Poly(lactic-co-glycolic) Acid Membranes Research Articles

Plasma-Treated Electrospun PLGA Nanofiber Scaffold Supports Limbal Stem Cells

The corneal epithelial layer is continuously replaced by limbal stem cells. Reconstructing this layer in vitro using synthetic scaffolds is highly needed. Poly-lactic-co-glycolic acid (PLGA) is approved for human use due to its biocompatibility and biodegradability. However, PLGA is hydrophobic, preventing cell adherence to PLGA membranes. PLGA scaffolds were prepared by electrospinning on a custom-made target drum spinning at a rate of 1000 rpm with a flow rate of 0.5 mL/h and voltage at 20 kV, then treated with oxygen plasma at 30 mA using a vacuum coater. Scaffolds were characterized by SEM, mechanically by tensile testing, and thermally by DSC and TGA. In vitro degradation was measured by weight loss and pH drop. Wettability was assessed through water uptake and contact angles measurements. Human limbal stem cells (hLSCs) were isolated and seeded on the scaffolds. Cell attachment and cytotoxicity assay were evaluated on day 1 and 5 after cell seeding. SEM showed regular fiber morphology with diameters ranging between 150 nm and 950 nm. Tensile strength demonstrated similar average stress values for both plasma- and non-plasma-treated samples. Scaffolds also showed gradual degradability over a period of 7–8 weeks. Water contact angle and water absorption were significantly enhanced for plasma-treated scaffolds, indicating a favorable increase in their hydrophilicity. Scaffolds have also supported hLSCs growth and attachment with no signs of cytotoxicity. We have characterized a nanofiber electrospun plasma-treated PLGA scaffold to investigate the mechanical and biological properties and the ability to support the attachment and maintenance of hLSCs.

Physical Characteristics and Biocompatibility of 3D-Printed Polylactic-Co-Glycolic Acid Membranes Used for Guided Bone Regeneration

Bioresorbable polymeric membranes for guided bone regeneration (GBR) were fabricated using the three-dimensional printing technique. Membranes made of polylactic-co-glycolic acid (PLGA), which consist of lactic acid (LA) and glycolic acid in ratios of 10:90 (group A) and 70:30 (group B), were compared. Their physical characteristics including architecture, surface wettability, mechanical properties, and degradability were compared in vitro, and their biocompatibilities were compared in vitro and in vivo. The results demonstrated that the membranes of group B had mechanical strength and could support the proliferation of fibroblasts and osteoblasts significantly better than those of group A (p < 0.05). The degradation rate in Group B was significantly lower than that in Group A, but they significantly produced less acidic environment (p < 0.05). In vivo, the membranes of group B were compared with the commercially available collagen membranes (group C). The amount of newly formed bone of rat's calvarial defects covered with the membranes of group C was stable after week 2, whereas that of group B increased over time. At week 8, the new bone volumes in group B were greater than those in group C (p > 0.05). In conclusion, the physical and biological properties of the PLGA membrane (LA:GA, 70:30) were suitable for GBR.

Investigation of Cell Adhesion and Cell Viability of the Endothelial and Fibroblast Cells on Electrospun PCL, PLGA and Coaxial Scaffolds for Production of Tissue Engineered Blood Vessel.

Endothelialization of artificial scaffolds is considered an effective strategy for increasing the efficiency of vascular transplantation. This study aimed to compare the biophysical/biocompatible properties of three different biodegradable fibrous scaffolds: Poly (ɛ-caprolactone) (PCL) alone, Poly Lactic-co-Glycolic Acid (PLGA) alone (both processed using Spraybase® electrospinning machine), and Coaxial scaffold where the fiber core and sheath was made of PCL and PLGA, respectively. Scaffold structural morphology was assessed by scanning electron microscope and tensile testing was used to investigate the scaffold tension resistance over time. Biocompatibility studies were carried out with human umbilical vein endothelial cells (HUVEC) and human vascular fibroblasts (HVF) for which cell viability (and cell proliferation over a 4-day period) and cell adhesion to the scaffolds were assessed by cytotoxicity assays and confocal microscopy, respectively. Our results showed that all biodegradable polymeric scaffolds are a reliable host to adhere and promote proliferation in HUVEC and HVF cells. In particular, PLGA membranes performed much better adhesion and enhanced cell proliferation compared to control in the absence of polymers. In addition, we demonstrate here that these biodegradable membranes present improved mechanical properties to construct potential tissue-engineered vascular graft.

