pH-Compensation Effect of Lysine on the Acidic Degradation of Electrospun Poly( lactide-co-glycolide) Fibers in PBS

Electrospun aligned ultrafine fibers of poly( lactide-coglycolide)( PLGA) can be used to construct biomimetic scaffolds for engineering those structurally anisotropic and dense tissues( e. g.,tendon,ligament,etc.). But the acidic degradation products of the PLGA could result in p H decrease in the vicinity of the scaffolds,which may give rise to biocompatibility concerns. To address the noted problem, this study was designed to evaluate the p Hcompensation capacity of using Lysine( Lys) —a kind of basic amino acid on the acidic degradation products of PLGA. Ultrafine PLGA( 50∶ 50) fibers with 0,10%,20%,and 30% by weight of Lys loadings were prepared by a stable jet electrospinning( SJES)approach. The morphology,structure,and mechanical properties of the electrospun aligned fibrous mats of Lys-incorporated PLGA( 50∶50) were characterized by scanning electron microscope( SEM),Fourier transform infrared spectroscopy( FTIR),and tensile testing,respectively. Thereafter,the fibrous PLGA( 50 ∶50) scaffolds were subjected to degradation by being immersed in phosphate buffered saline( PBS,p H 6. 86) solution at 37 ℃ for 5weeks. Our results show that the formed Lys / PLGA composite ultrafine fibers have a well-aligned and uniform morphology with a fineness of ca. 1 #m in diameter. Introduction of Lys led to increased mechanical performance; that is,when the Lys loading is less than 30%,tensile strength and Young's modulus of the aligned Lys / PLGA fibers reached up to the impressive values of 84. 5 MPa and 2. 4 GPa,respectively. Degradation results show that the p H of the PLGA group fell to 5. 6 in 5 weeks while the p H of the Lys /PLGA groups with 10%,20%, and 30% of Lys loadings was maintained at 6. 3, 6. 5 and 6. 7, respectively. This work demonstrated that incorporation of Lys into electrospun PLGA fibers could be an effective approach in mediating the p H decrease caused by the acidic degradation products of the PLGA.

Synthesis and Characterization of Poly(L-lactide-co-glycolide)

Poly （ l- lactide- co-glycolide ） （ PLGA ） with different compositions was prepared using stannous octaoate as catalyst by bulk ring-opening copolymerization of l-lactide and glycolide. The structure and properties of the PLGA copolymers were cbaracterized by means of attenuated total reflectance-Fourier transform infrared （ATR-FTIR）, ^1H NMR, differential scanning calorimeter （ DSC and X-ray diffraction （XRD） methods, The experimented results indicate that the synthetic conditions and the composition of copolymers have art obvious influence on the structure of PLGA copolymers, The degradation rate of eopolymers increased with the increasing of the glycolide component in the copolymers.

Synthesis and Physicochemical Characterization of Biodegradable Star-Shaped Poly Lactide-Co-Glycolide-<i>β</i>-Cyclodextrin Copolymer Nanoparticles Containing Albumin

The purposes of this research were to synthesize and characterize star-shaped poly lactide-co-glycolide-β-cyclo-dextrin (PLGA-β-CD) copolymer by reacting L-lactide, glycolide and β-cyclodextrin in the presence of stannous octoate as a catalyst. The structure of PLGA-β-CD copolymer was confirmed with 1H-NMR, 13C-NMR and FT-IR spectra. Albumin as a model peptide drug was encapsulated within nanoparticles made of PLGA-β-CD with a modified double emulsion method. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) photomicrographs showed that the nanoparticles have the mean diameter within the range of 80 - 210 nm. Also they were almost spherical in shape. Effects of the experimental parameters, such as copolymer composition, copolymer concentration, and reaction temperature, on particular size and encapsulation efficiency were investigated.

Effect of the implant composite of poly lactide-co-glycolide and bone mesenchymal stem cells modified by basic fibroblast growth factor on injured spinal cord in rats

Objective To investigate the effect of the implant composite of poly lactide-co-glycolide(PLGA)and bone mesenchymal stem cells (BMSCs) modified by basic fibroblast growth factor (bFGF) on injured spinal cord in rats.Methods Two hundred and

Evaluating the Effects of Crystallinity on Drug Release Behaviour in Itraconazole- or Miconazole-Loaded PLGA Microparticles Prepared Using a Co-Grinding Method

