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Chun-Jui Weng,1– 3 Chieh-Tun Liao,2 Ming-Yi Hsu,2,4 Fu-Pang Chang,5 Shih-Jung Liu1,2 1Department of Orthopedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 3Department of Orthopaedics, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 4Department of Radiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, TaiwanCorrespondence: Shih-Jung Liu, Department of Orthopedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital at Linkou and Department of Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Taoyuan, 33302, Taiwan, Tel +886-3-2118166, Fax +886-3-2118558, Email shihjung@mail.cgu.edu.twIntroduction: In this study, simvastatin-incorporated poly(D,L-lactide-co-glycolide) (PLGA) nanofibrous mats were fabricated via electrospinning, and their efficacy in the repair of the Achilles tendon was evaluated.Methods: The morphology of spun nanofibers and the in vitro drug release kinetics were assessed, while the in vivo efficacy in tendon repair was tested using a rat model.Results: Images obtained by scanning electron microscopy revealed that spun nanofibers exhibit a porous structure with a fiber diameter of approximately 350 nm. Fourier-transform infrared spectrometry and differential scanning calorimetry demonstrated successful incorporation of pharmaceutical agents into the PLGA nanofibers. The drug-loaded nanofibrous membranes sustainably discharged high concentrations of simvastatin for > 28 days at the target site, and drug concentrations in blood were low. Tendons repaired using simvastatin-eluting nanofibers exhibited superior mechanical strength and animal activities to those repaired without nanofibers or with pure PLGA nanofibers.Discussion: Simvastatin-loaded nanofibers demonstrated effectiveness and sustainable capability for the repair of Achilles tendons. Eventually biodegradable drug-eluting nanofibrous mats may be used in humans for the treatment of tendon ruptures.Keywords: simvastatin, nanofibers, tendon repair, sustainable release

Kuo-Sheng Liu,1 Ching-Wei Kao,2 Yuan-Yun Tseng,3 Shih-Kuang Chen,4 Yu-Ting Lin,4 Chia-Jung Lu,4,5 Shih-Jung Liu4,5 1Department of Thoracic and Cardiovascular Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Anesthesiology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 3Department of Neurosurgery, New Taipei Municipal Tu-Cheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan; 4Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 5Department of Orthopedic Surgery, Bone and Joint Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, TaiwanTel +886-3-2118166Fax +886-3-2118558Email shihjung@mail.cgu.edu.twBackground: Postoperative tissue adhesion is a major concern for most surgeons and is a nearly unpreventable complication after abdominal or pelvic surgeries. This study explored the use of sandwich-structured antimicrobial agents, analgesics, and human epidermal growth factor (hEGF)-incorporated anti-adhesive poly(lactic-co-glycolic acid) nanofibrous membranes for surgical wounds.Materials and Methods: Electrospinning and co-axial electrospinning techniques were utilized in fabricating the membranes. After spinning, the properties of the prepared membranes were assessed. Additionally, high-performance liquid chromatography and enzyme-linked immunosorbent assays were utilized in assessing the in vitro and in vivo liberation profiles of the pharmaceuticals and the hEGF from the membranes.Results: The measured data suggest that the degradable anti-adhesive membranes discharged high levels of vancomycin/ceftazidime, ketorolac, and hEGF in vitro for more than 30, 24, and 27 days, respectively. The in vivo assessment in a rat laparotomy model indicated no adhesion in the peritoneal cavity at 14 days post-operation, demonstrating the anti-adhesive capability of the sandwich-structured nanofibrous membranes. The nanofibers also released effective levels of vancomycin, ceftazidime, and ketorolac for more than 28 days in vivo. Histological examination revealed no adverse effects.Conclusion: The outcomes of this study implied that the anti-adhesive nanofibers with sustained release of antimicrobial agents, analgesics, and growth factors might offer postoperative pain relief and infection control, as well as promote postoperative healing of surgical wounds.Keywords: nanofibrous anti-adhesive membrane, poly(lactic-co-glycolic acid), extended release, vancomycin, ceftazidime, ketorolac, hEGF

