Degradation Of Aliphatic Polyesters Research Articles

Crystalline aliphatic polyesters from eight‐membered cyclic (di)esters

AbstractRing‐opening polymerization (ROP) of lactones or cyclic (di)esters is a powerful method to produce well‐defined, high‐molecular‐weight (bio)degradable aliphatic polyesters. While the ROP of lactones of various ring sizes has been extensively studied, the ROP of the simplest eight‐membered lactone, 7‐heptanolactone (7‐HL), has not been reported using metal‐based catalysts. Accordingly, this contribution reports the ROP of 7‐HL via metal‐catalyzed coordinative‐insertion polymerization to the corresponding high‐molecular‐weight polyester, poly(7‐hydroxyheptanoate) (P7HHp). The resulting P7HHp is a semi‐crystalline material, with a Tm of 68 °C, which is ~10 °C higher than poly(ε‐caprolactone) derived from the seven‐membered lactone. Mechanical testing showed that P7HHp is a hard and tough plastic, with elongation at break >670%. P7HHp‐based polyesters with higher Tm values have been achieved through stereoselective copolymerization of 7‐HL with an eight‐membered cyclic diester, racemic dimethyl diolide (rac‐8DLMe), known to lead to high Tm poly(3‐hydroxyburtyrate) (P3HB). Notably, catalyst's strong kinetic preference for polymerizing rac‐8DLMe over 7‐HL in the 1/1 comonomer mixture rendered the formation of di‐block copolymer P3HB‐b‐P7HHp, showing two crystalline domains with Tm1 ~ 65 °C and Tm2 ~ 160 °C. Semi‐crystalline random copolymers with Tm up to 164 °C have also been obtained by adjusting copolymerization conditions. Mechanical testing showed that P3HB‐b‐P7HHp can synergistically combine the high modulus of isotactic P3HB with the high ductility of P7HHp.

Effect of Antibacterial Drugs on Hydrolytic Degradation of Aliphatic Polyesters

Effect of Antibacterial Drugs on Hydrolytic Degradation of Aliphatic Polyesters

Organobase/urea catalyzed ring opening polymerization of 3‐methyl‐1, 4‐dioxan‐2‐one to prepare chemically recyclable poly(ether ester)

AbstractIt is greatly desirable to develop degradable polymers from easily accessible chemicals. In addition to well‐known degradable aliphatic polyesters, poly(ether‐ester) prepared from 1, 4‐dioxan‐2‐one with perfectly alternative ether and ester bonds is a new type of degradable polymer. Due to the low strain of six‐membered 1, 4‐dioxan‐2‐one ring, it remains a challenge to realize the effective and controllable ring‐opening polymerization (ROP) of 1, 4‐dioxan‐2‐one derived monomers despite several catalysts have been attempted. In recent years, the combination of organobase/(thio)urea binary catalytic system has displayed great activity and versatility in the ROP of cyclic esters. Herein, we studied the ROP of 3‐methyl‐1, 4‐dioxan‐2‐one (MDO) using the combinations of various organobases and ureas as catalysts at relatively low temperature. We found that 1, 8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU)/urea pair showed great overall performance in the ROP of MDO, achieving monomer conversion up to 82% within 7 h at −40 °C. Notably, DBU/urea binary catalytic system achieved higher catalytic activity as well as better control over molecular weights and molecular weight distributions compared to previously reported catalysts. The obtained PMDO can completely depolymerize to recover MDO monomer by simple thermolysis, thus established a close‐loop life cycle.

Minimise thermo-mechanical batch variations when processing medical grade lactide based copolymers in additive manufacturing

Additive manufacturing is suitable for producing complex geometries; however, variation in thermo-mechanical properties is observed during one batch cycle when degradable aliphatic polyesters are used in melt extrusion-based methods. This is one important reason for why additive manufacturing has not yet been fully utilised to produce degradable medical implants. Herein, the internal variation has been minimised during one batch cycle by assessing the effect of different processing parameters when using commercially available medical grade copolymers.To minimise the molar mass, thermal and mechanical variation within one batch cycle, the rheological fingerprint of the commercially available medical grade poly(L-lactide-co-ε- caprolactone) and poly(L-lactide-co-trimethylene carbonate) has been correlated to the process parameters of the ARBURG Plastic Freeforming. An increase in the temperature up to 220°C and the associated increase in pressure are beneficial for the viscoelastic and thermally stable poly(L-lactide-co-ε-caprolactone). In contrast, a temperature below 220°C should be used for the poly(L-lactide-co-trimethylene carbonate) to reduce the variation in strain at break during one batch cycle. The residence time is decreased through the increase of the discharge parameter. An increase in temperature is however required to reduce the viscosity of the polymer and allow the pressure to stay within the machine limitations at higher discharge parameters.The results are highly relevant to the development of additive manufacturing for the production of degradable medical devices with identical properties. In fact, Food and Drug Administration guidelines for additive manufacturing of medical implants specify the need to control changes in for example material properties during the process.

