Open access peer-reviewed chapter
Abstract
The aim of this chapter is to introduce to the use and possible applications of polylactide‐based composites. Polylactides are biodegradable aliphatic polyesters, which are widely used in medical and ecological‐friendly fields. First of all, a deep description of main characteristics of polylactides is shown. This chapter summarizes many concepts, which comprehend a general view of polylactide biopolymers such as synthesis and structures, physical‐chemical and mechanical characterization and possible applications of final products. Then, an overview of composites based on polylactides and their benefits compared with bare polylactides are described.
Keywords
- Polylactide
- poly(lactic acid)
- composite
- biodegradable
- biopolymer
- polyester
- biocompostable
- bone repair
- nanocomposite
1. Introduction
Polylactide or poly(lactic acid) (PLA) is the front runner in the emerging biopolymer market with the best availability and the most attractive cost structure [1]. Although PLA existed for several decades, its use has been limited to biomedical applications due its high cost. However, in the new century processing of PLA has been developed in the industry in a large‐scale production promoting its commercialization as a commodity plastic [2].
To date, PLA is one of the most used biodegradable polymers in the field of biomedical applications and eco‐friendly industrial production. A clear advantage of this polymer is its possibility of polymerization coming from renewable resources as starch, but it is not the only one: stiffness of polylactides are similar to some commodity polymers as polyethylene, polypropylene and polystyrene [3] and products derived from its degradation process are nontoxic for the human body and also do not leave any footprint in the landfills [4].
2. Synthesis
The monomer of PLA is lactic acid. Although this monomer can synthesize from petroleum, almost all lactic acid available on the market is produced by fermentation. During fermentation a suitable carbohydrate is converted to lactic acid by microorganisms without the presence of oxygen, hence, under anaerobic conditions. Fermentation of sour whey resulted in the discovery of lactic acid in 1780, when it was isolated by C. W. Scheele [5].
Lactic acid is the simplest α‐hydroxyacid that contains a chiral carbon atom and exists in the following two enantiomeric forms: L‐lactic acid and D‐lactic acid. Monomer forms a stable cycled dimer, that is, lactide. Consequently, dimer presents three different structures, namely L‐lactide, D‐lactide and DL‐lactide. Isotactic, optically active and crystalline homopolymers are obtained if either L‐ or D‐lactide dimers are polymerized. However, DL‐lactide or copolymers of L‐ and D‐dimers polymerize obtain atactic, nonactive optically and amorphous polymers [6].
Polymerization of this lactic acid is carried out by polycondensation [7], instead of polymerization of the dimer that occurs by ring opening polymerization [8]. Polymerization started from lactide dimer allows to obtain high level of molecular mass due to a chain polymerization mechanism and this is the mechanism that is normally used for production.
3. Polylactide characterization
3.1. Physical‐chemical and mechanical characterization
Polylactides have a glass transition (
Isotactic polylactides (pure PLLA and PDLA have same properties) crystallize forming a homocrystal, which melts in the range of 160–190°C depending on the molecular mass and shows a crystallinity fraction around 35% [9]. This value is calculated using one of the different values for theoretic melting enthalpy extrapolated from experimental analysis by different researches, being the most common values 93.6 [11] and 106 J/g [12].
Depending on the crystallization conditions, PLLA can crystallize in α, β or γ polymorphs [13, 14]. The most common form usually is the orthorhombic α crystal [15], while trigonal β form is obtained under high drawing conditions and high temperatures [16, 17]. Besides, γ polymorph is obtained through epitaxial crystallization on special substrates with organic solvents [18]. Recently, the existence of a α’ crystal has been reported, which can be identified as a disordered α form, with the same 103 helical conformation but different lateral packing [19].
As with other enantiomeric polymers occurs [20], polylactides also form thermally stable crystals when 50–50 wt.% of PLLA and PDLA enantiomers are blended [21]. The formation of stereocomplex crystals is favored with low molecular mass [22, 23] or isothermal treatments above homocrystal melting [24, 25]. These crystals melt at 50°C above the homocrystals and their formation is favored if a pretreatment at temperatures above the melting temperature of α crystals is carried out. This pretreatment allows the formation of homocrystal nuclei and increases the crystallization rate of stereocomplex during the isothermal crystallization step [26].
In regard to the mechanical properties, PLAs display high tensile modulus (3 GPa [27]) and yield strength (50–70 MPa [28]) but low elongation at break (5–7%) that result in a brittle behavior of the material.
3.2. Biodegradability
Ester groups in polylactides allow hydrolytic degradation of polymer chains. The degradation mechanism depends on factors, which can be assigned to two groups: (a) related to material as molecular weight, crystallinity, comonomer structure, porosity, etc; and (b) related to the media: temperature, pH, solute concentration, enzymes, etc. [29].
For bulky materials, there are three kinds of degradation mechanisms: surface erosion, bulk erosion and core‐accelerated bulk erosion [30]. A surface erosion mechanism takes place when the hydrolytic degradation rate of the material surface in contact with water (containing catalytic substances as alkalis and enzymes) is much higher than the diffusion within the material. In contrast, a bulk erosion mechanism occurs when hydrolytic degradation takes place homogeneously, irrespective of the depth from the material surface. As it can be foreseen, the hydrolytic degradation mechanism changes from the bulk to surface erosion when material thickness becomes higher than the critical [31]. On the other hand, some authors report that polylactides degradation mechanism proceeds via core‐accelerated bulk erosion, when the material is thicker than 0.5–2 mm, due to the accelerated degradation sustained by oligomers and monomers trapped and accumulated in the core part of the materials [32]. Hence, depending of the thickness of the PLA piece, the degradation mechanism proceeds via bulk (<0.5–2 mm), core accelerated (between 0.5–2 and 74 mm) and surface erosion (>7.4 cm). In general, chains in the crystalline region are hydrolysis resistant compared to those in the amorphous regions because the access of water molecules to the chains inside the rigid crystalline regions is prohibited. Such crystalline regions are called “crystalline residues.”
