Copolymerization Of Glycolide Research Articles

The Influence of Ionizing Radiation on Paclitaxel-Loaded Nanoparticles Based on PLGA

The effect of ionizing radiation (γ-rays and electron beam) on anticancer drug delivery systems (DDSs) properties was evaluated concerning potential sterilization. For this purpose, paclitaxel (PTX)-loaded nanoparticles were obtained using a biodegradable, self-developed copolymer of l-lactide and glycolide (PLGA), synthesized in the presence of bismuth 2-ethylhexanoate catalyst. The nanoparticles were obtained with a high encapsulation efficiency of PTX (EE = 94.2%). The average size of the nanoparticles was 253.5 nm. The influence of irradiation (sterilization dose, 25 kGy) on the microstructure and the physicochemical and thermal properties of the polymer matrix was investigated, as well as the effect of irradiation on the morphology and physicochemical properties of the pharmaceutical formulations of the nanoparticles. Additionally, an in vitro drug release study was conducted regarding any alterations in the kinetic profiles of drug release. It was confirmed that the irradiation with both types of ionizing radiation, i.e., γ-rays and electron-beam (EB), slightly decreased the average molecular weight of the polymer matrix. While only negligible changes in the microstructure and thermal properties of PLGA were observed after irradiation with EB, the average length of lactidyl blocks (lLL) in the copolymer chains irradiated with γ-rays decreased from 4.33 to 3.35. Moreover, the contribution of crystalline phase (Xc) in γ-irradiated samples decreased significantly from 35.1% to 22.7%, suggesting a dominant mechanism of chain scission over cross-linking in PLGA samples irradiated with γ-rays. In vitro drug release results demonstrate a sustained and controlled release of PTX from the nanoparticles based on PLGA. The kinetics of drug release was defined as first order with non-Fickian diffusion. Only negligible differences in the kinetic profiles of PTX release from PLGA drug carriers were observed after irradiation. The overall results suggest good resistance of PLGA nanoparticles to irradiation within the conditions used and the great potential of EB in the sterilization process of the polymeric DDSs.

Role of the Lactide:Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders.

Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal conditions. Hyaluronidase, deficient in mucopolysaccharidosis IX, was encapsulated in NPs synthesized using 50:50, 60:40, or 75:25 lactide:glycolide copolymers. All NPs had diameters compatible with cellular transport (≤168 nm) and polydispersity indexes (≤0.16) and ζ-potentials (≤-35 mV) compatible with colloidal stability. Yet, their encapsulation efficiency varied, with 75:25 NPs and 60:40 NPs having the lowest and highest EE, respectively (15% vs. 28%). Under lysosomal conditions, the 50:50 copolymer degraded fastest (41% in 1 week), as expected, and the presence of a targeting antibody coat did not alter this result. Additionally, 60:40 NPs destabilized fastest (<1 week) because of their smaller diameter, and 75:25 NPs did not destabilize in 4 weeks. All formulations presented burst release under lysosomal conditions (56-78% of the original load within 30 min), with 50:50 and 60:40 NPs releasing an additional small fraction after week 1. This provided 4 weeks of sustained catalytic activity, sufficient to fully degrade a substrate. Altogether, the 60:40 NP formulation is preferred given its higher EE, and 50:50 NPs represent a valid alternative, while the highest stability of 75:25 NPs may impair lysosomes. These results can guide future studies aiming to translate PLGA NP-based ERT for this and other LSDs.

Degradation Behavior of Poly(Lactide-Co-Glycolide) Monolayers Investigated by Langmuir Technique: Accelerating Effect.

Among biodegradable polymers, polylactides (PLAs) have attracted considerable interest because the monomer can be produced from renewable resources. Since their initial degradability strongly affects commercial application fields, it is necessary to manage the degradation properties of PLAs to make them more commercially attractive. To control their degradability, poly(lactide-co-glycolide) (PLGA) copolymers of glycolide and isomer lactides (LAs) were synthesized, and their enzymatic and alkaline degradation rates of PLGA monolayers as functions of glycolide acid (GA) composition were systematically investigated by the Langmuir technique. The results showed that the alkaline and enzymatic degradations of PLGA monolayers were faster than those of l-polylactide (l-PLA), even though proteinase K is selectively effective in the l-lactide (l-LA) unit. Alkaline hydrolysis was strongly affected by their hydrophilicity, while the surface pressure of monolayers for enzymatic degradations was a major factor.

