Shih-Jung Liu

Sustainable release of vancomycin, gentamicin and lidocaine from novel electrospun sandwich-structured PLGA/collagen nanofibrous membranes.

This study investigated the in vitro release of vancomycin, gentamicin, and lidocaine from novel electrospun sandwich-structured polylactide-polyglycolide (PLGA)/collagen nanofibrous membranes. For the electrospinning of biodegradable membranes, PLGA/collagen and PLGA/vancomycin/gentamicin/lidocaine were separately dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). They were then electrospun into sandwich structured membranes, with PLGA/collagen for the surface layers and PLGA/drugs for the core layer. After electrospinning, an elution method and HPLC assay were employed to characterize the in vitro release rates of the pharmaceutics over a 30-day period. The experiment showed that biodegradable nanofibrous membranes released high concentrations of vancomycin and gentamicin (well above the minimum inhibition concentration) for 4 and 3 weeks, respectively, and lidocaine for 2 weeks. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity of vancomycin and gentamicin ranged from 30% to 100% and 37% to 100%, respectively. In addition, results indicated that the nanofibrous membranes were functionally active in responses in human fibroblasts. By adopting the electrospinning technique, we will be able to manufacture biodegradable biomimetic nanofibrous extracellular membranes for long-term drug delivery of various pharmaceuticals.

Novel biodegradable sandwich-structured nanofibrous drug-eluting membranes for repair of infected wounds: an in vitro and in vivo study

Background The purpose of this study was to develop novel sandwich-structured nanofibrous membranes to provide sustained-release delivery of vancomycin, gentamicin, and lidocaine for repair of infected wounds. Methods To prepare the biodegradable membranes, poly(D, L)-lactide-co-glycolide (PLGA), collagen, and various pharmaceuticals, including vancomycin, gentamicin, and lidocaine, were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into sandwich-structured membranes with PLGA/collagen as the surface layers and PLGA/drugs as the core. An elution method and a high-pressure liquid chromatography assay were used to characterize in vivo and in vitro drug release from the membranes. In addition, repair of infected wounds in rats was studied. Histological examination of epithelialization and granulation at the wound site was also performed. Results The biodegradable nanofibrous membranes released large amounts of vancomycin and gentamicin (well above the minimum inhibition concentration) and lidocaine in vivo for more than 3 weeks. A bacterial inhibition test was carried out to determine the relative activity of the antibiotics released. The bioactivity ranged from 40% to 100%. The nanofibrous membranes were functionally active in treating infected wounds, and were very effective as accelerators in early-stage wound healing. Conclusion Using the electrospinning technique, we will be able to manufacture biodegradable, biomimetic, nanofibrous, extracellular membranes for long-term delivery of various drugs.

Bone healing of tibial lengthening is enhanced by hyperbaric oxygen therapy: a study of bone mineral density and torsional strength on rabbits.

We investigated the effect of intermittent hyperbaric oxygen (HBO) therapy on the bone healing of tibial lengthening in rabbits. Twelve male rabbits were divided into two groups of six animals each. The first group went through 2.5 atmospheres absolute of hyperbaric oxygenation for 2 hours daily, and the second group did not go through hyperbaric oxygenation. Each animals right tibia was lengthened 5 mm using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all of the animals at 1 day before operation and at 3, 4, 5, and 6 weeks after operation. All of the animals were killed at 6 weeks postoperatively for biomechanical testing. Using the preoperative BMD as an internal control, we found that the BMD of the HBO group was increased significantly compared with the non HBO group. The mean %BMD at 3, 4, 5, and 6 weeks were 69.5%, 80.1%, 87.8%, and 96.9%, respectively, in HBO group, whereas the mean %BMD were 51.6%, 67.7%, 70.5%, and 79.2%, respectively, in non-HBO group (two tailed t test, p < 0.01, p < 0.01, p < 0.01, and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). Using the contralateral nonoperated tibia as an internal control, we found that torsional strength of lengthened tibia of the HBO group was increased significantly compared with the non-HBO group. The mean percent of maximal torque was 88.6% in HBO group at 6 weeks, whereas the mean percent of maximal torque was 76.0% in non-HBO group (two-tailed t test, p < 0.01). The results of this study suggest that the bone healing of tibial lengthening is enhanced by intermittent hyperbaric oxygen therapy.