Concerning to enzymatic degradation, no study of specific enzymes for the biodegradation of polylactides has been reported [33]. Williams reported the enzymatic hydrolysis of polylactides in the presence of proteases as pronase, bromelain and proteinase K, being the latter a protease with a strong activity in hydrolizing proteins, particularly keratin [34, 35].
4. Strategies to changes polylactide properties
4.1. Blending
Easier strategy to change properties of a pure polymer is blending with other polymers. These blends could be miscible or immiscible depending on solubility parameters and specific interactions established between counterparts. Miscibility of blends is governed by thermodynamic law, in which the free energy of mixing in the blend must be negative [30]. Polylactide is miscible with polyvinylphenol (PVPh) [36–39], poly(styrene‐co‐vinylphenol) [40, 41], polyhydroxybutirate (PHB) [42], poly(methyl methacrylate) (PMMA) [43], poly(vinyl acetate) [44] and poly(ethylene oxide) [45].
Phase separation induced by immiscible blends has been commonly used for improving fragile commodity polymers as PS and PMMA with a rubber modification leading into HIPS [46] and high impact PMMA [47]. However, the modifications in polylactides with biodegradable polymers as polycaprolactone (PCL) are an efficient way to toughen polylactides [48].
4.2. Copolymerization
Modification in the synthesis process with other monomers is other way to tune the properties of polylactides. Comonomers as etylenglycol or ethylene oxide [49, 50], propylene oxide [51] and trimethylcarbonate [52] have been reported for polymerization with lactide units. However, cyclic comonomers are suitable to polymerize by ring opening polymerization (ROP) with lactide such as lactones or macrolactones. The most investigated systems are poly(glycolide‐lactide) [53, 54] and poly(lactide‐co‐caprolactone) copolymers [55–57]. Recently, some studies in search of more biodegradable copolymers are using macrolactones as γ‐valerolactone [58].
Moreover, starting the polymerization of lactide or lactic acid with polymer containing hydroxyl groups leads into graft copolymers. This strategy is welcomed to increase the miscibility with other polymers and hydrophobicity as it occurs with poly(vinyl alcohol) [59].
5. Polylactide‐based composites
Composites combine two (or more) different components: a continuous phase, called matrix, acts as binder and distributs homogeneously the forces through whole composite; and a discontinuous phase, called reinforcement, fundamentally is used to carry the applied load. Depending on the form of the reinforcements, they are arranged in different groups, of which two most important are fibers and particles. Normally, the aim of the reinforcements is to enhance the stiffness and tensile strength of the matrix, although sometimes fillers are used to reduce the price of the final product or modify the physical, rheological, optical or other properties. However, more important is the interface between both components to assure good transmission among constituents of the composite.
Efforts made for advancing in technology lead to the scientific community to introduce nanoscale in material science and consequently in polymer science. It must pay special attention in nanocomposites, because it is foreseen remarkable improvement in properties with less quantity of reinforcement than micro or macroscale composites.
Different families of reinforcements can be classified into function of their chemical nature and it is analyzed the effect that induces in polylactides.
5.1. Organic reinforcements
5.1.1. Natural fibers
These composites are very attractive because both matrix and reinforcement are obtained from renewable resources. But comparing to synthetic ones they have some characteristics to take into account [60]:
Natural fibers degrade at low temperatures (<200°C). Hence, processing of polylactide/natural fibers composite must be made carefully.
Natural fibers are hydrophilic and absorb moisture easily. Polylactides can degrade faster and wettability of fibers produces swelling and distorsion in the interface due to a lack in dimensional stability.
Natural fibers have low microbial resistance. Long‐time storages are not ideal for these composites.
Environmental friendly materials with a full degradation capability promote the interest of these composites, especially in the automotive industry. Different natural plant fibers have been used to obtain polylactide‐based composites: agricultural natural fibers as jute, kenaf, sisal and flax and also inexpensive agricultural residues as wheat straw, corn stover, soy stalks and their hybrids [61].
Jute/polylactide [62]: Alkali‐, permanganate‐ and peroxide‐treated composites exhibit lower thermal stability, whereas silane‐treated composites show a higher thermal stability when compared to untreated composites. However, a better fiber matrix adhesion improves the abrasive wear resistance of the jute fiber‐reinforced composites.
Kenaf/polylactide [63]: The effects of the silane‐coupling agent on composite properties is highly beneficial leading to increased moduli and heat deflection temperatures as well as reduced water swelling. Moreover, an optimal formulation comprised of 50% kenaf and 50% PLA fibers with three parts of silane‐coupling agent represents an optimal formulation to manufacture automotive headliners.
Sisal/polylactide [64]: Mechanical properties of PLLA/sisal fiber composites (improved with caustic soda treatment) confer high strength, high modulus sisal‐PLLA composites, because of effective stress transfer at well‐bonded fiber to matrix interfaces.
Flax/polylactide [65]: Mechanical properties of polylactide and its composites with flax are greater than those of related polypropylene/flax fiber composites and concretely the specific tensile strength and modulus have demonstrating to be very close to values obtained in glass fiber polyester composites.
Moreover, micro‐ and nanoscale improve the mechanical properties of natural fiber‐based composites; hence, cellulose microfibrils (CMF), cellulose nanofibrils (CNF) and cellulose nanocrystals (CNC) are the new tendencies.
Composites of polylactide with silane‐modified cellulose microfibrils (CMFs) coming from sisal fiber (SF) showed a maximum impact strength which was 24% higher than that of virgin PLA [66].
However, the most important feature of using nanofibrils is the dispersion in the matrix, because fibrils are hydrophilic and the matrix hydrophobic. To overcome this, feature some researches disperse CNF in polylactides by a new method obtaining increments in the modulus and strength (up to 58 and 210%, respectively) demonstrated the load‐bearing capability of the CNF network in the composites [67].
Although crystallinity degree of polylactide/CNC nanocomposites remain similar to that of neat homopolymer, the crystallization rate has been notably increased (1.7–5 times) boosted by the presence of CNC, which act as nucleating agents during the crystallization process. In addition, structural relaxation kinetics of PLLA chains has been drastically reduced by 53 and 27% with the addition of CNC [68].