Investigation of Lyophilized Microspheres Loaded with Leuprolide Acetate

Abstract: Leuprolide acetate (LA) - a nonapeptide, used for the treatment of some hormone-depending diseases, is unstable and very susceptible to degradation in the aqueous media. Poly (lactic-co-glycolic) acid (PLGA) is a copolymer of lactide and glycolide, that has generated tremendous interest in pharmaceutics because of their excellent biocompatibility, biodegradability, and mechanical strength. PLGA is used for the preparation of biocompatible biodegradable extended-release microspheres. However, the PLGA undergoes hydrolytic degradation in an aqueous environment through cleavage of its backbone ester linkages. As a consequence, PLGA-based microspheres loaded with LA are usually lyophilized to ensure the stability of LA and PGLA and reduce agglomeration, sedimentation, and size change of microspheres during storage. The aim of this present study is to evaluate the influence of lyoprotectants namely mannitol, trehalose, lactose, and saccharose on the stability of LA and characteristics of PLGA-based microspheres loaded with LA upon lyophilization. DSC and FTIR were used to evaluate the biocompatibility of LA and lyoprotectants. The results showed that there was no incompatibility between the LA and lyoprotectants. Mannitol solution 1.25% was used in freeze-drying PLGA-based microspheres loaded with LA. The obtained lyophilized microspheres had a good appearance and low moisture. Lyophilized microspheres after reconstitution had no significant change in drug content, size, and size distribution in comparison to that before freeze-drying.&#x0D; Keywords: Leuprolide acetate, PGLA, lyophilized, stability, biodegradable microspheres.&#x0D; &#x0D;

Bioabsorbable Glycolide Copolymer is Effective in Reducing Staple Line Bleeding in Sleeve Gastrectomy.

Postoperative bleeding from the staple line after sleeve gastrectomy occurs in 2-8% of patients and it is associated with increased length and cost of hospitalization and may demand reoperation to gain hemostasis. Reinforced staplers are used by bariatric surgeons to reduce the incidence of postoperative leak but can have a role in avoiding bleeding. The aim of this study is to analyze the effects of reinforcement on the whole gastric staple line during sleeve gastrectomy on postoperative bleeding. Four hundred forty-eight consecutive patients undergoing sleeve gastrectomy from November 2012 to April 2019 were divided into two groups. In the Top-only group only the top staple shot was realized with reinforced material (GORE® SEAMGUARD®) while in the Bottom-to-Top group, patients received full staple line reinforcement. Statistical analysis focused on postoperative leak and bleeding, and length of stay; a propensity score matching analysis was performed to reduce between-group characteristics imbalance. One hundred forty-five (Top-only) and 303 (Bottom-to-Top) patients were included. Four (2.8%) patients in the Top-only group and none in the Bottom-to-Top group experienced severe bleeding (p = 0.004); the difference was still significant after propensity score matching. Length of stay was significantly shorter for the Bottom-to-Top group before and after propensity score matching (4 vs. 5days, p < 0.001). Staple line buttressing reduces the incidence of severe postoperative bleeding when performed on the whole staple line, and it is associated with a shorter hospitalization.

Can magnetisation transfer magnetic resonance imaging help for the follow-up of synthetic hernia composite meshes fate? A pilot study.

