**1. Introduction**

Today, bioplastics, compounds derived from sustainable sources, are one of the best alternatives to petroleum-based plastics. They are natural or synthetic biopolymers, and include poly(lactic acid) (PLA), which is of grea<sup>t</sup> commercial interest due to various factors. First, PLA is produced by polymerizing lactide, a derivative of lactic acid industrially produced from plants, making it a biosourced thermoplastic. As such, extrusion, molding, injection molding, thermoforming, and fiber spinning are largely used to process PLA for many industrial applications. Lastly, it forms an intrinsically biocompatible system in a living environment and is biodegradable, with a tunable degradability as a function of its molecular weight and tacticity, which makes it suitable for many applications in biomedical and environmental fields such as tissue engineering, drug delivery, "green" packaging, textiles, etc. [1,2].

Despite these clear advantages, PLA suffers from some limitations. From an economical point of view, it remains more expensive than many non-biodegradable commodity polymers. Moreover, regarding its thermomechanical properties, it has a low toughness and poor impact strength. To overcome these limitations, polymer blends can provide the desired properties at a low cost through simple physical processes, rather than chemical approaches such as copolymerization reactions. Polymer blends and composites [3], as

**Citation:** Coudane, J.; Van Den Berghe, H.; Mouton, J.; Garric, X.; Nottelet, B. Poly(Lactic Acid)-Based Graft Copolymers: Syntheses Strategies and Improvement of Properties for Biomedical and Environmentally Friendly Applications: A Review. *Molecules* **2022**, *27*, 4135. https://doi.org/ 10.3390/molecules27134135

Academic Editors: Marek Brzezi ´nski and Małgorzata Ba´sko

Received: 8 June 2022 Accepted: 23 June 2022 Published: 28 June 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

well as plasticizers [4], are used to improve the mechanical properties of polymers. The melt blending of dissimilar polymers is a classic method for obtaining new enhanced properties. Unfortunately, PLA-based blends exhibit an insufficient performance because the blended polymers are often thermodynamically immiscible, resulting in a poor compatibility between the blended components [5]. This phenomenon is particularly important in high-molecular-weight polymers commonly found in the field of orthopedics.

In order to circumvent the compatibility problem, compatibilizers have been proposed [6]. Compatibilizers are used to improve the properties of immiscible or partially miscible polymer blends. They improve the adhesion between the blended polymers. Compatibilizers can be "reactive" (they chemically react with at least one of the two blended polymers) or "non-reactive" (they have secondary interactions with both polymers). More generally, these PLA compatibilizers may consist of a copolymer comprising the PLA and the polymer to be compatibilized. PLA-based copolymers can be of a "block" or "graft" architecture. It is necessary to have at least one reactive function on the PLA to obtain these blocks or graft copolymers. However, PLA only has reactive functions at its chain ends, typically alcohol and carboxylic acid functions. Therefore, it is quite easy to prepare block copolymers (di-, tri- or multi-blocks) from PLA. The most common PLA-based block copolymers are probably the amphiphilic PLA-*b*-Poly(ethylene glycol) (PEG) di-block copolymers and PLA-*b*-PEG-*b*-PLA triblock copolymers, in which the hydrophobicity of PLA is decreased and its toughness is improved [7]. There are many review articles on the formation of PLA-based block copolymers and their applications, especially in the biomedical field [7–9].

The reactive functions at the chain ends of PLA can also react with the reactive functions in the chain of certain polymers, such as polysaccharides, to give polymer-*g*-PLA graft copolymers in a so-called "classic" structure (Figure 1), where the polymer backbone is grafted with PLA side chains [10]. The synthesis of "reverse" structures, i.e., with a PLA main chain grafted with other polymer side chains is more challenging because, unlike polysaccharides, the PLA backbone is not functionalized. Therefore, it is necessary to first functionalize the PLA chain before subsequent grafting of polymer segments onto the PLA backbone. From a theoretical point of view, two methods can be used to obtain a functionalized PLA backbone: (i) copolymerization of a lactide with a pre-functionalized lactide and (ii) direct chemical modification of a preformed PLA chain. It is therefore the aim of the present review to focus on these relatively uncommon reverse PLA-*g*-polymer structures.

**Figure 1.** Illustration of "classic" and "reverse" structures of PLA-based graft copolymers.
