Search

Yi-Hsun Yu,1,2 Demei Lee,2 Yung-Heng Hsu,1,2 Ying-Chao Chou,1,2 Steve WN Ueng,1 Che-Kang Chen,2 Shih-Jung Liu1,2 1Department of Orthopedic Surgery, Musculoskeletal Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Taoyuan, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Department of Mechanical Engineering, Chang Gung University, No. 259 Wen-Hwa 1st Road, Guishan District, Taoyuan 333, TaiwanTel +886 3 211 8166Fax +886 3 211 8558Email shihjung@mail.cgu.edu.twIntroduction: Masquelet proposed a new solution for the healing of segmental bone defects, thus minimizing the disadvantages associated with traditional bone grafting. However, a major factor leading to the failure of this technique pertains to be the residual infection. Accordingly, we developed an antibiotic- and osteo-inductive agent-loaded composite scaffold to solve this problem.Methods: A mesh-like polycaprolactone scaffold was prepared using a lab-exploited solution-type three-dimensional printer, and hybrid sheath-core structured poly(lactic-co-glycolic-acid) nanofibers were fabricated using co-axial electrospinning technology. Vancomycin, ceftazidime, and bone morphological protein (BMP)-2 were employed. The in vitro and in vivo (rabbit fracture model) release patterns of applied agents from the composite scaffold were investigated.Results: The results revealed that the drug-eluting composite scaffold enabled the sustainable release of the medications for at least 30 days in vitro. Animal tests demonstrated that a high concentration of medications was maintained. Abundant growth factors were induced within the bioactive membrane stimulated by the applied scaffold. Finally, satisfactory bone healing potential was observed on radiological examination and biomechanical evaluation.Discussion: The developed composite scaffold may facilitate bone healing by inducing bioactive membrane formation and yielding high concentrations of

Malaria is caused by Plasmodium parasites and Plasmodium vivax is the dominant Plasmodium spp. in low-transmission regions outside of Africa. Due to the unique biological characteristics of this parasite, such regions often feature asymptomatic patients with sub-microscopic parasitaemia and relapses. Naturally acquired antibody responses are induced after Plasmodium infection, providing partial protection against high parasitaemia and clinical episodes. Serology is a promising tool for monitoring transmission levels, estimating past and recent exposure and identifying populations at risk of infections. However, due to key gaps in our knowledge of naturally acquired antibody responses to P. vivax, the full potential of serology has not yet been reached. This thesis aimed to establish antibody kinetics against a large panel of P. vivax antigens following infections in western Thailand, and investigate the factors potentially associated with the acquisition and development of antibody responses. A multiplexed bead-based assay was first established and antibody measurements against more than 50 antigens were taken in P. vivax-infected individuals from western Thailand following symptomatic and asymptomatic infections. I found that most P. vivax antigens followed a highly similar post-infection kinetic pattern in the absence of any boosting infections. The magnitude and longevity of antibody responses varied between antigens, antibody subclasses and subtypes. An assay quantifying the antigen-specific memory B cell responses was established and verified to determine the role of memory B cells on antibody kinetics for future experiments. Lastly, I reported that the genetic diversity of an antigen sequence had a significant impact on antigen-specific antibody responses, and such impact increased in individuals with more past exposure and mature immunity. The findings presented in this thesis provide novel insights into naturally acquired immunity development to P. vivax and

Lee CH, Hsieh MJ, Chang SH, et al. Int J Nano. 2019;14:7503–7513. The authors noticed a mistake in the published paper which was overlooked during the revision stages. On page 7511, in the Acknowledgments section, the sentence “… Chang Gung Memorial Hospital (Contract No. CMRPG3G1291) for financially supporting this research.” should read “… Chang Gung Memorial Hospital (Contract No. CMRPG3G1291 and CMRPG3G1292) for financially supporting this research.” The authors apologize for this oversight.Read the original article

