Bioinspired Nanolayered Structure Tuned by Extensional Stress: A Scalable Way to High-Performance Biodegradable Polyesters.

The nacre-inspired multi-nanolayer structure offers a unique combination of advanced mechanical properties, such as strength and crack tolerance, making them highly versatile for various applications. Nevertheless, a significant challenge lies in the current fabrication methods, which is difficult to create a scalable manufacturing process with precise control of hierarchical structure. In this work, a novel strategy is presented to regulate nacre-like multi-nanolayer films with the balance mechanical properties of stiffness and toughness. By utilizing a co-continuous phase structure and an extensional stress field, the hierarchical nanolayers is successfully constructed with tunable sizes using a scalable processing technique. This strategic modification allows the robust phase to function as nacre-like platelets, while the soft phase acts as a ductile connection layer, resulting in exceptional comprehensive properties. The nanolayer-structured films demonstrate excellent isotropic properties, including a tensile strength of 113.5 MPa in the machine direction and 106.3 MPa in a transverse direction. More interestingly, these films unprecedentedly exhibit a remarkable puncture resistance at the same time, up to 324.8 N mm-1, surpassing the performance of other biodegradable films. The scalable fabrication strategy holds significant promise in designing advanced bioinspired materials for diverse applications.

Melt-spun polylactide/ethylene vinyl alcohol copolymer fiber.

Polylactide/ethylene vinyl alcohol copolymer (PLA/EVOH) blends and fibers with different weight ratios were prepared by melt blending, and two-step melt spinning, respectively. PLA and EVOH in PLA/EVOH blends were immiscible. When EVOH content was ≤60 %, EVOH with the average diameter of about 3 µm was dispersed in PLA matrix uniformly. The dual continuous phases could be observed in PLA/EVOH blend with 70 wt% EVOH. When the EVOH content was ≥80 %, the spherical PLA phase with the diameter of 0.25 to 1 µm was dispersed in EVOH matrix. The introduction of EVOH as nucleating agent could promote the crystallization of PLA. Both PLA and EVOH components in PLA/EVOH blends formed individual crystal phases. The viscosity of PLA/EVOH blend with 5 % EVOH was lower than that of neat PLA. The viscosity of PLA/EVOH blends with the EVOH content of ≥10 % was much higher than that of neat PLA, which showed obvious shear thinning behavior. With the increase of EVOH content, the shear thinning behavior became obvious and the critical shear rate decreased gradually. The drawn PLA/EVOH fibers with the tensile strength of ≥16 cN/tex exhibited good mechanical properties. In addition, the introduction of EVOH could improve the hydrophilicity of PLA fibers.

The Impacts of the Sterilization Method and the Electrospinning Conditions of Nanofibrous Biodegradable Layers on Their Degradation and Hemocompatibility Behavior.

The use of electrospun polymeric biodegradable materials for medical applications is becoming increasingly widespread. One of the most important parameters regarding the functionality of nanofiber scaffolds during implantation and the subsequent regeneration of damaged tissues concerns their stability and degradation behavior, both of which are influenced by a wide range of factors (the properties of the polymer and the polymer solution, the technological processing approach, the sterilization method, etc.). This study monitored the degradation of nanofibrous materials fabricated from degradable polyesters as a result of the sterilization method applied (ethylene oxide and gamma irradiation) and the solvent system used to prepare the spun polymer solution. Aliphatic polyesters PCL and PLCL were chosen for this study and selected with respect to the applicability and handling in the surgical setting of these nanofibrous materials for vascular bandaging. The results revealed that the choice of solvent system exerts a significant impact on degradation during sterilization, especially at higher gamma irradiation values. The subsequent enzyme-catalyzed degradation of the materials following sterilization indicated that the choice of the sterilization method influenced the degradation behavior of the materials. Whereas wave-like degradation was evident concerning ethylene oxide sterilization, no such behavior was observed following gamma-irradiation sterilization. With concern for some of the tested materials, the results also indicated the potential for influencing the development of degradation within the bulk versus degradation from the surface of the material. Both the sterilization method and the choice of the spinning solvent system were found to impact degradation, which was observed to be most accelerated in the case of PLCL (L-lactide-co-caprolactone copolymer) electrospun from organic acids and subsequently sterilized using gamma irradiation. Since we planned to use these materials in cardiovascular applications, it was decided that their hemocompatibility would also be tested. The results of these tests revealed that changes in the structures of the materials initiated by sterilization may exert thrombogenic and anticoagulant impacts. Moreover, the microscopic analysis suggested that the solvent system used in the preparation of the materials potentially affects the behavior of erythrocytes; however, no indication of the occurrence of hemolysis was detected.

Design strategy for blends of biodegradable polyester and thermoplastic starch based on a molecular dynamics study of the phase-separated interface.

Molecular insight into the phase-separated interface formed when biodegradable polyesters and thermoplastic starch (TPS) are melt-blended is valuable for the design of composites. In this study, eight different interfaces combining four major biodegradable polyesters (PLA, PBS, PHB and PBAT) and two TPSs [unmodified TPS (nTPS) and citrate-modified TPS (cTPS)] were investigated by using molecular dynamics (MD) simulations. According to the MD simulation results, PBS, PHB and PBAT diffuse readily into the TPS and form compatible interfaces, whereas PLA is less compatible with the TPS. The results of tensile simulations show that PBS and PBAT adhere well to TPS; in particular, PBS/cTPS and PBAT/cTPS exhibit high interfacial-fracture energy (G). Both PLA and PHB blended with TPS exhibit low G because PLA is less compatible with TPS and PHB and TPS have low electrostatic interaction. The reason for the high G of PBS/cTPS and PBAT/cTPS is thought to be a combination of three factors: (i) formation of a deep compatible interface, (ii) suppression of void growth by electrostatic interactions and (iii) absorption of strain energy by a change in the conformation of the molecular chains. These three interfacial adhesion mechanisms should be considered when designing biodegradable polyester/TPS blends with good mechanical properties.

