Use of triethylcitrate plasticizer in the production of poly-L-lactic acid implants with different degradation times

Bioabsorbable materials have been widely used in the repair of damaged tissue as well as in the controlled release of drugs and as a supports for cultured cells. The degradation time of poly-L-(lactic acid) (PLLA) may be controlled by altering the polymer porosity through the addition of the plasticizer triethylcitrate. This in turn influences the extent cellular infiltration. In this study, we examined the degradation of PLLA membranes containing different concentrations of plasticizer. PLLA discs were implanted subcutaneouly in rats and withdrawn 2, 14 and 60 days after implantation. The samples were processed for light microscopy and scanning electron microscopy (SEM). Polymer degradation was proportional to the concentration of plasticizer, indicating that triethylcitrate could affect the degradation time of the implants, without damaging the polymer biocompatibility.     

The microscopical characterization of membranes poly (<Emphasis Type="SmallCaps">l</Emphasis>-glycolic-co-lactic acid) with and without added plasticizer: an in vivo study

The development of biodegradable materials has lead to renewed interest in the study of their interactions with the host organism in order to make the resulting products appropriate for use as temporary materials in clinical research, as well as important therapeutic applications. The copolymer poly (l-lactic-co-glycolic acid) or PLGA membranes have been used for several purposes. The physical properties of these materials can be modified by the addition of a plasticizer, such as the triethylcitrate, to provide flexibility and porosity to the implants, and enhance control of the polymer degradation time. Membranes with 7% plasticizer and without plasticizer (triethylcitrate) were compared. Membranes without plasticizer were denser and more compact than those with plasticizer. Two days and 30 days after implantation, the membranes with and without plasticizer showed little degradation. Sixty days and 120 days after implantation, the membranes with 7% plasticizer showed more cell invasion, and tissue adherence, as well as rapid degradation when compared to membranes without plasticizer.     

Osteointegration of poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactic acid)PLLA and poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactic acid)PLLA/poly(ethylene oxide)PEO implants in rat tibiae

Natural or synthetic materials may be used to aid tissue repair of fracture or pathologies where there has been a loss of bone mass. Polymeric materials have been widely studied, aiming at their use in orthopaedics and aesthetic plastic surgery. Polymeric biodegradable blends formed from two or more kinds of polymers could present faster degradation rate than homopolymers. The purpose of this work was to compare the biological response of two biomaterials: poly(L: -lactic acid)PLLA and poly(L: -lactic acid)PLLA/poly(ethylene oxide)PEO blend. Forty four-week-old rats were divided into two groups of 20 animals, of which one group received PLLA and the other PLLA/PEO implants. In each of the animals, one of the biomaterials was implanted in the proximal epiphysis of the right tibia. Each group was divided into subgroups of 5 animals, and sacrificed 2, 4, 8 and 16 weeks after surgery, respectively. Samples were then processed for analysis by light microscopy. Newly formed bone was found around both PLLA and PLLA/PEO implants. PLLA/PEO blends had a porous morphology after immersion in a buffer solution and in vivo implantation. The proportion 50/50 PLLA/PEO blend was adequate to promote this porous morphology, which resulted in gradual bone tissue growth into the implant.     

The influence of triethylcitrate on the biological properties of poly (L-lactic-co-glycolic acid) membranes

Biodegradable polymers have a variety of uses in basic and clinical research, as well as important therapeutic applications. The most commonly used are poly (lactic acid), poly (glycolic acid) and their copolymer, poly (L-lactic-co-glycolic acid) or PLGA. The incorporation of a plasticizer into a polymer can be used to obtain a product with specific properties. In this work, we examined the influence of a plasticizer (triethylcitrate) on the properties of PLGA membrane implants for human clinical uses. Membranes with and without plasticizer were dense and compact and contained no pores. The incorporation of 7% plasticizer enhanced the degradation the polymer when compared to polymer without plasticizer. In membranes without plasticizer, the initiation of degradation was very slow and was seen only 60 days after implantation, should allow the use of this material in the repair of damage tissue. In both cases, macroscopic analysis showed that there was no adhesion of the membrane to capsule fibrous, and this adversely affected preservation of the polymer. With time, the adherence of the polymer to surrounding tissue increased. Overall there was little degradation of membranes without plasticizer compared to those containing plasticizer.     

