**1. Introduction**

Polylactide/poly(lactic acid) (PLA) is a biodegradable and biobased aliphatic polyester derived from renewable sources such as corn, potato, and sugar cane. Due to biodegradability and biocompatibility (PLA is approved by US Food and Drug Administration for contact with human cells) the early applications of polylactide (or its copolymers with polyglycolides) involved surgical sutures, implants or drug formulations [1–5]. The use of PLA was initially limited to these biomedical applications due to its high cost and low availability.

Biodegradability is considered as one of the major advantages of polylactide, thus, PLA materials (apart from biomedical applications) have been also used for the production of short-use items and packaging [1]. More recently, however, there have been some concerns related to the environmental impact of the utilization of biodegradable polymers as the dumping of biobased waste in landfills contributes to global warming and leachate [6,7]. Thus, in recent years the shift from degradability/"compostability" to "renewability" and an increasing interest in using PLA based products for long-term usage applications, even at the expense of reducing the biodegradability of the polymer may be observed [1]. It is expected that PLA will have broader applications in the medical and food industries, however, much has to be overcome to ensure actual sustainability, including enhancement of mechanical and thermal properties [8]. There are many e fforts to improve the performance of PLA via di fferent modification methods including copolymerization, blending, or crosslinking [9–12]. The design of novel structures such as networks based on polyesters o ffers a possibility for enhancing mechanical and thermal properties. The improvement of mechanical strength is needed for both medical devices and parts of daily-use items. However, when designing materials for these applications, an awareness that the crosslinking process leads not only to the enhancement of polymer toughness (usually with the improvement of thermal properties) but also to the modification of other properties as degradability, solubility, gas permeability, and so on must be maintained. Basically, crosslinking leads to a decrease in degradability and this may be a negative feature for materials designed for biomedical applications (implants and drug delivery systems). However, in some cases, longer times of implant destruction or longer delivery of the pharmaceutical agen<sup>t</sup> could be required. Thus, very detailed studies of crosslinking of biobased and biocompatible materials include investigation of their degradation in di fferent environments and their biocompatibility. The balance between mechanical strength and degradability of materials should be established at the stage of their design in order to fulfill the requirements of the target application.

Networks can be obtained through di fferent approaches. Applied methods are usually classified into several main groups, that is chemical crosslinking and crosslinking by exposure to low- energy light or ionizing radiation. Chemical crosslinking is one of the largest groups because, among others, this group includes all methods based on radical crosslinking induced by peroxides [13].

Both high-energy radiation crosslinking and photo-crosslinking are relatively easy methods in comparison with chemical crosslinking, however, some advantages and weakness of each of them are known. Photo-crosslinking requires the presence of reactive -unsaturated groups in polymer chains (functionalization of synthesized polymers) and the presence of photo-initiators but may be accomplished under mild conditions (room temperature) for di fferent materials (solid, liquid, containing di fferent encapsulated compounds including sensitive proteins, etc.) [14]. High energy radiation, such as gamma and electron beam radiation has been applied for various treatments of polymers, and also crosslinking [15,16]. Crosslinking by irradiation may be performed on pristine polymer without the necessity of functionalization because radicals may be generated directly on polymer chains. However, it is accompanied or even dominated by chain scission. Thus, even in this case using additives (crosslinking monomers) is preferred.

This review does not include chemical crosslinking which has been broadly covered by other articles [13,17]. Instead, the present state of the art concerning the formation of crosslinked PLA-based materials by photo-crosslinking and high energy irradiation is presented. Totally di fferent materials are obtained depending mainly on crosslinking density which, in turn, depends on the radiation type, its dose, conditions, and on PLA-based polymer (a composition and an architecture of this (co)polymer have an independent contribution to the overall properties).