Prospective Clinical Study with New Materials for Tissue Regeneration: A Study in Humans.

This study was performed to evaluate the clinical, radiographic, and histomorphometric outcomes of novel bone grafting materials and dental membranes and to compare the results with current data from the literature. New synthetic bone substitutes, consisting of biphasic calcium phosphate in the ratio of 60% hydroxyapatite and 40% β-tricalcium phosphate, were applied in bony defects and covered by either a novel synthetic poly(lactic-co-glycolic) acid (PLGA) or porcine collagen membrane. A sample of 51 biomaterials was placed in a total of 20 patients during different surgical protocols. Implants were simultaneously inserted, and in the case of sinus floor elevations 6 months later. Pre- and postoperative cone-beam computed tomographies were taken. Bone biopsies were harvested from augmented sides and processed for histomorphometric evaluation. Averages and ranges were calculated for the percentage of newly formed bone, residual biomaterial, and connective tissue. Data were submitted to analyze the radiological mean differences in length, width, and density. Paired t-tests were deployed for the analysis of differences within each group between the baseline (preoperative) and the final (postoperative) measurements. The mean bone gain in length and width were 0.96 ± 3.33 mm (+27.59%) and 1.22 ± 1.87 mm (+30.48%), respectively. The bone density was increased by a factor of 4, reaching an average of 387.47 ± 328.86 HU. Histomorphometric evaluations revealed new bone formation of 41.44 ± 5.37%, residual biomaterial of 24.91 ± 7.31%, and connective tissue of 33.64 ± 4.81%. The mean healing period was 8.32 ± 3.00 months. Data from this study confirmed the suitability of the tested materials in dental surgery. The biomaterials may be recommended for various clinical procedures. A satisfactory level of increase of new bone was reported in augmented sides. No significant differences were observed between the tested membranes. PLGA membranes might be superior to collagen membranes for their easier handling.

Preparation and in vivo bacteriostatic application of PPDO-coated Ag loading TiO2 nanoparticles

Implant-associated infections limit the clinical application of implants therapy; hence, exploiting strategies to prevent biomaterial-associated infections has become important. Therefore, in this study, a series of poly (p-dioxanone) (PPDO)-coated Ag loading TiO2 nanoparticles (Ag@TiO2-PPDO) was synthesized to be applied as bacteriostatic coating materials that could be easily dispersed in organic solvent and coated onto implantable devices via temperate methods such as electrospraying. The lattice parameters of TiO2 were a = 0.504 nm, b = c = 1.05 nm, alpha = beta = gamma = 90 degree and the size of crystallite was about 13 nm, indicating that part of Ag has been embedded into crystal defects of TiO2. Both XRD and TEM determinations indicated the successful grating of PPDO on the surface of Ag@TiO2. Among Ag@TiO2 nanoparticles with various Ag loading quantities, 12% Ag@TiO2 nanoparticles exhibited relatively higher grafting efficiency and Ag contents on the surface of grafted composites. In addition, 12% Ag@TiO2-PPDO exhibited the best bacteriostatic effect in vitro owing to its higher grafted efficiency and relatively short length of PPDO segments. Subsequently, Ag@TiO2-PPDO was coated on the surface of a poly lactic-co-glycolic acid (PLGA) electrospun membrane via the electrospraying method. Finally, the in vivo bacteriostatic effect of 12% Ag@TiO2-PPDO coating was verified by implanting 12% Ag@TiO2-PPDO-coated PLGA membrane into a rat subcutaneously combined with an injection of Staphylococcus aureus at implanting sites.

