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A novel bifurcation stent coated with bioabsorbable nanofibers that deliver the extended and controlled release of rosuvastatin and paclitaxel was developed. Bioabsorbable bifurcation stents, consisting of a double-slit tubular main body and two spiral branches, were manufactured. Bi-layered poly (lactic-co-glycolic acid) nanofibers that contained rosuvastatin and paclitaxel were used for treating the stents. Various properties of the fabricated stents, including compression strengths, collapse pressure, water contact angle and flow properties within a circulation model, were quantified. In vitro nanofibrous elution chromatography assays from the drug-loading bifurcation stents were carried out for the release patterns of pharmaceuticals. The effectiveness of eluted rosuvastatin and paclitaxel in inhibiting the adhesion of platelets as well as the proliferation of smooth muscle cells (SMCs) were studied, respectively. The experimental results suggest that bioabsorbable nanofibrous bifurcation stents released high concentrations of rosuvastatin and paclitaxel for 27 and 70 days, respectively. The eluted drugs of rosuvastatin and paclitaxel effectively reduced adherent platelets and the proliferation of SMCs. The developed bioabsorbable nanofibrous bifurcation stents herein may provide a promising means of treating cardiovascular bifurcation lesions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A composite biodegradable polymeric model was developed to enhance tendon graft healing. This model included a biodegradable polylactide (PLA) bolt as the bone anchor and a poly(D,L-lactide-co-glycolide) (PLGA) nanofibrous membrane embedded with collagen as a biomimic patch to promote tendon-bone interface integration. Degradation rate and compressive strength of the PLA bolt were measured after immersion in a buffer solution for 3 months. In vitro biochemical characteristics and the nanofibrous matrix were assessed using a water contact angle analyzer, pH meter, and tetrazolium reduction assay. In vivo efficacies of PLGA/collagen nanofibers and PLA bolts for tendon-bone healing were investigated on a rabbit bone tunnel model with histological and tendon pullout tests. The PLGA/collagen-blended nanofibrous membrane was a hydrophilic, stable, and biocompatible scaffold. The PLA bolt was durable for tendon-bone anchoring. Histology showed adequate biocompatibility of the PLA bolt on a medial cortex with progressive bone ingrowth and without tissue overreaction. PLGA nanofibers within the bone tunnel also decreased the tunnel enlargement phenomenon and enhanced tendon-bone integration. Composite polymers of the PLA bolt and PLGA/collagen nanofibrous membrane can effectively promote outcomes of tendon reconstruction in a rabbit model. The composite biodegradable polymeric system may be useful in humans for tendon reconstruction.

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. We further 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.

Biodegradable poly([D,L]-lactide-co-glycolide) (PLGA) nanofibrous membrane embedded with two drug-to-polymer weight ratios, namely 1:3 and 1:6, which comprised PLGA 180 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg, and PLGA 360 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg, respectively, was produced as an artificial periosteum in the treatment of segmental femoral fractures. The nanofibrous membrane's drug release behavior was assessed in vitro using high-performance liquid chromatography and the disk-diffusion method. A femoral segmental fracture model with intramedullary Kirschner-wire fixation was established for the in vivo rabbit activity study. Twenty-four rabbits were divided into two groups. Twelve rabbits in group A underwent femoral fracture fixation only, and 12 rabbits in group B underwent femoral fracture fixation and were administered the drug-loaded nanofibers. Radiographs obtained at 2, 6, and 12 weeks postoperatively were used to assess the bone unions. The total activity counts in animal behavior cages were also examined to evaluate the clinical performance of the rabbits. After the animals were euthanized, both femoral shafts were harvested and assessed for their torque strengths and toughness. The daily in vitro release curve for lidocaine showed that the nanofibers eluted effective levels of lidocaine for longer than 3 weeks. The bioactivity studies of vancomycin and ceftazidime showed that both antibiotics had effective and sustained bactericidal capacities for over 30 days. The findings from the in vivo animal activity study suggested that the rabbits with the artificial drug-eluting periosteum exhibited statistically increased levels of activity and better clinical performance outcomes compared with the rabbits without the artificial periosteum. In conclusion, this artificial drug-eluting periosteum may eventually be used for the treatment of open fractures.