Background Despite recent advancements in surgical techniques, the repair of tendon rupture remains a challenge for surgeons. The purpose of this study was to develop novel doxycycline-loaded biodegradable nanofibrous membranes and evaluate their efficacy for the repair of Achilles tendon rupture in a rat model. Materials and methods The drug-loaded nanofibers were prepared using the electrospinning process and drug release from the prepared membranes was investigated both in vitro and in vivo. Furthermore, the safety and efficacy of the drug-loaded nanofibrous membranes were evaluated in rats that underwent tendon surgeries. An animal behavior cage was employed to monitor the post-surgery activity of the animals. Results The experimental results demonstrated that poly(D,L-lactide-co-glycolide) (PLGA) nanofibers released effective concentrations of doxycycline for more than 40 days post-surgery, and the systemic plasma drug concentration was low. Rats receiving implantation of doxycycline-loaded nanofibers also showed greater activities and stronger tendons post-operation. Conclusion Nanofibers loaded with doxycycline may have great potential in the repair of Achilles tendon rupture.

Background The high lifetime risk of vascular disease is one of the important issues that plague patients with diabetes mellitus. Systemic oral vildagliptin administration favors endothelial recovery and inhibits smooth muscle cell (SMC) proliferation. However, the localized release of vildagliptin in the diabetic vessel damage has seldom been investigated. Research design and methods In this work, nanofiber-eluting stents that loaded with vildagliptin, a dipeptidyl peptidase-4 enzyme (DPP-4) inhibitor, was fabricated to treat diabetic vascular disease. To prepare nanofibers, the poly (D,L)-lactide-co-glycolide (PLGA) and vildagliptin were mixed using hexafluoroisopropanol and electrospinning process. In vitro and in vivo release rates of the vildagliptin were characterized using high-performance liquid chromatography. Results Effective vildagliptin concentrations were delivered for more than 28 days from the nanofibrous membranes coating on the surface of the stents in vitro and in vivo. The vildagliptin-eluting PLGA membranes greatly accelerated the recovery of diabetic endothelia and reduced SMC hyperplasia. The type I collagen content of the diabetic vascular intimal area that was treated by vildagliptin-eluting stents was lower than that of the non-vildagliptin-eluting group. Conclusion The experimental results revealed that stenting with vildagliptin-eluting PLGA membranes could potentially promote healing for diabetic arterial diseases.

Chemotherapy is ineffective for treating malignant glioma (MG) because of the low therapeutic levels of pharmaceuticals in tumour tissues and the well-known tumour resistance. The resistance to alkylators is modulated by the DNA repair protein O

Shang-Hung Chang,1 Cheng-Hung Lee,1 Yung-Hsin Yeh,1 Shih-Jung Liu,2 Chao-Jan Wang,3 Ming-Yi Hsu,3 Wei-Jan Chen1 1Cardiovascular Department, Chang Gung Memorial Hospital, Chang-Gung University College of Medicine, Tao-Yuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Background: The drug-eluting stent is a standard approach for the treatment of coronary artery disease. Propylthiouracil (PTU), an antithyroid drug, has been proven to suppress neointimal formation after balloon injury. Materials and methods: This study used a biodegradable polymer coating with PTU to test its effects on platelet function, re-endothelialization, and neointimal formation after vascular injury. Electrospinning was used to fabricate hybrid stents and generate PTU-loaded nanofibers.Results: PTU-eluting stents maintained a stable release of PTU for 3weeks. The PTU-coated stent markedly decreased the neointimal formation induced by vascular injury in the descending aorta of rabbits. Moreover, the PTU coating reduced platelet adhesion on the surface of the biodegradable membrane, which was reflected by the decreased expression of adhesion molecule in PTU-treated endothelial cells. The PTU coating enhanced re-endothelialization in injured aortas. In vitro, PTU exerted less suppressive effect on the proliferation and migration of endothelial cells than on those of vascular smooth muscle cells. Furthermore, treatment of endothelial cells with PTU induced phosphorylation (Ser1177) of endothelial nitric oxide synthase as well as its association with heat shock protein 90, supporting the protective role of PTU in endothelial function. The level of thyroid-stimulating hormone remained unchanged during the experimental period. Conclusion: This study indicates that PTU can be released locally and steadily in injured aortas, with some local effects but without systemic effects. Furthermore, PTU-coated stents may have beneficial effects on neointimal formation, endothelial cell, and platelet functions. Keywords: drug-eluting stent, propylthiouracil, neointimal formation, endothelial cell, platelet