Proof-of-concept study of electrospun PLGA membrane in the treatment of limbal stem cell deficiency

ObjectiveThe aim of this study was to assess the safety of poly-lactic co-glycolic acid (PLGA) electrospun membranes as carriers for limbal tissue explants for treatment of limbal stem cell deficiency...

Gelatin-CaO2/SAP/PLGA composite scaffold enhances the reparation of critical-sized cranial defects by promoting seed cell survival

One of the most hindrance for bone tissue engineering to reconstruct a bone defect is that the insufficient oxygen supply, which has an extremely negative influence upon the survival of seed cells in the scaffold, especially during the initial transplantation period. Herein, we devised a controlled-oxygen-generating composite scaffold that removes this limitation. This oxygen-generating composite scaffold consists of calcium peroxide (CaO2)-releasing microparticles, hydrogel, and a poly(lactic-co-glycolic acid (PLGA) membrane. The microparticles, which are composed of gelatin and CaO2, are hydrolytically activated to generate oxygen when they make contact with water. The hydrogel, self-assembling peptide(SAP), and PLGA membrane were designed to prevent direct exposure of the gelatin-CaO2 microspheres to a large quantity of water and provide a three-dimensional environment for cell growth. The oxygen-generating composite scaffold has the capability of sustainably controlling oxygen generation for about 21 days in vitro and 28 days in vivo. The capacities of this oxygen-generating composite scaffold to improve seed cell survival and the reparation of bone defects were tested using peripheral blood-derived mesenchymal stem cells and a critical-sized cranial defect. Compared with the control groups, survival of seed cells both in vitro and in vivo was significantly improved when the cells were co-cultured or co-transplanted with the oxygen-generating microspheres. Moreover, the presence of the gelatin-CaO2 microspheres significantly improved the repair of bone defects. These results indicated that the oxygen-generating composite scaffold in this study has great potential to increase seed cell survival and enhance bone defect reconstruction.

PLGA Membranes Functionalized with Gelatin through Biomimetic Mussel-Inspired Strategy.

Electrospun membranes have been widely used as scaffolds for soft tissue engineering due to their extracellular matrix-like structure. A mussel-inspired coating approach based on 3,4-dihydroxy-DL-phenylalanine (DOPA) polymerization was proposed to graft gelatin (G) onto poly(lactic-co-glycolic) acid (PLGA) electrospun membranes. PolyDOPA coating allowed grafting of gelatin to PLGA fibers without affecting their bulk characteristics, such as molecular weight and thermal properties. PLGA electrospun membranes were dipped in a DOPA solution (2 mg/mL, Tris/HCl 10 mM, pH 8.5) for 7 h and then incubated in G solution (2 mg/mL, Tris/HCl 10 mM, pH 8.5) for 16 h. PLGA fibers had an average diameter of 1.37 ± 0.23 µm. Quartz crystal microbalance with dissipation technique (QCM-D) analysis was performed to monitor DOPA polymerization over time: after 7 h the amount of deposited polyDOPA was 71 ng/cm2. After polyDOPA surface functionalization, which was, also revealed by Raman spectroscopy, PLGA membranes maintained their fibrous morphology, however the fiber size and junction number increased. Successful functionalization with G was demonstrated by FTIR-ATR spectra, which showed the presence of G adsorption bands at 1653 cm−1 (Amide I) and 1544 cm−1 (Amide II) after G grafting, and by the Kaiser Test, which revealed a higher amount of amino groups for G functionalized membranes. Finally, the biocompatibility of the developed substrates and their ability to induce cell growth was assessed using Neonatal Normal Human Dermal Fibroblasts.