The nanofibrous biodegradable drug-loaded membranes that sustainably released recombinant human platelet-derived growth factor (rhPDGF-BB) to repair diabetic wounds were developed in this work.rhPDGF-BB and poly(lactic-co-glycolic acid) (PLGA) were mixed in hexafluoroisopropyl alcohol, followed by the electrospinning of the solutions into biodegradable membranes to equip the nanofibrous membranes. An elution technique and an enzyme-linked immunosorbent assay kit were used to determine the rhPDGF-BB release rates in vitro and in vivo from this membrane. Eighteen Sprague-Dawley streptozotocin-induced diabetic rats were randomized into 3 groups: rhPDGF-BB-loaded nanofibrous membrane group, PLGA only membrane group, and conventional gauze sponge group for the wound associated with diabetes of rat in each group.The nanofibrous biodegradable membranes released effective concentrations of rhPDGF-BB for over 21 days. The nanofibrous rhPDGF-BB-loaded PLGA membranes contained more water and were further hydrophilic than PLGA only fibers. The rhPDGF-BB-loaded PLGA membranes considerably helped the diabetic wounds repairing. Furthermore, the proliferative cells and angiogenesis of rats associated with diabetes by rhPDGF-BB-loaded nanofibrous membranes were greater than those of other groups, owing to the increased matrix metalloproteinase 9.These biodegradable rhPDGF-BB-loaded membranes were effective in treating diabetic wounds as very advanced accelerators during the initial phases of wound-healing process., Competing Interests: The authors have no conflicts of interest to disclose.

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Successful treatment of a brain infection requires aspiration of the pus or excision of the abscess, followed by long-term (usually 4-8 weeks) parenteral antibiotic treatment. Local antibiotic delivery using biodegradable drug-impregnated carriers is effective in treating postoperative infections, thereby reducing the toxicity associated with parenteral antibiotic treatment and the expense involved with long-term hospitalization. We have developed vancomycin-loaded, biodegradable poly[lactic-co-glycol acid] nanofibrous membranes for the sustainable delivery of vancomycin to the brain tissue of rats by using the electrospinning technique. A high-performance liquid chromatography assay was employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the membranes. The experimental results suggested that the biodegradable nanofibers can release high concentrations of vancomycin for more than 8 weeks in the cerebral cavity of rats. Furthermore, the membranes can cover the wall of the cavity after the removal of abscess more completely and achieve better drug delivery without inducing adverse mass effects in the brain. Histological examination also showed no inflammation reaction of the brain tissues. By adopting the biodegradable, nanofibrous drug-eluting membranes, we will be able to achieve long-term deliveries of various antibiotics in the cerebral cavity to enhance the therapeutic efficacy of cerebral infections.

Objective: Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans. The only interstitial chemotherapy pharmaceutical approved to date for GBM treatment is the Gliadel® wafer. Despite the safety and efficacy of this approach that have been demonstrated in patients undergoing resection of both newly diagnosed and recurrent malignant gliomas, the wafer provides an effective release of the anticancer 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for only 5 days., Methods: In this study, the authors developed biodegradable poly[(d,l)-lactide-co-glycolide] nanofibrous membranes via electrospinning that provided a sustained release of BCNU. An elution method and a HPLC assay were employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the electrospun membranes., Results: The experimental results show that the biodegradable, nanofibrous membranes released high concentrations of BCNU for more than 6 weeks in the cerebral cavity of rats. Furthermore, the membranes can better conform to the geometry of the brain tissue and can cover more completely the tissue after the removal of tumors, achieving better drug transport without interfering with the normal function of the brain. Histological examination showed no obvious inflammation reactions of the brain tissues., Conclusion: Adopting the electrospinning technique will help in manufacturing biodegradable, nanofibrous membranes for the long-term deliveries of various anticancer drugs in the cerebral cavity, which will further enhance the therapeutic efficacy of GBM treatment.