Ching-Wei Kao,1,2 Demei Lee,2 Min-Hsuan Wu,2 Jan-Kan Chen,3 Hong-Lin He,4 Shih-Jung Liu2,5 1Department of Anesthesiology, Chiayi Chang Gung Memorial Hospital, Chiayi, 2Department of Mechanical Engineering, 3Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, 4Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, 5Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan Abstract: The aim of this study was to develop and evaluate the effectiveness of biodegradable nanofibrous lidocaine/ketorolac-loaded anti-adhesion membranes to sustainably release analgesics on abdominal surgical wounds. The analgesic-eluting membranes with two polymer-to-drug ratios (6:1 and 4:1) were produced via an electrospinning technique. A high-performance liquid chromatography (HPLC) assay was employed to characterize the in vivo and in vitro release behaviors of the pharmaceuticals from the membranes. It was found that all biodegradable anti-adhesion nanofibers released effective concentrations of lidocaine and ketorolac for over 20days post surgery. In addition, a transverse laparotomy was setup in a rat model for an in vivo assessment of activity of postoperative recovery. No tissue adhesion was observed at 2 weeks post surgery, demonstrating the potential anti-adhesion capability of the drug-eluting nanofibrous membrane. The postoperative activities were recorded for two groups of rats as follows: rats that did not have any membrane implanted (group A) and rats that had the analgesic-eluting membrane implanted (group B). Rats in group B exhibited faster recovery times than those in group A with regard to postoperative activities, confirming the pain relief effectiveness of the lidocaine- and ketorolac-loaded nanofibrous membranes. The experimental results suggested that the anti-adhesion nanofibrous membranes with sustainable elution of lidocaine and ketorolac are adequately effective and durable for the purposes of postoperative pain relief in rats. Keywords: biodegradable nanofiber, anti-adhesive membrane, sustainable release, lidocaine, ketorolac&nbsp

The high lifetime risk of vascular disease is one of the important issues that plague patients with diabetes mellitus. Systemic oral vildagliptin administration favors endothelial recovery and inhibits smooth muscle cell (SMC) proliferation. However, the localized release of vildagliptin in the diabetic vessel damage has seldom been investigated.In this work, nanofiber-eluting stents that loaded with vildagliptin, a dipeptidyl peptidase-4 enzyme (DPP-4) inhibitor, was fabricated to treat diabetic vascular disease. To prepare nanofibers, the poly (D,L)-lactide-co-glycolide (PLGA) and vildagliptin were mixed using hexafluoroisopropanol and electrospinning process. In vitro and in vivo release rates of the vildagliptin were characterized using high-performance liquid chromatography.Effective vildagliptin concentrations were delivered for more than 28 days from the nanofibrous membranes coating on the surface of the stents in vitro and in vivo. The vildagliptin-eluting PLGA membranes greatly accelerated the recovery of diabetic endothelia and reduced SMC hyperplasia. The type I collagen content of the diabetic vascular intimal area that was treated by vildagliptin-eluting stents was lower than that of the non-vildagliptin-eluting group.The experimental results revealed that stenting with vildagliptin-eluting PLGA membranes could potentially promote healing for diabetic arterial diseases.

Yung-Hen Hsu,1,2 Chang-Tun Lin,2 Yi-Hsun Yu,1,2 Ying-Chao Chou,1,2 Shih-Jung Liu,1,2 Err-Cheng Chan3 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, 2Department of Mechanical Engineering, 3Department of Medical Biotechnology and Laboratory Science, School of Medical Technology, Chang Gung University, Tao-Yuan, Taiwan Abstract: In this study, we developed biodegradable sheath-core-structured drug-eluting nanofibers for sustainable delivery of antibiotics (vancomycin and ceftazidime) and recombinant human bone morphogenetic protein (rhBMP-2) via electrospinning. To prepare the biodegradable sheath-core nanofibers, we first prepared solutions of poly(D,L)-lactide-co-glycolide, vancomycin, and ceftazidime in 1,1,1,3,3,3-hexafluoro-2-propanol and rhBMP-2 in phosphate-buffered solution. The poly(D,L)-lactide-co-glycolide/antibiotics and rhBMP-2 solutions were then fed into two different capillary tubes controlled by two independent pumps for coaxial electrospinning. The electrospun nanofiber morphology was observed under a scanning electron microscope. Wefurther characterized the in vitro antibiotic release from the nanofibers via high-performance liquid chromatography and that of rhBMP-2 via enzyme-linked immunosorbent assay and alkaline phosphatase activity. We showed that the biodegradable coaxially electrospun nanofibers could release high vancomycin/ceftazidime concentrations (well above the minimum inhibition concentration [MIC]90) and rhBMP-2 for >4 weeks. These experimental results demonstrate that novel biodegradable nanofibers can be constructed with various pharmaceuticals and proteins for long-term drug deliveries. Keywords: biodegradable sheath-core nanofibers, coaxial electrospinning, vancomycin, ceftazidime, rhBMP-2, release characteristics