Nondegradative additive manufacturing of medical grade copolyesters of high molecular weight and with varied elastic response

ABSTRACTAlthough additive manufacturing through melt extrusion has become increasingly popular as a route to design scaffolds with complex geometries the technique if often limited by the reduction in molecular weight and the viscoelastic response when degradable aliphatic polyesters of high molecular weight are used. Here we use a melt extruder and fused filament fabrication printer to produce a reliable nondegradative route for scaffold fabrication of medical grade copolymers of L‐lactide, poly(ε‐caprolactone‐co‐L‐lactide), and poly(L‐lactide‐co‐trimethylene carbonate). We show that degradation is avoided using filament extrusion and fused filament fabrication if the process parameters are deliberately chosen based upon the rheological behavior, mechanical properties, and polymer composition. Structural, mechanical, and thermal properties were assessed throughout the process to obtain comprehension of the relationship between the rheological properties and the behavior of the medical grade copolymers in the extruder and printer. Scaffolds with a controlled architecture were achieved using high‐molecular‐weight polyesters exhibiting a large range in the elastic response causing negligible degradation of the polymers. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48550.

Computer aided design of architecture of degradable tissue engineering scaffolds

One important factor affecting the process of tissue regeneration is scaffold stiffness loss, which should be properly balanced with the rate of tissue regeneration. The aim of the research reported here was to develop a computer tool for designing the architecture of biodegradable scaffolds fabricated by melt-dissolution deposition systems (e.g. Fused Deposition Modeling) to provide the required scaffold stiffness at each stage of degradation/regeneration. The original idea presented in the paper is that the stiffness of a tissue engineering scaffold can be controlled during degradation by means of a proper selection of the diameter of the constituent fibers and the distances between them. This idea is based on the size-effect on degradation of aliphatic polyesters. The presented computer tool combines a genetic algorithm and a diffusion-reaction model of polymer hydrolytic degradation. In particular, we show how to design the architecture of scaffolds made of poly(DL-lactide-co-glycolide) with the required Young’s modulus change during hydrolytic degradation.

Conformational Footprint in Hydrolysis-Induced Nanofibrillation and Crystallization of Poly(lactic acid).

The origin of hydrolysis-induced nanofibrillation and crystallization, at the molecular level, was revealed by mapping the conformational ordering during long-term hydrolytic degradation of initially amorphous poly(lactic acid) (PLA), a representative model for degradable aliphatic polyesters generally displaying strong interplay between crystallization and hydrolytic erosion. The conformational regularization of chain segments was essentially the main driving force for the morphological evolution of PLA during hydrolytic degradation. For hydrolysis at 37 °C, no significant structural variations were observed due to the immobilization of "frozen" PLA chains. In contrast, conformational ordering in PLA was immediately triggered during hydrolysis at 60 °C and was responsible for the transition from random coils to disordered trans and, further, to quasi-crystalline nanospheres. On the surfaces, the head-by-head absorption and joining of neighboring nanospheres led to nanofibrillar assemblies following a "gluttonous snake"-like manner. The length and density of nanofibers formed were in close relation to the hydrolytic evolution, both of which showed a direct rise in the initial 60 days and then a gradual decline. In the interior, presumably the high surface energy of the nanospheres allowed for the preferential anchoring and packing of conformationally ordered chains into lamellae. In accordance with the well-established hypothesis, the amorphous regions were attacked prior to the erosion of crystalline entities, causing a rapid increase of crystallinity during the initial 30 days, followed by a gradual fall until 90 days. In addition to adequate illustration of hydrolysis-induced variations of crystallinity, our proposed model elucidates the formation of spherulitic nuclei featuring an extremely wide distribution of diameters ranging from several nanometers to over 5 μm, as well as the inferior resistance to hydrolysis observed for the primary nuclei. Our work fuels the interest in controlling nanofibrillation mechanism during hydrolysis of PLA, opening up possibilities for straightforward nanofiber formation.

Cyclic comonomers for the synthesis of carboxylic acid and amine functionalized poly(L-lactic acid).