5.1.2. Synthetic fibers, nanofibers and nanotubes
5.1.2.1. Carbon‐based reinforcements
Carbon fiber (CF) is made from organic polymers, where hexagonal carbon structures acquired a fibrillate form. Helped by their excellent specific properties supported by low weight (high stiffness, tensile strength, chemical resistance, thermal stability and low thermal expansion) carbon fibers have a widespread application in different sectors such as aerospace, civil engineering, military and competition sports. However, still remain to overcome the price because they are relatively expensive when correlated with natural fibers, glass fibers or polymeric fibers. However, most futurist than carbon fiber composites are these with nanofibers, nanotubes or graphene.
Carbon nanotubes (CNT)
Since the discovery by Iijima in 1991 [69], carbon nanotubes have been investigated as their unique properties [70, 71, 72] make them interesting fillers to develop polymer nanocomposites. CNTs influence in the physical‐chemical properties, as well as in the mechanical, electrical and biocompatible properties of polylactides.
It has been reported that CNT influence in the crystallinity without changes in dimension of the crystal assisting in the disorder‐to‐order (alpha’‐to‐alpha) transition. However, results obtained from Hoffman‐Weeks plot reveal that equilibrium melting temperature increase with CNT content, while thickness of crystal layer and amorphous layer of PLLA both decreased with increasing CNT contents of polylactide matrix [73]. Moreover, structural aspects as physical aging [74] and thermal degradation [75] of polylactide matrix is notably affected by the presence of these CNTs.
However, compatibilization of CNTs increment the efficiency of the composites [76]. Pyrene‐end‐polylactide has been founded as a good interface stabilizer in polylactide/CNT composites. Therefore, modified CNT influence in polylactides in much greater manner than comparing results obtained without modification of CNTs [77].
Besides, polylactide stereocomplexation is clearly favored by CNT content [78]. The addition of small amounts of MWCNTs combined with a mild thermal treatment extends the processing window for the preparation of polylactides exclusively crystallized in the stereocomplex form, instead of the homocrystal formation.
With other point of view, conductivity of polymer matrices with nanofiller addition has been increased even with very low percentages of conductive carbon nanotubes composites [79].
In the biomedical field, also, polylactide/MWCNT composites have been carefully analyzed due to the possible cytocompatibility of the CNTs when polylactide matrix degrades [80, 81]. Instead of nanocomposite system shows adequate biocompatibility, degradation products may induce adverse effects on cell metabolism and proliferation, paying special attention in lactic acid presence and the quality of the MWCNT suspension [82]. However, an extensive
in vitro evaluation including final degradation products is needed to enable a comprehensive prediction of the overall success or failure of newly developed degradable nanocomposites.Graphene
Graphene is a single‐atom thick graphite sheet. It is structurally very similar to silicate layers and chemically analogous to carbon nanotubes, due to its huge specific surface area is considered as ideal reinforcing nanofiller in the fabrication of multifunctional polymer nanocomposites, superior mechanical strength, remarkable electronic and thermal properties [83]. As it could be expected to achieve its maximal reinforcing efficiency, graphene sheets must be homogeneously dispersed in the polymer matrix to prompt the interfacial stress transfer between graphene and polymer matrix [84].
An effective nanofiller has been found when graphene is functionallizated with octadecylamine (ODAG) in well‐exfoliated solution/casting process. Due to the good hydrophobic compatibility between organic counterparts, interfacial adhesion and consequently crystallization, mechanical properties and thermal stability are improved [85].
5.1.2.2. Other organic reinforcements
Slit die extrusion, hot stretching and quenching is proposed as a new technique to construct well‐aligned, stiff poly(butylene succinate) (PBS) nanofibrils in the PLA matrix for the first time [86]. The high strength, modulus and ductility are unprecedented for PLA and are in great potential need for packaging applications. However, this technique opens a new way for the development of new composite materials based on polymeric fibers.
5.1.3. Inorganic reinforcements
Bioresorbable polymers play great relevance in biomedical field. Due to its excellent mechanical properties related to stiffness and tensile strength, polylactides are proposed for using in implants with safety‐critical applications [87]. Hence, fixation and bone reconstruction are compulsory for a good health and reconstruction of the damaged zone. Most of implants based on polylactide polymer are focused on bone repair; however, radiopacity and other properties are too of great interest.
5.1.3.1. Bone repair
In this context, inorganic reinforcements play the most important role, because the natural bone is formed up to 70 wt. % by calcium phosphate very similar to hydroxyapatite (HA) [88]. HA is an inorganic compound, which helps the differentiation of osteoblasts in regeneration of the bone structure [89]. For this reason, incorporation of HA into PLA matrices has been widely reported [90, 91, 92, 93].
Tricalcium phosphate (β‐TCP) has been also widely used due its bioactivity and biodegradability. Its degradation rate is incremented 3–12 times compared with HA [94] and this favors bonding of bone to the bioceremic [95]. However, combination of β‐TCP and HA in denominated biphasic calcium phosphates (BCP) shows the advantages of both components: reactivity of β‐TCP and stability of HA. BCP with 60–40% of HA‐TCP incubed in simulated body fluid produces the precipitation of needle‐shaped apatite crystals [96], allowing polylactide/BCP composites for fracture fixation plates [97].
Furthermore, discovery of bioactive glasses by L. L. Hench in 1969 catapults the use of these inorganic particles in tissue engineering due to their excellent biocompatibility and the ability of bone bonding [98]. A common characteristic of bioactive glasses and ceramics is a time‐dependent kinetic modification of the surface that occurs upon implantation [99]. Bioactive glasses originate a superficial layer of calcium deficient carbonate, which permits a chemical adhesion to bone. This adhesion is appealed as bioactivity and is associated with the formation of carbonated hydrocyapatite (HCA) when glass is implanted or in contact with simulated body fluids [100, 101]. The HCA layers formed on a scaffold made of 45S5Bioglass® immersed in SBF takes a “cauliflower” typical morphology [99] and allows osteogenic formation [102].
