Electrospinning of Polycaprolactone (PCL) and Gelatin Polymeric Fibers

Electrospinning is one of the commonly used polymeric fiber production technique, owing to its versatility and flexibility in spinning a wide range of polymers for various applications including tissue engineering. However, recent researches have been extensively focusing on exploring the electrospinnability of different polymers without fully realizing how the electrospinning parameters influence the electrospun fibrous structure, as the microstructure morphology will significantly affect the performance of electrospun membranes. The present work demonstrates the robustness of electrospinning technique in producing electrospun fibrous membranes with different microstructure morphology by altering the electrospinning parameters. Both PCL and gelatin solutions have been successfully transformed into electrospun fibrous membranes using an electrospinning machine. The PCL fibrous membranes consisted of beads and non-homogenous fibers while the gelatin membranes showed homogenous size of electrospun fibers. Results also revealed that the electrospinning parameters including solution and process parameters determined the microstructure morphology of electrospun membrane. The spindle-like beads in PCL membrane transformed into spherical size at higher solution concentration and applied voltage. Meanwhile, the gelatin membrane demonstrated similar morphology at different tip-collector distance. The size of gelatin fibers was also similar. Through this work, basic understanding on how the electrospinning parameters affect the morphology of different types of polymeric fibrous membrane can provide an insight for other researchers in facilitate production of electrospun membranes with desired microstructure morphology

Synthetic and Natural Fibrous Scaffolds for Soft Tissue Engineering Applications / Weily Khoo ...[et al.]

Fibrous scaffolds have been extensively studied as grafts for damaged tissue, owing to their physical architecture mimicking the native tissues like articular cartilage and skin. Developing mechanical robust fibrous scaffolds is therefore a critical issue to prevent scaffold failure that limits their applications in tissue engineering. This paper demonstrates our latest development of synthetic and natural fibrous scaffolds having physical architectures and mechanical properties comparable to that of native biological soft tissues. Synthetic fibrous scaffold was produced from gelatin solution using electrospinning technique while natural fibrous scaffold was extracted from small intestinal submucosa (SIS) of cattle. The SIS membrane was first decellurized and further reinforced with alginate hydrogel to form 3D composite scaffold. The physical architectures of both synthetic and natural fibrous scaffolds including thickness and microstructure morphology were characterized. SIS fibrous membrane reinforced with alginate hydrogel demonstrated more than 10 times of increment in scaffold thickness. Through scanning electron microscope (SEM) visualization, the synthetic fibrous scaffold demonstrated microstructures that mimic nanometer fiber and porous structure of soft collagenous tissues. Uniaxial tensile and fracture tests were performed to determine the tensile properties and fracture toughness of fibrous scaffolds. Both types of scaffolds showed tensile strength (0.81 – 38.30 MPa) and fracture toughness (0.86 – 32.52 kJ/m2) comparable to natural soft collagenous tissues. The developed tissue engineered scaffolds not only exhibit physical architectures mimicking native tissue structures but also demonstrate mechanical properties comparable to the native soft tissues

Electrospinning of Polycaprolactone (PCL) and Gelatin Polymeric Fibers / Shing Chee Lim ...[et al.]

Electrospinning is one of the commonly used polymeric fiber production technique, owing to its versatility and flexibility in spinning a wide range of polymers for various applications including tissue engineering. However, recent researches have been extensively focusing on exploring the electrospinnability of different polymers without fully realizing how the electrospinning parameters influence the electrospun fibrous structure, as the microstructure morphology will significantly affect the performance of electrospun membranes. The present work demonstrates the robustness of electrospinning technique in producing electrospun fibrous membranes with different microstructure morphology by altering the electrospinning parameters. Both PCL and gelatin solutions have been successfully transformed into electrospun fibrous membranes using an electrospinning machine. The PCL fibrous membranes consisted of beads and non-homogenous fibers while the gelatin membranes showed homogenous size of electrospun fibers. Results also revealed that the electrospinning parameters including solution and process parameters determined the microstructure morphology of electrospun membrane. The spindle-like beads in PCL membrane transformed into spherical size at higher solution concentration and applied voltage. Meanwhile, the gelatin membrane demonstrated similar morphology at different tip-collector distance. The size of gelatin fibers was also similar. Through this work, basic understanding on how the electrospinning parameters affect the morphology of different types of polymeric fibrous membrane can provide an insight for other researchers in facilitate production of electrospun membranes with desired microstructure morphology