Degradable aliphatic polyesters such as poly(lactic acid) are widely used in biomedical applications, however, they lack functional moieties along the polymer backbone that are amenable for functionalization reactions or could be the basis for interactions with biological systems. Here we present a straightforward route for the synthesis of functional α-ω epoxyesters as comonomers for lactide polymerization. Salient features of these highly functionalized epoxides are versatility in functionality and a short synthetic route of less than four steps. The α-ω epoxyesters presented serve as a means to introduce carboxylic acid and amine functional groups into poly(lactic acid) polymers via ring-opening copolymerization.

Polyester-based (bio)degradable polymers as environmentally friendly materials for sustainable development.

This review focuses on the polyesters such as polylactide and polyhydroxyalkonoates, as well as polyamides produced from renewable resources, which are currently among the most promising (bio)degradable polymers. Synthetic pathways, favourable properties and utilisation (most important applications) of these attractive polymer families are outlined. Environmental impact and in particular (bio)degradation of aliphatic polyesters, polyamides and related copolymer structures are described in view of the potential applications in various fields.

Clickable degradable aliphatic polyesters via copolymerization with alkyne epoxy esters: synthesis and postfunctionalization with organic dyes.

Degradable aliphatic polyesters are the cornerstones of nanoparticle (NP)-based therapeutics. In this paradigm, covalent modification of the NP with cell-targeting motifs and dyes can aid in guiding the NP to its destination and gaining visual confirmation. Therefore, strategies to impart chemistries along the polymer backbone that are amenable to easy modification, such as 1,3-dipolar cycloaddition of an azide to an alkyne (the "click reaction"), could be significant. Here we present a simple and efficient way to introduce alkyne groups at high density in aliphatic polyesters without compromising their crystallinity via the copolymerization of cyclic lactones with propargyl 3-methylpentenoate oxide (PMPO). Copolymers of lactic acid and ε-caprolactone with PMPO were synthesized with up to 9 mol % alkyne content, and accessibility of the alkyne groups to the click reaction was demonstrated using several dyes commonly employed in fluorescence microscopy and imaging (Cy3, ATTO-740, and coumarin 343). In order to establish the suitability of these copolymers as nanocarriers, copolymers were formulated into NPs, and cytocompatibility, cellular uptake, and visualization studies undertaken in HeLa cells. Dye-modified NPs exhibited no quenching, remained stable in solution for at least 10 days, showed no cytotoxicity, and were readily taken up by HeLa cells. Furthermore, in addition to enabling the incorporation of multiple fluorophores within the same NP through blending of individual dye-modified copolymers, dye-modified polyesters offer advantages over physical entrapment of dye, including improved signal to noise ratio and localization of the fluorescence signal within cells, and possess the necessary prerequisites for drug delivery and imaging.

Control of hydration and degradation properties of triblock copolymers polycaprolactone‐b‐polydimethylsiloxane‐b‐polycaprolactone

ABSTRACTThe objectives of this study are to observe the effects of the introduction of polydimethylsiloxane (PDMS) on the hydration and degradation of aliphatic polyesters in water, such as poly(ε‐caprolactone) (PCL). The mechanism of PCL degradation in water is well known, and PDMS is a nonbiodegradable and hydrophobic polymer. The ligation of these two polymers should allow the synthesis of new polymers with hybrid properties in terms of degradation and surface energy. The deterioration in water should be controlled by the ratio of each polymer. The triblock copolymers were synthesized through ring opening polymerization with stannous octanoate as the catalyst. A film of each copolymer was prepared and immersed in distilled water to study their aging. Kinetic results of hydration and degradation show that the addition of PDMS on PCL does not change the profiles of hydration and degradation. But the variation of the structure of the triblock (molecular weight or ratio of each block) allows to increase or decrease the rate of hydration, so as to control its degradation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40431.

Integrin-mediated adhesion of human mesenchymal stem cells to extracellular matrix proteins adsorbed to polymer surfaces

In vitro, degradable aliphatic polyesters are widely used as cell carriers for bone tissue engineering, despite their lack of biological cues. Their biological active surface is rather determined by an adsorbed layer of proteins from the surrounding media. Initial cell fate, including adhesion and proliferation, which are key properties for efficient cell carriers, is determined by the adsorbed layer of proteins. Herein we have investigated the ability of human bone marrow derived stem cells (hBMSC) to adhere to extracellular matrix (ECM) proteins, including fibronectin and vitronectin which are present in plasma and serum. hBMSC expressed integrins for collagens, laminins, fibronectin and vitronectin. Accordingly, hBMSC strongly adhered to these purified ECM proteins by using the corresponding integrins. Although purified fibronectin and vitronectin adsorbed to aliphatic polyesters to a lower extent than to cell culture polystyrene, these low levels were sufficient to mediate adhesion of hBMSC. It was found that plasma- and serum-coated polystyrene adsorbed significant levels of both fibronectin and vitronectin, and fibronectin was identified as the major adhesive component of plasma for hBMSC; however, aliphatic polyesters adsorbed minimal levels of fibronectin under similar conditions resulting in impaired cell adhesion. Altogether, the results suggest that the efficiency of aliphatic polyesters cell carriers could be improved by increasing their ability to adsorb fibronectin.

