Electrospun biocomposite nanofibrous scaffolds for neural tissue engineering

Bridging of nerve gaps after injury is a major problem in peripheral nerve regeneration. Considering the potential application of a bio-artificial nerve guide material, polycaprolactone (PCL)/chitosan nanofibrous scaffolds was designed and evaluated in vitro using rat Schwann cells (RT4-D6P2T) for nerve tissue engineering. PCL, chitosan, and PCL/chitosan nanofibers with average fiber diameters of 630, 450, and 190 nm, respectively, were fabricated using an electrospinning process. The surface chemistry of the fabricated nanofibers was determined using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Simple blending of PCL with chitosan proved an easy and efficient method for fabricating PCL/chitosan nanofibrous scaffolds, whose surface characteristics proved more hydrophilic than PCL nanofibers. Evaluation of mechanical properties showed that the Young's modulus and strain at break of the electrospun PCL/chitosan nanofibers were better than those of the chitosan nanofibers. Results of cell proliferation studies on nanofibrous scaffolds using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay showed 48% more cell proliferation on PCL/chitosan scaffolds than on PCL scaffolds after 8 days of culture. PCL/chitosan scaffolds showed better cell proliferation than PCL scaffolds and maintained their characteristic cell morphology, with spreading bipolar elongations to the nanofibrous substrates. This electrospun nanofibrous matrix thus proved of specific interest in tissue engineering for peripheral nerve regeneration.     

Guided orientation of cardiomyocytes on electrospun aligned nanofibers for cardiac tissue engineering

Cardiac tissue engineering (TE) is one of the most promising strategies to reconstruct the infarct myocardium and the major challenge involves producing a bioactive scaffold with anisotropic properties that assist in cell guidance to mimic the heart tissue. In this study, random and aligned poly(ε-caprolactone)/gelatin (PG) composite nanofibrous scaffolds were electrospun to structurally mimic the oriented extracellular matrix (ECM). Morphological, chemical and mechanical properties of the electrospun PG nanofibers were evaluated by scanning electron microscopy (SEM), water contact angle, attenuated total reflectance Fourier transform infrared spectroscopy and tensile measurements. Results indicated that PG nanofibrous scaffolds possessed smaller fiber diameters (239 ± 37 nm for random fibers and 269 ± 33 nm for aligned fibers), increased hydrophilicity, and lower stiffness compared to electrospun PCL nanofibers. The aligned PG nanofibers showed anisotropic wetting characteristics and mechanical properties, which closely match the requirements of native cardiac anisotropy. Rabbit cardiomyocytes were cultured on electrospun random and aligned nanofibers to assess the biocompatibility of scaffolds, together with its potential for cell guidance. The SEM and immunocytochemical analysis showed that the aligned PG scaffold greatly promoted cell attachment and alignment because of the biological components and ordered topography of the scaffolds. Moreover, we concluded that the aligned PG nanofibrous scaffolds could be more promising substrates suitable for the regeneration of infarct myocardium and other cardiac defects.     

Biocompatibility evaluation of emulsion electrospun nanofibers using osteoblasts for bone tissue engineering

Emulsion electrospinning is an advanced technique to fabricate core-shell structured nanofibrous scaffolds, with great potential for drug encapsulation. Incorporation of dual factors hydroxyapatite (HA) and laminin, respectively, within the shell and core of nanofibers through emulsion electrospinning might be of advantageous in supporting the adhesion, proliferation, and maturation of cells instead of single factor-encapsulated nanofibers. We fabricated poly(L-lactic acid-co-?-caprolactone) (PLCL)/hydroxyapaptite (PLCL/HA), PLCL/laminin (PLCL/Lam), and PLCL/hydroxyapatite/laminin (PLCL/HA/Lam) scaffolds with fiber diameter of 388?±?35, 388?±?81, and 379?±?57?nm, respectively, by emulsion electrospinning. The elastic modulus of the prepared scaffolds ranged from 22.7–37.0?MPa. The osteoblast proliferation on PLCL/HA/Lam scaffolds, determined on day 21, was found 10.4% and 12.0% higher than the cell proliferation on PLCL/Lam or PLCL/HA scaffold, respectively. Cell maturation determined on day 14, by alkaline phosphatase (ALP) activity, was significantly higher on PLCL/HA/Lam scaffolds than the ALP activity on PLCL/HA and PLCL/Lam scaffolds (p???0.05). Results of the energy dispersive X-ray studies carried out on day 28 also showed higher calcium deposition by cells seeded on PLCL/HA/Lam scaffolds. Osteoblasts were found to adhere, proliferate, and mature actively on PLCL/HA/Lam nanofibers with enhanced cell proliferation, ALP activity, bone protein expression, and mineral deposition. Based on the results, we can conclude that laminin and HA individually played roles in osteoblast proliferation and maturation, and the synergistic function of both factors within the novel emulsion electrospun PLCL/HA/Lam nanofibers enhanced the functionality of osteoblasts, confirming their potential application in bone tissue regeneration.     

