanical properties following implantation in rats.

BACKGROUND: Pelvic organ prolapse (POP) is a multifactorial disease that manifests as the herniation of the pelvic organs into the vagina. Surgical methods for prolapse repair involve the use of a synthetic polypropylene mesh. The use of this mesh has led to significantly higher anatomical success rates compared with native tissue repairs, and therefore, despite recent warnings by the Food and Drug Administration regarding the use of vaginal mesh, the number of POP mesh surgeries has increased over the last few years. However, mesh implantation is associated with higher postsurgery complications, including pain and erosion, with higher consecutive rates of reoperation when placed vaginally. Little is known on how the mechanical properties of the implanted mesh itself change in vivo. It is assumed that the mechanical properties of these meshes remain unchanged, with any differences in mechanical properties of the formed mesh-tissue complex attributed to the attached tissue alone. It is likely that any changes in mesh mechanical properties that do occur in vivo will have an impact on the biomechanical properties of the formed mesh-tissue complex. OBJECTIVE: The objective of the study was to assess changes in the multiaxial mechanical properties of synthetic clinical prolapse meshes implanted abdominally for up to 90 days, using a rat model. Another objective of the study was to assess the biomechanical properties of the formed mesh-tissue complex following implantation. STUDY DESIGN: Three nondegradable polypropylene clinical synthetic mesh types for prolapse repair (Gynemesh PS, Polyform Lite, and Restorelle) and a partially degradable polypropylene/polyglecaprone mesh (UltraPro) were mechanically assessed before and after implantation (n = 5/ mesh type) in Sprague Dawley rats for 30 (Gynemesh PS, Polyform Lite, and Restorelle) and 90 (UltraPro and Polyform Lite) days. Stiffness and permanent extension following cyclic loading, and breaking load, of the preimplanted mesh types, explanted mesh-tissue complexes, and explanted meshes were assessed using a multi-axial (ball-burst) method. RESULTS: The 4 clinical meshes varied from each other in weight, thickness, porosity, and pore size and showed significant differences in stiffness and breaking load before implantation. Following 30 days of implantation, the mechanical properties of some mesh types altered, with significant decreases in mesh stiffness and breaking load, and increased permanent extension. After 90 days these changes were more obvious, with significant decreases in stiffness and breaking load and increased permanent extension. Similar biomechanical properties of formed mesh-tissue complexes were observed for mesh types of different preimplant stiffness and structure after 90 days implantation. CONCLUSION: This is the first study to report on intrinsic changes in the mechanical properties of implanted meshes and how these changes have an impact on the estimated tissue contribution of the formed mesh-tissue complex. Decreased mesh stiffness, strength, and increased permanent extension following 90 days of implantation increase the biomechanical contribution of the attached tissue of the formed mesh-tissue complex more than previously thought. This needs to be considered when using meshes for prolapse repair.

HER2 assessment on core biopsy specimens using monoclonal antibody CB11 accurately determines HER2 status in breast carcinoma.

AIMS: HER2 status is a prognostic factor in breast carcinoma and predicts response to trastuzumab therapy. Trastuzumab is effective in the neoadjuvant, adjuvant and advanced disease settings. Knowledge of HER2 status early in the diagnostic and therapeutic process is vital for treatment planning. HER2 analysis is usually carried out by immunohistochemistry or fluorescence in situ hybridization (FISH). The aim of this study was to establish whether HER2 immunohistochemistry using monoclonal antibody CB11 and carried out on the initial diagnostic core biopsy specimen accurately predicts HER2 amplification status. METHODS AND RESULTS: This is the largest study to date in which HER2 protein expression has been assessed by CB11 immunohistochemistry on the diagnostic core biopsy specimen and correlated with the result of FISH. Using FISH as the definitive HER2 status, we studied 568 invasive breast cancers using CB11 immunohistochemistry on core biopsy. This analysis had a sensitivity of 99.4%, specificity of 93.9%, false-positive frequency of 3.9% and false-negative frequency of 1.1%. These data are as good as those obtained from analysing resection specimens alone in UK national reference centres. CONCLUSIONS: CB11 immunohistochemistry accurately predicts HER2 amplification status and can be reliably carried out on core biopsy specimens of breast carcinoma.

Pathophysiology of acid base balance: the theory practice relationship.