This study aimed to prepare and characterize itraconazole (ITCZ)- or miconazole (MCZ)-loaded poly (lactide-co-glycolide) (PLGA) microparticles (MP) using a co-grinding method with ball milling, which is a solvent-free and convenient procedure. PLGA MP was prepared by grinding for 60 min, and the fixed theoretical drug loading was set at 9.1% and 16.7% for both drugs. The obtained loading efficiency for both drugs was estimated to be approximately 100%. The average diameters of the drug-loaded PLGA MP were approximately 20 - 35 μm. Powder X-ray diffraction (PXRD) or differential scanning calorimetry (DSC) confirmed amorphization of ITCZ and MCZ in ITCZ- or MCZ-loaded PLGA MP in all formulations. The drug release percentage from 9.1%-loaded ITCZ-PLGA7505 MP at 24 h was almost 50%, which was higher than that of ITCZ powder. The drug release percentage from MCZ-loaded PLGA7505 MP at 4 h was over 80%, which was higher than that of MCZ powder. This enhancement of release rate is caused by the amorphization of ITCZ or MCZ in the PLGA matrix. MCZ-loaded PLGA7510 MP showed a sustained release profile up to 24 h, suggesting that MCZ exists in an amorphous form in the PLGA matrix;however, the release rate declined owing to the large molecular weight of PLGA. Therefore, the release enhancement of antifungal drugs loaded on PLGA MP could be achieved by their amorphization using a co-grinding method with ball milling.

Development of a fast and precise method for simultaneous quantification of the PLGA monomers lactic and glycolic acid by HPLC

Poly(lactide-co-glycolide acid)(PLGA) is an extraordinary well-described polymer and has excellent pharmaceutical properties like high biocompatibility and good biodegradability. Hence, it is one of the most used materials for drug delivery and biomedical systems, also being present in several US Food and Drug Administration-approved carrier systems and therapeutic devices. For both applications, the quantification of the polymer is inalienable. During the development of a production process, parameters like yield or loading efficacy are essential to be determined. Although PLGA is a well-defined biomaterial,it still lacks a sensitive and convenient quantification approach for PLGA-based systems. Thus, we present a novel method for the fast and precise quantification of PLGA by RP-HPLC. The polymer is hydrolyzed into its monomers, glycolic acid and lactic acid. Afterwards, the monomers are derivatized with the absorption-enhancing molecule 2,4′-dibromoacetophenone. Furthermore, the wavelength of the derivatized monomers is shifted to higher wavelengths, where the used solvents show a lower absorption,increasing the sensitivity and detectability. The developed method has a detection limit of 0.1 mg/mL,enabling the quantification of low amounts of PLGA. By quantifying both monomers separately, information about the PLGA monomer ratio can be also directly obtained, being relevant for degradation behavior. Compared to existing approaches, like gravimetric or nuclear magnetic resonance measurements, which are tedious or expensive, the developed method is fast, ideal for routine screening, and it is selective since no stabilizer or excipient is interfering. Due to the high sensitivity and rapidity of the method, it is suitable for both laboratory and industrial uses.

Study on the surface-modification of nano-hydroxyapatite with lignin and the corresponding nanocomposite with poly (lactide-co-glycolide)

To obtain nano-hydroxyapatite/poly(lactideco-glycolide)(n-HA/PLGA)nanocomposite with superior mechanical properties,here,lignin was chosen to surfacemodify for n-HA through co-precipitation method.The different reaction conditions of reaction time,phosphorus source,and the lignin addition amount were studied by fourier transformation infrared spectra,X-ray diffraction,the intuitionistic dispersion experiment,transmission electron microscope and thermal gravimetric analysis.The reaction mechanism and the best appropriate reaction condition were obtained.More importantly,the results of electromechanical universal tester,scanning electron microscope,differential scanning calorimetric analyzer,polarized optical microscopy and dynamic mechanical analysis confirmed that the obtained n-HA could greatly increase the mechanical strength of PLGA,owing to the excellent dispersion and promotion crystallization effect.Moreover,in vitro cell culture experimental results indicated that the n-HA surface-modified by lignin was favorable to improve the cell biocompatibility of PLGA.The study suggested that the introduction of lignin was a novel method to acquire a highly dispersed n-HA,which would provide a new idea to achieve the n-HA/PLGA nanocomposite as bone materials in future,and it would pave the way towards a new application of lignin in biomedical field.