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., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Inadequate localized drug concentrations and systemic adverse effects are among the concerns when regional infections are treated with systemic antibiotics. We designed and fabricated a poly(D,L)-lactide-co-glycolide (PLGA)-based biodegradable drug delivery system and evaluated the release of antibiotics both in vitro and in vivo., Methods: PLGA copolymer and penicillin G sodium were mixed, compressed, and sintered to fabricate biodegradable antibiotic beads. The beads were placed in phosphate-buffered saline to test the characteristics of in vitro drug release. The beads then were introduced into the pleural cavities through chest tubes of six New Zealand white rabbits. Daily pleural effusion was collected to measure the antibiotic concentration and bacterial inhibitory characteristics., Results: Forty percent of the penicillin was released in the first day in the in vitro study. The rest of the antibiotic was then gradually released in the following 30 days. All six animals survived the experiment. The initial surge of drug release was less significant in the pleural cavity than in the phosphate-buffered saline. The drug concentrations were well above the minimum inhibitory concentration breakpoint for penicillin susceptibility throughout the study period in both in vitro (30 days) and in vivo (14 days) studies., Conclusions: These preliminary findings demonstrated that the biodegradable PLGA antibiotic beads could achieve a fairly steady antibiotic release in the pleural cavity for at least 2 weeks. This drug delivery system may have the potential to serve as an adjuvant treatment of pleural cavity infection.

This paper developed solvent-free drug-eluting implants for metronidazole delivery for the treatment of periodontal disease and investigated the characteristics of the drug's release from the implants, both in vitro and in vivo, using an HPLC assay. The metronidazole exhibited a two-stage release behavior in vitro with an initial burst release followed by a diffusion-controlled release and then a secondary burst release. The accumulated drug release reached 100% on the 18th day, and the drug-eluting implant was totally dissolved on the same day. Additionally, the drug-eluting disks were implanted within the sub-gingival space of both lower incisors of six rabbits. The curve of in vivo drug release was smoother and showed a predominantly diffusion-controlled release. The implants were totally dissolved at 2 weeks after implantation. The concentration of metronidazole remained above the MIC(90) during the entire investigation.

The purpose of this report was to develop novel biodegradable occlusion devices for closure of atrial septal defects (ASD). To manufacture the biodegradable occluders, polycaprolactone (PCL) components were first fabricated by a lab-scale micro-injection molding machine. They were then assembled and hot-spot welded into double umbrella-like devices of 50 mm in diameter. A special mechanism at the axis of the occluder was designed to self-lock the occluder after the two umbrellas were expanded. Furthermore, a nanofibrous matrix of poly-D-L-lactide-glycolide (PLGA)/type I collagen blend was produced via electrospinning to develop biodegradable and biomimetic anti-shunt membranes for the occluders. Characterization of the biodegradable PCL occluders was carried out. PCL occluders exhibited mechanical properties comparable to that of commercially available Amplatzer occluders. The sealing capability of biodegradable occluders was found superior to that of Amplatzer occluders. In addition, the cell attachment and spreading of endothelial cells seeded on the PLGA/collagen nanofibrous matrix and the interaction between cells and PLGA/collagen nanofibers were studied. The nanofibrous membranes made of PLGA/collagen were very effective in promoting cell proliferation during culture.