This study aims at evaluating the non-invasive Magnetic Resonance Imaging (MRI) technic to visualize a synthetic composite hernia mesh using a rodent model and to document the integration of this device over 4months. Uncoated polyethylene terephthalate mesh and synthetic composite mesh-faced on the visceral side with a chemically engineered layer of copolymer of glycolide, caprolactone, trimethylene carbonate, and lactide to minimize tissue attachment-were placed intraperitoneally in rats, facing the caecum previously scraped to promote petechial bleeding and subsequent adhesions. Meshes fate follow-up was performed 4, 10, and 16-weeks post-implantation using a rodent dedicated high field MRI. Magnetization transfer (MT) images were acquired, associated with pneumoperitonealMRI performed after intraperitoneal injection of 8mL gas to induce mechanical stress on the abdominal wall. Uncoated meshes were clearly visible using both T2-weighted and MT imaging during the whole study while composite meshes conspicuity was not so evident on T2-weighted MRI and could be improved using MT imaging. Adhesions and collagen infiltration were massive for the uncoated meshes as expected. On the contrary, composite meshes showed very limited adhesion, and, if any, occurring at the edge of the mesh, starting at the fixation points. Magnetization transfer imaging allows to detect mesh integration and, associated with pneumoperitoneum, was able to probe the effective minimizing effect of the synthetic polymeric barrier on visceral attachments. However, magnetization transfer imaging could not unambiguously allow the visualization of the mesh through the polymeric barrier.

Additive Manufacturing of α-Amino Acid Based Poly(ester amide)s for Biomedical Applications.

α-Amino acid based polyester amides (PEAs) are promising candidates for additive manufacturing (AM), as they unite the flexibility and degradability of polyesters and good thermomechanical properties of polyamides in one structure. Introducing α-amino acids in the PEA structure brings additional advantages such as (i) good cytocompatibility and biodegradability, (ii) providing strong amide bonds, enhancing the hydrogen-bonding network, (iii) the introduction of pendant reactive functional groups, and (iv) providing good cell–polymer interactions. However, the application of α-amino acid based PEAs for AM via fused deposition modeling (FDM), an important manufacturing technique with unique processing characteristics and requirements, is still lacking. With the aim to exploit the combination of these advantages in the creation, design, and function of additively manufactured scaffolds using FDM, we report the structure–function relationship of a series of α-amino acid based PEAs. The PEAs with three different molecular weights were synthesized via the active solution polycondensation, and their performance for AM applications was studied in comparison with a commercial biomedical grade copolymer of l-lactide and glycolide (PLGA). The PEAs, in addition to good thermal stability, showed semicrystalline behavior with proper mechanical properties, which were different depending on their molecular weight and crystallinity. They showed more ductility due to their lower glass transition temperature (Tg; 18–20 °C) compared with PLGA (57 °C). The rheology studies revealed that the end-capping of PEAs is of high importance for preventing cross-linking and further polymerization during the melt extrusion and for the steadiness and reproducibility of FDM. Furthermore, our data regarding the steady 3D printing performance, good polymer–cell interactions, and low cytotoxicity suggest that α-amino acid based PEAs can be introduced as favorable polymers for future AM applications in tissue engineering. In addition, their ability for formation of bonelike apatite in the simulated body fluid (SBF) indicates their potential for bone tissue engineering applications.

Obtaining Biocompatible Porous Composite Material Based on Zinc-Modified Hydroxyapatite and Lactide-Glycolide Copolymer

The development of surgery in the field of bone tissue reconstruction provides a stable demand for new materials for implants. Of particular interest are materials based on hydroxyapatite, which are close in chemical composition to the elemental composition and structure of bone and have similar biologically active properties. In this work, the regularities of the formation of new composite materials based on a zinc-modified hydroxyapatite framework coated with a copolymer of lactide and glycolide were revealed for the first time. The aim of this work was to obtain porous composite materials based on zinc-modified hydroxyapatite and a copolymer of lactide and glycolide with properties suitable for use as a material for bone implants. The phase and elemental composition of the composites was studied by infrared spectroscopy, X-ray diffraction, and X-ray spectral microanalysis. Regularities have been established between the surface properties and the composition of materials, as well as their biocompatibility, determined using monocytes isolated from human peripheral blood. The antibacterial activity of the materials against gram-positive and gram-negative bacteria was determined.

Ring‐Expansion Polymerization of ε‐Caprolactone, Glycolide, and l‐lactide with a Spirocyclic Tin(IV) Catalyst Derived from or 2,2′‐Dihydroxy‐1,1′‐Binaphthyl – New Results and a Revision

AbstractIn contrast to other cyclic tin bisphenoxides, polymerizations of glycolide and l‐lactide with the spirocyclic tin(IV) bis‐1,1′‐bisnapthoxide yield linear chains having a 1,1′‐bisnapthol end group and no cycles. In the case of l‐lactide, LA/Cat ratio and temperature are varied and at 160 °C or below, all polylactides mainly consist of even‐numbered chains. A total predominance of even‐numbered chains is also found for homopolymerization of glycolide, or the copolymerization of glycolide and l‐lactide, when conducted &lt;120 °C. Linear chains having a bisnaphthol end group are again the main reaction products of ring‐expansion polymerizations (REP) of ε‐caprolactone, but above 150 °C cycles are also formed.