The Construction and Investigation of PLGA Artificial Bone by Biomimetic Mineralization

To modify the surface property of poly lactide-co-glycolide （PLGA） by biomimetic mineralization to construct a new kind of artificial bone. PLGA films and 3-diamensional （3-D） porous scaffolds hydrolyzed in alkaline solution were minerilized in SBF for 14 days. The morphology and composition of the mineral grown on PLGA were analyzed with SEM, FTIR and XRD. The porosity of the scaffolds was detected by using the liquid displacement method. The compressive strength of the scaffolds was detected by using a Shimadzu universal mechanic tester. An obvious mineral coating was detected on the surface of films and scaffolds. The main compqnent of the mineral was carbonated hydroxyapatite （HA） similar to the major mineral component of bone tissues. The porosity of the un-mineralized and mineralized porous scaffolds was （84.86±8.52） % and （79.70 ± 7.70） % respectively. The compressive strength was 0. 784±0. 156 N/mm^2 in un-mineralized 3-D porous PLGA and 0. 858±0. 145 N/mm^2 in mineralized 3-D porous PLGA. There were no significant differences between the mineralized and un-mineralized scaffolds （P〉0, 05） in porosity and biomechanics. Biomimetic mineralization is a suitable method to construct artificial bone.

Prevention of Postoperative Tendon Adhesion by Biodegradable Electrospun Membrane of Poly(lactide-co-glycolide)

An electrospun poly（lactide-co-glycolide） （PLGA） membrane was prepared and used to perform the anti-adhesion of Achilles tendon. Throughout the experiments, the membrane showed an appropriate degradation rate, and the pH values of degradation media were maintained at around 7.4. Simultaneously, the excellent biocompatibility of the membrane in vitro and in vivo was confirmed by live/dead and histopathological analyses. Meanwhile, the membrane can reduce tendon adhesion significantly and promote functional recovery effectively. The encouraging results were further demonstrated by hematoxylin and eosin （H＆E）, and Masson＇s trichrome stainings, and type I collagen immunohistochemical analysis. It was concluded that the model treated with the electrospun PLGA membrane was significantly better with respect to the adhesion prevention and tissue repair than that without treatment. Considering the results of degradation and adhesion prevention efficacy, the electrospun PLGA membrane would be a great candidate for the prevention of postoperative tendon adhesion.

Optimization of Parameters for Preparation of Docetaxel-loaded PLGA Nanoparticles by Nanoprecipitation Method

The purpose of this study was to develop docetaxel-poly （lactide-co-glycolide） （PLGA） loaded nanoparticles by using nanoprecipitation method and optimize the relative parameters to obtain nanoparticles with higher encapsulation efficiency and smaller size. The physicochemical characteristics of nanoparticles were studied. The optimized parameters were as follows： the oil phase was mixture of acetone and ethanol, concentration of tocopheryl polyethylene glycol succinate （TPGS） was 0.2%, the ratio of oil phase to water phase was 1：5, and the theoretical drug concentration was 5%. The optimized nanoparticles were spherical with size between 130 and 150 nm. The encapsulation efficiency was （40.83±2.1）%. The in vitro release exhibited biphasic pattern. The results indicate that docetaxel-PLGA nanoparticles were successfully fabricated and may be used as the novel vehicles for docetaxel, which would replace Taxotere and play great roles in future.

Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells and Schwann cells

Background The most important objective of transplant studies in the injured spinal cord has been to provide a favorable environment for axonal growth. Moreover, the continuing discovery of new grafts is providing new potentially interesting transplant candidates. Our purpose was to observe the morphological and functional repair effects of the co-transplantation of neural stem cell （NSC）, Schwann ceils （SCs） and poly lactide-co-glycolide acid （PLGA） on the spinal cord injury of rats.Methods A scaffold of PLGA was fabricated. NSCs and SCs were cultured, with the NSCs labeled with 5-bromodeoxyuridine, and the complex of NSC/PLGA or NSC＋SCs/PLGA were constructed. Thirty-six Wistar rats were randomly divided into three groups： group A （transplantation of PLGA）, group B （transplantation of NSC/PLGA） and group C （transplantation of NSC＋SCs/PLGA）. The 3 mm length of the right hemicord was removed under the microscope in all rats. The PLGA or the complex of PLGA-celIs were implanted into the injury site. Basso-Beattie-Bresnahan （BBB）locomotion scores, motor and somatosensory evoked potential of lower limbs were examined to learn the rehabilitation of sensory and motor function at 4 weeks, 8 weeks, 12 weeks and 24 weeks after injury. All the recovered spinal cord injury （SCI） tissues were observed with HE staining, immunohistochemistry, and transelectronmicroscopy to identify the survival, migration and differentiation of the transplanted cells and the regeneration of neural fibres at 4 weeks, 8 weeks,12 weeks and 24 weeks after injury.Results （1） From 4 weeks to 24 weeks after injury, the BBB locomotion scores of cell-transplanted groups were better than those of the non-cell-transplanted group, especially group C （P 〈0.05）. The amplitudes of the somatosensory evoked potential （SEP） and motor-evoked potential （MEP） were improved after injury in groups B and C, but the amplitude of SEP and MEP at 4 weeks was lower than that at 12 weeks and 24 weeks after injury. Compared with group B, the amplitude of SEP and MEP in group C was improved. The amplitude of SEP and MEP was not improved after injury in group A. （2） HE staining revealed the volume of the scaffold decreased and the number of cells in the scaffold increased. Newly-grown capillaries also could be seen. Immunohistochemistry staining showed the transplanted NSCs could survive and migrate until 24 weeks and they could differentiate into neurons and oligodendrocytes. The regenerated axons were observed in the scaffold-cell complex with transelectronmicroscopy. The above manifestations were more extensive in group C.Conclusions The transplanted NSC can survive and migrate in the spinal cord of rats up to 24 weeks after injury, and they can differentiate into various neural cells. Co-transplantation of cells/PLGA can promote the functional recovery of the injured spinal cord. The effect of co-transplanting NSC＋SCs/PLGA is better than transplanting NSC/PLGA alone.