There are many disorders/diseases that lead to changes in acid base balance. These conditions are not rare or uncommon in clinical practice, but everyday occurrences on the ward or in critical care. Conditions such as asthma, chronic obstructive pulmonary disease (bronchitis or emphasaemia), diabetic ketoacidosis, renal disease or failure, any type of shock (sepsis, anaphylaxis, neurogenic, cardiogenic, hypovolaemia), stress or anxiety which can lead to hyperventilation, and some drugs (sedatives, opioids) leading to reduced ventilation. In addition, some symptoms of disease can cause vomiting and diarrhoea, which effects acid base balance. It is imperative that critical care nurses are aware of changes that occur in relation to altered physiology, leading to an understanding of the changes in patients' condition that are observed, and why the administration of some immediate therapies such as oxygen is imperative.

A review of TiO2 NTs on Ti metal: Electrochemical synthesis, functionalization and potential use as bone implants.

Degenerative diseases of bone such as osteoarthritis and osteoporosis can lead to bone fractures and immobility, compromising quality of life. Titanium (Ti)-based implants have been intensively investigated for bone repair, with these implants, demonstrating improved outcomes compared to stainless steel and cobalt-chrome alloys, owing to superior mechanical properties and biocompatibility. However, osseointegration between the Ti-based implants and the surrounding bone tissue needs to be improved. Surface modification of Ti-based implants provides a solution for addressing this, with electrochemical anodization becoming a realistic approach for the fabrication of hierarchical structured for example nanotubes (NTs), implant surfaces. Using this technique, biocompatibility and osteogenesis of the implant may be improved, by providing an appropriate site for bone cell attachment. In this review, we discuss the anodization of Ti-based implants as an approach for creating titanium dioxide nanotubes (TiO2 NTs) on the implant surface. We further discuss the various ways of functionalizing the NT surface, to reduce post-operative infection and improve implant biocompatibility and osseointegration.

Ovine multiparity is associated with diminished vaginal muscularis, increased elastic fibres and vaginal wall weakness: implication for pelvic organ prolapse.

Pelvic Organ Prolapse (POP) is a major clinical burden affecting 25% of women, with vaginal delivery a major contributing factor. We hypothesised that increasing parity weakens the vagina by altering the extracellular matrix proteins and smooth muscle thereby leading to POP vulnerability. We used a modified POP-quantification (POP-Q) system and a novel pressure sensor to measure vaginal wall weakness in nulliparous, primiparous and multiparous ewes. These measurements were correlated with histological, biochemical and biomechanical properties of the ovine vagina. Primiparous and multiparous ewes had greater displacement of vaginal tissue compared to nulliparous at points Aa, Ap and Ba and lower pressure sensor measurements at points equivalent to Ap and Ba. Vaginal wall muscularis of multiparous ewes was thinner than nulliparous and had greater elastic fibre content. Collagen content was lower in primiparous than nulliparous ewes, but collagen organisation did not differ. Biomechanically, multiparous vaginal tissue was weaker and less stiff than nulliparous. Parity had a significant impact on the structure and function of the ovine vaginal wall, as the multiparous vaginal wall was weaker and had a thinner muscularis than nulliparous ewes. This correlated with "POP-Q" and pressure sensor measurements showing greater tissue laxity in multiparous compared to nulliparous ewes.

Tissue viability: understanding the mechanisms of injury and repair.

This article provides an overview of the pathophysiological processes that relate to tissue viability. Processes such as cellular damage, oedema and the inflammatory response are also discussed. Nursing management and the role of tissue viability nurses are briefly examined.

The Personal Narrative of a Nurse: A Journey Through Practice.

This article examines my phases of holistic learning concerning how I became a nurse, using story presented in a personal narrative style. I have incorporated my own stories to elaborate my journey. First, my early life in the East End of London and how this influenced my becoming a nurse. Second, I give an account of my journey through practice, where I examine how I developed my own learning from professional practice, drawing on some personal illustrations presented as stories. I have set out to explore how my stories of practice have influenced my progress, and I present a personal account of such learning in general from the lens of a nurse educator.

Maintaining calcium balance: physiology and implications.

This article provides an overview of the physiology of calcium balance and the associated implications for practice. Understanding the physiological principles is vital to ensure patients' levels of this essential electrolyte are maintained.

Myocardial infarction: nursing responsibilities in the first hour.

The aim of this article is to provide a comprehensive review of the physiological processes that occur during the first hour following a myocardial infarction (MI). It will identify the general principles and the physiological processes that occur in response to a MI, outlining the consequences of cellular hypoxia to the heart. The implications for clinical practice and how they link to the physiological processes are detailed. Understanding the physiological principles involved in a MI is important for identification and to ensure patient management is initiated. This, together with prompt diagnosis and interventions, will assist in reducing mortality within the first hour following a MI.

