- Research article
- Open Access
Effects of poly(L-lactide-ε-caprolactone) and magnesium hydroxide additives on physico-mechanical properties and degradation of poly(L-lactic acid)
© Kang et al. 2016
- Received: 11 January 2016
- Accepted: 26 February 2016
- Published: 15 March 2016
Biodegradable poly(L-lactic acid) (PLLA) is one of the most widely used polymer in biomedical devices, but it still has limitations such as inherent brittleness and acidic degradation products. In this work, PLLA blends with poly(L-lactide-ε-caprolactone) (PLCL) and Mg(OH)2 were prepared by the thermal processing to improve their physico-mechanical and thermal properties. In addition, the neutralizing effect of Mg(OH)2 was evaluated by degradation study.
The elongation of PLLA remarkably increased from 3 to 164.4 % and the glass transition temperature (Tg) of PLLA was slightly reduced from 61 to 52 °C by adding PLCL additive. Mg(OH)2 in polymeric matrix not only improved the molecular weight reduction and mechanical strength of PLLA, but also neutralized the acidic byproducts generated during polyester degradation.
Therefore, the results demonstrated that the presence of PLCL and Mg(OH)2 additives in PLLA matrix could prevent the thermal decomposition and control degradation behavior of polyester.
- Poly(L-lactic acid)
- Magnesium hydroxide
- Thermal decomposition
One of the most important disadvantages of PLLA is brittleness due to its semi-crystalline character, which can limit its applicability. Many papers have reported the PLLA blends with ductile and biodegradable polymers such as polyglycolic acid (PGA) [10, 11], polyamide 6 (PA6)  and poly(butylene succinate-co-adipate) (PBSA) [13, 14]. Aliphatic polyester based on polycaprolactone such as poly(L-lactide-ε-caprolactone) (PLCL) has been used to improve the processability and thermal stability of PLLA because PLCL has flexible characteristics, low melting temperature, and aliphatic chain of polycaprolactone segment. The PLLA blends with polycaprolactone based polyester exhibit remarkable increase in their elongation at break due to relative increase of the amorphous region compared with PLLA [15–17].
Magnesium hydroxide, which is widely used as an antacid agent, is a basic inorganic compound with the chemical formula of hydrated Mg(OH)2. Mg(OH)2 is in vivo absorbable in the form of magnesium and hydroxide ions as well as biocompatible . The magnesium ions can be interact with anionic compounds and neutralize the acidic degradation products of PLLA . In addition, Mg(OH)2 also can be used to mechanically reinforce the PLLA matrix, which is a key factor resulting in effective improvement in mechanical properties .
In this work, the PLLA blends with PLCL and Mg(OH)2 additives were developed by thermal processing to improve the flexibility and thermal stability of PLLA matrix and enhance the tensile strength of thermally-processed PLLA. The physic-mechanical properties of PLLA control and PLLA/PLCL blends were measured by gel permeation chromatography (GPC) and universal testing machine (UTM), and their thermal properties were evaluated by using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The effect of Mg(OH)2 in PLLA and PLLA/PLCL matrix was determined by measuring molecular weight and mechanical properties such as tensile strength and elongation. The degradation study was performed, and the degraded samples were assessed by following pH change and calculating molecular weight reduction to evaluate the the neutralizing effect of Mg(OH)2.
Poly(L-lactide) raw material (PLLA, average Mw = 380 kDa) was supplied by Samyang Co. (Seoul, Korea). Poly(L-lactide-co-ε-caprolactone) (PLCL, average Mw = 380 kDa) composed with 50:50 or 75:25 ratio of L-lactide and ε-caprolactone units was obtained from DURECT Co. (Birmingham, AL, USA). Chloroform and magnesium hydroxide (Mg(OH)2) were purchased by Baker Chemicals Inc. (Center Valley, PA, USA) and Junsei Chemical Co., Ltd. (Tokyo, Japan), respectively. All chemicals were reagent grade and used without further purification.