Проблема використання композитних імплантів, що біодеградують, у лікуванні переломів кісток (огляд літератури)

Захворювання та травми опорно-рухової системи посідають друге місце серед причин травматизму і третє місце серед хвороб, що призводять до інвалідності дорослого населення. Ортопедичні імпланти займають особливе місце як у клінічній практиці, так і в біомедичній промисловості. Найбільшу зацікавленість викликають імпланти, здатні біодеградувати у разі їх імплантації в організм людини. Концепція імплантів, що біодеградують, з’явилася завдяки становленню й розвитку застосування шовних матеріалів, що розсмоктуються в організмі. Згодом цей вид матеріалу стали використовувати в процесі лікування переломів, оскільки в багатьох випадках кісткові уламки потребують лише тимчасового підтримання фіксатором, доти, поки не настане їх зрощення. Імплантувальні пристрої для внутрішньої фіксації для відновлення переломів, виготовлені з використанням полігліколевої кислоти (PGA), полімолочної кислоти (PLA) та сополімеру молочної кислоти та гліколіду (PLGA), набули популярності. Однак механічні властивості високопористих каркасів були порівняно більш слабкі проти тих, які потрібні для інженерії кісткової тканини. У процесі створення оптимального полімерного матеріалу, що біодеградує, необхідно подолати суперечність між міцністю та біодеградацією. PGA, забезпечуючи високу міцність фіксації, занадто швидко деградують, а PLGA, маючи високу кристалічність, практично не деградують, водночас поступаючись за міцністю і PGA, і біостабільним матеріалам. На сьогодні вчені докладають багато зусиль для розроблення композитів із фосфату кальцію та полімеру, зокрема гідроксилапатиту і трикальційфосфату (ТКФ). ТКФ з трьома поліморфними модифікаціями, зокрема α-ТКФ, β-ТКФ і α’-ТКФ, є ще однією добре відомою біокерамічною речовиною для відновлення кісток. β-TКФ привертає все більшу увагузавдяки його чудовій біосумісності, біоактивності і здатності до біодеградації. Композиційні матеріали на основі біоактивної кераміки здебільшого належать до матеріалів із додатковими перевагами, як полімери та кераміка, що біодеградують. Загалом ці композити відзначаються біосумісністю, остеокондуктивністю, механічною міцністю й остеогенними характеристиками. Водночас завдяки новим технологіям виготовлення, що з’явилися останніми роками, ці композитні матеріали є найперспективнішими матеріалами в галузі відновлення кісткових дефектів. Лікування переломів за допомогою імплантів усе частіше пов’язане з композиційними матеріалами. Біоматеріали мусять мати певні механічні властивості: біосумісність, біодеградацію, контрольовану швидкість біодеградації, хорошу механічну міцність і біоактивність. Біоматеріали, що використовують у процесі лікування переломів кісток, мають розпадатися впродовж певного часу, а додавання нанонаповнювачів може уповільнити швидкість розпадання композиту, що біодеградує.

Biocompatible Composite Materials Based on Porous Hydroxyapatite Ceramics and Copolymer of Lactide and Glycolide

The intensive development of reconstructive surgery and traumatology provides a stable demand for new materials for implants. Of particular interest are materials based on hydroxyapatite, which are chemically close to the elemental composition and structure of bone and have similar bioactive properties. The aim of this work was to obtain porous composite materials based on hydroxyapatite and a copolymer of lactide and glycolide with properties suitable for use as a material for bone implants. The phase and elemental composition of composites was investigated by infrared spectroscopy, X-ray diffraction, and X-ray photoelectronic spectroscopy methods, and it was established how the production process affects the composition of materials. Regularities of the formation of porosity by the methods of low-temperature adsorption of nitrogen, immersion in a liquid (determination of the pore space volume), measurement of the diffusion coefficient through the material (Franz cell), and surface properties of composite materials by the Hammett indicator method, by the lying drop method were revealed. Regularities were established between the surface properties and the composition of materials and their biocompatibility determined using monocytes isolated from human peripheral blood.