“Clip” and “Click” Chemistries Combination: Toward Easy PEGylation of Degradable Aliphatic Polyesters

α-Methoxy-ω-alkyne poly(ethylene glycol) (PEG) was tagged with pendent N-hydroxy-succinimidyl activated esters by photografting of a molecular clip. This easily synthesized heterofunctional PEG was found to be a versatile building block for (i) conjugation with an amino derivative and (ii) grafting to azido functional aliphatic polyesters backbone by Huisgen's 1,3-dipolar cycloaddition. This original combination of "clip" and "click" reactions provides a versatile and straightforward pathway for the synthesis of functional amphiphilic and degradable copolymers valuable for biomedical applications such as in drug-delivery.

Degradation of Aliphatic Polyesters in the Presence of Inorganic Fillers

Aliphatic polyesters are melt mixed with bioactive fillers and converted into sheets in order to compare their degradation behavior in a phosphate buffer saline (PBS) solution as a function of processing method, polymer type, and crystallinity and type of filler. The samples are tested for weight changes, pH, intrinsic viscosity (IV), and thermal and mechanical property changes as a function of time. The study establishes that although the fillers appear to enhance the polymer degradation, they also have an effect on crystallinity after several immersion periods. Intrinsic viscosity measurements show degradation in the form of molecular weight reduction even after short periods of immersion.

Degradation of Aliphatic Polyesters by Vacuum Ultraviolet Irradiation

The photon energy of vacuum ultraviolet (VUV) light is higher than the binding energy of some chemical bonds in organic molecules, such as C–C, C–H, or C–O. Therefore, VUV light is able to cause the scission of various bonds in polymer molecules, which can lead to the decomposition of the polymeric molecules. Degradation of polymers by VUV has been studied with the purpose of investigating damage to polymeric materials by VUV, developing new photoresist materials, revealing the degradation mechanism, and modifying polymer surfaces, etc. The degradation mechanism of poly(methyl methacrylate) (PMMA) has been extensively studied for evaluation as a new photoresist material. It was found that the side chain ester group is decomposed by VUV irradiation, leading to a polymer containing carboncarbon double bonds. In addition, scission of the main chain also occurred. If an ester group is easily cleaved by VUV, it may be expected that aliphatic polyesters, which contain ester groups in the main chain, will be degraded to small volatile molecules and may function as good photoresist materials. Aliphatic polyesters are soluble in common organic solvents, which enables good thin films to be easily formed. It is well known that aliphatic polyesters are easily degraded by biological reactions, and although many studies have been performed regarding the biodegradation of aliphatic polyesters, only a few studies have investigated degradation by irradiation with UV or VUV light. In this report, the degradation of aliphatic polyesters by VUV was investigated and compared with that of PMMA. The study concentrated on the reaction mechanism, the effect of oxygen and application of an external electric field during irradiation. EXPERIMENTAL

Growth of various cell types in the presence of lactic and glycolic acids: the adverse effect of glycolic acid released from PLAGA copolymer on keratinocyte proliferation

Poly(α-hydroxy-acid)s derived from lactic acid (LA) and glycolic acid (GA) are bioresorbable polymers that are currently used in human surgery and in pharmacology to make temporary therapeutic devices. Nowadays, increasing attention is paid to these polymers in the field of tissue engineering. However, the literature shows that a large number of factors can affect many of their properties and the responses of biological systems. As part of our investigation of the biocompatibility of degradable aliphatic polyesters, the effects of LA and GA on the proliferation of various cells under in vitro cell culture conditions were studied. The release of LA and GA from films made of a copolymer synthesized by the zinc lactate method and composed of 37.5% L-lactyl, 37.5% D-lactyl, and 25% glycolyl repeating units was first investigated over a period of 30 days under abiotic conditions in a cell culture medium in order to identify a range of acid concentrations consistent with releases to be expected in real cell cultures. Four cell lines, namely 3T3-J2, C3H101/2, A431, and HaCat, and three primary cell cultures, namely rat endothelial cells, rat smooth muscle cells, and human dermal fibroblasts, were then allowed to grow in the presence of LA and GA at various concentrations taken within the selected 10–1000 mg/cm3 range. Little or no effect was observed on the proliferation of all cells except human keratinocytes, whose growth was dramatically inhibited by GA at concentrations as low as 10 mg/cm3. The inhibiting effect of GA was confirmed by considering the growth of keratinocytes on films made of the same copolymer, in comparison with poly(DL-lactic acid) and polystyrene taken as references. This work shows that GA-releasing degradable matrices are not adapted to the culture of keratinocytes with the aim of making skin grafts.