Fabrication of PLLA/PLCL/Mg(OH)2 blends
Various blend compositions of PLCL and Mg(OH)2 in PLLA
The PLLA only, PLLA/PLCL, PLLA/Mg(OH)2, and PLLA/PLCL/Mg(OH)2 composites underwent the thermally melting and hot-pressing process using Carver Press 30-12H (Carver Inc., Wabash, IN, USA). Four grams of polymer mixture put on the hot-press plate, and the plate temperature was then raised to 190 °C. After melting time of 3 min, the pressure increased to about 7 tons and maintained for press time of 6 min. The dimension of compressively molded specimens was 150 × 150 mm2 and its thickness was 200 μm. All specimens were stored in vacuum oven.
Characterizations of PLLA/PLCL/Mg(OH)2 blends
To evaluate the effects of PLCL and Mg(OH)2 additives on the prevention of the molecular weight (Mw) of PLLA during thermal processing, Mw of processed PLLA and PLLA blends was measured by gel permeation chromatography (GPC). The sample was dissolved in chloroform (HPLC grade) at 3 mg/mL concentration, and then the polymer solutions were filtered with a 0.45 μm PTFE filter to remove dust and contaminants. The GPC measurements were performed on an equipment consisted of a Waters 515 HPLC pump, a Waters 717 plus auto sampler and a Waters 410 refractive index (RI) detector (Waters, USA) with KF 804 L and KF 803 (7 μm, 8 × 300 mm, Shodex, Japan) columns (molecular weight resolving range of 500–400,000 Da). The GPC columns were performed using chloroform as the eluent with flow rate of 1 mL/min, and Mw were calibrated with polystyrene standard.
The mechanical properties such as tensile strength and elongation were measured by a universal testing machine (UTM, Instron Co., USA) in accordance with ASTM standard D638. For dynamic tensile test, the processed PLLA and composites with PLLA and additives were prepared with dumbbell shaped specimens (45 × 6 × 2 mm3, length × width × thickness) cut by a punch of a compression-molding machine. All test samples were tested after 1 week to remove the internal stress. The specimens were carried out with crosshead speed of 4 mm/min till failure to determine the influence of additives in PLLA on mechanical property.
The thermal properties of processed PLLA and PLLA blends were investigated by differential scanning calorimetry (DSC, TA Instrument, USA) and thermogravimetric analyser (TGA, TA Instruments, USA), respectively. The glass transition temperature (Tg) of samples was determined by using DSC analysis. The temperature scan was performed with a heating and cooling rate of 10 °C/min under nitrogen atmosphere. The samples were heated from 30 to 210 °C, held for 1 min to erase thermal history effects and cooled to 30 °C, held for 1 min and then heated to 210 °C again for the second scan, which was used to determine the Tg. The effects of additives types and contents on the thermal stability were assessed through TGA. The melting (Tm) and crystallization (Tc) temperatures, in addition to the associated enthalpy of melting (∆Hm) were measured using a heating/cooling ramp from 20 to 600 °C. A heating rate of 10 °C/min was used under nitrogen atmosphere and at a flow rate of 20 mL/min. Dry sample weighing about 1 mg was used. The standard uncertainty of the sample mass measurement is ±1 %.
To study the degradation behavior including pH change, mass loss, and molecular weight reduction of PLLA and PLLA blends, four groups (PLLA, PLLA/PLCL, PLLA/Mg(OH)2, PLLA/PLCL/Mg(OH)2) were prepared in replicate experiments (n = 20, each). Pre-weighted specimens (W 0 ) were immersed into 5 mL of phosphate-buffered saline (PBS, pH 7.4) solution at 60 °C under accelerated weathering conditions [21, 22]. The pH of the PBS solution was monitored every 2 days by a pH meter (Hanna Instrument, USA). Temperature and pH of the PBS solution were monitored during the degradation period and they remained at 37 °C and 7.4, respectively.