The effects of flying: processes, consequences and prevention.

The dangers of flying have recently been highlighted in the media; however, the available literature is contradictory, as are current recommendations for travellers. The purpose of this article is to provide an account of the research that has been undertaken to investigate the possible consequences of air travel. It will examine the effect that flying has on the body, especially the respiratory and circulatory systems, by studying the theoretical and empirical literature. The aim is to provide nurses with a sound insight into the effects of long-distance flying on the body, and the potential adverse effects/complications, such as deep vein thrombosis and pulmonary embolism, that may occur as a result. In addition, it provides information on the treatment options available and should enable nurses to give sound prophylactic advice after discharge. By encouraging passengers to take precautions, the number of people affected by flight could be reduced.

Using personal narrative to deepen emotional awareness of practice.

Storytelling is intrinsic to human beings, and stories can explain events, stances taken and actions engaged in. When experience is represented as story it can become more organised and be used for analysis, critique and learning. Experience is important in nursing, as it is in many other practice-based professions, and it can contribute much to nurses' learning. Through a process of sharing and engaging with the author's personal stories, this article encourages nurses to begin to organise their own experiences in story form for use in learning and as part of their personal and professional development.

Regional variation in tissue composition and biomechanical properties of postmenopausal ovine and human vagina.

OBJECTIVE: There are increasing numbers of reports describing human vaginal tissue composition in women with and without pelvic organ prolapse with conflicting results. The aim of this study was to compare ovine and human posterior vaginal tissue in terms of histological and biochemical tissue composition and to assess passive biomechanical properties of ovine vagina to further characterise this animal model for pelvic organ prolapse research. STUDY DESIGN: Vaginal tissue was collected from ovariectomised sheep (n = 6) and from postmenopausal women (n = 7) from the proximal, middle and distal thirds. Tissue histology was analyzed using Masson's Trichrome staining; total collagen was quantified by hydroxyproline assays, collagen III/I+III ratios by delayed reduction SDS PAGE, glycosaminoglycans by dimethylmethylene blue assay, and elastic tissue associated proteins (ETAP) by amino acid analysis. Young's modulus, maximum stress/strain, and permanent strain following cyclic loading were determined in ovine vagina. RESULTS: Both sheep and human vaginal tissue showed comparable tissue composition. Ovine vaginal tissue showed significantly higher total collagen and glycosaminoglycan values (p<0.05) nearest the cervix. No significant differences were found along the length of the human vagina for collagen, GAG or ETAP content. The proximal region was the stiffest (Young's modulus, p<0.05), strongest (maximum stress, p<0.05) compared to distal region, and most elastic (permanent strain). CONCLUSION: Sheep tissue composition and mechanical properties showed regional differences along the postmenopausal vaginal wall not apparent in human vagina, although the absolute content of proteins were similar. Knowledge of this baseline variation in the composition and mechanical properties of the vaginal wall will assist future studies using sheep as a model for vaginal surgery.

Induction of endometrial mesenchymal stem cells into tissue-forming cells suitable for fascial repair.

Pelvic organ prolapse is a major hidden burden affecting almost one in four women. It is treated by reconstructive surgery, often augmented with synthetic mesh. To overcome the growing concerns of using current synthetic meshes coupled with the high risk of reoperation, a tissue engineering strategy has been developed, adopting a novel source of mesenchymal stem cells. These cells are derived from the highly regenerative endometrial lining of the uterus (eMSCs) and will be delivered in vivo using a new gelatin-coated polyamide scaffold. In this study, gelatin properties were optimized by altering the gelatin concentration and extent of crosslinking to produce the desired gelation and degradation rate in culture. Following cell seeding of uncoated polyamide (PA) and gelatin-coated meshes (PA+G), the growth rate of eMSCs on the PA+G scaffolds was more than that on the PA alone, without compromising cell shape. eMSCs cultured on the PA+G scaffold retained their phenotype, as demonstrated by W5C5/SUSD2 (eMSC-specific marker) immunocytochemistry. Additionally, eMSCs were induced to differentiate into smooth muscle cells (SMC), as shown by immunofluorescence for smooth muscle protein 22 and smooth muscle myosin heavy chain. eMSCs also differentiated into fibroblast-like cells when treated with connective tissue growth factor with enhanced detection of Tenascin-C and collagen type I as well as new tissue formation, as seen by Masson's trichrome. In summary, it was demonstrated that the PA+G scaffold is an appropriate platform for eMSC delivery, proliferation and differentiation into SMC and fibroblasts, with good biocompatibility and the capacity to regenerate neo-tissue.