Control of Bacterial Proliferation and Formation of Biofilm in Membranes for Food Packaging Manufactured by Electrospinning

The application of micro/nanotechnologies in the development of food contact materials is currently of great interest for the food technology sector. The materials for this purpose include various types of polymers, among which are PLGA (polylactic-co-glycolic acid) and PCL (polycaprolactone), biodegradable synthetic polymers. Electrospinning is a low-cost and easily reproducible technique for the production of polymeric micro/nanofiber membranes that can be used in the packaging of food. This work establishes the parameters for the manufacturing, by means of electrospinning, of micro/nanofiber membranes made of PLGA, PCL and a combination of both of these polymers. The resulting fibers were characterized via scanning electron microscopy. Given the importance, within the food industry, of knowing the effect that the package components may have on bacterial proliferation, the resulting fibers were incubated with three of the most frequent microorganisms that contaminate food: Staphylococcus aureus, Enterococcus faecalis and Escherichia coli. Both the viability and the bacterial adhesion were quantitatively determined in terms of the biofilm formation capacity. The formation of biofilms was greater in the PLGA membranes. When any of the microorganisms were exposed to the membranes made of the mixture of the two polymers, or with only PCL, a marked reduction in the formation of biofilm was observed. These results show that it is possible, by means of a proper selection of the materials, to reduce the possibility of contamination in both the packaging and the food, without the need to add products that might be inconvenient due to their possible side effects.

Human Conjunctival Epithelial Sheets Grown on Poly(Lactic-Co-Glycolic) Acid Membranes and Cocultured With Human Tenon's Fibroblasts for Corneal Repair.

We determine the feasibility of human conjunctival epithelial cells (hCjECs) on poly(lactic-co-glycolic) acid (PLGA) membranes for corneal epithelium regeneration. hCjECs on PLGA or polyester (PET) membranes with or without coculture of human Tenon's fibroblasts (hTFs) were compared in vitro, and to determine whether epithelial sheets grown on PLGA membranes can repair injured rabbit corneal epithelium by transplantation for 2 weeks in vivo. Primary hCjECs were cultured on PLGA or the original PET membrane-based transwell inserts with or without coculture of hTFs on the floor of the culture plate. Cell behaviors, such as proliferation and differentiation, were compared. For in vivo assessment, the corneas of rabbits were burned, and PLGA-based epithelial sheets then were transplanted for 2 weeks before histologic staining was conducted and analyzed to determine the effectiveness of the repair. Primary human epithelial cells on the PLGA membrane showed an increased proliferation when cocultured with fibroblasts, which was confirmed by CCK-8 analysis, and upregulation of Ki67, with the expression of the epithelial marker CK19. The stratified squamous cell marker MUC1 and conjunctival cell marker MUC5AC also were expressed in the epithelial sheet. The epithelial defect in the burned corneas was decreased in the PLGA-based epithelial sheet treatment group (6.1% ± 1.6% of the area) compared to that in the no-treatment group (30.5% ± 6.3%) 2 weeks postoperatively. We developed a coculture system using a human feeder cell layer and PLGA membrane-based transwell inserts to create human conjunctival epithelial sheets. This system represents a promising strategy to regenerate corneal epithelium by transplantation.

Viability and Biomechanics of Diced Cartilage Blended With Platelet-Rich Plasma and Wrapped With Poly (Lactic-Co-Glycolic) Acid Membrane.