Bone healing of tibial lengthening is delayed by cigarette smoking : Study of bone mineral density and torsional strength on rabbits

OBJECTIVE We investigated the effect of intermittent cigarette smoke inhalation on the bone healing of tibial lengthening in rabbits. METHODS Twelve male rabbits were divided into two groups of six animals each. The first group underwent intermittent cigarette smoke inhalation, and the second group did not undergo intermittent cigarette smoke inhalation. Each animals right tibia was lengthened 5 mm by using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all of the animals 1 day before operation and 3, 4, 5, and 6 weeks after operation. All of the animals were killed 6 weeks postoperatively for biomechanical testing. RESULTS By using the preoperative BMD as an internal control, we found that the BMD of the smoke-inhalation group was decreased significantly compared with the non-smoke-inhalation group. The mean %BMD at 3, 4, 5, and 6 weeks were 49.9%, 61.2%, 65.9%, and 71.0%, respectively, in the smoke-inhalation group, whereas the mean %BMD were 54.9%, 71.8%, 76.4%, and 82.0%, respectively, in the non-smoke-inhalation group (two-tailed t test, p > 0.05, p < 0.01, p < 0.01 and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). By using the contralateral nonoperated tibia as internal control, we found that torsional strength of the smoke-inhalation group was decreased significantly compared with the non-smoke-inhalation group. The mean percentage of maximal torque was 63.8% in the smoke-inhalation group, whereas the mean percentage of maximal torque was 77.1% in the non-smoke-inhalation group (two tailed t test, p < 0.01). CONCLUSION This study suggests that cigarette smoking delays the mineralization during the bone healing process of distraction osteogenesis and, thus, decreases the mechanical strength of the regenerating bone.

Development of a biodegradable antibiotic delivery system.

Antibiotic beads have been used as a drug delivery system for the treatment of various surgical infections. In this study, the copolymer 50:50 poly(DL-lactide):co-glycolide was mixed with vancomycin powder and hot compressing molded at 55 degrees C to form five types of biodegradable antibiotic beads. The beads were placed in 1 mL of phosphate buffered saline and incubated at 37 degrees C. The phosphate buffered saline was changed daily, and the removed buffer solutions were stored at -70 degrees C until the antibiotic concentration in each sample was determined by high performance liquid chromatography system assay. The concentration of vancomycin in each sample was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for more than 32 days. The release was most marked during the first 48 hours. All copolymer 50:50 poly(DI lactide):co-glycolide biodegradable beads released high concentrations of the antibiotics in vitro for the time needed to treat bone infections (4 to 6 weeks). The diameter of the sample inhibition zone ranged from 6.5 mm to 10 mm, and the relative activity of vancomycin ranged from 12.5% to 100%. Copolymers with low heat of formation temperatures are required for making a controlled release system to prevent antibiotic decomposition, which occurs when using the hot compressing molded method. The rate and duration of release from the antibiotic beads can be adjusted by varying the diameter of the beads. This offers a convenient method to adjust the release rate to meet the specific antibiotic requirements for different patients.

Hyperbaric oxygen therapy mitigates the adverse effect of cigarette smoking on the bone healing of tibial lengthening : An experimental study on rabbits

OBJECT We investigated whether -intermittent hyperbaric oxygen (HBO) therapy can mitigate the adverse effects of cigarette smoking on the bone healing of tibial lengthening by using a previously validated rabbit model. METHODS Eighteen male rabbits were randomly divided into three groups of six animals each. Group 1 (smoking plus HBO) went through intermittent cigarette smoke inhalation and hyperbaric oxygen therapy, group 2 (control) did not go through intermittent cigarette smoke inhalation or hyperbaric oxygen therapy and group 3 (smoking) went through intermittent cigarette smoke inhalation. Each animals right tibia was lengthened 5 mm by using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all the animals at 1 day before operation and 3, 4, 5, and 6 weeks after operation. All of the animals were killed at 6 weeks postoperatively for biomechanical testing. RESULTS By using the preoperative BMD as an internal control, we found that the BMD of group 1 (smoking plus HBO)and group 2 (control) was superior to that of group 3 (smoking). The mean %BMD at 3, 4, 5, and 6 weeks were 58.6%, 66.6%, 73.7%, and 83.8%, respectively, in group 1, whereas the mean %BMD were 52.0%, 64.3%, 70.1%, and 76.2%, respectively, in group 2, and the mean %BMD were 46.2%, 54.0%, 64.9%, and 69.4%, respectively, in group 3 (two-tailed t test, p > 0.05, p > 0.05, p > 0.05, and p < 0.05 at 3, 4, 5, and 6 week respectively between group 1 and group 2, p < 0.01,p < 0.01,p < 0.01, and p < 0.01 at 3, 4, 5, and 6 week, respectively, between group 1 and group 3 and p < 0.05, p < 0.05, p < 0.05, and p < 0.05 at 3, 4, 5, and 6 week respectively between group 2 and group 3). By using the contralateral nonoperated tibia as an internal control, we found that the torsional strength of group 1 (smoking plus HBO) and group 2 (control) was superior to that of group 3 (smoking). The mean percentage of maximum torque was 80.9% in group 1 (smoking plus HBO) and was 78.0% in group 2 (control), whereas the mean percentage of maximum torque was 59.6 % in group 3 (smoking) (two-tailed t test, p < 0.05 between groups land 3 and between groups 2 and 3, whereas p > 0.05 between groups 1 and 2). CONCLUSION This study suggests that smoke inhalation delays the bone healing in tibial lengthening; however, HBO mitigates the delayed healing effect of smoke inhalation and, thus, helps the smoking animal in achieving an expeditious bone healing in tibial lengthening.