Electrospun poly(epsilon-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering

Nerve tissue engineering is one of the most promising methods to restore nerve systems in human health care. Scaffold design has pivotal role in nerve tissue engineering. Polymer blending is one of the most effective methods for providing new, desirable biocomposites for tissue-engineering applications. Random and aligned PCL/gelatin biocomposite scaffolds were fabricated by varying the ratios of PCL and gelatin concentrations. Chemical and mechanical properties of PCL/gelatin nanofibrous scaffolds were measured by FTIR, porometry, contact angle and tensile measurements, while the in vitro biodegradability of the different nanofibrous scaffolds were evaluated too. PCL/gelatin 70:30 nanofiber was found to exhibit the most balanced properties to meet all the required specifications for nerve tissue and was used for in vitro culture of nerve stem cells (C17.2 cells). MTS assay and SEM results showed that the biocomposite of PCL/gelatin 70:30 nanofibrous scaffolds enhanced the nerve differentiation and proliferation compared to PCL nanofibrous scaffolds and acted as a positive cue to support neurite outgrowth. It was found that the direction of nerve cell elongation and neurite outgrowth on aligned nanofibrous scaffolds is parallel to the direction of fibers. PCL/gelatin 70:30 nanofibrous scaffolds proved to be a promising biomaterial suitable for nerve regeneration.     

Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for bone tissue engineering

The development of bioinspired or biomimetic materials is essential and has formed one of the most important paradigms in today's tissue engineering research. This paper reports a novel biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan (HAp/CTS) prepared by combining an in situ co-precipitation synthesis approach with an electrospinning process. A model HAp/CTS nanocomposite with the HAp mass ratio of 30wt% was synthesized through the co-precipitation method so as to attain homogenous dispersion of the spindle-shaped HAp nanoparticles (ca. 100x30nm) within the chitosan matrix. By using a small amount (10wt%) of ultrahigh molecular weight poly(ethylene oxide) (UHMWPEO) as a fiber-forming facilitating additive, continuous HAp/CTS nanofibers with a diameters of 214+/-25nm had been produced successfully and the HAp nanoparticles with some aggregations were incorporated into the electrospun nanofibers. Further SAED and XRD analysis confirmed that the crystalline nature of HAp remains and had survived the acetic acid-dominant solvent system. Biological in vitro cell culture with human fetal osteoblast (hFOB) cells for up to 15 days demonstrated that the incorporation of HAp nanoparticles into chitosan nanofibrous scaffolds led to significant bone formation oriented outcomes compared to that of the pure electrospun CTS scaffolds. The electrospun nanocomposite nanofibers of HAp/CTS, with compositional and structural features close to the natural mineralized nanofibril counterparts, are of potential interest for bone tissue engineering applications.     

Biomaterials and scaffolds for ligament tissue engineering

Tissue engineering has achieved much progress in an attempt to improve and recover impaired functions of tissues and organs. Although many studies have been done, progress for tissue-engineered anterior cruciate ligaments (ACLs) has been slow due to their complex structures and mechanical properties. In this review, the ACL anatomical structure, progresses achieved, material selection, structure design, and future direction have been discussed, while the challenges and requirements from materials and scaffolds are highlighted. There is a considerably huge amount work that needs to be carried out; as such, future direction in ligament tissue engineering is proposed in hope that this review will give information on future ligament tissue engineering.     