The objective of this study was to investigate the viability and biomechanics of diced cartilage blended with platelet-rich plasma (PRP) and wrapped with poly (lactic-co-glycolic) acid (PLGA) membrane in a rabbit model. A total of 10 New Zealand rabbits were used for the study. Cartilage grafts were harvested from 1 side ear. The grafts were divided into 3 groups for comparison: bare diced cartilage, diced cartilage wrapped with PLGA membrane, and diced cartilage blended with PRP and wrapped with PLGA membrane. Platelet-rich plasma was prepared using 8 mL of auricular blood. Three subcutaneous pockets were made in the backs of the rabbits, and the grafts were placed in these pockets. The subcutaneous implant tests were conducted for safety assessment of the PLGA membrane in vivo. All of the rabbits were sacrificed at the end of 3 months, and the specimens were collected. The sections were stained with hematoxylin and eosin, toluidin blue, and collagen II immunohistochemical. Simultaneously, biomechanical properties of grafts were assessed. This sample of PLGA membrane was conformed to the current standard of biological evaluation of medical devices. Moderate resorption was seen at the end of 3 months in the gross assessment in diced cartilage wrapped with PLGA membrane, while diced cartilage blended with PRP had no apparent resorption macroscopically and favorable viability in vivo after 3 months, and the histological parameters supported this. Stress-strain curves for the compression test indicated that the modulus of elasticity of bare diced cartilage was 7.65 ± 0.59 MPa; diced cartilage wrapped with PLGA membrane was 5.98 ± 0.45 MPa; and diced cartilage blended with PRP and wrapped with PLGA membrane was 7.48 ± 0.55 MPa, respectively. Diced cartilage wrapped with PLGA membrane had moderate resorption macroscopically after 3 months. However, blending with PRP has beneficial effects in improving the viability of diced cartilages. Additionally, the compression modulus of diced cartilage blended with PRP and wrapped with PLGA membrane was similar to bare diced cartilage.

Reliability of new poly (lactic-co-glycolic acid) membranes treated with oxygen plasma plus silicon dioxide layers for pre-prosthetic guided bone regeneration processes.

BackgroundThe use of cold plasmas may improve the surface roughness of poly(lactic-co-glycolic) acid (PLGA) membranes, which may stimulate the adhesion of osteogenic mediators and cells, thus accelerating the biodegradation of the barriers. Moreover, the incorporation of metallic-oxide particles to the surface of these membranes may enhance their osteoinductive capacity. Therefore, the aim of this paper was to evaluate the reliability of a new PLGA membrane after being treated with oxygen plasma (PO2) plus silicon dioxide (SiO2) layers for guided bone regeneration (GBR) processes.Material and MethodsCircumferential bone defects (diameter: 11 mm; depth: 3 mm) were created on the top of eight experimentation rabbits’ skulls and were randomly covered with: (1) PLGA membranes (control), or (2) PLGA/PO2/SiO2 barriers. The animals were euthanized two months afterwards. A micromorphologic study was then performed using ROI (region of interest) colour analysis. Percentage of new bone formation, length of mineralised bone, concentration of osteoclasts, and intensity of ostheosynthetic activity were assessed and compared with those of the original bone tissue. The Kruskal-Wallis test was applied for between-group com Asignificance level of a=0.05 was considered.ResultsThe PLGA/PO2/SiO2 membranes achieved the significantly highest new bone formation, length of mineralised bone, concentration of osteoclasts, and ostheosynthetic activity. The percentage of regenerated bone supplied by the new membranes was similar to that of the original bone tissue. Unlike what happened in the control group, PLGA/PO2/SiO2 membranes predominantly showed bone layers in advanced stages of formation.ConclusionsThe addition of SiO2 layers to PLGA membranes pre-treated with PO2 improves their bone-regeneration potential. Although further research is necessary to corroborate these conclusions in humans, this could be a promising strategy to rebuild the bone architecture prior to rehabilitate edentulous areas. Key words:Guided bone regeneration (GBR), poly(lactic-co-glycolic acid) (PLGA), membrane; oxygen plasma (PO2), nanocomposite, silicon dioxide layers.