Enhancement of posterolateral lumbar spine fusion using low-dose rhBMP-2 and cultured marrow stromal cells.

We tested the hypothesis that the dose of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) required to induce spine fusion can be reduced by combination with mesenchymal stem cells (MSCs). Twenty‐four adult rabbits underwent posterolateral intertransverse fusion at the L4–L5 level. The animals were divided into four groups based on the implant material: autologous iliac graft, Alginate‐MSCs composite, Alginate‐BMP‐2‐MSCs composite, and Alginate‐BMP‐2 composite. After 16 weeks, the rabbits were euthanized for radiographic examination, manual palpation, biomechanical testing, and histology. Radiographic union of 12 intertransverse fusion areas for the autogenous iliac graft, Alginate‐MSCs, Alginate‐BMP‐2‐MSCs, and Alginate‐BMP‐2 groups was 11, 8, 11, and 0, respectively. Moreover, manual palpation of six fusion segments in each subgroup found solid union to be 6, 1, 5, and 0, respectively. The average torques at failure of the first three groups were 2278 ± 135, 1943 ± 140, and 2334 ± 187 N‐mm, respectively. The failure torque did not differ significantly between the autograft and Alginate‐BMP‐2‐MSCs groups; both groups were significantly higher than the Alginate‐MSCs group. The results indicate that MSCs delivered with in vitro cellular doses of rhBMP‐2 are more osteoinductive than MSCs without rhBMP‐2. In combination with MSCs, a low dose (2.5 µg) of rh‐BMP‐2 could enhance bone formation and posterolateral spine fusion success in the rabbit model.

A novel soft-mold roller embossing method for the rapid fabrication of micro-blocks onto glass substrates

This paper reports a novel UV soft-mold roller embossing technique for the rapid fabrication of polymeric micro-block arrays onto glass substrates. A soft-mold roller embossing facility with UV exposure capacity has been designed, constructed and tested in our laboratory. To fabricate the soft mold with an array of micro-block cavities, a silicon mold with a micro-cavity array was first fabricated by photolithography and deep reactive ion etching. A polycarbonate film was gas pressurized hot embossed against the silicon mold to obtain a master of micro-blocks. The soft mold for the roller stamp was obtained by casting the polydimethylsiloxane over the polycarbonate master to obtain an array of micro-block cavities. During rolling operation, a step motor drove the roller and pressed the UV-curable photopolymer layer on the glass substrate through the rolling zone. A micro-block array was obtained. At the same time, the micro-block array was cured by the UV light radiation while traveling through the rolling zone. The effect of various processing parameters on the replicability of the micro-blocks was investigated. Under the proper processing conditions, 100 × 140 arrays of polymeric micro-blocks, with a dimension of 100 µm × 80 µm × 40 µm can be successfully fabricated. The experimental results in this study suggest that UV soft-mold roller embossing provides an effective way of fabricating microstructures onto glass substrates. The technique can eventually be developed to be used as an effective roll-to-roll process at room temperature and with low pressure. This would provide significant advantages in terms of a shorter cycle time as well as improved product quality.

Sintering Rheology of Semi-Crystalline Polymers

Abstract The focus of this study is to investigate the sintering mechanism of polyethylene. Experiments were conducted to observe the high temperature sintering behaviors of low density polyethylene (LDPE) and linear low density polyethylene (LLDPE). It was found that the sintering of polyethylene follows Frenkes model and is basically a Newtonian viscous flow. The sintering rate decreases as the viscosity of the resin increases. By increasing the temperature, one can shorten the time needed to complete the coalescence process. Experimental investigation will provide an improved understanding of the sintering of semi-crystalline polymers.

Augmentation of diabetic wound healing and enhancement of collagen content using nanofibrous glucophage-loaded collagen/PLGA scaffold membranes

This work developed nanofibrous drug-loaded collagen/poly-D-L-lactide-glycolide (PLGA) scaffold membranes that provided the sustained release of glucophage for the wounds associated with diabetes. PLGA, glucophage, and collagen were firstly dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol and were spun into nanofibrous membranes by electrospinning. High-performance liquid chromatography assay was used to characterize the in vivo and in vitro release rates of the pharmaceuticals from the membranes. High concentrations of glucophage were released for over three weeks from the nanofibrous membranes. The nanofibrous glucophage-loaded collagen/PLGA membranes were more hydrophilic than collagen/PLGA membranes and exhibited a greater water-containing capacity. The glucophage-loaded collagen/PLGA membranes markedly promoted the healing of diabetic wounds. Moreover, the collagen content of diabetic rats using drug-eluting membranes was higher than that of the control rats, because of the down-regulation of matrix metalloproteinase 9. The experimental results herein suggest that the nanofibrous glucophage-loaded collagen/PLGA membranes had effect for increasing collagen content in treating diabetic wounds and very effective promoters of the healing of such wounds in the early stages.