Biodegradable electrospun PLLA/chitosan membrane as guided tissue regeneration membrane for treating periodontitis

This paper explores the application potential of a biodegradable PLLA/chitosan electrospun composite membrane for guided periodontal tissue regeneration which in addition serves as a fibroblast barrier. Electrospinning was applied to fabricate the PLLA membrane and aminolysis method was applied to graft chitosan on its surface. The morphology of the PLLA/chitosan membrane was observed by SEM. The surface chemical composition was analyzed by XPS. The appearance of N 1s peak in XPS demonstrated the successful grafting of chitosan on the PLLA electrospin membrane. After the modification, the water contact angle decreased from 136.9 ± 2.18° to 117.0 ± 2.10°, representing an improved hydrophilicity of the membrane. The bioactivity of the membrane was analyzed by XPS after soaking in SBF. The deposits had a Ca/P ratio of 1.6, indicating the hydroxyapatite formation on PLLA/chitosan membrane. The degradation rate was determined by measuring mass loss after immersion in PBS at different time periods. Compared to pure PLLA electrospun membrane which was almost non-degradable, the degradation rate of PLLA/chitosan composite membrane was up to 20 % in 6 weeks while maintaining its basic architecture to keep supporting the regenerated tissue. Live–dead cell staining of MC3T3 E1 cells cultured on the surface of the membrane showed a good biocompatibility of the PLLA/chitosan membrane. Furthermore, fibroblast cell line NIH 3T3 was cultured on surface of the membrane for the evaluation of cell penetration. The result demonstrated that the membrane worked as a fibroblast barrier to minimize the unfavorable effect of fibroblasts on periodontal tissue regeneration. Therefore, this electrospun PLLA/chitosan composite membrane has more potential for clinical application compared to old generation regeneration membrane with both suitable degradation rate and non-fibroblast penetration property.     

The effects of types of degradable polymers on porcine chondrocyte adhesion, proliferation and gene expression

Understanding how a specific biomaterial may influence chondrocyte adhesion, proliferation and gene expression is important in cartilage tissue engineering. In this study several biodegradable polymers that are commonly used in tissue engineering were evaluated with respect to their influence on chondrocyte attachment, proliferation and gene expression. Primary cultures of porcine chondrocytes were performed in films made of poly-L-lactic acid (PLLA), poly-D,L-lactic acid (PDLLA), poly-(lactide-co-glycolide) (PLGA), or polycaprolactone (PCL). Chondrocytes adhered to PDLLA or PLGA after 1-day incubation better than to PLLA or PCL. After 7 or 14 day culture, the cell numbers on PDLLA or PLGA was still higher than PLLA or PCL. The results suggested that cell attachment and growth might depend on degradation rate of biodegradable polymers. Along with the fact that PDLLA or PLGA supported expression of chondrocyte specific genes more than PLLA or PCL, the former two materials seemed to be more suitable for cartilage tissue engineering than the latter ones. Besides, we found that chondrocyte phenotype prior to seeding was important in the expression of ECM proteins.     