Ring‐Expansion Copolymerization of l‐Lactide and Glycolide

Abstract1:1 Copolymerizations of glycolide (GL) and l‐lactide (LA) are performed in bulk at 100 C and at 160 C with four cyclic tin catalysts. The resulting copolyesters are characterized by size exclusion chromatography measurements, 1H and 13C NMR spectroscopy and by MALDI‐TOF mass spectrometry. At 160 °C and longer reaction time (22 h), nearly complete conversion of both monomers is achieved, and cyclic copolymers with nearly random sequences are formed. At shorter times (0.5–3.0 h, depending on catalyst) the conversion of LA is incomplete, and only cyclics having even numbers of lactyl units are obtained. At 100 C and 22 h again cycles mainly consisting of even numbered lactyl units are formed, but with even and odd numbers of glycolyl units. Copolymerization of lactide at 160 C with small amounts of GL show that formation of high Tm crystallites (Tm &gt; 190 C) is hindered even when only &gt;2% of GL is added. For polyglycolide containing a smaller amount of lactide complete solubility in hexafluoroisopropanol is only observed around and above 20 mol% of lactide.

Electrospray preparation of biocompatible lactide–glycolide copolymer capsules with incorporation of interferon

The electrospray method was used for the first time to prepare polymeric capsules from bioresorbable dl-lactide and glycolide copolymer loaded with biological molecules from the cell secretome and, in particular, human interferon a-2b (IFN a-2b). The obtained nearly spherical submicron capsules were studied by scanning electron and confocal laser microscopy. The capsules retain the structural integrity and the cytotoxic activity of IFN a-2b towards tumor cells. The electrospray method is distinguished by high adaptability and environmental safety and is suitable for manufacture of a broad range of materials with different composition and morphology promising for the targeted delivery of drugs and biological molecules.

Lipoyl Ester Terminated Star PLGA as a Simple and Smart Material for Controlled Drug Delivery Application

PLGA, a copolymer of lactide and glycolide, is one of the most used biodegradable polymers that find a wide range of biomedical applications including drug delivery and tissue engineering. However, in spite of remarkable advancement, nanotherapeutics based on PLGA might have drawbacks of inadequate stability, drug leakage, and slow drug release at the tumor site, which reduces its targeting ability and therapeutic efficacy. Here, we report that direct modification of star PLGA ends with lipoic acid, a natural antioxidant present in our human body, affords a smart material (sPLGA-LA) that forms reversibly crosslinked and bioresponsive multifunctional nanoparticles (sPLGA XNPs). Interestingly, sPLGA XNPs obtained in the presence of 23.0 wt % PEG-PDLLA displayed a small hydrodynamic size of 73 ± 1.2 nm, high stability against dilution and 10% serum, while fast destabilization under a reductive environment. Moreover, sPLGA XNPs achieved efficient loading of lipophilic anticancer drug model, doxorubicin (DOX), at a theoretical drug loading content of 13.3 wt %, giving DOX-loaded sPLGA XNPs with reduced drug leakage under physiological conditions as well as significantly accelerated drug release under 10 mM glutathione condition compared with both linear and star PLGA controls (denoted as lPLGA NPs and sPLGA NPs, respectively). Confocal microscopy and flow cytometry displayed obviously stronger DOX fluorescence in B16F10 melanoma cells treated with DOX-loaded sPLGA XNPs than with lPLGA and sPLGA counterparts. MTT assays revealed that DOX-sPLGA XNPs caused 2.4- and 4.2-fold higher antitumor activity toward B16F10 cells than DOX-sPLGA NPs and DOX-lPLGA NPs, respectively. Notably, in vivo pharmacokinetics studies showed prolonged circulation time and significantly improved AUC for DOX-sPLGA XNPs over lPLGA NPs control. Hence, lipoyl ester terminated star PLGA emerges as a simple and smart material for better-controlled anticancer drug delivery.