#### **2. PLA Crosslinking by Electron Beam or Gamma Irradiation**

Ionizing radiation has been well known as a very convenient tool for the modification of polymeric materials through crosslinking, grafting, and degradation. PLA however, undergoes predominantly degradation under the influence of ionizing radiation. Thus, the mechanical and physical properties of polymers exposed to gamma rays or an electron beam, decrease due to the reduction in molecular weight.

Beginning with the advent of research related to the development of polyester materials for the production of implants, surgical sutures, and drug delivery systems, high energy irradiation, mainly gamma but also electron irradiation has been used for sterilization [18–21]. It has been found that, depending on the chemical structure of the polymers, the absorbed dose, the dose rate, and the temperature of irradiation, various reactions involving radicals generated along the polymer chain proceeded such as chain scission and crosslinking reactions which were often accompanied by the evolution of gaseous products [15,22–27]. Radical processes which may proceed during high energy irradiation [27] (see Figure 1) have been proposed.

**Figure 1.** Possible processes involving radicals on polylactide (PLA) chains formed by irradiation with an electron beam (on the basis of Reference [27]).

Reactions under high energy radiation leading to the destruction of the PLA chain were useful for the controlled PLA degradation [19,28,29].

Many authors studied gamma radiation-induced changes (decreases) in the enthalpy of melting and cold crystallization, the degree of crystallinity, the glass transition temperature, and the thermal stability of polylactides [24,27,29]. It is obvious that the extent of the drop of mentioned parameters increases with the increase of radiation dose. The chain scission of polymer chains under irradiation is accompanied by the crosslinking process especially when higher doses are applied [20]. The polymer crosslinking may dominate at appropriate conditions (below doses of 250 kGy mainly chain scission proceeds [19]) and can be done on purpose. Biodegradable polymers that could be crosslinked by irradiation would be valuable not only in the medical field but for other industrial applications as well. Introducing crosslinking into biodegradable polymers, should result in an enhancement of mechanical properties and delayed hydrolysis of the polymer. To overcome the effect of significant molecular weight decrease, the curing of PLA is frequently performed in the presence of polyfunctional monomers. In irradiation-induced crosslinking such compounds as triallyl isocyanurate (TAIC), trimethallyl isocyanurate (TMAIC) trimethylolpropane triacrylate (TMPTA), trimethylolpropane trimethacrylate (TMPTMA), 1,6-hexanediol diacrylate (HDDA) and ethylene glycol bis (pentakis (glycidyl allyl ether)) ether were applied [30]. The structures of these monomers are shown in Figure 2.

Polyfunctional monomers have been applied predominantly in electron beam-induced crosslinking [27,30–35] although they have been also used for curing by γ-irradiation [36–38].

Mitomo and his group studied the effects of the type and the concentration of polyfunctional monomer as well as parameters of the irradiation with electron beam (the irradiation dose, temperature) on the crosslinking of poly(l-lactide) (PLLA) or mixture of poly(l-lactide)/poly(d-lactide) (PLLA/PDLA), the thermal properties, and the biodegradation of obtained crosslinked polymers [30,31]. It was found that the most optimal conditions to introduce crosslinking were around 3% of TAIC and the irradiation dose of 30–50 kGy [30,33]. The crosslinked PLA films had much improved heat stability and mechanical properties. The resultant properties of PLA samples were governed by crosslinking density which depended on the structure and length of PLA chains and on the radiation dose. The crosslinked PLA became harder and more brittle at low temperatures, but was rubbery, soft, and stable at higher temperatures, even over Tm. The degradation of irradiated – crosslinked PLA samples was considerably retarded.

**Figure 2.** Multifunctional crosslinking agents applied in radiation-induced crosslinking [30]. (Adapted with permission from Elsevier, 2005).

Some authors studied the results of the crosslinking of PLA blends and composites with other materials (PCL, poly(butylene adipate-co-terephthalate) (PLA/PBAT), flax fibers, montmorillonite, and others) under electron beam irradiation [34,39–43]. The physical properties, apart from crosslinking conditions, depended strongly on the blend composition. It was stated that TAIC was an efficient agen<sup>t</sup> that hindered the phase separation and linked macromolecules of both the same and the different polymers. On the other hand, the addition of crosslinking monomers (TAIC) was claimed to hamper polyester degradation [41].