Bone response to polymers based on poly-lactic acid and having different degradation times

Authors studied two degradable and resorbable polymers derived from lactic acid: poly-L-Lactic acid (PLLA), with a relatively long time of degradation (longer than 6 months, PL10 Purac NL); poly-DL-Lactic acid (PDLLA), with a relatively short time of degradation (shorter than 6 months, PDL Purac NL). The animal species was the young adult New Zealand White rabbit. The in-vivo study was performed by implantation of small cylinders of 10 × 3 mm in size (length × diameter) in the distal metaepiphysis of the femur; 34 cylinders have been implanted. Retrievals of PLLA specimens took place at 3, 6, 9, 12 and 24 months; for PDLLA specimens at 1, 2, 4 months. Polarized light microscopy of undecalcified tissue sections was performed. The analysis for PLLA and PDLLA has shown a favorable response of bone tissue: alterations in the bone repair, growth and remodeling have not been observed. PLLA is persistent at the times studied; there is never a tight apposition between bone and PLLA implant and an intervening fibrous layer has often been observed. PDLLA is not persistent at the times studied and it degrades quite fast; bone repair of the empty implantation's hole occurs by bony growth from the endosteal trabeculae. The newly formed bone covers the hole's walls with an elongation parallel to them. For both polymers, whether the degradation is fast or slow, the material's substitution by newly formed bone never starts from the walls of the implantation hole. Only after the complete disappearance of the polymeric material newly formed bone begins to fill the hole. © 2001 Kluwer Academic Publishers     

Morphometrical analysis of multinucleated giant cells in subdermal implants of poly-lactic acid in rats

The use of bioabsorbable polymers in (bio)medical applications has increased greatly in recent years, mainly because of their good bioreabsorption and biocompatibility. In this work, we examined the development of foreign body giant cells in intimate contact with porous membranes of poly L–lactic acid containing 7% of plasticizer triethylcitrate implanted in the backs of rats. The membranes were removed 2, 7, 14, 21, 28, 60, 90 and 180 days after implantation, along with a portion of the tissue around the implant. Histological analysis of the implant and tissue revealed the formation of a fibrous capsule from the seventh day of implantation onwards. Foreign body giant cells appeared from the seventh day and increased in number up to the twenty-eighth day and then up to the ninetieth day of implantation, remaining constant up to the end of the study onwards, and increased in number up to the ninetieth day after implantation and then remained constant. The number of nuclei in these cells increased from the seventh day of implantation up to the ninetieth day and then up to the end of the study.     

A review on biodegradable materials for cardiovascular stent application

A stent is a medical device designed to serve as a temporary or permanent internal scaffold to maintain or increase the lumen of a body conduit. The researchers and engineers diverted to investigate biodegradable materials due to the limitation of metallic materials in stent application such as stent restenosis which requires prolonged anti platelet therapy, often result in smaller lumen after implantation and obstruct re-stenting treatments. Biomedical implants with temporary function for the vascular intervention are extensively studied in recent years. The rationale for biodegradable stent is to provide the support for the vessel in predicted period of time and then degrading into biocompatible constituent. The degradation of stent makes the re-stenting possible after several months and also ameliorates the vessel wall quality. The present article focuses on the biodegradable materials for the cardiovascular stent. The objective of this review is to describe the possible biodegradable materials for stent and their properties such as design criteria, degradation behavior, drawbacks and advantages with their recent clinical and preclinical trials.     

Poly(L-lactic acid) nanocylinders as nanofibrous structures for macroporous gelatin scaffolds

Electrospun Nanofiber sheets have been shown to mimic the structure of extracellular matrix (ECM). Although these nanofibers have shown great potential for use as tissue engineering scaffolds, it is difficult for the electrospun nanofiber based sheets to be shaped into the desired three-dimensional structure. In this study, poly(L-lactic acid) (PLLA), a biodegradable and biocompatible polyester, was electrospun to produce nanofibers that were treated with an amino group containing base in order to fabricate polymeric nanocylinders. The aspect ratio of the PLLA nanocylinders was tunable by varying the aminolysis time and density of the amino group containing base. The effects of changes in nanofibrous morphology of the PLLA nanocylinders/macro-porous gelatin scaffolds on cell adhesion and proliferation were evaluated. The results revealed different cell morphology, adhesion, and proliferation in the nanocylinders composite gelatin scaffold versus gelatin scaffold alone. Confocal laser scanning microscopy observation showed more spreading and a more flattened cell morphology after NIH3T3 cells were cultured on PLLA nanocylinders/gelatin scaffolds for 10 hours and 4 days. These results indicate that the gelatin/PLLA nanocylinder composite is a promising way to fabricate 3D nanofibrous scaffolds that accelerates cell adhesion and proliferation for tissue engineering.     