Synthesis, characterization and application of biodegradable polymer grafted novel bioprosthetic tissue

Animal tissue has an extended history of clinical use in applications like heart valve bioprosthesis devices, cardiovascular surgical applications etc. but often does not last long after implantation in the body due to rapid unwanted degradation. The goal of this work is to develop novel composite biomaterials by grafting biological tissue with synthetic, biodegradable polymers. In the current research phase, porcine submucosa, ureter and bovine pericardial tissue are grafted with poly DL-lactide (PLA), poly glycolide (PGA) and poly DL-lactide glycolide (PLGA) copolymers. The grafted and control tissues are characterized by FTIR and SEM. The biodegradability of the tissue-graft composite materials is determined by pepsin and collagenase digestion assays, showing it can be tailored by varying the grafted polymer type and amount. The grafted tissues can be tuned for a particular clinical or tissue engineering applications including drug delivery with little or no burst release and sustained/controlled delivery.

Biological Properties of Low-Toxicity PLGA and PLGA/PHB Fibrous Nanocomposite Implants for Osseous Tissue Regeneration. Part I: Evaluation of Potential Biotoxicity.

In response to the demand for new implant materials characterized by high biocompatibility and bioresorption, two prototypes of fibrous nanocomposite implants for osseous tissue regeneration made of a newly developed blend of poly(l-lactide-co-glycolide) (PLGA) and syntheticpoly([R,S]-3-hydroxybutyrate), PLGA/PHB, have been developed and fabricated. Afibre-forming copolymer of glycolide and l-lactide (PLGA) was obtained by a unique method of synthesis carried out in blocksusing Zr(AcAc)4 as an initiator. The prototypes of the implants are composed of three layers of PLGA or PLGA/PHB, nonwoven fabrics with a pore structure designed to provide the best conditions for the cell proliferation. The bioactivity of the proposed implants has been imparted by introducing a hydroxyapatite material and IGF1, a growth factor. The developed prototypes of implants have been subjected to a set of in vitro and in vivobiocompatibility tests: in vitro cytotoxic effect, in vitro genotoxicity and systemic toxicity. Rabbitsshowed no signs of negative reactionafter implantation of the experimental implant prototypes.

Preparation of poly(glycolide-co-lactide)s through a green process: Analysis of structural, thermal, and barrier properties

We have successfully synthesized poly(lactide), poly(glycolide), and poly(lactide-co-glycolide) copolymers in bulk by ring-opening homo- and copolymerization of glycolide and l-lactide, using sodium hydride as the environmentally friendly and nontoxic initiator. Random copolymers were obtained, and the microstructure was characterized by nuclear magnetic resonance (1H and 13C NMR) and matrix-assisted laser desorption ionization mass spectrometry (MALDI MS). The mechanism of reaction was elucidated by analysis of the polymer end groups. Homopolymer and copolymers films and their blends were obtained, and structure and physical properties analyzed. Thermal degradation analysis showed superior characteristics of copolymers with respect to the blends. Transport properties of water vapor were also evaluated and correlated to the copolymer composition.

Biodegradable Thermoplastic Elastomers Incorporating POSS: Synthesis, Microstructure, and Mechanical Properties

A need exists for biodegradable thermoplastic elastomers with tailorable mechanical and degradation properties. Toward meeting this need, we introduce a family of biodegradable thermoplastic elastomers that feature soft segments based on caprolactone–d,l-lactide or caprolactone–glycolide copolymers of low crystallinity, combined with a POSS-based hard segment with relatively low melting transition. Molecular characterization of the polyols and polyurethanes indicates good control over the composition and molecular weights, with high molecular weights for the polyurethanes, as desired. Thermal, mechanical, and microstructural characterization enabled establishment of structure–property relationships. Incorporation of two different comonomers was effective in diminishing soft segment crystallinity, positively impacting elasticity, while increasing POSS content proved effective in establishing thermally robust elastic behavior as well as mechanically reinforcing the polyurethanes. Prestraining the new thermo...

