PLA was first synthesised by polycondensation by Théophile-Jules Pelouze in 1845. In 1932, Wallace Hume Carothers developed a novel synthetic method based on the ring-opening polymerisation (ROP) of the cycle lactide monomer to synthesise PLLA. ROP was later patented by Du Pont in 1954 to synthesise vinyl fluoride (U.S. Patent No. 2674632, 1954). However, HM_w PLA by ROP on an industrial scale was only attained by the mid-1990s [31].

The lactic acid monomer can be converted to PLA through a polycondensation process by the reaction of the hydroxyl (–OH) and carboxylic acid (–COOH) groups with the removal of the detrimental byproducts such as water. Generally, catalysts are added to polymerisation to increase the reaction rate. The removal of water, enhanced under vacuum pressure, is critical to producing HM_w polymers due to the increased viscosity of the reaction mixture as the reaction proceeds. However, side reactions, such as transesterification, can also occur during the polycondensation of lactic acid, resulting in the formation of ring structures of different sizes, such as lactides. Transesterification reactions lower the overall M_w and the stereocontrol over the chain architecture, decreasing the physical properties of the PLA afforded as well as reducing the reaction yield [35]. The HM_w PLA is mainly synthesised by ROP due to the accurate chemical control in terms of molecular weight, polydispersity, polymer chain-ends, and tacticity. Moreover, ROP requires relatively mild conditions (130 °C) when compared to polycondensation (180–200 °C) [35,66]. Three reaction mechanisms have been proposed for ROP of lactide: anionic, cationic, and coordination-insertion mechanisms. In both anionic and cationic polymerisations, a monomer-activation mechanism occurs first, which permits the catalyst to be independent of the propagating polymer and can thus be easily removed as the polymerisation finishes. However, undesirable side and racemisation reactions are likely to occur due to the highly activated monomers. On the contrary, coordination-insertion polymerisation attains HM_w PLA with higher control over the M_w distribution [14,35]. Metal complexes of several metals have been widely employed as the catalysts for the ROP of lactides [35], of which the most studied are stannous 2-ethylhexanoate [Sn(Oct)₂], aluminium isopropoxide [Al(O i-Pr)₃], and zinc(II) lactate [Zn(Lact)₂] [66]. Sn(Oct)₂, is the catalyst utilised for the industrial synthesis of PLA, largely due to its approval by the FDA for use in medical (<20 ppm [67]) and food applications. Moreover, lauryl alcohol (1-dodecanol) is usually added as an initiator [35].

The polymerisation is induced by a coordination-insertion three-step mechanism supported by the catalyst [66], which was first formulated in 1971 by Dittrich and Schulz [14]. Firstly, Sn(Oct)₂ reacts with the lauryl alcohol to form a tin alkoxide. Subsequently, the exocyclic carbonyl oxygen of lactide temporarily coordinates with the tin atom of the catalyst in the alkoxide form. The formed coordination system enhances the nucleophilicity of the alkoxide part of the initiator as well as the electrophilicity of the lactide carbonyl group that enables the reaction to each other. Finally, the acyl-oxygen bond of lactide is disrupted, and the generated linear chain of the lactide turns into the alkoxide part of the catalyst, promoting the coordination with a new lactide molecule and, thus, the polymerisation propagation [35]. Finally, the active metal-alkoxide bond is hydrolysed as the monomer is entirely consumed, and the formation of a hydroxyl end-group occurs [66]. In the last stage of the propagation step, as the monomer concentration becomes significantly lower (~80%), both intra- and inter-molecular transesterification reactions occur, and the molecular weight distribution increases. However, the degrees of racemisation and chain scrambling achieved by metal complexes that follow coordination-insertion mechanisms are notably lower than those obtained by anionic or cationic catalysis [35]. The microstructure of the final polymers depends both on the initial monomers added to the reaction mixture and the catalyst stereocontrol. The control exerted by the catalyst over the nanostructure of the PLA, particularly to synthesise the PLA stereo block copolymers of HM_w, is essential to tailor the properties of the final product, and the synthesis of novel catalysts, particularly metal-based catalysts, for polymerisation by the coordination mechanism has attracted much attention since the pioneering work of Kleine et al. in the 1950s [66,68,69]. However, several drawbacks to controlling the synthesis of stereoblock HM_w PLA have emerged since then, such as the decrease in the living character of the catalyst due to the increase in the reaction heterogeneity [70], the detrimental side reactions due to the multiple nuclearities exhibited by the catalysts [71], as well as the long reaction time required to achieve the desired architectures and molecular weight [14]. Recently, novel catalysts that fulfil the synthetic requirements whilst exhibiting low toxicity for the application of the PLA derivatives in the biomedical and pharmaceutical fields were just attained [54,72,73], which offer the possibility to design multiblock copolymers simultaneously featuring the PLA stereoblock to attain higher physicochemical properties with other complementary blocks to tackle the PLA limitations.