Synthesis and characterization of biodegradable poly(l-lactide)/layered double hydroxide nanocomposites

This study reports the preparation and physical properties of biodegradable nanocomposites fabricated using poly(l-lactide) (PLLA) and magnesium/aluminum layered double hydroxide (MgAl-LDH). The MgAl-LDH with molar ratio of Mg/Al = 2 were synthesized by the co-precipitation method. In order to improve the chemical compatibility between PLLA and LDH, the surface of LDH was organically-modified by polylactide with carboxyl end group (PLA–COOH) using ion-exchange process. Then, the PLLA/LDH nanocomposites were prepared by solution intercalation of PLLA into the galleries of PLA–COOH modified LDH (P-LDH) in tetrahydrofuran solution. Both X-ray diffraction data and Transmission electron microscopy images of PLLA/P-LDH nanocomposites indicate that the P-LDHs are randomly dispersed and exfoliated into the PLLA matrix. Mechanical properties of the fabricated 1.2 wt.% PLLA/P-LDH nanocomposites show significant enhancements in the storage modulus when compared to that of neat PLLA. Adding more P-LDH into PLLA matrix induced a decrease in the storage modulus of PLLA/P-LDH nanocomposites, probably due to the excessive content of PLA–COOH moleculars with low mechanical properties. The thermal stability and degradation activation energies of the PLLA and PLLA/P-LDH nanocomposites can also be discussed.     

Preparation,crystallization behaviors,and mechanical properties of biodegradable composites based on poly(L-lactic acid) and recycled carbon fiber

The biodegradable composites based on poly(L-lactic acid) (PLLA) and recycled carbon fiber (RCF) were prepared through melting extrusion. The surface-treatment of RCF with silane coupling agent enhanced the interfacial adhesion between RCF and PLLA, and thus the PLLA/RCF composites achieved a significant improvement in mechanical properties. The morphologies of fracture surfaces indicated that the RCF obtained a homogeneous dispersion in PLLA matrix due to a good interfacial interaction. The investigations on the crystallization behaviors and kinetics demonstrated that the RCF acted as a nucleation agent for the crystallization of PLLA, and the crystallization rate and the nucleation density of PLLA matrix were improved remarkably due to the heterogeneous nucleating effect of RCF in the matrix. These features may be advantageous for the enhancement of mechanical properties, heat resistance, and processability of PLLA-based materials. The PLLA-based composites made from RCF can be used as low cost biodegradable materials for many applications.     

In vitro predegradation at elevated temperatures of poly(lactide)

In this study in vitro predegradation at elevated temperatures, used to obtain an increased degradation rate, was investigated. The in vitro degradation was followed by mass loss, molecular weight loss and changes in thermal properties. Two biodegradable polymers, the homopolymer PLLA and a copolymer PLA96 (96% L4%D lactide), were hydrolytically degraded at 90°C in a phosphate buffered solution. Both polymers, PLLA and PLA96, showed an initial linear degradation rate, but with longer implantation periods the degradation rate decreased and total degradation was best described as an asymptotic. Mass loss of the copolymer PLA96 was twice that of PLLA. The chemical analysis of the in vitro predegraded polymers coincided for both the decrease in molecular weight and the thermal properties with physiologically degraded poly(lactide). The results of this study show that although the degradation temperature is well above the glass transition temperature and not comparable to physiological temperatures, there seems to be good correlation between the in vitro degraded material and physiologically degraded material. In vitro predegradation enables investigation of the entire degradation process of a polymer in a short-term study. Moreover, in vitro predegradation allows direct comparison of the degradation rate of various polymers.     