Chen-Hung Lee,1 Ming-Jer Hsieh,1 Shang-Hung Chang,1 Kuo-Chun Hung,1 Chao-Jan Wang,2 Ming-Yi Hsu,2 Jyuhn-Huarng Juang,3 I-Chang Hsieh,1 Ming-Shien Wen,1 Shih-Jung Liu4,5 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Chang Gung University College of Medicine, Linkou, Taiwan; 2Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; 4Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 5Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan 33305, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Department of Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, TaiwanTel +886 3 211 8166Fax +886 3 211 8558Email profsjliu5347@gmail.comBackground: 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 vildaglipt

Ching-Wei Kao,1,2 Yuan-Yun Tseng,3,4 Kuo-Sheng Liu,5 Yen-Wei Liu,5 Jin-Chung Chen,6 Hong-Lin He,7 Yi-Chuan Kau,8 Shih-Jung Liu2,91Department of Anesthesiology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 3Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; 4Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Department of Thoracic and Cardiovascular Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Graduate Institute of Biomedical Science, Chang Gung University, Taoyuan, Taiwan; 7Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan; 8Department of Anesthesiology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 9Department of Orthopedic Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanBackground: This study exploited sheath-core-structured lidocaine/human EGF (hEGF)-loaded anti-adhesive poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous films for surgical wounds via a co-axial electrospinning technique.Materials and methods: After spinning, the properties of the co-axially spun membranes were characterized by scanning electron microscopy, laser-scanning confocal microscopy, Fourier Transform Infrared spectrometry, water contact angle measurements, and tensile tests. Furthermore, a HPLC analysis and an ELISA evaluated the in vitro and in vivo release curves of lidocaine and hEGF from the films.Results: PLGA anti-adhesion nanofibers eluted high levels of lidocaine and hEGF for over 32 and 27 days, respectively, in vitro. The in vivo evaluation of post-surgery recovery in a rat model demonstrated that no adhesion was noticed in tissues at 2 weeks after surgery illustrating the anti-adhesive performance of the sheath-core-structured nanofibers. Nanofibrous films effectively released lidocaine and hEGF for >2

Yi-Pin Chen,1,2 Yen-Wei Liu,3 Demei Lee,3 Jiantai Timothy Qiu,4,5 Tzung-Yan Lee,6,7 Shih-Jung Liu3,8 1Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 2Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 4Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; 5Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 6Graduate Institute of Traditional Chinese Medicine, School of Chinese Medicine, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 7Department of Traditional Chinese Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 8Department of Orthopedic Surgery, Linkou Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Background: In this study, we developed biodegradable andrographolide (AG)-eluting nanofibrous mats and evaluated their efficacy in treating cervical cancer. Materials and methods: Membranes of two different poly[(D,L)-lactide-co-glycolide] (PLGA)-to-AG ratios (6:1 and 3:1) were prepared via electrospinning technology. The liberation behavior of AG was evaluated. A cervical cancer model with C57BL/6J mice was created and employed for an in vivo efficacy assessment of the drug-eluting nanofibers. Twelve mice with cervical cancer were stochastically divided into three different groups (four animals per group): group A received no treatment as the control, group B was treated with pure PLGA mats, and group C was treated with AG-loaded nanofibrous membranes. The changes in tumor sizes were recorded. Results: All membranes eluted high concentrations of AG at the target area for three weeks, while the systemic drug concentration in the blood remained low. Histological analysis showed no obvious tissue inflammation. Compared with the mice in groups A and B, the tum