Strategy on the production of bead free electrospun gelatin scaffolds

Electrospun scaffolds consist of micro-scale or nano-scale porous fibrous networks. These electrospun scaffolds had become increasingly popular in tissue engineering filed as it could provide nano-environment for cell culture and produced by using biodegrable polymer. One of the important key to provide such environment for cell culture is the porosity of the electrospun scaffolds as it is highly related with the cell-cell interaction. The porosity of the electrospun scaffolds could be affected by bead formation which is one of the common problems faced in electrospinning process. However, the formation of beads are difficult to be controlled as it depends on environmental factors such as humidity and operating temperature. Controlling these two environmental factors normally requires an expensive control system. This paper aims to solve the problem of bead formation by adjusting material concentration and process parameters without controlling the environmental factors. The parameters studied in this paper include polymer concentration, flow rate, distance between the syringe needle tip and collector and applied voltage. The microstructure of the electrospun scaffolds produced were visualised using scanning electron microscopy (SEM) and were analysed in terms of bead formation and fiber diameter. This study shows that polymer concentration is the best strategy to prevent bead formation in gelatin scaffolds while other process parameters such as applied voltage, distance between the syringe needle tip and the collector as well as flow rate can be used to control the fiber diameter. An understanding of the effects of each parameter provides a guideline to control microstructure morphology by producing bead-free electrospun gelatin scaffolds

A New RBFNDDA-KNN Network and Its Application to Medical Pattern Classification

Abstract. In this paper, a new variant of the Radial Basis Function Network with Dynamic Decay Adjust (RBFNDDA) is introduced for undertaking pattern classification problems with noisy data. The RBFNDDA network is integrated with the k-nearest neighbours algorithm to form the proposed RBFNDDA-KNN model. Given a set of labelled data samples, the RBFNDDA network undergoes a constructive learning algorithm that exhibits a greedy insertion behaviour. As a result, many prototypes (hidden neurons) that represent small (with respect to a threshold) clusters of labelled data are introduced in the hidden layer. This results in a large network size. Such small prototypes can be caused by noisy data, or they can be valid representatives of small clusters of labelled data. The KNN algorithm is used to identify small prototypes that exist in the vicinity (with respect to a distance metric) of the majority of large prototypes from different classes. These small prototypes are treated as noise, and are, therefore, pruned from the network. To evaluate the effectiveness of RBFNDDA-KNN, a series of experiments using pattern classification problems in the medical domain is conducted. Benchmark and real medical data sets are experimented, and the results are compared, analysed, and discussed. The outcomes show that RBFNDDA-KNN is able to learn information with a compact network structure and to produce fast and accurate classification results

Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization

Rapamycin synergizes cisplatin sensitivity in basal-like breast cancer cells through up-regulation of p73.

Recent gene expression profiling studies have identified five breast cancer subtypes, of which the basal-like subtype is the most aggressive. Basal-like breast cancer poses serious clinical challenges as there are currently no targeted therapies available to treat it. Although there is increasing evidence that these tumors possess specific sensitivity to cisplatin, its success is often compromised due to its dose-limiting nephrotoxicity and the development of drug resistance. To overcome this limitation, our goal was to maximize the benefits associated with cisplatin therapy through drug combination strategies. Using a validated kinase inhibitor library, we showed that inhibition of the mTOR, TGFβRI, NFκB, PI3K/AKT, and MAPK pathways sensitized basal-like MDA-MB-468 cells to cisplatin treatment. Further analysis demonstrated that the combination of the mTOR inhibitor rapamycin and cisplatin generated significant drug synergism in basal-like MDA-MB-468, MDA-MB-231, and HCC1937 cells but not in luminal-like T47D or MCF-7 cells. We further showed that the synergistic effect of rapamycin plus cisplatin on basal-like breast cancer cells was mediated through the induction of p73. Depletion of endogenous p73 in basal-like cells abolished these synergistic effects. In conclusion, combination therapy with mTOR inhibitors and cisplatin may be a useful therapeutic strategy in the treatment of basal-like breast cancers

Development of auditing in Malaysia: Legal, political and historical influences

This work investigates the role and contribution of external auditing as practised in the Malaysian society during the forty year period from independence in 1957 to just before the onset of the Asian Financial Crisis in 1997.It applies the political economic theory introduced by Tinker (1980) and refined by Cooper & Sherer (1984), which focuses on the social relations aspects of professional activity rather than economic forces alone.In a case study format where qualitative data was gathered mainly from primary and secondary source materials, the study found that the function of auditing in the Malaysian society in most cases is devoid of any essence of mission; instead it is created, shaped and transformed by the pressures which give rise to its development over time.The largely insignificant role that it serves is intertwined within the contexts in which it operates