The pH change, was measured at the predetermined time point (1, 3, 5, and 7 days) to confirm acidity of samples as well as the neutralization of lactic acids with Mg(OH)2. At time intervals, the specimens were accurately weighed after deionized water rinse and vacuum drying for 48 h (W t ) to determine the mass loss and the reduction of molecular weight. The residual weight percentage was calculated according to the following equation: Mass loss (%) = (W 0 − W t )/W 0 × 100 . The reduced molecular weight of degraded specimens (M t ) was estimated using GPC and compared with an initial molecular weight of samples (M 0 ). The reduction of molecular weight (%) was also calculated according to the following equation: Mw reduction (%) = (M 0 − M t )/M 0 × 100.
The data were presented as mean ± standard deviation (SD). The results obtained by ANOVA were carried out using origin programs. The significance level considered was 0.05 and data groups were different from others.
Thermal properties of PLLA control and PLLA/PLCL blends
The molecular weights of degraded samples were evaluated to confirm the effects of Mg(OH)2 on molecular weight reduction as well as pH balance (Fig. 7b). The PLLA only and PLCL90/PLCL10 blends almost degraded and their molecular weights were dropped to about 10 % for 14 days. On the other hand, the molecular weight of Mg(OH)2-containing blends slowly declined, and, in particular, PLLA100/Mg5 scarcely decomposed as compared with other groups due to higher Tg value of PLLA than that of PLLA90/PLCL10. During degradation, a large amount of the acidic degradation products were released, which usually resulted in a rapid decrease in the pH of the soaking medium . The acidic byproduct reacted like a nucleophile to ester linkage of PLLA and PLCL backbones and then accelerated the decomposition of polymer chains. In PLLA blends with Mg(OH)2, the Mg(OH)2 hindered the accumulation of acidic byproducts and averted backbiting and intermolecular transesterification. These results demonstrated that the Mg(OH)2 affected the prevention of molecular weight reduction by neutralizing acidic substance.
The new PLLA blends with PLCL and Mg(OH)2 additives successfully fabricated by thermal processing, and the effects of PLCL and Mg(OH)2 additives on physico-chemical and thermal properties under thermal decomposition of PLLA matrix were assessed using various analyses. With increasing the amount of PLCL, the PLLA/PLCL blends exhibited the alleviation of molecular weight reduction and the improvement of flexibility compared with thermally processed PLLA control. The PLLA/PLCL blends with increasing proportion of polycaprolactone depicted proper thermal stability as well as mechanical strength including tensile strength and elongation. In Mg(OH)2-containing matrix, the molecular reduction and mechanical strength were dramatically improved because the dehydrated magnesium ion inhibited the decomposition of polyester substrate by counteracting acidic compounds, which is a kind of nucleophile at ester linkage. In particular, the Mg(OH)2 in matrix certainly neutralized the acidic byproducts involved during polyester degradation, that caused the acid-induced inflammatory reaction in vivo. The obtained results suggested that PLCL and Mg(OH)2 additives were effective to enhance flexibility and control degradation behavior of biodegradable PLLA matrix, and therefore the PLLA/PLCL/Mg(OH)2 composites have the potential as a material for bio-absorbable biomedical devices such as implants and stents.