Environmental degradation of biodegradable polyesters 2. Poly( ε-caprolactone), poly[(R)-3-hydroxybutyrate], and poly(L-lactide) films in natural dynamic seawater

The (bio)degradation of aliphatic polyesters, poly( ε-caprolactone) (PCL), poly[(R)-3-hydroxybutyrate] (R-PHB), and poly(L-lactide) (PLLA) films in natural dynamic seawater was investigated using polarizing optical microscopy, gravimetry, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and tensile testing. The results were compared with those reported for the polyester films biodegraded in the controlled static seawater to reveal the physical effects in the natural dynamic seawater on the degradation of the aliphatic polyesters. The gravimetry and tensile testing showed that the mechanical stresses and strains in the natural dynamic seawater caused mechanical destruction or degradation of the films, resulting in seemingly accelerated (bio)degradation of all the films compared with that in the controlled static seawater. Such mechanical acceleration effects in the natural dynamic seawater were higher for the R-PHB and PLLA films with relatively high T g than for the PCL films with relatively low T g, when their (bio)degradation was monitored by gravimetry. The polarizing microscopy showed that the R-PHB films were (bio)degraded predominantly at the centers of and between the spherulites. The tensile strength and Young's modulus were lower for the initially crystallized PLLA films than for the initially amorphous PLLA films when compared at the same degradation time.

Capillary zone electrophoresis to study the hydrolytic degradation of a novel gluconic/glycolic/lactic acid copolymer

A typical member of the novel family of hydrolytically degradable aliphatic polyesters resulting from the copolymerisation of (3-(1,2-3,4-tetraoxobutyl-diisopropylidene)-dioxane-2,5-dione) (DIPAGYL) and racemic lactide under powder form was allowed to degrade in phosphate buffer saline at 55°C. Capillary zone electrophoresis was used to monitor the water-soluble derivatives present in the ageing medium. Indirect UV detection using p-anisate as the absorbing anion was described and the conditions to achieve quantitative determination were defined. The method was applied to monitor the fate of a couple of dimeric intermediates, namely lactyllactate and gluconylglycolate and glycolylgluconate. The method can also be used to evaluate the total amount of released compounds, despite the fact that higher water-soluble oligomers could not be detected because of a too short lifetime. Last but not least, it was proved that the copolymer did return to its ultimate building blocks, namely gluconic, glycolic and lactic acids.

Synthesis and Enzymatic Degradation of Aliphatic Polyesters Copolymerized with Trimesic Acid

Network copolyesters were made from adipic acid and ethylene glycol with 10–40 mol% trimesic acid (Y). Prepolymers prepared by melt polycondensation were cast from dimethylformamide solution and postpolymerized at 260°C for various times to form a network. The degree of reaction (D R), estimated from the infrared absorbance of hydroxyl and methylene groups, increased with increasing postpolymerization time and leveled out at about 90% after 4–6 hours. Heat distortion temperatures (T h) measured by thermomechanical analysis increased greatly from −83 to 48°C upon the incorporation of Y. Wide-angle x-ray diffraction patterns showed that the copolymer films are amorphous. Density, tensile strength, and Young's modulus decreased for the copolymers with 10–30 mol% Y, whereas they increased drastically for the copolymer with 40 mol% Y. The enzymatic degradation was estimated by the weight loss of the copolymer films in buffer solutions with a lipase at 37°C. The weight loss decreased remarkably with increasing Y and showed no weight loss for the copolymer with 40 mol% Y. On the other hand, the weight loss by alkali hydrolysis increased for the copolymers with 10 and 20 mol% Y, implying a difference in the degradation mechanism between enzymatic degradation and alkali hydrolysis.

Hydrolytic Degradation of Aliphatic Polyesters Copolymerized with Polyethylene glycols

Hydrolytic Degradation of Aliphatic Polyesters Copolymerized with Polyethylene glycols