Effect of PLGA-IB on ICAM-1 and VCAM-1 expression in a mice adhesion model

Background: In this study, we compared the effect of ibuprofen (IB) while incorporating by Poly Lactic-co-Glycolic Acid (PLGA) nanofiber on expression of adhesion molecules ICAM-1 and VCAM-1 in a mice adhesion model. M aterials and Methods: Using an adhesion model were induced in mice, PLGA-IB and PLGA membranes and IB were sutured between the abdominal wall and peritoneum after surgical operation to reveal the best membrane for prevention of postoperative adhesion bands by comparison of ICAM-1 and VCAM-1 expression. R es ults: Compared with other groups, PLGA-IB showed a greater ability to reduce ICAM-1 and VCAM-1 expression. C onclusion: These results suggested that in considering the FDA approved polymers, PLGA-IB could be introduced as a potential candidate for prevention of abdominal post-surgery inflammation and adhesion band formation after surgeries.

A Totally Absorbable Multilayer PLGA Implant Device Containing Doxorubicin Inhibited Tumor Growth and Metastasis without Systemic Toxicity in Murine Breast Cancer and an Ideal Pharmacological Paradigm for Regional Chemotherapy

We hypothesize that a cylinder implant made of multilayer Poly-lactic-co-glycolic-acid (PLGA) membrane can be a method for controlled and extended drug release. We fashioned a multilayer cylindrical implant termed STID100 that released doxorubicin for 3 weeks in an orthotopic 4T1 breast cancer model in Balb/C mice. This implant starts as a thin doxorubicin-embedded PLGA membrane, and is then rolled into a cylinder containing an air gap between the membrane layers. Its controlled sustained release delivered 2× the amount of the intravenous (IV) equivalent of doxorubicin, inhibited the primary tumor, and prevented lung metastasis. Importantly it did not cause weight loss, splenomegaly, or cardiac toxicity vs systemically administrated doxorubicin. This favorable safety profile is further substantiated by the finding of no detectable plasma doxorubicin in multiple time points during the 3-week period, and low tumor doxorubicin concentration. The implant system delivered to the specification of an ideal pharmacological paradigm might offer a better coverage of the local tumor, significantly preventing metastatic spread with less drug toxicity to many vital organs, compared to the traditional pharmacology of IV route. The profile of STID made it an attractive therapeutic alternative in metastatic tumor prevention, pain management and many other diverse clinical scenarios.

Abstract 300: A Biodegradable Wrap for Peri-vascular Delivery of Pro-resolving Lipid Mediators

Introduction: Persistent inflammation following vascular injury leads to excessive scarring, limiting the success of vascular interventions. Recent work has identified that endogenous specialized proresolving lipid mediators (SPM) such as resolvin D1 (RvD1) actively orchestrate the process of resolution, exerting vasculo-protective effects without associated toxicity. We propose local vascular delivery of SPM through a biodegradable wrap. Methods: RvD1 (200 ng) was heat-sealed between thin layers of polycaprolactone (PCL) or poly-lactic-co-glycolic acid (PLGA). PLGA membranes differed in their composition of lactic versus glycolic acid (%-lactide). Directional drug release was measured via EIA in a cell-free system in vitro and into rabbit aortas exposed to pulsatile flow ex vivo. Bioactivity was confirmed on human vascular smooth muscle cells (VSMC) using migration and proliferation assays. Results: Of the constructs tested, a 3-layered PLGA wrap consisting of 85%/75%/50%-lactide provided the most favorable drug elution (Fig1a), with sustained release of &gt;800 pg/day for at least 14 days and nearly all elution occurring from the 50%-lactide side (Fig1b). Perivascular application of this wrap ex vivo with the 50%-lactide side facing “in” demonstrated uptake into rabbit aortic walls at 8 hours (0.4 ± 0.1 pg/mg). VSMC cultures exposed to drug-loaded wraps showed inhibition of migration (40%) and proliferation (25%). Conclusion: We demonstrate sustained and directional elution of therapeutically relevant amounts of biologically-active RvD1 through a biodegradable perivascular wrap, providing opportunity for translational studies of SPM in vascular injury.