Influence of reproductive status on tissue composition and biomechanical properties of ovine vagina.

OBJECTIVE: To undertake a comprehensive analysis of the biochemical tissue composition and passive biomechanical properties of ovine vagina and relate this to the histo-architecture at different reproductive stages as part of the establishment of a large preclinical animal model for evaluating regenerative medicine approaches for surgical treatment of pelvic organ prolapse. METHODS: Vaginal tissue was collected from virgin (n = 3), parous (n = 6) and pregnant sheep (n = 6; mean gestation; 132 d; term = 145 d). Tissue histology was analyzed using H+E and Masson's Trichrome staining. Biochemical analysis of the extracellular matrix proteins used a hydroxyproline assay to quantify total collagen, SDS PAGE to measure collagen III/I+III ratios, dimethylmethylene blue to quantify glycosaminoglycans and amino acid analysis to quantify elastin. Uniaxial tensiometry was used to determine the Young's modulus, maximum stress and strain, and permanent strain following cyclic loading. RESULTS: Vaginal tissue of virgin sheep had the lowest total collagen content and permanent strain. Parous tissue had the highest total collagen and lowest elastin content with concomitant high maximum stress. In contrast, pregnant sheep had the highest elastin and lowest collagen contents, and thickest smooth muscle layer, which was associated with low maximum stress and poor dimensional recovery following repetitive loading. CONCLUSION: Pregnant ovine vagina was the most extensible, but the weakest tissue, whereas parous and virgin tissues were strong and elastic. Pregnancy had the greatest impact on tissue composition and biomechanical properties, compatible with significant tissue remodeling as demonstrated in other species. Biochemical changes in tissue protein composition coincide with these altered biomechanical properties.

Characterisation of clinical and newly fabricated meshes for pelvic organ prolapse repair.

Clinical meshes used in pelvic organ prolapse (POP) repair are predominantly manufactured from monofilament polypropylene (PP). Complications from the use of these meshes in transvaginal kits, including mesh exposure and pain, have prompted two public health notifications by the FDA. The aim of this study was to compare several clinical PP POP meshes to new fabricated POP meshes, knitted from alternative polymers, for their mechanical properties using standard and clinically relevant multi-axial testing methods. Five new meshes were warp knitted to different architectures and weights from polyamide and polyetheretherketone monofilaments. A composite mesh of a polyamide mesh incorporating a gelatin layer was also fabricated to enable the potential delivery of cells on these meshes. Meshes were assessed for their structural characteristics and mechanical properties, using uniaxial stiffness, permanent strain, bending rigidity and multi-axial burst strength methods. Results were compared to three clinical urogynaecological polypropylene meshes: Polyform®, Gynemesh(TM)PS, and IntePro®. New fabricated meshes were uniaxially less stiff (less than 0.24 N/mm and 1.20 N/mm in toe and linear regions, respectively) than the Gynemesh (0.48 N/mm and 2.08 N/mm in toe and linear regions, respectively) and IntePro (0.57 N/mm in toe region) clinical meshes, with the gelatin coated PA mesh exhibiting lower permanent strain than Polyform clinical mesh (8.1% vs. 23.5%). New meshes had lower burst stiffness than Polyform (less than 16.9 N/mm for new meshes and 26.6N/mm for Polyform). Within the new mesh prototypes, the PA meshes, either uncoated (4.7-5.7 µN m) or with gelatin coating (16.7 µN m) possessed lower bending rigidity than both Polyform and Gynemesh (46.2 µN m and 36.4 µN m, respectively). The new fabricated mesh designs were of similar architecture, but with some improved mechanical properties, compared to clinical POP meshes. Multi-axial analysis of new and clinical mesh designs provides greater discriminatory power in analysing mesh mechanical properties for clinical applications.

A preclinical evaluation of alternative synthetic biomaterials for fascial defect repair using a rat abdominal hernia model.