In vitro fabrication of extracellular matrix-rich tissue equivalents

Event Abstract Back to Event In vitro fabrication of extracellular matrix-rich tissue equivalents Kyriakos Spanoudes1, 2*, Yves Bayon3*, Abhay Pandit2* and Dimitrios I. Zeugolis1, 2* 1 National University of Ireland Galway, Regenerative, Modular and Developmental Engineering Laboratory (REMODEL), Ireland 2 National University of Ireland Galway, Centre for Research in Medical Devices (CURAM), Ireland 3 Covidien, Sofradim Production, France Introduction: Tendon tissue engineering is becoming increasingly important, as current surgical treatment modalities based on tissue grafts and non-degradable polymers have numerous drawbacks, including disease transmission, foreign body response and scar tissue formation[1]. Injectable cell based therapies are characterised by poor cell localisation at the site of injection[2]. Herein, we hypothesise that provision of a more relevant microenvironment with anisotropic topography and macromolecular crowding will maintain tenogenic phenotype in vitro[3],[4] and facilitate the fabrication of an extracellular matrix-rich tendon equivalent, promoting functional repair and regeneration in vivo. Materials and Methods: Glycomer™ 631, co-polymer of glycolide (60%), trimethylene carbonate (26%) and dioxanone (14%) was dissolved in hexafluoro-isopropanol (HFIP) at 100mg/ml concentration. Using a rotating collector (3000 RPM) anisotropic electro-spun fibres were produced. Human patellar tendon tenocytes were expanded up to passage 3 in DMEM media, supplemented with 10% foetal bovine serum and 1% penicillin / streptomycin. 50,000 cells / cm2 were subsequently cultured for up to 28 days under the influence of Carragennan 75 μg/ml (crowder). Fibre orientation and fibre diameter distribution were assessed with Scanning Electron Microscopy (SEM). The influence of electro-spun fibres on cell viability and metabolic activity was assessed using Live/Dead® and alamarBlue® assays respectively. Cell morphometric analysis was carried out using DAPI and rhodamine conjugated phalloidin and subsequent image analysis (ImageJ). Tendon specific extracellular matrix (ECM) deposition was assessed with immunocytochemistry. Results: The scaffold obtained by electrospinning Glycomer™ 631 at 3000RPM, is characterised by high degree of alignment, a fibre diameter distributed at the submicron level and adequate mechanical and thermal properties (Figure 1). Macromolecular crowding enhances tendon-specific matrix deposition from cells. This allows the fabrication of an ECM-rich tendon equivalent in vitro, where tenocytes obtain and maintain their physiological bidirectional morphology (Figure 2). Conclusion: These in vitro data indicate that anisotropic electro-spun Glycomer™ 631 scaffolds along with macromolecular crowding provide a suitable microenvironment for tenocyte growth, facilitating the in vitro fabrication of a matrix-rich tendon equivalent. Further mechanical analysis, protein and gene assays and in vivo studies are under way. Irish Research Council

SINTESIS POLI (GLIKOLIDA-CO-LAKTIDA) DAN UJI BIODEGRADABILITASNYA

Polylactide and polyglycolide are important aliphatic polyester consist of lactide and glycolide repeats unit. It is considered as green polymer due to it is produced from renewable agricultural resources. The development of biodegradable plastics based on agricultural resources is still important to be done. Copolymerization of glycolide with D-lactide, L-lactide, and DL-lactide using a Sn(Oct)2 as catalyst had been carried out. Polymerization was conducted by ring-opening of lactide and glycolide without the solvents but melting polymerization. Polymerization were conducted at 130 °C for 130 hours. Result of this study showed that polymerization of glycolide with D-lactide produce polymers with an average molecular weight of 8.2x103 and a yield of 72 %. Polymerization of glycolide with L-lactide produce polymer with an average molecular weight of 2.8x103 and a yield of 36 %. Polymerization glycolide with DL-lactide produce polymer with an average molecular weight of 2.5x103 with a 48 % yield. The burial test for 28 days showed poly (glycolide-co-Llaktida) degraded faster than other polymers, namely degraded 32 %. While poly (glycolide-co-DL-lactide) and poly (glycolide-co-D-lactide) showed similar degradation that is equal to 20 %. Compared with PHB (polyhydroxybutyrate), poly (glycolide-co-lactide) degraded more slowly.Keywords: Glycolide, lactide, copolymerization, biodegradable plastic