The authors investigated poly(lactide-co-glycolide) (PLGA) capsule and collagen composite system for antibiotics and bone cells delivery to treat infected bone defects. Poly(lactide-co-glycolide) was mixed with vancomycin and hot compressing molded to form an antibiotic capsule. Rabbit mesenchymal stem cells (MSCs) were entrapped in collagen gel phase and dispersed throughout the void volume of capsule. In vitro study, the composite systems were cultured in complete or osteogenic medium for 21 days. The profiles of vancomycin released from the systems were evaluated using the high-performance liquid chromatography method. Relative activity of vancomycin against Staphylococcus aureus was determined by an antibiotic disk diffusion method. The expression of osteogenic gene was determined by reverse-transcription polymerase chain reaction. The alkaline phosphatase activity and calcium level of the MSCs were assessed. Analytical results demonstrated that the concentrations of vancomycin eluted from the composite system were above the minimal inhibitory concentration for 21 days. Sample inhibition zone was 10 to 24 mm, and the relative activity was 17.6% to 100%. mRNA of Cbfa1 and osteocalcin were detected, and increased alkaline phosphatase activity and calcium levels were noted. In in vivo investigation, the PKH 26-labeled MSCs and composite systems were implanted in the distal femoral cavities of four rabbits. The local concentration of vancomycin was above the minimal inhibitory concentration for 56 days. Sample inhibition zone was 9 mm to 24 mm, and the relative activity was 11.8% to 100%. Implanted PKH 26-labeled MSCs were identified in the newly formed bony trabeculae in specimens at 2 and 4 months after implantation. The results offer a potential approach to meet clinical requirements in the treatment of infected bone defects.

Background: Posterolateral spinal fusion is used to treat patients with degenerative spinal disorders. In this study, we investigated the effectiveness of a mesenchymal stem cell (MSC)/hydroxyapatite/type I collagen hybrid graft for posterolateral spinal fusion in a rabbit model., Methods: In vitro study, the hybrid graft was cultured in complete or osteogenic medium for 7 days and 14 days and examined by scanning electron microscopy. The alkaline phosphatase activity of the MSCs was assessed and the expression of osteogenic gene was determined by reverse transcription polymerase chain reaction. In vivo investigation, spinal fusion was examined using radiography, manual palpation, computed tomography, torsional loading tests, and histologic analysis. Furthermore, using a PKH fluorescence labeling system, we examined whether the newly formed bone was derived from the transplanted MSCs., Results: Our data suggested that the MSCs differentiated into osteoblasts and produced extracellular matrix in the hybrid graft. Increased alkaline phosphatase activity was noted and mRNA of Cbfa-1 and osteopontin were detected. Radiographs and computed tomography images showed a continuous bone bridge and a satisfactory fusion mass incorporated into the transverse processes. The results of manual palpation and biomechanical data did not significantly differ between the two groups. Histologic examination of both groups revealed the presence of cartilage and endochondral ossification in the gaps between the grafted fragments. In situ tracing of the PKH 67-labeled MSCs indicated that the transplanted MSCs were partly responsible for the new bone formation., Conclusion: The hybrid graft could be effectively used to achieve posterolateral spinal fusion.

Infection has been one of the most common causes of problems and complications after the operation despite the advance in surgical techniques and the availability of newly developed antibiotics. Local antibiotic delivery beads for treatment of various surgical infections had been studied recently especially in osteomyelitis. This current paper used cefazolin sodium and gentamicin sulfate combined with biodegradable polymers (50:50 poly(DL-lactide):co-glycolide) as antibiotic beads for a long-term drug release. To manufacture an antibiotic bead, polylactide-polyglycolide copolymers were mixed with the antibiotics. The mixture was compressed and sintered at 55 degrees C to form beads of different sizes. The beads were placed in 3 ml of phosphate buffered saline and incubated at 37 degrees C. An elution method combined with a bacterial inhibitory test was employed to characterize the release rate of the antibiotics over a 30-day period. The results suggested that the biodegradable beads released high concentrations of antibiotic (well above the minimum inhibitory concentration) in vitro for the period of time needed to treat bone infection; i.e. 2-4 weeks. This provides advantages as a first line choice of long-term antibiotics for patients with osteomyelitis and various infections such as thoracic, abdominal, and pelvic infections, as well as for the prophylaxis of these infections.