The effect of gamma radiation sterilization on dental biomaterials

Biomaterials are used in the field of bone and tissue engineering, orthopaedics and dentistry. Dental biomaterials including commercially available biodegradable materials act as physical barriers to help quicker healing while stimulating the regeneration of periodontal tissues, which is defined as Guided Tissue Regeneration (GTR). Amongst natural and synthetic biomaterials, collagen and aliphatic polyesters, such as polylactic acid (PLA) and poly (lactic-co-glycolic) acid (PLGA) are the most frequently used biomaterials for regenerative therapies due to their excellent biocompatibility and biodegradability. Due to their resorption in the body and interaction with biological systems, the GTR membranes must be sterile and pyrogen free. The sterility and apyrogenicity of the GTR membranes before human use is a regulatory requirement, however the sterilization of biomaterials is challenging due to the physicochemical changes and toxic residues with the commonly used sterilization techniques. The purpose of the present study was to evaluate the effect of gamma radiation and ethylene oxide sterilization on dental biomaterials with analytical, microbiological and histological examinations. PLGA-based GTR dental biomaterial is selected as the most gamma stable membrane according to the FTIR, DSC, TGA, and SEM results. This dental membrane was sterilized with ethylene oxide (EtO) and the effect of sterilization method on PLGA-based membrane was also investigated. Animal experiments were carried out to evaluate the regenerative properties and inflammatory responses of gamma and EtO sterilized PLGA-based GTR membrane after implantation. Histological examinations showed that resorption and bone formation of gamma sterilized PLGA-based GTR membrane was completed in 12 weeks without any inflammatory response; while only 60.095 ± 2.019% of new bone formation was observed with EtO sterilized one. Gamma sterilized PLGA membrane had significantly faster (P < 0.05) resorption and bone formation in comparison with EtO sterilization. In conclusion, the PLGA-based biomaterials could be sterilized safely and time- and cost-effectively with validated radiation doses for the tissue engineering applications.

Combined Effects of Brain-Derived Neurotrophic Factor Immobilized Poly-Lactic-Co-Glycolic Acid Membrane with Human Adipose-Derived Stem Cells and Basic Fibroblast Growth Factor Hydrogel on Recovery of Erectile Dysfunction

Erectile dysfunction (ED) is the most frequent long-term problem after radical prostatectomy. We aimed to evaluate whether the use of combination therapy with basic fibroblast growth factor (bFGF)-hydrogel on corpus cavernosum and with adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF)-immobilized poly-lactic-co-glycolic acid (PLGA) membrane on the cavernous nerve (CN) could improve erectile function in a rat model of bilateral cavernous nerve crush injury (BCNI). Rats were randomly divided into five groups (n=15 per group): a normal group (N group), a group receiving saline application after bilateral cavernous nerve crush injury (BCNI), a group undergoing bFGF-hydrogel injection in the corpus cavernosum after BCNI (bFGF), a group receiving ADSC application covered with BDNF-membrane after BCNI (ADSC/BDNF), and a group undergoing coadministration of bFGF-hydrogel injection and BDNF-membrane with ADSCs after BDNF (bFGF+ADSC/BDNF). Four weeks postoperatively, the erectile function was assessed by detecting the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP). Smooth muscle and collagen contents were measured using Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. The protein expression of the α-smooth muscle actin (α-SMA) and the cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by western blot and cGMP assay, respectively. In the bFGF+ADSC/BDNF group, the erectile function was significantly elevated compared with the BCNI and other treated groups and showed a significantly increased smooth muscle/collagen ratio, nNOS content, α-SMA expression, and cGMP level. In particular, there were no statistical differences in the ICP/MAP ratio, smooth muscle/collagen ratio, and α-SMA and cGMP levels between the bFGF+ADSC/BDNF group and normal group. Application of the BDNF-immobilized PLGA membrane with human ADSC into the CN and bFGF-incorporated hydrogel into the corpus carvernosum improved nearly normal erectile function in a rat model of postprostatectomy ED. This result suggests that a combined application of bFGF+ADSC/BDNF might be a promising treatment for postprostatectomy ED.