Various additives have been also added for PLA crosslinking by γ-rays. For example, blends of PLA with flax fibers were subjected to γ-irradiation [37], octavinyl-POSS (octavinyl polyhedral oligomeric silsesquioxane) was used as an additional crosslinking agen<sup>t</sup> [44], or PLA was blended with epoxy-functional acrylic oligomer as a chain extender in order to receive higher Mn and improved properties of PLA-based material [38].

These composite materials have been prepared with the support of ionizing radiation in order to modify the PLA properties, mainly with the aim of their use in packaging and in the production of consumer goods. The radiation-induced radicals on different components of blend/composite are able to react forming linkages between separate phases leading to the increase of the compatibility between components or to the formation of a multicomponent network. Some examples of the preparation of composite materials for daily use applications are shown in Section 4.

The attempted crosslinking of different polylactide-based polymers by using high-energy irradiation and different crosslinking agents is presented in Table 1.


**Table 1.** Ionizing radiation curing of polylactide.


**Table 1.** *Cont.*


**Table 1.** *Cont.*

diacrylate; EG—ethylene glycol bis(pentakis(glycidyl allyl ether))ether, hydroxy terminated; PDLLA—polylactide prepared from racemic mixture of D-LA and L-LA; PBAT—poly(butylene adipate-co-terepthalate); PEGM—poly(ethylene-co-glycidyl methacrylate); HBN—hexagonal boron nitride; Ov-POSS—octavinyl polyhedral oligomeric silsesquioxane; MMT—montmorillonite; NA—not available.

## **3. Photo-Crosslinked PLA**

Photo-initiated crosslinking has many advantages for biomedical applications because it allows fast crosslinking under mild reaction conditions without solvents. Radical crosslinking using peroxides is not appropriate for biomedical applications because of the toxicity of the decomposition products of peroxides and not defined degradation products. Electron beam and γ-irradiation crosslinking require a large amount of radiation energy and the presence of a crosslinking agen<sup>t</sup> to ge<sup>t</sup> the advantage of crosslinking over chain scission. Photo-crosslinking provides significant advantages over these two approaches, such as ease of use, safety, especially in connection to living systems, and low cost [45], although it may also be accompanied by other processes leading to polymer degradation. UV was also intentionally used to induce polylactide degradation (through, e.g., radiolysis or photo-oxidation) [46].

Polylactide intended for crosslinking is first functionalized at the chain ends with double bonds and then subjected to UV or visible light/laser irradiation which induces radical polymerization. To initiate radical polymerization photoactive additives are added such as substituted phenylacetophenones (irgacures) or camphorquinone. In comparison with peroxide-induced crosslinking, the photo-crosslinking can be accomplished at low temperatures [47].

As it was mentioned PLA-based materials which were photo-crosslinked were designed for medical applications (tissue sca ffolds or drug carriers), thus, this crosslinking method concerns mostly lactide copolymers i.e., PLA/ polyethylene glycol (PEG), poly(tetramethylene oxide) (PTMO), poly(ε-caprolactone) (PCL), polyglycolide (PGA), poly(trimethylene carbonate) (TMC) copolymers [46,47]. These were ABA type copolymers or statistical copolymers obtained by tin octanoate catalyzed ring-opening (co)polymerization of lactide initiated by polyether diol (ABA block copolymers), alternatively, by low molecular diols or multifunctional alcohols in the case of the statistical or star-shape copolymer. Obtained difunctional or multifunctional –OH terminated polylactides were functionalized by esterification, usually with (meth)acryloyl chloride. Low molecular weight polymers (oligomers) were mixed with photoinitiator and, often in molds, were exposed to UV lamp irradiation.