Some researches of PLA/bioactive glass composites have been reported [103, 104]. However, melt processing of bioglass with polylactides affects the thermal stability of the composite [105], and to overcome this handicap, protection of bioactive ceramic with and acrylic plasma treatment has been proposed [106]. An easier treatment than plasma has been proposed by A. Larrañaga by covering these particles with a mussel inspired polydopamine coating, which results in a bioactive composite [107].
5.1.3.2. Radiopacity
Although alternative radiopacifiers have been proposed in bibliography [108, 109], barium sulfate (BaSO4) is still the gold standard for medical applications [110]. Incorporation of BaSO4 particles to polymer matrices enables surgeons to accurately place and to monitor any migration of the implant over time.
Singularly, barium sulfate submicron particles added to polylactide matrix enhance deformation at rupture and confer high toughness to fragile polylactides [111]. Consequently, the addition of these submicron barium sulfate particles enables a radiopaque and tough polylactide composite.
5.1.3.3. Nucleating effect
The influence of the nature of the filler on the mechanical properties of PLA has been reported for two silicated clays, both having a platelet‐like shape [112]. Talc is a more efficient filler regarding mechanical reinforcement of PLA as compared to kaolin. This better reinforcing effect in the case of talc is ascribed to its higher affinity with the PLA. It was also evidenced that talc has a nucleating effect on the PLA crystallization [113], while kaolin has no or very limited effect on the crystallization behavior of PLA. In conclusion, the existence of crystallographic relationships between the structures of the filler and the polymer crystals is also a key parameter for the observation of a nucleating effect.
6. Future trends and perspectives
Although polylactide has been researched for various decades, still remain being the gold standard in biodegradable polymers. In fact, development of new techniques as 3D printing includes in its commercial version polylactide material. It seems as if polylactides will be investigated for long years and could carve out a place in commodity plastics.
7. Conclusions
Polylactide composites broaden the possibilities of application of neat polylactides. Biodegradable matrix allows validity for ecological packaging and biomedical applications and their composites improve the potential use of these materials.
References
- 1.
Auras R., Lim L.T., Selke S.E.M., Tsuji H. editors. Poly(lactic acis): synthesis, properties and applications. New Jersey: Wiley; 2010. 499 p. - 2.
Auras R., Harte B., Selke S. An overview of polylactides as packaging materials. Macromolecular Bioscience. 2004; 4 (835‐864). - 3.
Sinclair R.G. The case for polylactic acid as a commodity packaging plastic. Journal of Macromolecular Science‐Pure and Applied Chemistry. 1996; A33 (585‐597). - 4.
Musiol M., Sikorska W., Adamus G., Janeczek H., Richert J., Malinowski R., Jiang G.Z., Kowalczuk M. Forensic engineering of advanced polymeric materials. Part III ‐ Biodegradation of thermoformed rigid PLA packaging under industrial composting conditions. Waste Management. 2016; 52 (69‐76). - 5.
Dobbin L. The collected papers of Carl Wilhelm Scheele. London: G. Bell & Sons Ltd.; 1931. 367p. - 6.
Sarasua J.R., Prud’homme R.E., Wisniewski M., Leborgne A., Spassky N. Crystallization and melting behavior of polylactides. Macromolecules. 1998; 12 (3895‐3905). - 7.
Bendix D. Chemical synthesis of polylactides and its copolymers for medical applications. Polymer Degradation and Stability. 1998; 59 (129‐135). - 8.
Kricheldorf H.R., Kreiser‐Sunders I., Stricker, A. Polylactones: 48. SnOct2‐initiated polymerizations of lactide: a mechanistic study. Macromolecules. 2000; 33 (702‐709). - 9.
Zuza E., Ugartemendia J.M., Lopez A., Meaurio E, Lejardi A., Sarasua J.R. Glass transition behavior and dynamic fragility in polylactides containing mobile and rigid amorphous fractions. Polymer. 2008; 48 (4427‐4432). - 10.
Sarasua J.R., Zuza E., Imaz N., Meaurio E. Crystallinity and crystalline confinement of the amorphous phase in polylactides. Macromolecular symposia. 2008; 272 (81‐86). - 11.
Fischer E.W., Sterzel H.J., Wegner G. Investigation of structure of solution grown crystals of lactide copolymers by means of chemical‐reactions. Kolloid‐Zeitschrift and Zeitschrift für Polymere. 1973; 251 (980‐990). - 12.
Cho T.Y., Strobl G. Polymer. Temperature dependent variations in the lamellar structure of poly(l-lactide). 2006; 47 (1036–1043). - 13.
Lizundia E., Petisco S., Sarasua J.R. Phase‐structure and mechanical properties of isothermally melt‐ and cold‐crystallized poly (L‐lactide). Journal of the Mechanical Behavior of Biomedical Materials. 2012; 17 (242‐251). - 14.
Meaurio E., Zuza E., Lopez‐Rodriguez N., Sarasua J.R. Conformational behavior of poly(l‐lactide) studed by infrared spectroscopy. Journal of Physical Chemistry B. 2006; 110 (5790‐5800). - 15.
Del Rio J., Etxeberria A., Lopez‐Rodriguez N., Lizundia E., Sarasua J.R. A PALS contribution to the supramolecular structure of poly(L‐lactide) Macromolecules. 2010; 43 (4698‐4707). - 16.
Engelberg I., Kohn J. Physicomechanical properties of degradable polymers used in medical applications—a comparative‐study. Biomaterials. 1991; 12 (292‐304). - 17.
Hoogsteen W., Postema A.R., Pennings A.J., Brinke G.T., Zugenmaier P. Macromolecules. Crystal structure, conformation and morphology of solution-spun poly(L-lactide) fibers. 1990; 23 (634). - 18.
Furuhashiv Y., Iwata T., Kimura Y., Doi Y. Structural characterization and enzymatic degradation of alpha‐, beta‐, and gamma‐crystalline forms for poly(beta‐propiolactone). Macromolecular Bioscience. 2003; 3 (462‐470). - 19.