INTRODUCTION: Fascial defects are a common problem in the abdominal wall and in the vagina leading to hernia or pelvic organ prolapse that requires mesh enhancement to reduce operation failure. However, the long-term outcome of synthetic mesh surgery may be unsatisfactory due to post-surgical complications. We hypothesized that mesh fabricated from alternative synthetic polymers may evoke a different tissue response, and provide more appropriate mechanical properties for hernia repair. Our aim was to compare the in vivo biocompatibility of new synthetic meshes with a commercial mesh. METHODS: We have fabricated 3 new warp-knitted synthetic meshes from different polymers with different tensile properties polyetheretherketone (PEEK), polyamide (PA) and a composite, gelatin coated PA (PA+G). The rat abdominal hernia model was used to implant the meshes (25 × 35 mm, n = 24/ group). After 7, 30, 60, 90 days tissues were explanted for immunohistochemical assessment of foreign body reaction and tissue integration, using CD31, CD45, CD68, alpha-SMA antibodies. The images were analysed using an image analysis software program. Biomechanical properties were uniaxially evaluated using an Instron Tensile® Tester. RESULTS: This study showed that the new meshes induced complex differences in the type of foreign body reaction over the time course of implantation. The PA, and particularly the composite PA+G meshes, evoked a milder early inflammatory response, and macrophages were apparent throughout the time course. Our meshes led to better tissue integration and new collagen deposition, particularly with the PA+G meshes, as well as greater and sustained neovascularisation compared with the PP meshes. CONCLUSION: PA, PA+G and PEEK appear to be well tolerated and are biocompatible, evoking an overlapping and different host tissue response with time that might convey mechanical variations in the healing tissue. These new meshes comprising different polymers may provide an alternative option for future treatment of fascial defects.

Modeling tissue growth within nonwoven scaffolds pores.

In this study we present a novel approach for predicting tissue growth within the pores of fibrous tissue engineering scaffolds. Thin nonwoven polyethylene terephthalate scaffolds were prepared to characterize tissue growth within scaffold pores, by mouse NR6 fibroblast cells. On the basis of measurements of tissue lengths at fiber crossovers and along fiber segments, mathematical models were determined during the proliferative phase of cell growth. Tissue growth at fiber crossovers decreased with increasing interfiber angle, with exponential relationships determined on day 6 and 10 of culture. Analysis of tissue growth along fiber segments determined two growth profiles, one with enhanced growth as a result of increased tissue lengths near the fiber crossover, achieved in the latter stage of culture. Derived mathematical models were used in the development of a software program to visualize predicted tissue growth within a pore. This study identifies key pore parameters that contribute toward tissue growth, and suggests models for predicting this growth, based on fibroblast cells. Such models may be used in aiding scaffold design, for optimum pore infiltration during the tissue engineering process.

Management of in situ lobular neoplasia detected on needle core biopsy of breast.

AIMS: To evaluate the risk of having occult ductal carcinoma in situ or invasive carcinoma in the region of a focus of lobular (in situ) neoplasia (LN) diagnosed on needle core biopsy (NCB) of breast. METHODS: All cases of LN diagnosed on NCB of breast over 10 years (2000-2009 inclusive) were reviewed. The clinical presentation, radiological appearances and final pathological diagnosis on open diagnostic biopsy (ODB) were correlated. RESULTS: 125 cases of LN on NCB were identified from diagnostic codes. Of these, 72 (58%) had a coexistent, higher-grade lesion that mandated surgery. Fifty of the remaining 53 (94%) underwent ODB. The majority of patients were asymptomatic, with 68% presenting through the breast screening programme, and in 89% of patients, the target abnormality was microcalcification. Of the 50 patients, 13 (26%) had a final diagnosis of in situ or invasive carcinoma requiring therapeutic surgery. When the cases of pleomorphic LN were excluded, 21% (10/47) were upgraded. Two of these 10 cases had discordant radiology which could have been diagnosed on repeat NCB leaving an upgrade rate of 18% (8/45). In four of the eight cases of invasive malignancy, the disease was multifocal. CONCLUSIONS: LN is frequently asymptomatic, being identified by mammographic microcalcification alone. In 21% of classical LN cases, it is associated with an undiagnosed, higher-grade lesion requiring oncological management. In our view, patients with LN discovered on NCB should undergo open diagnostic biopsy.

Carbon nanotubes in scaffolds for tissue engineering.

Carbon nanotubes are hollow graphitic cylinders of nanoscale dimensions. They are electrically conductive, chemically and thermally stable, and exceptionally strong. Given this unique combination of properties there has been much interest in carbon nanotubes, and finding applications for them. One application where this combination of properties may prove useful is in the area of tissue regeneration, incorporating carbon nanotubes into scaffolds for tissue engineering. It is believed that carbon nanotubes may improve scaffold properties and enhance tissue regeneration. This report aims to discuss the suitability of carbon nanotubes as a biomaterial for scaffold production, and the fabrication, properties and performance of carbon nanotube-based scaffolds.