Injection molding has been one of the most important polymer processing methods for the manufacturing of plastic parts. This article discusses an innovative and effective infrared assisted injection molding process, which enables the rapid fabrication of surface-relief plastic diffusers. A mold insert bearing microfeatures is fabricated using a tungsten carbide turning machine. An infrared radiation system, which consists of four 1,000 W halogen infrared lamps and a semi-spherical reflective cover, is employed to provide additional heating for the mold surface that bears microfeatures. Before each molding cycle, the infrared energy is converted into heat at the master mold/plastic plate interface to increase the cavity surface temperature and to facilitate the replication of the microfeatures. After molding, the properties of the fabricated diffusers are verified with an optical microscope, scanning electronic microscope, surface profiler, and hazemeter. The results suggest that with a minimal heating of ...

In water assisted injection moulded parts, structural ribs are usually designed to reinforce the parts as well as to serve as water channels. Water penetration in the channels results in improved mouldability and minimises sinkmarks. However, water leaves a rib core void, which reduces part rigidity. The present study examines the core out shapes of channels in water assisted injection moulded parts. The effects of channel geometry as well as processing conditions such as water injection delay time, water temperature, water pressure, etc., on the core out shapes were investigated. For the parameters selected, melt temperature, short shot size and water injection delay time were found to be the principal factors affecting the core out shapes of moulded parts. The core out geometries in water assisted injection moulded parts were compared with those in gas assisted injection moulded products. Water penetrated the parts with higher core out ratios, which are the ratios of the cross-sectional area of ...

The present study is devoted to investigating the gloss difference phenomenon occurring on the surface of water assisted injection moulded parts. Experiments were carried out on an 80-ton injection moulding machine equipped with a laboratory scale water injection system, which included a water pump, a water injection pin, a water tank equipped with a temperature regulator, and a control circuit. The material used was pigmented polypropylene. A plate cavity with a rib across the centre was used. Various processing variables were studied in terms of their influence on the surface gloss difference of moulded parts: melt temperature, mould temperature, melt filling speed, short-shot size, water pressure, water temperature, water hold and water injection delay time. After moulding, a glossmeter was used to measure the surface gloss profiles of the parts. A roughness meter and differential scanning calorimeter were also employed to characterise the surface quality of moulded parts. It was found that the...

This report investigates the filling phenomena of the water assisted injection moulding process by using a flow visualisation technique. Experiments were carried out on an 80-tonne injection-moulding machine equipped with a laboratory-developed water injection unit. The material used was semi-crystalline polypropylene. A flow visualisation mould was specially designed and made for this study. A high-speed video camera was used to record the mould filling phenomena of rectangular cavities with three-channel geometry and layouts: a flat plate, a plate with two zones of different depths and a plate with symmetric ribs. The interaction between the assisting water and the polymer melt during moulding was observed, and insight into the water penetration behaviour was summarised.

This report investigated, both experimentally and numerically, the cooling process in water assisted injection moulded parts. Experiments were carried out on a laboratory developed water assisted injection moulding system, which included an injection moulding machine, a water pump, a water injection pin, a water tank equipped with a temperature regulator, and a control circuit. The resin used was semi-crystalline polypropylene. The in-mould temperature of the polymeric materials during the cooling process was measured. A transient heat transfer finite element model was adopted to simulate and predict the temperature variation within water assisted injection moulded products. Simulated results matched well with the experimental data. Experimental investigation and numerical simulations of a water assisted injection moulding cooling process can provide an improved understanding of the influence of water related parameters on the cooling process of water assisted injection moulded parts.