Based on acrylated PDLLA-PEG-PDLLA copolymers or functionalized with fumarate groups, upon crosslinking, either hydrolyzable gels [48,49] or tissue sca ffolds with controlled macroscopic architecture, potentially for bone regeneration [50,51] were prepared. Water-soluble PEG/PLA copolymers consisted of PEG fragment with Mn = 1000–10,000 and the attached 2–40 LA units [48]. The authors claim that obtained nontoxic macromers could be photo-polymerized in vivo in direct contact with tissue. Prepared by another group, hydrogels (with about 2–4 LA units attached to PEG with Mn = 4000) were applied for encapsulation of model proteins [49].

Mechanical properties of networks for sca ffold were highly dependent on the number of lactic acid and ethylene glycol units in the oligomer backbone ranging from 2–8 EG units and 6-10 LA units [52]. Also, hydrophobicity/hydrophilicity balance varied with copolymer compositions what was important with regard to polymer degradation and cell attachment. In both studies, the complete degradation of networks to water-soluble products was performed in physiological conditions.

The authors of another work [53] prepared copolymers consisting of polyethers such as PEG, poly(propylene glycol) (PPG) or poly(tetramethylene glycol) (PTMG) and 7–65 wt % of <sup>d</sup>,<sup>l</sup>-lactide units which, after functionalization introducing acrylate end groups, were subjected to UV irradiation. Photo-polymerization resulted in the network with gel content equal to 78% for copolymers with long PEG chain (Mn = 10,000) and over 97% for PEG and PPG with Mn around 400. Hydrophilic PEG-based networks rapidly degraded into completely water-soluble products within 1 day, while the degradation times of the more hydrophobic PPG and PTMG-based networks varied from 1 to 7 days. Obtained materials can potentially be used as biodegradable lubricants for coating various medical products.

In several articles, the syntheses of PLA-based copolymers by copolymerization of <sup>d</sup>,<sup>l</sup>-lactide with ε-caprolactone (CL), or L-lactide with ε-caprolactone and glycolide (GL) initiated with diethylene glycol or tetra(ethylene glycol), followed by the end-(meth)acrylation and crosslinking were described [51,54]. In the case of the first cited work PLA/PCL copolymers with Mn in the range 1500–2400 resulted in a

rather dense network after crosslinking while in a second work, Mn of PLA/PCL/PGA terpolymers was in the range 1800–10,200 giving networks with varied mechanical properties depending on copolymer composition and molecular weight. Degradation of all networks has been studied as well as their biocompatibility, both in respect to their potential application in tissue engineering. Copolymerization of <sup>d</sup>,<sup>l</sup>-lactide with glycolide was also initiated by PEG (Mn = 1500) leading to PLGA–PEG–PLGA copolymers which were further functionalized with itaconic anhydride [55]. Crosslinking by UV irradiation resulted in hydrogels which, according to the authors, could be used in moist wound healing or as carriers for controlled drug release.

For tissue elastic implants, materials from PDLLA/1,3-trimethylenecarbonate (TMC) copolymers have been synthesized by UV coupling of linear macromers with methacrylate groups and relatively high molecular weights (~30,000) [56]. Obtained networks with tunable thermal and mechanical properties depending on DLLA to TMC ratio could be used as implantable devices having different geometries as well as porous scaffolds with shape-memory properties.

Many authors used star-shaped polylactides and lactide copolymers instead of linear ones for the photo-crosslinking. Starting their works with homopolymers, Grijpma group prepared star-shaped poly(<sup>d</sup>,<sup>l</sup>-lactide) oligomers with 3 and 6 arms, with arm molecular weight in the range 200–5700 [57], which, after functionalization with methacryloyl chloride, were diluted with ethyl lactate and subjected to photo-crosslinking. Networks prepared from macromers of which the molecular weight per arm was 600 or higher had good mechanical properties, similar to linear high molecular weight poly(<sup>d</sup>,<sup>l</sup>-lactide). Films and porous scaffolds with gyroid architecture have been prepared by stereolithography, using a liquid resin based on a 2-arm PDLLA macromer and ethyl lactate. It appeared that pre-osteoblasts showed good adherence to these photo-crosslinked networks. The same group prepared 3-arm copolymers of <sup>d</sup>,<sup>l</sup>-lactide with ε-caprolactone and 1,3-trimethylenecarbonate with Mn = 3100–4000 which subsequently were functionalized with fumarate groups [58]. UV-initiated polymerization proved the sufficient reactivity of these groups and resulted in networks with high gel content (up to 96%) which physical properties varied depending on the composition, and molecular weight of the oligomeric precursors.

