Poly(lactic acid)/ poly(lactide) (both PLA) is the first biopolymer produced on large scale.33 It is a homopolymer consisting of several lactic acid molecules coupled together. As a material, PLA is compostable and it is generally produced from renewable sources, such as from starch and sugar.3 It can be used in many different applications, such as in different packaging materials, films, fibers, and foams. It is also used in the medical field including tissue scaffolds, sutures and implant devices. PLA is also thermoplastic meaning that it is remoldable with heat and pressure.2,13
PLA can be produced with different methods and direct polymerization (such as azeotropic dehydration) together with ROP are the most generally exploited methods.2 Of these two, the ROP method is more utilized.35 In all of the common PLA production routes, lactic acid is used as the raw material but it is also possible to produce PLA from petrochemical feedstock.32
If only the conventional polycondensation is used in the PLA production, the PLA chains obtained are quite short and have a low molar mass.2 This is because the reaction is an equilibrium reaction and the equilibrium does not favor the polymers with high molar masses.35 PLA with low molar mass does not have sufficient properties for many applications but if the chains are longer and the formed polymers have high molar masses (Mn > 100 000 g/mol),5 they have better mechanical properties.1,5 That is why it is profitable to try to produce high molar mass PLA.
There are several different reaction routes to produce high molar mass PLA but these routes demand accurate reaction conditions (pH, pressure, and temperature).2 That is why the production of a high molar mass PLA is not so straightforward. Three different production routes are presented in Figure 4.
Figure 4. Three different reaction routes to produce a high molar mass PLA.32
One way to produce a long chain PLA is to utilize chain coupling agents in the reaction chain.5 At the beginning, PLA with a low molar mass (prepolymer) is produced using conventional lactic acid condensation. Then, these short PLA chains are linked with each other using coupling agents (for example, 1,6-hexamethylene diisocyanate)2 to form a high molar mass PLA.
Another way to produce a high molar mass PLA is azeotropic dehydrative condensation.20 In this process, the water formed in polycondensation is removed with drying agent (often organic solvent) and a high molar mass PLA is produced directly from lactic acid. With this method, the weight average molar masses of the produced PLA can be more than 300000 g/mol.36
The third route is the most used on industrial scale and the molar mass of forming PLA can be controlled.2 First of all, a low molar mass prepolymer (PLA, DP < 100,1 Mw = 1000-5000 g/mol32) from lactic acid is produced by polycondensation.33 After this, the prepolymer is depolymerized and the depolymerization yields a product called lactide (3,6-dimethyl-1,4-dioxane-2,5-dione). Lactide is a cyclic dimer of lactic acid and is formed via transesterification by back-biting reaction mechanism.5 Now, lactide is the monomer for the forming PLA and the ring structure is opened with the help of catalysts (usually tin octoate, Sn(Oct)2, also known as Sn(II)2-ethylhexanoate).20 When the lactide rings are opened, they join quickly together and form long PLA chains.5 This step is called ROP. In many points of this route, purification is needed and these purification steps are expensive and complex.2
A lactide ring is a chiral molecule with two chiral centres and it has three different optical structures (Figure 5).33 The structure of the lactide ring can be D (R,R), L (S,S) or meso (R,S) and the structure depends on the stereochemistry of the reactant, the lactic acid. If the lactide sample is the mixture of L- and D-lactides, it is called rac-lactide (also known as DL-lactide).
Respectively as before, the structures of the reacting lactides affect to the structure of the forming PLA chain. If the lactides are purely L-type, the formed PLA chain is called PLLA and if the lactides are purely D-type, the PLA is called PDLA.2 If the formed PLA chain consist of either meso-lactides or rac-lactides (a mixture of L- and D-lactides), it is called PDLLA.
However, normally only PLLA and PDLLA forms are used.3,37
Figure 5. Constitutional formulas of L-, D-, and meso-lactides.33
PLLA and PDLA have different characteristics and the ratio of the enantiomers (L and D) in their mixtures determines the properties of the material.3,33 When seeking better mechanical properties, pure PLLA is often used because it is highly crystalline (about 37 %).38 Pure PLLA has the highest melting point of different PLA grades and adding the D-comonomer to the polymer decreases the melting point. This also causes the mixture to crystallize slower and when the D-content is higher than 12-15 %, the end product turns amorphous.14,33 However, there is also a downside for resistant PLLA because it degrades very slowly compared to the PDLLA.1 The poor degradation of PLLA results from the reinforcing crystalline domains formed in the PLLA structure.
The properties of PLA polymers can also be changed by adding different type of monomers into the reaction mixture. In that case, different copolymers of PLA are formed.2,39 Other ways to alternate the properties of PLA are to change the structure of the PLA polymers by branching the molecules, adding nanoparticles to the PLA to form nanocomposites and coating PLA with high barrier materials.3,20
PLA has many advantages from the perspective of many applications and it is used, for example, in suturing materials, in drug delivery, and surgical implants.40 Formerly, titanium and other metals have been used in different orthopedic screws and plates, but they are not degradable and stay in the body.2 To remove them, another surgery is needed. There is always a risk in surgeries and, in addition, the extra surgery increases the expenses of the total operation. Due to this, the researchers are interested in bioabsorbable materials utilized in the medical field.
PLA is ecological, deformable, water resistant and in the production energy can be saved compared to the petroleum-based plastics.39 It has been estimated that it takes about 25-55 % less energy to produce PLA than petroleum-based polymers. Nevertheless, PLA can be brittle and does not endure hard hits. PLA is also comparatively hydrophobic (contact angle with water approximately 80°) and there are not many reactive side-chain groups in this polymer to chemically modify the polymers.
PLA is also generally considered as biocompatible meaning that after implantation to the body, immunological rejection because of the polymer or its degradation products is not observed or observed reaction is much smaller than the advantage gained from the implant.41–43 Additionally, the biocompatible implants may not be toxic for the system and the degradation products must be eliminated from the system without traces. However, in some studies, reactions with PLA and tissue have been reported.41,44 It has been discovered that the long degradation times and high crystallinity of the material (especially with pure PLLA) can induce some inflammatory reactions. However, these properties can be changed by copolymerizing the D-form PLA among the L-form and because the reaction has been observed only in few studies PLA is considered as viable for medical use.3,45