This work was supported by Pioneer Research Center Program (2014M3C1A3056052) and the Bio & Medical Technology Development Program (2014M3A9D3033887) through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (MSIP) and Core Material Development Program (10048019) funded by Ministry of Trade, Industry and Energy (MOTIE), Republic of Korea.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Ray SS, Okamoto M. Biodegradable polylactide and its nanocomposites: opening a new dimension for plastics and composites. Macromol Rapid Commun. 2003;24:815–40.View ArticleGoogle Scholar
- Zhang Z, Feng S-S. The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly (lactide)–tocopheryl polyethylene glycol succinate nanoparticles. Biomaterials. 2006;27:4025–33.View ArticleGoogle Scholar
- Rasal RM, Hirt DE. Micropatterning of covalently attached biotin on poly (lactic acid) film surfaces. Macromol Biosci. 2009;9:989–96.View ArticleGoogle Scholar
- Auras R, Harte B, Selke S. An overview of polylactides as packaging materials. Macromol Biosci. 2004;4:835–64.View ArticleGoogle Scholar
- Vink ET, Rabago KR, Glassner DA, Gruber PR. Applications of life cycle assessment to NatureWorks™ polylactide (PLA) production. Polym Degrad Stab. 2003;80:403–19.View ArticleGoogle Scholar
- Yu H, Huang N, Wang C, Tang Z. Modeling of poly (L‐lactide) thermal degradation: Theoretical prediction of molecular weight and polydispersity index. J Appl Polym Sci. 2003;88:2557–62.View ArticleGoogle Scholar
- Jamshidi K, Hyon S-H, Ikada Y. Thermal characterization of polylactides. Polymer. 1988;29:2229–34.View ArticleGoogle Scholar
- Kopinke F-D, Remmler M, Mackenzie K, Möder M, Wachsen O. Thermal decomposition of biodegradable polyesters—II. Poly (lactic acid). Polym Degrad Stab. 1996;53:329–42.View ArticleGoogle Scholar
- Amid P. Classification of biomaterials and their related complications in abdominal wall hernia surgery. Hernia. 1997;1:15–21.View ArticleGoogle Scholar
- Agrawal CM, Athanasiou KA. Technique to control pH in vicinity of biodegrading PLA-PGA implants. J Biomed Mater Res. 1997;38:105–14.View ArticleGoogle Scholar
- Linhart W, Peters F, Lehmann W, Schwarz K, Schilling AF, Amling M, et al. Biologically and chemically optimized composites of carbonated apatite and polyglycolide as bone substitution materials. J Biomed Mater Res. 2001;54:162–71.View ArticleGoogle Scholar
- Khankrua R, Pivsa-Art S, Hiroyuki H, Suttiruengwong S. Effect of chain extenders on thermal and mechanical properties of poly (lactic acid) at high processing temperatures: Potential application in PLA/Polyamide 6 blend. Polym Degrad Stab. 2014;108:232–40.View ArticleGoogle Scholar
- Lee S, Lee JW. Characterization and processing of biodegradable polymer blends of poly (lactic acid) with poly (butylene succinate adipate). Korea Aust Rheol J. 2005;17:71–7.Google Scholar
- Park JW, Im SS. Phase behavior and morphology in blends of poly (L‐lactic acid) and poly (butylene succinate). J Appl Polym Sci. 2002;86:647–55.View ArticleGoogle Scholar
- Li Q, Yoon J-S, Chen G-X. Thermal and biodegradable properties of poly (L-lactide)/poly (ε-Caprolactone) compounded with functionalized organoclay. J Polym Environ. 2011;19:59–68.View ArticleGoogle Scholar
- Wang L, Ma W, Gross R, McCarthy S. Reactive compatibilization of biodegradable blends of poly (lactic acid) and poly (ε-caprolactone). Polym Degrad Stab. 1998;59:161–8.View ArticleGoogle Scholar
- Wu D, Zhang Y, Zhang M, Yu W. Selective localization of multiwalled carbon nanotubes in poly (ε-caprolactone)/polylactide blend. Biomacromolecules. 2009;10:417–24.View ArticleGoogle Scholar