Compressive mechanical properties and deformation behavior of porous polymer blends of poly(ε-caprolactone) and poly(l-lactic acid)

Porous biodegradable polymeric scaffolds are developed by physically blending two different kinds of biodegradable polymers, PCL, and PLLA, for application in tissue engineering. The main objective of the development of this material is to control the mechanical properties, such as, elastic modulus and strength. The results from mechanical testing showed that the compressive mechanical properties of PCL/PLLA scaffold can be varied by changing the blend ratio. It also showed that these properties can be well predicted by the rule of mixture. The primary deformation mechanism of the scaffolds was found to be localized buckling of struts surrounding the pores. Localized ductile failure caused by PCL phase tends to be suppressed with increasing PLLA content. The immiscibility of PCL and PLLA caused the phase-separation morphology that strongly affected the macroscopic mechanical properties and the microscopic deformation behavior.     

Study of biodegradable and self-expandable PLLA helical biliary stent in vivo and in vitro

Biodegradable stents have advantages for the treatment of benign and malignant biliary stricture, especially eliminating the need for stent removal. In our present work, helical poly-l-lactic acids (PLLA) stent was fabricated and evaluated in vivo and in vitro. For in vivo study, bile duct injury canine models were made by transection of common bile ducts. Duct to duct anastomosis was done with helical PLLA biodegradable stents. Scanning electron microscopy (SEM) and histopathology were performed after three months. For In vitro study, sludge attachment assessment was performed. Polyethylene (PE) and PLLA membranes were immersed in human bile for two months. The samples were taken out and characterized by SEM. Self-expanding property of the helical stent was tested in 37°C water. The results demonstrate that the biodegradable stent had not only good biocompatibility, but also self-clearing effect to clear the attached sludge away. The self-expanding property facilitated stent implantation and also suggested possibility to be implanted endoscopically.     

金属氧化物对PLLA降解性能的影响

将分别添加微量金属氧化物CaO、MgO、ZnO 的生物可降解聚酯聚乳酸(PLLA)薄膜放入陕西当地土壤的提取液中进行微生物兹化反应,以研究薄膜中金属氧化物对PLLA降解性能的影响,并通过红外光谱中官能团吸收强度的变化,表征了其降解前后的化学结构。研究结果表明：添加金属氧化物的PLLA在陕西当地土壤的提取液中能够降解,添加微量的 CaO、MgO加快了PLLA的降解速度,而添加ZnO对PLLA 的降解没有太大影响。用显微镜对降解前后膜的观察发现：纯 PLLA 薄膜降解后的膜表面变得明显粗糙,有显著的微生物侵蚀痕迹;而添加微量金属氧化物的薄膜中,由于均匀分散金属氧化物的存在,导致降解后膜表面出现了更大的缺陷和侵蚀痕迹。     

Effect of starch-based biomaterials on the <Emphasis Type="Italic">in vitro</Emphasis> proliferation and viability of osteoblast-like cells

The cytotoxicity of starch-based polymers was investigated using different methodologies. Poly-L-lactic acid (PLLA) was used as a control for comparison purposes. Extracts of four different starch-based blends (corn starch and ethylene vinyl alcohol (SEVA-C), corn starch and cellulose acetate (SCA), corn starch and polycaprolactone (SPCL) and starch and poly-lactic acid (SPLA70) were prepared in culture medium and their toxicity was analysed. Osteoblast-like cells (SaOs-2) were incubated with the extracts and cell viability was assessed using the MTT test and a lactate dehydrogenase (LDH) assay. In addition DNA and total protein were quantified in order to evaluate cell proliferation. Cells were also cultured in direct contact with the polymers for 3 and 7 days and observed in light and scanning electron microscopy (SEM). LDH and DNA quantification revealed to be the most sensitive tests to assess respectively cell viability and cell proliferation after incubation with starch-based materials and PLLA. SCA was the starch blend with higher cytotoxicity index although similar to PLLA polymer. Cell adhesion tests confirmed the worst performance of the blend of starch with cellulose acetate but also showed that SPCL does not perform as well as it could be expected. All the other materials were shown to present a comparable behaviour in terms of cell adhesion showing slight differences in morphology that seem to disappear for longer culture times.The results of this study suggest that not only the extract of the materials but also their three-dimensional form has to be biologically tested in order to analyse material-associated parameters that are not possible to consider within the degradation extract. In this study, the majority of the starch-based biomaterials presented very promising results in terms of cytotoxicity, comparable to the currently used biodegradable PLLA which might lead the biocompatibility evaluation of those novel biomaterials to other studies.     