Meaurio E., Martinez de Arenaza I., Lizundia E., Sarasua J.R. Analysis of the C=O stretching band of the alpha‐crystal of poly(L‐lactide). Macromolecules. 2009; 42 (5717‐5727). - 20.
Marín R., Martínez de Ilarduya A., Romero P., Sarasua J.R., Meaurio E., Zuza E., Muñoz‐Guerra S. Spectroscopic evidence for stereocomplex formation by enantiomeric polyamides derived from tartaric acid. Macromolecules. 2008; 41 (3734‐3738). - 21.
Sarasua J.R., Lopez‐Arraiza A., Balerdi P., Maiza I. Crystallization and thermal behaviour of optically pure polylactides and their blends. Journal of Materials Science. 2005; 40 :1855‐1862. - 22.
Tsuji H., Ikada Y. Polymer. Stereocomplex formation between enantiomeric poly(lactic acid)s. XI. Mechanical properties and morphology of solution-cast films. 1999; 40 (6699‐6708). - 23.
Tsuji H.. Poly(lactide) stereocomplexes: formation, structure, properties, degradation, and applications. Macromolecular Bioscience. 2005; 5 (569‐597). - 24.
Sarasua J.R., López‐Rodríguez N., Lopez‐Arraiza A., Meaurio E. Stereoselective crystallization and specific interactions in polylactides. Macromolecules. 2005; 38 (8362‐8371). - 25.
Sarasua J.R., Lopez‐Arraiza A., Balerdi P., Maiza I. Crystallinity and mechanical properties of optically pure polylactides. Polymer Engineering and Science. 2005; 45 (745‐753). - 26.
López‐Rodríguez N., Martinez de Arenaza I., Meaurio E., Sarasua J.R. Efficient stereocomplex crystallization in enantiomeric blends of high molecular weight polylactides. RSC Advances. 2015; 5 (34525‐34534). - 27.
Bergstroem J.S., Hayman D. Annals of Biomedical Engineering. An Overview of Mechanical Properties and Material Modeling of Polylactide (PLA) for Medical Applications. 2016; 44 (330‐340). - 28.
Sodergard A., Stolt M. Progress in Polymer Science. Properties of lactic acid based polymers and their correlation with composition. 2002; 27 (1123‐1163). - 29.
Tsuji H. Degradation of polylactide‐based biodegradable materials. New York: Nova Science Publishers; 2007. - 30.
Tsuji H. Polylactides. In: Doiand Y., Steinbüchel A. editors. Biopolymers. Weinheim: Wiley‐VCH; 2002. p. V/129ff. - 31.
von Bukersroda F, Schedl L., Göpferich A. Biomaterials. Why degradable polymers undergo surface erosion or bulk erosion. 2002; 23 (4221‐4231). - 32.
Li S.M., Vert M. Biodegradation of aliphatic polyesters. In: Scott G., Gilead D. editors. Biodegradable polymers: principles and applications. Cambridge: Chapman & Hall; 1995. pp. 43‐87. - 33.
Iwata T., Abe H. Kikkawa Y. Enzymatic degradation. In: Auras R., Lim L.T., Selke S.E.M., Tsuji H. editors. Poly(lactic acis): synthesis, properties and applications. New Jersey: Wiley; 2010. pp. 383‐399. - 34.
Williams D.F. Engineering Medicine. Enzymatic hydrolysis of poly(lactic acid). 1981; 10 (5‐7). - 35.
Ebeling W., Hennrich N.M., Klockow M., Orth H.D., Lang H. European Journal of Biochemistry. Proteinase K from Tritirachium album Limber. 1974; 47 (91‐97). - 36.
Meaurio E., Hernández‐Montero N., Zuza E., Sarasua J.R. Miscible blends based on biodegradable polymers. In: Interfaces S. Thomas, Y. Grohens, and P. Jyotishkumar editors. Characterization of polymer blends: miscibility, morphology, and interfaces. Weinhein: Wiley‐VCH; 2014. - 37.
Meaurio E., Zuza E., Sarasua J.R. Miscibility and specific interaction of poly(L‐lactide) with poly(vinyl phenol). Macromolecules. 2005; 38 (1207‐1215). - 38.
Meaurio E., Zuza E., Sarasua J.R. Direct measurement of the enthalpy if mixing in miscible blends of poly(DL‐lactide) with poly(vinyl phenol). Macromolecules. 2005; 38 (9221‐9228). - 39.
Zuza E., Meaurio E., Etxebarria A., Sarasua J.R. Exothermal process in miscible polylactide/poly(vinyl phenol) blends: mixing enthalpy or chemical reaction? Macromolecules. 2006; 27 (2026‐2031). - 40.
Zuza E., Lejardi A., Ugartemendia J.M., Monasterio N., Meaurio E., Sarasua J.R. Compatibilization through specific interactions and dynamic fragility in poly(DL‐lactide)/polystyrene blends. Macromolecular Chemistry and Physics. 2008; 209 (5354‐5358). - 41.
Zuza E., Lejardi A., Meaurio E., Sarasua J.R. Phase behavior and interactions in poly(DL‐lactide)/poly(styrene‐co‐vinylphenol) blends. European Polymer Journal. 2015; 63 (58‐66). - 42.
Focarate M.L., Scandola M., Dobrzynski P., Kowalczuk M. Miscibility and mechanical properties of blends of (L‐lactide copolymers with atactic poly(3‐hydroxybutyrate). Macromolecules. 2002; 35 (8472‐8477). - 43.
Eguiburu J.L., Iruin J.J., Fernandez‐Berridi M., San Roman J. Blends of amorphous and crystalline polylactides with poly(methyl methacrylate) and poly(methyl acrylate): a miscibility study. Polymer. 1998; 39 (6891‐6897). - 44.
Gajra A.M., Dave V., Gross R.A., McCarthy S.P. Miscibility and biodegradability of blends of poly(lactic acid) and poly(vinyl acetate). Polymer. 1999; 40 (2303‐2313). - 45.