Other authors prepared 4-arm PDLLA/PCL copolymers functionalized with (meth)acrylate groups [59,60]. One of these works concerned the investigation of thermal properties of prepared thermoresponsive membranes from prepolymers with Mn in the range 3200–12,000, designed for drug delivery [60]. The other was focused on different techniques of resistor preparation to achieve shape accuracy and edge sharpness of samples prepared from crosslinked PLLA/PCL stars with short arm length, i.e., ~2500 [59].

Significant achievements in the field of synthesis of photo-crosslinked materials based on polylactide, designed for biomedical applications has a group of Amsden [61]. They worked on bioelastomers which could be used for the production of tissue scaffolds and implantable devices for drug delivery. For this reason, copolymers of lactide with such comonomers as ε-caprolactone and trimethylene carbonate (or substituted carbonate) introducing flexibility were prepared. Similarly as it was in the study by other researches, star 3-arm <sup>d</sup>,<sup>l</sup>-LA (co)polymers, or occasionally linear oligomers with Mn usually in the range 1000–5000 were functionalized with acrylate groups. Alternatively, acrylate groups were introduced as side groups by copolymerization of lactide with cyclic carbonate substituted with these groups [62,63]. Functionalized prepolymers were crosslinked in the presence of photo-active compounds and sometimes together with co-crosslinkers as, e.g., poly(ethylene glycol) diacrylate [64–67]. Obtained networks were studied concerning for their mechanical properties, degradation, and biocompatibility. A large part of the works concerned the study of the encapsulation of biologically active compounds and their release. Specific properties achieved in particular studies described by group of Amsden in numerous articles are shown in Table 2 (at the end of this section).

A similar approach as described above has been also used by other authors. Thus, 4-arm star PDLLA oligomers (containing ethylene glycol units in the initiator fragment), of different Mn (1500–9500) with either methacrylated or urethane methacrylated end groups have been synthesized and photochemically crosslinked [68]. High gel content networks (90–99%) had Tg strongly dependent on prepolymer molar mass. Mechanical properties depended on both the type of introduced end groups of prepolymer (methacrylate or urethane methacrylate) and molar mass [68].

Crosslinking of methacrylate-terminated linear <sup>d</sup>,<sup>l</sup>-lactide oligomers with Mn around 1300 has been also applied for the preparation of potential composite resin for stereolithography [69]. To enhance crosslinking, triethylene glycol dimethacrylate (TEGDMA) as reactive diluent has been added in the amount of 30% and 50%. PLAs together with TEGDMA was blended with hydroxyapatite (HA) in the amount of 20%, 30%, 40% and 60% to prepare composites that were next photopolymerized in the presence of photoinitiator giving products with gel content up to ~100 %. Analysis of the thermal properties of crosslinked composites showed that Tg significantly shifted to a higher temperature when HA was incorporated. It indicated the interaction between HA particles and PLA matrix, leading to a mobility restriction of the polymeric chains. The addition of HA also a ffected the thermal stability, as known from the thermogravimetric analysis—the shift to higher temperature was observed for crosslinked PLA containing HA. Degradation of composites has been investigated as well as changes in thermal and mechanical properties during degradation. Additionally, the cytocompatibility of cells in contact with composites with di fferent HA contents during degradation has been studied. Lower cytotoxicity of degradation products was observed for a sample with a higher content of HA. As a conclusion, the authors claim, that materials showed their potential in a stereolithographic fabrication of bone implants.