Gas assisted injection moulding has proved to be a breakthrough in moulding technology for thermoplastic materials. However, there are still unsolved problems that limit the overall success of this technique. The aim of this work was to study the phenomenon of gloss variations occurring across the surfaces of gas assisted injection moulded parts. Experiments were carried out on an 80 t injection moulding machine equipped with a high pressure, nitrogen gas injection unit. The materials used were pigmented acrylonitrile/butadiene/ styrene and polypropylene. A plate cavity with a gas channel across its centre was used to mould the parts. Various processing parameters were varied: melt temperature; mould temperature; melt filling speed; short shot size; gas pressure; and gas injection delay time. After moulding, a glossmeter was used to determine the effects of these processing parameters on the surface gloss profiles of the parts. A roughness meter and scanning electronic microscope were also employ...

Gas assisted injection moulding has become one of the most important methods for the manufacture of plastic products. However, there are several unsolved problems that confound the overall success of this technique. The weldline caused by the flow lead effect in the polymer melt is one of them. In this report, an L′18 orthogonal array design based on the Taguchi method has been conducted to investigate the flow lead induced weldlines in gas assisted injection moulded parts. A plate cavity with a gas channel on the side was used for moulding. Experiments were carried out on an 80 t reciprocating screw injection moulding machine equipped with a high pressure gas injection unit. After moulding, the depth of the weldline was measured. For the factors selected in the main experiments, melt injection temperature and mould temperature were found to be the principal factors affecting the weldline depth of gas assisted injection moulded parts. Experimental investigation of a gas assisted injection moulding...

The effects of different processing parameters on sinkmarks, which occur on the surface of injection moulded parts, have been investigated. An L'18 orthogonal array design based on the Taguchi method was conducted to minimise the sinkmarks of injection moulded thermoplastic parts and the relative significance of each processing parameter on the sinkmarks was considered. The polymeric material used was polypropylene and a plate cavity with various ribs was used for moulding. Experiments were carried out on a reciprocating injection moulding machine. After moulding, sinkmarks on the surface of moulded parts were measured using a profile meter. For the factors selected in the main experiments, the size of the gate, the melt temperature, and the width of the rib were found to be the principal parameters affecting sinkmark formation on injection moulded polypropylene. In this way experimental investigation can help in the understanding of the formation mechanism of sinkmarks, so that steps can be take...

Rotational moulding is one of the most important methods of manufacture of hollow plastic products. However, there are several unsolved problems that confound the overall success of this technique, including surface pin holes and internal bubbles of moulded parts, caused by inappropriate mould design and processing conditions. In this report, an L′18 experimental matrix design based on the Taguchi method was conducted to optimise the bubble size of rotationally moulded parts. Experiments were carried out on a laboratory scale biaxial rotation moulding unit. The polymeric material used to mould the parts was linear low density polyethylene. After moulding, the size of the bubbles on the surface of moulded parts was characterised by an image analysis system. For the factors selected in the main experiments, the cooling conditions and the particle size of the material were found to be the principal factors affecting the bubble size of rotationally moulded thermoplastics. In addition, mould pressuris...

Yin-Kai Chao,1 Cheng-Hung Lee,2 Kuo-Sheng Liu,1 Yi-Chuan Wang,3 Chih-Wei Wang,4 Shih-Jung Liu3 1Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 4Department of Pathology, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan Background: Inadequate intrapleural drug concentrations caused by poor penetration of systemic antibiotics into the pleural cavity is a major cause of treatment failure in empyema. Herein, we describe a novel antibiotic-eluting pigtail catheter coated with electrospun nanofibers used for the sustained release of bactericidal concentrations of penicillin in the pleural space.Methods: Electrospun nanofibers prepared using polylactide-polyglycolide copolymer and penicillin G sodium dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol were used to coat the surface of an Fr6 pigtail catheter. The in vitro patterns of drug release were tested by placing the catheter in phosphate-buffered saline. In vivo studies were performed using rabbits treated with penicillin either intrapleurally (Group 1, 20 mg delivered through the catheter) or systemically (Group 2, intramuscular injection, 10 mg/kg). Penicillin concentrations in the serum and pleural fluid were then measured and compared.Results: In vitro studies revealed a burst release of penicillin (10% of the total dose) occurring in the first 24 hours, followed by a sustained release in the subsequent 30 days. Intrapleural drug levels were significantly higher in Group 1 than in Group 2 (P