Nakafuku C., Sakoda M. Melting and crystallization of poly(L‐lactic acid) and poly(ethylene oxide) binary mixture. Polymer Journal. 1993; 25 (909‐917). - 46.
Zhu L.D., Yang H.Y., Di Cai G., Chao Z., Wu G.F., Zhang M.Y., Gao G.H., Zhang H.X. Journal of Applied Polymer Science. Submicrometer-sized rubber particles as “craze-bridge” for toughening polystyrene/high-impact polystyrene. 2013; 129 (224‐229). - 47.
Lalande L., Plummer C.J.G., Manson J.A.E., Gerard P. Polymer. The Influence of Matrix Modification on Fracture Mechanisms in Rubber Toughened Polymethylmethacrylate. 2006; 47 (2389‐2401). - 48.
López‐Rodríguez N., Lopez‐Arraiza A., Meaurio E., Sarasua J.R.. Crystallization, morphology and mechanical behavior of polylactide/poly(ɛ‐caprolactone) blends. Polymer Engineering and Science. 2006; 46 (1299‐1308). - 49.
Li S.M., Vert M. Synthesis, characterization, and stereocomplex‐induced gelation of block copolymers prepared by ring‐opening polymerization of L(D)‐lactide in the presence of poly(ethylene glycol). Macromolecules. 2003; 36 (8008‐8014). - 50.
Yu G.H., Ji J., Zhu H.G., Shen J.C. Poly(D,L‐lactic acid)‐block‐(ligand‐tethered poly(ethylene glycol)) copolymers as surface additives for promoting chondrocyte attachment and growth. Journal of Biomedical Materials Research Part B‐Applied Biomaterials. 2006; 76B (64‐75). - 51.
Yang D., Lu Q., Fan Z., Li S.M., Tu J.J., Wang W. Synthesis and characterization of degradable triarm low unsaturated poly(propylene oxide)‐block‐polylactide copolymers. Journal of Applied Polymer Science. 2010; 118 (2304‐2313). - 52.
Pospiech D., Komber H., Jehnichen D., Haussler K., Eckstein K., Scheibner H., Janke A., Kricheldorf H.R., Petermann O. Biomacromolecules. Multiblock Copolymers of l-Lactide and Trimethylene Carbonate. 2005; 6 (439). - 53.
Khang G., Choee J.H., Rhee J.M., Le H.B. Interactions of different types of cells on physicochemically treated poly (L‐lactide‐glycolide) surfaces. Journal of Applied Polymer Science. 2002; 85 (1253‐1262). - 54.
Barakat I., Dubois P., Grandfils C., Jerome R. Poly(epsilon‐caprolactone‐b‐glycolide) and poly(D,L‐lactide‐b‐glycolide) diblock copolyesters: controlled synthesis, characterization, and colloidal dispersions. Journal of Polymer Science Part A‐Polymer Chemistry. 2001; 39 (294‐306). - 55.
Fernandez J., Etxeberria A., Ugartemendia J.M., Petisco S., Sarasua J.R. Effects of chain microstructures on mechanical behavior and aging of poly(L‐lactide‐co‐ɛ‐caprolactone) biomedical thermoplastic‐elastomer. Journal of the mechanical behavior of biomedical materials. 2012; 12 (29‐38). - 56.
Fernandez J., Larrañaga A., Etxeberria A., Sarasua J.R. Effects of chain microstructures and derived crystallization capability on hydrolytic degradation on poly(L‐lactide/‐ɛ‐caprolactone) copolymer. Polymer Degradation and stability. 2013; 98 (481‐489). - 57.
Fernandez J., Etxeberria A., Sarasua J.R. Effects of repeat unit sequence distribution and residual catalyst on thermal degradation of poly(L‐lactide‐co‐ɛ‐caprolactone) statistical copolymers. Polymer Degradation and Stability. 2013; 98 (1293‐1299). - 58.
Fernandez J., Larrañaga A., Etxeberria A., Sarasua J.R. Tensile behavior and dynamic analysis of novel poly(lactide/valerolacton) statistical copolymers. Journal of the Mechanical Behavior of Biomedical Materials. 2014; 35 (39‐50). - 59.
Lejardi A., Etxeberria A., Meaurio E., Sarasua J.R. Novel poly(vinyl alcohol)‐g‐poly(hydroxy acid) copolymers: synthesis and characterization. Polymer. 2012; 53 (50‐59). - 60.
Ghosh S.B., Bandyopadhyay‐Ghosh S., Sain M. Composites. In: Auras R., Lim L.T., Selke S.E.M., Tsuji H. editors. Poly(lactic acis): synthesis, properties and applications. New Jersey: Wiley; 2010. pp. 293‐310. - 61.
Nyambo C., Mohanty A.K., Misra M. Polylactide‐based renewable green composites from agricultural residues and their hybrids. Biomacromolecules. 2010; 11 (1654‐1660). - 62.
Goriparthi B.K., Suman K.N.S., Rao N.M. Effect of fiber surface treatments on mechanical and abrasive wear performance of polylactide/jute composites. Composites Part A‐Applied Science and Manufacturing. 2012; 43 (1800‐1808). - 63.
Lee B.H., Kim H.S., Lee S., Kim H.J., Dorgan, J.R. Bio‐composites of kenaf fibers in polylactide: role of improved interfacial adhesion in the carding process. Composites Science and Technology. 2009; 69 (2573‐2579). - 64.
Prajer M., Ansell M.P. Bio‐composites for structural applications: poly‐L‐lactide reinforced with long sisal fiber bundles. Journal of Applied Polymer Science. 2014; 131 (40999). - 65.
Bodros E., Pillin I., Montrelay N., Baley C. Could biopolymers reinforced by randomly scattered flax fibre be used in structural applications? Composites Science and Technology. 2007; 67 (462‐470). - 66.
Johari A.P., Mohanty S., Kurmvanshi S.K., Nayak S.K.. Influence of different treated cellulose fibers on the mechanical and thermal properties of poly(lactic acid). ACS Sustainable Chemistry & Engineering. 2016; 4 (1619‐1629). - 67.