Biodegradable effect of PLGA membrane in alveolar bone regeneration on beagle dog.

Guided bone regeneration (GBR) is a principle adopted from guided tissue regeneration (GTR). Wherein, GBR is used for the healing of peri-implant bony dehiscences, for the immediate placement of implants into extraction sockets and for the augmentation of atrophic alveolar ridges. This procedure is done by the placement of a resorbable or non-resorbable membrane that will exclude undesirable types of tissue growth between the extraction socket and the soft tissue to allow only bone cells to regenerate in the surgically treated lesion. Here, we investigated the biodegradable effect of polylactic-co-glycolic acid (PLGA) membrane in the alveolar bone on Beagle dogs. Results show that both collagen and PLGA membrane had been fully resorbed, biodegraded, at four weeks post-operative reentry into the alveolar bone. Histological results under light microscopy revealed formation of new bone trabeculae in the extraction sites on both collagen and PLGA membrane. In conclusion, PLGA membrane could be a potential biomaterials for use on GBR and GTR. Nevertheless, further studies will be necessary to elucidate the efficiency and cost effectiveness of PLGA as GBR membrane in clinical.

Studies Based on Preparation, Physical Characteristics, and Cellular Pharmacological Activities of Thin PLGA Film Loaded with Geniposide

In this primary study, thin polylactic-co-glycolic acid (PLGA) film loaded with geniposide was first prepared and demonstrated on both physical and pharmacological aspects for its potential application on drug-eluting vascular stents. Physical parameters of geniposide-loaded thin film, such as crystal structure, molecular spectral characteristics, and release behavior in the whole process were detected. From X-Ray diffraction, the characteristic peak of crystal geniposide disappeared on geniposide-loaded PLGA film (GLPF) after it formed, which meant there was no agglomeration phenomenon, as geniposide was distributed in the form of single molecule. According to scanning electron microscopy (SEM) figure, the GLPF was more flat and uniform with better compactness. It inferred that release behavior of geniposide at the early stage (0~15 d) was in the form of free diffusion. Carrier PLGA began to degrade 15 days later, so the residual geniposide was also dissolved. Cellular pharmacological effects of geniposide on endothelial cells (ECs) and smooth muscle cells (SMCs) were also demonstrated on GLPF. 5% and 10% (w/w) geniposide-loaded PLGA (60 : 40) membrane indicated its significant effect on ECs promotion and SMCs inhibition. All provided feasible evidences for the development of new geniposide-coating vascular stent using PLGA as carrier.

Emulsion Electrospinning as an Approach to Fabricate PLGA/Chitosan Nanofibers for Biomedical Applications

Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA) and chitosan have been produced through an emulsion electrospinning process. The spinning solution employed polyvinyl alcohol (PVA) as the emulsifier. PVA was extracted from the electrospun nanofibers, resulting in a final scaffold consisting of a blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat was adjusted from 0 to 33%. Analyses by scanning and transmission electron microscopy show uniform nanofibers with homogenous distribution of PLGA and chitosan in their cross section. Infrared spectroscopy verifies that electrospun mats contain both PLGA and chitosan. Moreover, contact angle measurements show that the electrospun PLGA/chitosan mats are more hydrophilic than electrospun mats of pure PLGA. Tensile strengths of 4.94 MPa and 4.21 MPa for PLGA/chitosan in dry and wet conditions, respectively, illustrate that the polyblend mats of PLGA/chitosan are strong enough for many biomedical applications. Cell culture studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and proliferation compared to PLGA membranes. It can be assumed that the nanofibrous composite scaffold of PLGA/chitosan could be potentially used for skin tissue reconstruction.