Multiple primary malignancies in patients with Merkel cell carcinoma1

Background Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumour, the incidence of which is increasing. Second malignancies have been reported to occur with high incidence in these patients. Objectives We report the rate and nature of multiple malignancies in patients with MCC treated over a 10 year period in Addenbrooke’s Hospital in Cambridge, United Kingdom, as well as the temporal relationship of these additional malignancies to the diagnosis of MCC. Results The 27 patients had an approximately equal sex incidence with a median age at diagnosis of 79 years. Seventy percent (n=19) of patients had a second primary malignant tumour; and 7 of these patients had two or more tumours in addition to the MCC. Eighteen patients had additional cutaneous malignancies: melanoma, squamous cell carcinoma and basal cell carcinoma, and 8 patients presented non‐cutaneous malignancy including colorectal, haematological and breast tumours. Of the 28 additional tumours in our patients, half were diagnosed prior to presentation of MCC, 32% within 6 months of diagnosis, and 18% between 6 months and 3 years after diagnosis. Possible reasons for the high rate of additional tumours in this population are discussed. Conclusions Our figures reflect a higher incidence of multiple malignancies in those with Merkel cell tumour than has previously been reported. This has important implications for the care and surveillance of these patients.     

Percutaneous Excisional Biopsy of Palpable Breast Masses under Ultrasound Visualization

Abstract:   A palpable breast mass is a common reason for surgical consultation. Our goal was to determine whether ultrasound-guided vacuum-assisted core biopsy (US-VACB) is safe and effective in completely removing presumed benign palpable breast masses. We conducted a cohort study of 201 consecutive patients with presumed benign palpable masses who underwent removal with US-VACB. The main outcome measured was the successful removal of palpable masses. Palpable masses were successfully removed with US-VACB in 99% of cases; 2% were cancer and 7.5% were atypical ductal hyperplasia or phyllodes tumor. Two clinical recurrences representing a seroma were seen on follow-up. US-VACB is safe and effective in the initial diagnosis and management of presumed benign palpable breast masses. It provides the benefits of percutaneous biopsy and the palpable abnormality no longer remains.      

Improving on National Quality Indicators of Breast Cancer Care in a Large Public Hospital as a Means to Decrease Disparities for African American Women

Background

In April 2007, the National Quality Forum (NQF) endorsed the first nationally recognized hospital-based performance measures for stage I, II, and III breast cancer. The purpose of this study was to document compliance with the 3 NQF breast quality indicators during 2 time intervals in a metropolitan public hospital.

Materials and Methods

Tumor registry and medical records were used to identify patient demographics and treatments before (2005–2006) and after (2008) implementations in 2007 as a result of the NQF audit. Program changes included: hiring a dedicated medical oncology nurse practitioner, requiring the radiation oncology case manager to attend weekly multidisciplinary conferences, educating Patient Navigators of the importance of multimodal care, and providing support groups for patients addressing importance of completion of all treatment options.

Results

A total of 213 female patients were diagnosed with and treated for stage I, II, or III breast cancer in 2005–2006 and 2008. Of these, 189 (89%) were African American (AA) women. Also, 70 patients of 86 (81.3%) received radiation therapy, 60 of 77 (77.9%) received or were considered for adjuvant chemotherapy, and 124 of 144 (86.1%) for hormonal therapy according to NQF indicators. After 2007, patients receiving radiation therapy increased from 75.8 to 95.8%. Patients receiving or considered for adjuvant chemotherapy or hormonal therapy increased from 73.7 to 93.7% and from 84.1 to 90.0%, respectively.

Conclusions

NQF breast cancer indicators provided a mechanism to improve compliance of multimodal treatment in our center. Raising awareness of these indicators in the multidisciplinary conference, hiring dedicated personnel, and educating patients has led to major improvements in breast cancer care.     

18F‐fluorodeoxyglucose positron emission tomography imaging in brain tumours: The Western Australia positron emission tomography/cyclotron service experience

¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scans in the first 49 patients referred with either possible brain tumour or brain tumour recurrence were reviewed. FDG‐PET imaging was reported with reference to anatomical imaging. Based on the report the FDG study was classified as either positive or negative for the presence of tumour. Thirty‐eight cases were included in the analysis, 21 having pathological data and 17 with diagnostic clinical follow up. Eleven were excluded, as they had inadequate follow‐up data. Of the 21 cases with pathology, 18 were shown to have tumour. In this group there were five false‐negative scans and two false‐positive PET scans. Seventeen cases were assessed by clinical follow up, nine were considered to have been tumour. There were two false negatives with one false positive. The overall sensitivity, specificity and positive and negative predictive values were 74, 73, 87 and 53% respectively. This is similar to figures previously quoted in published work. Despite relatively limited numbers, the utility of FDG PET imaging in our hands is similar to published reports. With a positive predictive value of 87%, a positive FDG study indicates a high likelihood that there is brain tumour present. A negative study does not exclude the presence of tumour.