Functionalized with (meth)acrylate groups star low molecular weight polylactides have been used for stereolithography also by other groups where two-photon polymerization (2PP) technique was applied for crosslinking [70–75]. Star-shaped methacrylate-terminated oligo(<sup>d</sup>,<sup>l</sup>-lactide)s with Mn = 2800 were prepared, and it was demonstrated that oligomer synthesis and their functionalization can be carried out in the same reactor [71]. Subsequently, 2PP technique was used to prepare hexagonal porous sca ffold with 3D structures in the presence of photoinitiator. These fabricated sca ffolds were shown as a beneficial microenvironment for osteogenesis and bone regeneration in vitro and in vivo. Similarly, fabricated sca ffolds (2PP technique) were also used for supporting of Schwann cells growth and thus, as neural sca ffolds in nerve repair [70]. Laser-induced crosslinked star-shaped methacrylate-terminated oligo(<sup>d</sup>,<sup>l</sup>-lactide)s (Mn = 2400) were used as a reinforcement of collagen materials [74,75]. The material exhibited improved resistance to biodegradation, while the direct multipotent stromal cell growth during their culture was observed. Reinforcement of collagen sponges resulted in near one order of magnitude increase of Young's modulus without a ffecting of cytotoxicity and developed matrix provided cell adhesion and proliferation. Based on the results, the authors suggested this material for tissue engineering applications.

All previous studies (above-mentioned works) were focused on crosslinking of PLA or PLA copolymers where curable groups were sited at the ends of polymer chains (end-functionalized polymers). In an alternative approach, poly(lactide-co-glycidyl methacrylate) (P(LA-co-GMA)) copolymer has been synthesized by ring-opening polymerization where curable C=C groups were placed in side-chains of the copolymer (pendant unsaturated groups) [76]. The copolymer was irradiated in the presence of an initiator and the influence of irradiation time, initiator concentration, as well as GMA content in polymer chain on crosslinking e fficiency were followed by gel content measurement. Crosslinking led to the enhancement of mechanical and thermal properties and was dependent on the content of GMA units. In another study, P(LA-co-GMA) copolymer and its partly UV crosslinked counterpart were grafted with a pH-responsive polyacrylamide (PAAm), by UV-assisted reactions using acrylamide (AAm) and *<sup>N</sup>*,*N*-methylene bisacrylamide monomers, and various photoinitiator systems [77]. These materials have the potential for use in biomedical and environmental applications due to their amphiphilic and pH-responsible properties.

A di fferent example of crosslinking is the application of high molecular weight/commercial PLLA for UV-induced crosslinking [78]. PLLA powders containing di fferent concentrations of benzophenone (2–3.6 mol% per LA repeating unit) were hot-pressed at 190 ◦C and obtained films were continuously UV irradiated from both sides using different energy. Networks with gel content up to 98.5% have been prepared. By 1H and solid state 13C analyses of pristine PLA, the gel, and soluble fractions of the products, the authors suggested the mechanism of crosslinking which is presented in Figure 3. According to them, the photo-crosslinking may result from the recombination between primary and tertiary carbon radicals generated by the hydrogen abstraction from the PLA chain by the excited benzophenone.

**Figure 3.** The proposed mechanism of photo-crosslinking of not functionalized PLA in the presence of benzophenone [78]. (Reproduced with permission from Wiley, 2013).