- Gu X-N, Li S-S, Li X-M, Fan Y-B. Magnesium based degradable biomaterials: A review. Front Mater Sci. 2014;8:200–18.View ArticleGoogle Scholar
- Kum CH, Cho Y, Joung YK, Choi J, Park K, Seo SH, et al. Biodegradable poly (l-lactide) composites by oligolactide-grafted magnesium hydroxide for mechanical reinforcement and reduced inflammation. J Mater Chem B. 2013;1:2764–72.View ArticleGoogle Scholar
- Wen W, Luo B, Qin X, Li C, Liu M, Ding S, et al. Strengthening and toughening of poly (L-lactide) composites by surface modified MgO whiskers. Appl Surf Sci. 2015;332:215–23.View ArticleGoogle Scholar
- Kaci M, Benhamida A, Zaidi L, Touati N, Remili C. Photodegradation of Poly (Lactic Acid)/Organo-Modified Clay Nanocomposites under Natural Weathering Exposure. Ecosustainable Polymer Nanomaterials for Food Packaging: Innovative Solutions, Characterization Needs, Safety and Environmental Issues. 2013: 281Google Scholar
- Scoponi M, Pradella F, Kaczmarek H, Amadelli R, Carassiti V. A reappraisal of the photo-oxidation mechanism at short and long wavelengths for poly (2, 6-dimethyl-1, 4-phenylene oxide). Polymer. 1996;37:903–16.View ArticleGoogle Scholar
- Li AD, Sun Z, Zhou M, Xu X, Ma J, Zheng W, et al. Electrospun Chitosan-graft-PLGA nanofibres with significantly enhanced hydrophilicity and improved mechanical property. Colloids Surf B. 2013;102:674–81.View ArticleGoogle Scholar
- Coltelli M-B, Toncelli C, Ciardelli F, Bronco S. Compatible blends of biorelated polyesters through catalytic transesterification in the melt. Polym Degrad Stab. 2011;96:982–90.View ArticleGoogle Scholar
- Sivalingam G, Karthik R, Madras G. Kinetics of thermal degradation of poly (ε-caprolactone). J Anal Appl Pyrolysis. 2003;70:631–47.View ArticleGoogle Scholar
- Douglas JF. A dynamic measure of order in structural glasses. Comput Mater Sci. 1995;4:292–308.View ArticleGoogle Scholar
- Seidel A. Processing and finishing of polymeric materials Vol. 2. New Jersey, NJ: Wiley; 2011.Google Scholar
- Lim L-T, Auras R, Rubino M. Processing technologies for poly (lactic acid). Prog Polym Sci. 2008;33:820–52.View ArticleGoogle Scholar
- Draye A-C, Persenaire O, Brožek J, Roda J, Košek T, Dubois P. Thermogravimetric analysis of poly (ε-caprolactam) and poly [(ε-caprolactam)-co-(ε-caprolactone)] polymers. Polymer. 2001;42:8325–32.View ArticleGoogle Scholar
- Persenaire O, Alexandre M, Degée P, Dubois P. Mechanisms and kinetics of thermal degradation of poly (ε-caprolactone). Biomacromolecules. 2001;2:288–94.View ArticleGoogle Scholar
- Pampaloni F, Reynaud EG, Stelzer EH. The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol. 2007;8:839–45.View ArticleGoogle Scholar
- Hutmacher DW. Biomaterials offer cancer research the third dimension. Nat Mater. 2010;9:90–3.View ArticleGoogle Scholar
- DesRochers TM, Palma E, Kaplan DL. Tissue-engineered kidney disease models. Adv Drug Deliv Rev. 2014;69:67–80.View ArticleGoogle Scholar
- Garrod M, San Chau DY. An Overview of Tissue Engineering as an Alternative for Toxicity Assessment. J Pharm Pharm Sci. 2016;19:31–71.Google Scholar
- Van der Meer S, De Wijn J, Wolke J. The influence of basic filler materials on the degradation of amorphous D-and L-lactide copolymer. J Mater Sci Mater Med. 1996;7:359–61.View ArticleGoogle Scholar
- Gibbons D. Tissue response to resorbable synthetic polymers. Degradation phenomena on polymeric biomaterials: Springer; 1992. p. 97–105.Google Scholar