Wang T., Drzal L.T. Cellulose‐nanofiber‐reinforced poly(lactic acid) composites prepared by a water‐based approach. ACS Applied Materials and Interfaces. 2012; 4 (5079‐5085). - 68.
Lizundia E., Vilas J.L., Leon L.M. Crystallization, structural relaxation and thermal degradation in poly(L‐lactide)/cellulose nanocrystal renewable nanocomposites. Carbohydrate Polymers. 2015; 123 (256‐265). - 69.
Iijima S. Helical microtubules of graphitic carbon. Nature 1991; 6348 (56). - 70.
Ruoff R.S., Lorents D.C. Mechanical and thermal properties of carbon nanotubes. Carbon. 1995; 7 (925). - 71.
Berber S., Kwon Y., Tomanek D. Physical Review Letters. Unusually High Thermal Conductivity of Carbon Nanotubes. 2000; 20 (4613). - 72.
Treacy M.M.J., Ebbesen T.W., Gibson J.M. Nature. Exceptionally high Young's modulus observed for individual carbon nanotubes. 1996; 6584 (678). - 73.
Shieh Y.T., Liu G.L., Twu Y.K., Wang T.L., Yang C.H. Effects of carbon nanotubes on dynamic mechanical property, thermal property, and crystal structure of poly(L‐lactic acid). Journal of Polymer Science Part B‐Polymer Physics. 2010; 48 (145‐152). - 74.
Lizundia E., Sarasua J.R. Physical aging in poly(L‐lactide) and its multiwall carbon nanotube composites. Macromolecular Symposia. 2012; 1 (321‐322). - 75.
Lizundia E., Sarasua J.R. Improvement of thermal degradation of PLLA/MWCNT composites by nanotube purification. SPE EUROTEC: Barcelona; 2011. - 76.
Tunckol M., Zuza E., Sarasua J.R., Durand J., Serp P. Polymerized ionic liquid functionalized multi‐walled carbon nanotubes/polyetherimide composites. European Polymer Journal. 2013; 49 (3370‐3377). - 77.
Martínez de Arenaza I., Obarzanek‐Fojt M., Sarasua J. R., Meaurio E., Meyer F., Raquez J. M., Dubois P., Bruinink A. Pyrene‐end‐functionalized poly(L‐lactide) as efficient carbon nanotube dispersing agent in poly(L‐lactide): mechanical performance and biocompatibility study. Biomedical Materials. 2015; 10 (1‐9). - 78.
I. Martínez de Arenaza, H. Amestoy, N. López‐Rodríguez, E. Zuza, E. Meaurio, J.R. Sarasua, F. Meyer, J.I. Santos, J.M. Raquez, P. Dubois. Polylactide stereocomplex crystallization prompted by multiwall carbon nanotubes. Journal Applied of Polymer Science. 2013; 130 (4327‐4337). - 79.
Lizundia E., Oleaga A., Salazar A., Sarasua J.R. Nano‐ and microstructural effects on thermal properties of poly (L‐lactide)/multi‐wall carbon nanotube composites. Polymer. 2012; 53 (2412‐2421). - 80.
I. Martínez de Arenaza, M. Obarzanek‐Fojt, J. R. Sarasua, E. Meaurio, F. Meyer, J. M. Raquez, P. Dubois, A. Bruinink Pyrene‐end‐functionalized poly(L‐lactide) as efficient carbon nanotube dispersing agent in poly(L‐lactide): mechanical performance and biocompatibility study. Biomedical Materials. 2015; 10 (1‐9). - 81.
Lizundia E., Sarasua J. R., D’Angelo F., Martino S., Orlacchio A., Kenny J.M., Armentano I.. Biocompatible poly(L‐lactide)/MWCNT nanocomposites: morphological characterization, electrical properties and stem cell interaction. Macromolecular Bioscience. 2012; 12 (870‐888). - 82.
Obarzanek‐Fojt M., Elbs‐glatz Y., Lizundia E., Diener L., Sarasua J.R., Bruinink A. From implantation to degradation—are poly (L‐lactide)/multiwall carbon nanotube composite materials really cytocompatible? Nanomedicine. 2014; 10 (1041‐1051). - 83.
Huang X., Qi X.Y., Boeyab F., Zhang H. Graphene‐based composites. Chemical Society Reviews. 2012; 41 (666‐686). - 84.
M. Fang, Wang K.G., Lu H.B., Yang Y.L., Nutt S. Single‐layer graphene nanosheets with controlled grafting of polymer chains. Journal of Material Chemistry. 2010; 20 (1982‐1992). - 85.
Zhang L., Li Y., Wang H., Qiao Y., Chen J., Cao S. Strong and ductile poly(lactic acid) nanocomposite films reinforced with alkylated graphene nanosheets. Chemical Engineering Journal. 2015; 264 (538‐546). - 86.
Xie L., Xu H., Niu B., Ji X., Chen J., Li Z.M., Hsiao B.S., Zhong G.J. Unprecedented access to strong and ductile poly(lactic acid) by introducing in situ nanofibrillar poly(butylene succinate) for green packaging. Biomacromolecules. 2014; 10 (4054‐4064). doi: 10.1021/bm5010993. - 87.
Sarasua J.R., López‐Rodríguez N., Zuza E., Petisco S., Castro B., Del Olmo M., Palomares T., Alonso‐Varona A. Crystallinity assessment and in vitro cytotoxicity of polylactide scaffolds for biomedical applications. Journal of Materials Science—Materials in Medicine. 2011; 22 (2513‐2523). - 88.
Junqueira L.C., Carneiro J. In: Foltin J., Lebowitz H., Boyle P.J. editors. Basic histology, text and atlas (10th ed.). McGraw‐Hill Companies; New York. 2003. p. 144. - 89.
Rizzi S.C., Heath D.T., Coombes A.G.A., Bock N., Texto M., Downes S. Biodegradable polymer/hydroxyapatite composites: surface analysis and initial attachment of human osteoblasts. Journal of Biomedical Materials Research. 2001; 55 (475‐486). - 90.