Effects of the Molecular Weight of PLGA on Degradation and Drug Release In vitro from an mPEG-PLGA Nanocarrier

We successfully synthesized four kinds of copolymers with varying molecular weights of poly（lactide- co-glycolide）（PLGA） to yield methoxy-poly（ethylene glycol）-block-poly（lactide-co-glycolide）（mPEG-PLGA） nano- carriers： mPEG-PLGA（3k）, mPEG-PLGA（9k）, mPEG-PLGA（llk） and mPEG-PLGA（16k）. An antitumor drug, 10-hydroxycamptothecin（HCPT）, was encapsulated into the mPEG-PLGA nanocarrier cores by self-assembly in dialysis. The lower molecular weight nanocarriers degraded more quickly, resulting in mass loss, pH decline, and a rapid HCPT release rate in vitro. The degradation and drug release of the nanocarriers were dependent on the PLGA molecular weight. However, the larger molecular weight nanocarriers could not increase the loading content and encapsulation efficiency. Considering the antitumor effect of these nanocarriers, the mPEG-PLGA（9k） nanocarrier, which had the highest drug loading content[（7.72±0.57）%] and a relatively high encapsulation efficiency [（22.71±5.53）%], is an optimum agent for drug delivery.

Evaluating and Modeling the Mechanical Properties of the Prepared PLGA/nano-BCP Composite Scaffolds for Bone Tissue Engineering

In this paper, preparation of nano-biphasic calcium phosphate （nBCP）, mechanical behavior and load-bearing of poly （lactide-co-glycolide） （PLGA） and PLGA/nBCP are presented. The nBCP with composition of 63/37 （w/w） HA/-TCP （hydroxyapatite/fl-tricalcium phosphate） was produced by heating of bovine bone at 700℃. Composite scaffolds were made by using PLGA matrix and 10-50 wt% nBCP powders as reinforcement material. All scaffolds were prepared by thermally induced solid-liquid phase separation （TIPS） at -60~C under 4 Pa （0.04 mbar） vacuum. The results of elastic modulus testing were adjusted with Ishai-Cohen and Narkis models for rigid polymeric matrix and compared to each other. PLGA/nBCP scaffolds with 30 wt% nBCP showed the highest value of yield strength among the scaffolds. In addition, it was found that by increasing the nBCP in scaffolds to 50 wt%, the modulus of elasticity was highly enhanced. However, the optimum value of yield strength was obtained at 30 wt% nBCP, and the agglomeration of reinforcing particles at higher percentages caused a reduction in yield strength. It is clear that the elastic modulus of matrix has the significant role in elastic modulus of scaffolds, as also the size of the filler particles in the matrix.

PARTICLE-COLLISION AND POROGEN-LEACHING TECHNIQUE TO FABRICATE POLYMERIC POROUS SCAFFOLDS WITH MICROSCALE ROUGHNESS OF INTERIOR SURFACES

A facile technique is herein reported to fabricate three-dimensional （3D） polymeric porous scaffolds with interior surfaces of a topographic microstructure favorable for cell adhesion. As demonstration, a well-known biodegradable polymer poly（lactide-co-glycolide） （PLGA） was employed as matrix. Under the porogen-leaching strategy, the large and soft porogens of paraffin were modified by colliding with small and hard salt particles, which generated micropits on the surfaces of paraffin spheres. The eventual PLGA scaffolds after leaching the modified porogens had thus interior surfaces of microscale roughness imprinted by those micropits. The microrough scaffolds were confirmed to benefit adhesion of bone marrow stromal cells （BMSCs） of rats and meanwhile not to hamper the proliferation and osteogenic differentiation of the cells. The insight and technique might be helpful for biomaterial designing in tissue engineering and regenerative medicine.