Anticorrosion and cytocompatibility behavior of MAO/PLLA modified magnesium alloy WE42

Recently, biodegradable magnesium alloys have been introduced in the field of cardiovascular stents to avoid the specific drawbacks of permanent metallic implants. However, the major obstacle of the clinical use of magnesium-based materials is their rapid corrosion rate. In this paper, a composite micro-arc oxidation/poly-l-lactic acid (MAO/PLLA) coating was fabricated on the surface of the magnesium alloy WE42 to improve its corrosion resistance and the cytocompatibility of the modified materials was also investigated for safety aim. In our study, the morphology of materials was analyzed by Scanning electron microscopy. Potentiodynamic polarization was used to evaluate the corrosion behavior of the samples and corrosion weight loss was used to demonstrate their degradation rate. Furthermore, we applied cytotoxicity test in testing the cytocompatibility of the modified samples. The results showed that the PLLA coating effectively sealed the microcracks and micropores on the surface of the MAO coating by physical interlocking to interfere the corrosion ions. The corrosion rate was decreased and the cyototoxicity test showed that the MAO/PLLA composite coating WE42 had good cytocompatibility.     

医用牙周组织引导再生胶原材料的特性

用酶消化法从牛腱中提取出胶原蛋白，采用涂复法制成胶原膜材料，将该膜用０．２５％的甲醛交联后得到用于牙周组织引导再生的材料．在对胶原材料进行物理、化学性能测试后表明：该材料的力学性能超过国外同类制品并具有较好的吸水性，而且胶原材料的羰基、羧基、羟基和胺基等主要结构基团依然存在经体外胶原酶和体内肌肉包埋降解吸收观察，材料在体外约２４０小时降解完全，降解产物为羟脯氨酸，体内吸收时间为６０天左右．对该材料进行生物学评价后证明：该材料无三致反应和其它毒副作用，无热原和过敏反应及溶血现象等，生物相容性优良．因此，该材料可用于牙周组织引导再生术及更广泛的生物隔膜技术中．     

Synthesis and characterization of a biodegradable elastomer featuring a dual crosslinking mechanism

The need for advanced materials in emerging technologies such as tissue engineering has prompted increased research to produce novel biodegradable polymers elastic in nature and mechanically compliant with the host tissue. We have developed a soft biodegradable elastomeric platform biomaterial created from citric acid, maleic anhydride, and 1,8-octanediol, poly(octamethylene maleate (anhydride) citrate) (POMaC), which is able to closely mimic the mechanical properties of a wide range of soft biological tissues. POMaC features a dual crosslinking mechanism, which allows for the option of the crosslinking POMaC using UV irradiation and/or polycondensation to fit the needs of the intended application. The material properties, degradation profiles, and functionalities of POMaC thermoset networks can all be tuned through the monomer ratios and the dual crosslinking mechanism. POMaC polymers displayed an initial modulus between 0.03 and 1.54 MPa, and elongation at break between 48% and 534% strain. In vitro and in vivo evaluation using cell culture and subcutaneous implantation, respectively, confirmed cell and tissue biocompatibility. POMaC biodegradable polymers can also be combined with MEMS technology to fabricate soft and elastic 3D microchanneled scaffolds for tissue engineering applications. The introduction of POMaC will expand the choices of available biodegradable polymeric elastomers. The dual crosslinking mechanism for biodegradable elastomer design should contribute to biomaterials science.