Kasuga T., Ota Y., Nogami M., Abe Y. Preparation and mechanical properties of polylactic acid composites containing hydroxyapatite fibers. Biomaterials. 2001; 22 (19‐23). - 91.
Deng X.M., Hao J.Y., Wang C.S. Preparation and mechanical properties of nanocomposites of poly (D,L‐lactide) with Ca‐deficient hydroxyapatite nanocrystals. Biomaterials. 2001; 22 (2867‐2873). - 92.
Kothapalli C.R., Shaw M.T., Wei M. Biodegradable HA‐PLA 3‐D porous scaffolds: effect of nano‐sized filler content on scaffold properties. Acta Biomaterialia. 2005; 1 (653‐662). - 93.
Jeong S.I., Ko E.K., Yum J., Jung C.H., Lee Y.M., Shin H. Nanofibrous poly(lactic acid)/hydroxyapatite composite scaffolds for guided tissue regeneration. Macromolecular Bioscience. 2008; 8 (328‐338). - 94.
Oonishi H., Oomamiuda K. Degradation/resorption in bioactive ceramics in orthopaedics. In: Black J., Hastings G.W. editors. Handbook of Biomaterial Properties. London: Chapman & Hall; 1998. pp. 406‐419. - 95.
Wang J., Chen W., Li Y., Fan S., Weng J., Zhang X. Biological evaluation of biphasic calcium phosphate ceramic vertebral laminae. Biomaterials. 1998; 19 (1387‐1392). - 96.
Rohanizadeh R., Padrines M., Bouler J.M., Couchourel D., Fortun Y., Daculsi G. Apatite precipitation after incubation of biphasic calcium phosphate ceramic in various solutions: influence of seed species and proteins. Journal of Biomedical Materials Research. 1998; 42 (530‐539). - 97.
Bleach N.C., Nazhat S.N., Tanner K.E., Kellomaki M., Tormala P. Effect of filler content on mechanical and dynamic mechanical properties of particulate biphasic calcium phosphate‐polylactide composites. Biomaterials. 2002; 23 (1579‐1585). - 98.
Hench L.L., Splinter R.J., Allen W.C. Bonding mechanisms at the interface of ceramic prosthetic materials. Journal of Biomedical Material Research Symposia. 1971; 5 (117‐141). - 99.
Rezwana K., Chena Q.Z., Blakera J.J., Boccaccini A.R. Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials. 2006; 27 (3413‐3431). - 100.
L.L. Hench. Bioceramics. Journal of American Ceramic Society. 1998; 81 (1705‐1728). - 101.
Wilson J., Pigott G.H., Schoen F.J., Hench L.L. Toxicology and biocompatibility of bioglass. Journal of Biomedical Material Research. 1981; 15 (805‐811). - 102.
Larrañaga A., Martín F.J., Aldazabal P., Palomares T., Alonso‐Varona A., Sarasua J.R. Effect of bioactive glass particles on osteogenic differentiation of adipose‐derived mesenchymal stem cells seeded on lactide and caprolactone based scaffolds. Journal of Biomedical Materials Research Part A. 2015; 103 (3815‐3824). - 103.
Kim H.W., Lee H.H., Chun G.S. Bioactivity and osteoblast responses of novel biomedical nanocomposites of bioactive glass nanofiber filled poly(lactic acid). Journal of Biomedical Materials Research Part A. 2008; 85A (651‐663). - 104.
Zhang K., Wang Y.B., Hillmyer M.A., Francis L.F. Processing and properties of porous poly(L‐lactide)/bioactive glass composites. Biomaterials. 2004; 25 (2489‐2500). - 105.
Larrañaga A., Sarasua J.R. Effect of bioactive glass particles on the thermal degradation behaviour of medical polyesters. Polymer Degradation and Stability. 2013; 98 (751‐758). - 106.
Larrañaga A., Petisco S., Sarasua J.R. Improvement of thermal stability and mechanical properties of medical polyester composites by plasma surface modification of the bioactive glass particles. Polymer Degradation and Stability. 2013; 98 (1717‐1723). - 107.
Larrañaga A., Ramos D., Amestoy H., Zuza E., Sarasua J.R. Coating of bioactive glass particles with mussel‐inspired polydopamine as a strategy to improve the thermal stability of poly (L‐lactide)/bioactive glass composites. RSC Advances. 2015; 5 (65618‐65626). - 108.
Ruddy A.C., McNally G.M. Annual Technical Conference – Society of Plastic Engineering. Rheological, Mechanical and Thermal Behaviour of Radiopaque Filled Polymers. 2005; 63 (3078–3082). - 109.
Kusiak E., Zaborski M. Composite Interfaces. Characteristic of natural rubber composites absorbing X-radiation. 2012; 19 (7)(433–439). - 110.
Meagher M.J., Leone B., Turnbull T.L., Ross R.D., Zhang Z., Roeder R.K. Journal of Nanoparticles Research. Dextran-encapsulated barium sulfate nanoparticles prepared for aqueous dispersion as an X-ray contrast agent. 2013; 15 (2146/1–2146/10). - 111.
Martínez de Arenaza I., Sadaba N., Larrañaga A., Zuza E., Sarasua J.R. High toughness biodegradable radiopaque composites based on polylactide and barium sulphate. European Polymer Journal. 2015; 73 (88‐93). - 112.
Ouchiar S., Stoclet G., Cabaret C., Georges E., Smith A., Martias C., Addad A., Gloaguen V. Comparison of the influence of talc and kaolinite as inorganic fillers on morphology, structure and thermomechanical properties of polylactide based composites. Applied Clay Science. 2015; 116‐117 (231‐240). - 113.
Ouchiar S., Stoclet G., Cabaret C., Gloaguen V. Influence of the filler nature on the crystalline structure of polylactide‐based nanocomposites: new insights into the nucleating effect. Macromolecules. 2016; 49 (2782‐2790).