Cheng-Hung Lee,1 Ming-Jer Hsieh,1 Kuo-Sheng Liu,2,3 Che-Wei Cheng,3 Shang-Hung Chang,1 Shih-Jung Liu,3,4 Chao-Jan Wang,5 Ming-Yi Hsu,5 Kuo-Chun Hung,1 Yung-Hsin Yeh,1 Wei-Jan Chen,1 I-Chang Hsieh,1 Jyuhn-Huarng Juang,6 Ming-Shien Wen1 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan; 2Department of Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 4Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; 5Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan; 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Objective: The current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction.Methods: In this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents. The in vitro and in vivo ticagrelor concentrations were measured using a high-performance liquid chromatography assay. The effectiveness of ticagrelor-eluting stents was examined relative to that of sirolimus-eluting stents. Results: Adequate ticagrelor levels were detected for four weeks in vitro. Less HES5-positive labeling was found near the ticagrelor-eluting stented vessels (0.33±0.12) than close to the sirolimus-eluting stented

Kuo-Sheng Liu,1 Wei-Hsun Chen,1 Cheng-Hung Lee,2 Yong-Fong Su,3 Shih-Jung Liu3,4 1Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, Republic of China; 2Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, Republic of China; 3Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan, Republic of China; 4Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, Republic of China Background: The most common complaint after the Nuss procedure is severe postoperative chest pain. The aim of this study was to evaluate the effectiveness of analgesic-eluting biodegradable nanofibers in pain relief after the Nuss procedure.Materials and methods: Poly(D,L)-lactide-co-glycolide, lidocaine, and ketorolac were dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. This solution was electrospun into a nanofibrous membrane. The elution method and high-performance chromatography were used to characterize the in vitro drug release. Stainless steel bars with and without coating of the analgesic-eluting nanofibrous membrane were implanted underneath the sternums of New Zealand white rabbits. The in vivo characteristics were further investigated.Results: The in vitro study showed that the biodegradable nanofibers released high doses of lidocaine and ketorolac within 10 days. The in vivo study demonstrated high local and systemic concentrations of lidocaine and ketorolac. The serum creatinine level was unaffected. Animals that received implants of the analgesic-eluting nanofiber-coated stainless steel bar exhibited significantly greater food and water ingestion and physical activity than the control group did, indicating effective pain relief.Conclusion: The proposed analgesic-eluting biodegradable nanofibers contribute to the achievement of extended pain relief after the Nuss procedure, without obvious adverse effects, in an animal

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 3 weeks. 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 with

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 20 days 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 p

Yuan-Yun Tseng,1,2 Tao-Chieh Yang,3 Yi-Chuan Wang,4 Wei-Hwa Lee,5 Tzu-Min Chang,4 Yi-Chuan Kau,6 Shih-Jung Liu4,7 1Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, 2Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 3Department of Neurosurgery, Asia University Hospital, Taichung, 4Department of Mechanical Engineering, Chang Gung University, Taoyuan, 5Department of Pathology, Shuang Ho Hospital, Taipei Medical University, Taipei, 6Department of Anesthesiology, 7Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan Abstract: Glioblastoma is the most frequent and devastating primary brain tumor. Surgery followed by radiotherapy with concomitant and adjuvant chemotherapy is the standard of care for patients with glioblastoma. Chemotherapy is ineffective, because of the low therapeutic levels of pharmaceuticals in tumor tissues and the well-known tumor-cell resistance to chemotherapy. Therefore, we developed bilayered poly(d,l)-lactide-co-glycolide nanofibrous membranes that enabled the sequential and sustained release of chemotherapeutic and antiangiogenic agents by employing an electrospinning technique. The release characteristics of embedded drugs were determined by employing an in vitro elution technique and high-performance liquid chromato­graphy. The experimental results showed that the fabricated nanofibers showed a sequential drug-eluting behavior, with the release of high drug levels of chemotherapeutic carmustine, irinotecan, and cisplatin from day 3, followed by the release of high concentrations of the antiangiogenic combretastatin from day 21. Biodegradable multidrug-eluting nanofibrous membranes were then dispersed into the cerebral cavity of rats by craniectomy, and the in vivo release characteristics of the pharmaceuticals from the membranes were investigated. The results suggested that the nanofibrous membranes released high concentrat