DSC and XRD analyses indicated that prepared networks were partially crystalline up to 93% of gel content. Tg slightly increased because of the introduction of crosslinked structure in PLA, both Tc and Tm shifted to higher temperatures and finally disappeared with increasing gel fraction. The authors found that the crosslinks have been formed not only in the amorphous region but also in the crystalline region incorporating into the crosslinked network. The photoinitiator may penetrate into the crystalline region by the sublimation during the film formation. The photo-crosslinking improved mechanical properties by increasing both tensile strength and modulus by 70% with a little less decrease in elongation at break. Unexpectedly the toughness of the crosslinked PLA also increased by 22.5%. The authors named this type of crosslinking "crystal crosslinking" and claimed that described by them photo-crosslinking was more efficient compared with conventional amorphous crosslinking (much more significant improvements in thermal and mechanical properties).

Photo-crosslinking has also been applied by several authors for the curing of PLA-based prepolymers using quite an alternative approach. In this approach, photochemically active groups were introduced not as photosensitive additives but directly into PLA chains. As photosensitive sites cinnamoyl groups were used which are able to dimerize upon UV light of appropriate wavelength according to the scheme shown in Figure 4, forming cyclobutane rings [79] and so bridges between PLA chains.

**Figure 4.** Cyclodimerization of cinnamoyl groups.

The dimerization of cinnamoyl groups has been mainly used for the preparation of reversible networks (dimerization of cinnamoyl groups is reversible and cyclobutane ring undergoes cleavage under UV irradiation with another wavelength) [80,81], however, some authors didn't study the mentioned reversibility. Thus, cinnamoyl groups were introduced into PLA chain by polycondensation [82,83] of PLLA diols (Mn in the range 1260–3010 or 2300–8900) with diacyl dichlorides containing these groups, i.e., with 5-cinnamoyloxyisophthalic acid (ICA) [82] or with diacyl chloride of 4,4-(adipoyldioxy)dicinnamic acid (CAC) [83] (see Figure 5).

**Figure 5.** Compounds used for polycondensation with PLA diols.

Polycondensates were subsequently crosslinked with the light of λ = 282 nm. Dimerization of cinnamoyl groups appeared effective and after 2 h of irradiation, approximately 90% of these groups disappeared [82]. The authors observed a decrease of crosslinking rate and the amount of formed gel with increasing Mn of ICA/PLLA copolymer, which they assigned to lower concentration of a photosensitive component in the sample. While for PLLA with Mn ~ 4000 the amount of gel content was 100%, for PLLA with Mn ~ 9000 it was only 50 % [82]. From a comparison of the crosslinking rate of copolymers ICA/PLLA and CAC/PLLA with the same Mn of PLLA-diols, the authors concluded that cinnamoyl moiety in the side-chain was more photoreactive than that in the main-chain [82]. In both cases, decrease in degradation rate was observed after crosslinking in comparison with un-crosslinked functionalized PLLA and neat telechelic PLLA.

In another work, cinnamoyl moiety has been introduced into the PLLA side chain by copolymerization of lactide with cyclic carbonate monomer, i.e., 5-methyl-5-cinnamoyloxymethyl-1,3-dioxan-2-one (MC). Polymers of different ratios of MC/LA and Mn ranging from 12,900 to 65,100 were prepared. The crosslinking of the copolymer was followed by FTIR but no further properties of crosslinked material were discussed [84].

An original approach to PLA crosslinking has been recently presented by authors who applied multi(aryl azide) crosslinker for UV curing of PLA-Pluronic® copolymer not containing unsaturated groups [85]. They adopted an earlier reported strategy of UV-induced polyester crosslinking [86] relying on the UV-activation of the aryl azide group to generate highly reactive nitrene species that can insert into carbon-hydrogen bonds of the polymer backbone, thereby leading to crosslinking via amine groups (see scheme in Figure 6).

**Figure 6.** Mechanism of the formation of covalent bond between species bearing azide group and the compound with reactive hydrogen.

Applying this elegant and straightforward strategy, using polymeric multi-azide crosslinker, which can be also used for the crosslinking of other not pre-functionalized polymers, the authors prepared degradable elastomers for soft tissue engineering. Interesting elastic scaffold prepared by electrospinning from above described materials will be shown in the last section of the review.


*Molecules* **2020**, *25*, 4919

