## 2 Results  
### Copolymerization of Lactic with a Functionalized Lactic for the Preparation of PLA Graft Copolymers  
To the best of our knowledge, according to the first method mentioned above, few functionalized lactides are described in the literature, and only a small proportion of these substituted lactides has been copolymerized with lactic to yield functionalized  
Figure 1: Illustration of “classic” and “reverse” structures of PLA-based graft copolymers.  
PLA backbones [11; 12; 13; 14]. For example, some lactides functionalized with benzyl, allyl and propargyl groups have also been prepared and copolymerized with lactic, but no polymer chains were subsequently grafted onto the PLA backbone [15].  
[PERSON] et al. prepared an alkyne-functionalized lactic that was copolymerized with lactic to give an alkyne-functionalized PLA. An azide-paclitaxel-PEG was then reacted with the alkyne-functionalized PLA via a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction to give a novel graft polymer-drug conjugate (GPDC): PLA-_g_-Paclitaxel-PEG (Figure 2) targeting sustained release of Paclitaxel [16]. [PERSON] et al. prepared and (co)polymerized a dipropargyloxlactide by ring opening polymerization (ROP) in the presence of Sn(Oct)\({}_{2}\) and TBBA (tertiobutylbenzyl alcohol). An azido-PEG (PEG-N3) was then grafted via CuAAC click chemistry (Figure 3) [17]. Turbidity, dynamic light scattering and NMR results suggested that these grafted copolymers exhibit a reversible thermo-responsive property, with LCST ranging from 22 to 69 \({}^{\circ}\)C depending on the molecular weight of the PEG.  
Figure 2: Reaction scheme for the synthesis of PLA-_g_-Paclitaxel-PEG (adapted from [PERSON] et al. [16], Copyright American Chemical Society, reproduced with permission).  
In another synthetic method, [PERSON] et al. prepared a spirolactide-heptene monomer that yielded a PEG-grafted lactic after reaction with an azido-PEG (Figure 4) [18]. This PEG-grafted lactic was then polymerized with molecular weights above 10 kDa. Typically, polymerization was carried out in anhydrous CH\({}_{2}\)Cl\({}_{2}\) with 1,5,7-triazabicyclo [4.4.0]dec-5-ene (TBD)/benzyl alcohol as the catalyst/initiator system. Preliminary biological studies showed that PLA-\(g\)-PEG reduced non-specific protein adsorption and cell adhesion compared to the original PLA.  
This limited number of examples illustrates that this approach based on functional-lactides is time-consuming, requires many steps and often gives low yields. For example, the global yields of the syntheses are 20% for dipropargyloxylactide [17] and 10% for PLA-\(g\)-Paclitaxel-PEG [16]. These copolymers are therefore expensive, and while this is not a fundamental problem for biomedical applications, it is a real drawback for environmental applications that use much larger amounts of product. Therefore, the second method, chemical modification of a preformed PLA chain, is the most widely used to obtain a functionalized PLA backbone allowing for the grafting of a second polymer.  
Figure 4: Reaction scheme for the preparation of PLA-\(g\)-PEG (from [PERSON] et al. [18], copyright American Chemical Society, reproduced with permission).  
Figure 3: Reaction scheme for the synthesis of dipropargyloxymethyl PLA and the grafting of PEG via click a reaction (adapted from [PERSON] et al. [17], Copyright Royal Society of Chemistry, reproduced with permission).