Biodegradable polyester-based nano drug delivery system in cancer chemotherapy: a review of recent progress (2021-2023).

Cancer presents a formidable threat to human health, with the majority of cases currently lacking a complete cure. Frequently, chemotherapy drugs are required to impede its progression. However, these drugs frequently suffer from drawbacks such as poor selectivity, limited water solubility, low bioavailability, and a propensity for causing organ toxicity. Consequently, a concerted effort has been made to seek improved drug delivery systems. Nano-drug delivery systems based on biodegradable polyesters have emerged as a subject of widespread interest in this pursuit. Extensive research has demonstrated their potential for offering high bioavailability, effective encapsulation, controlled release, and minimal toxicity. Notably, poly (ε-caprolactone) (PCL), poly (lactic-co-glycolic acid) (PLGA), and polylactic acid (PLA) have gained prominence as the most widely utilized options as carriers of the nano drug delivery system. This paper comprehensively reviews recent research on these materials as nano-carriers for delivering chemotherapeutic drugs, summarizing their latest advancements, acknowledging their limitations, and forecasting future research directions.

Development of biodegradable nanogels for lipase accelerated drug release of 5-aminolevulinic acid.

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an important approach for the treatment of some skin diseases and cancers. A major defect of this approach is that it is difficult for 5-ALA to accumulate around lesions in deeper regions of tissue, resulting in poor conversion to the active fluorophore and photodynamic efficiencies. Because of their targeting and controlled release abilities, nanogel carriers could solve this problem. In this paper, nanogels were prepared by using micro-emulsion polymerization with various biodegradable polyester crosslinkers (L-lactide and ε-caprolactone). The swelling and degradation properties and entrapment efficiency, drug loading and drug release ability of the nanogels were investigated. Nanogels co-cultured with skin cancer cells (A2058) allowed the efficiency of the PDT in vitro to be demonstrated. The results showed that the swelling rate of hydrogels reduced with increasing crosslinker levels, which caused a slow-down in the release of 5-ALA, but lipase accelerated degradation of nanogels increased 5-ALA concentrations in tumor cells and leading to higher PDT efficiency. It was proved by in vivo experiment indicating that the development of skin cancer tissues were efficiently inhibited by the 5-ALA loaded nanogels.

The effect of polyethylene glycol sorbitan monostearate on the morphological characteristics and performance of thermoplastic starch/biodegradable polyester blend films.

Although thermoplastic starch (TPS) has been developed to mitigate greenhouse gas emissions and environmental and health-related impacts from plastics, high moisture sensitivity and poor mechanical properties limited its practical applications. Blending TPS with biodegradable polyesters, i.e., poly(lactic acid) (PLA) and poly(butylene succinate-co-butylene adipate) (PBSA), is an alternative approach; however, the compatibility among polymer phases needs to be improved. Here, polyethylene glycol sorbitan monostearate (Tween 60), an amphiphilic surfactant, was proposed to improve the compatibility and performance of the TPS/PLA/PBSA 40/30/30 blend. The concentration of Tween 60 varied in the range of 0.5-2.5 wt%. The blends were fabricated using an extruder through two different melt-mixing routes, i.e., direct mixing and masterbatch mixing, and then converted to film using a blown film extrusion line. Tween 60 could improve compatibility between TPS dispersed phase and PLA/PBSA matrix, resulting in increased tensile strength, extensibility, impact strength, thermal stability, and water vapor and oxygen barrier properties of the ternary blend. In addition, better performance of the blend was obtained from the direct mixing route. Tween 60 could thus be considered a potential compatibilizer for the TPS/PLA/PBSA blend film, which can be further used as a biodegradable packaging material.

Synthesis of Biodegradable Polyester-Polyether with Enhanced Hydrophilicity, Thermal Stability, Toughness, and Degradation Rate.

Novel poly(butylene succinate-butylene furandicarboxylate/polyethylene glycol succinate) (PBSF-PEG) was synthesized using two-step transesterification and polycondensation in the melt. There are characterized by intrinsic viscosity, GPC, 1H NMR, DSC, TGA, tensile, water absorption tests, and water degradation at different pH. GPC analysis showed that PBSF-PEG had high molecular weight with average molecular weight (Mw) up to 13.68 × 104 g/mol. Tensile tests showed that these polymers possessed good mechanical properties with a tensile strength as high as 30 MPa and elongation at break reaching 1500%. It should be noted that the increase of PEG units improved the toughness of the polyester material. In addition, the introduction of PEG promoted the water degradation properties of PBSF, and the copolymer showed a significantly faster water degradation rate when the PEG unit content was 20%. This suggests that the amount of PEG introduced could be applied to regulate the water degradation rate of the copolymers. Hence, these new polymers have great potential for application as environmentally friendly and sustainable plastic packaging materials.

Maleic Anhydride-Grafted PLA Preparation and Characteristics of Compatibilized PLA/PBSeT Blend Films.

Poly(butylene sebacate-co-terephthalate) (PBSeT) is a biodegradable flexible polymer suitable for melt blending with other biodegradable polymers. Melt blending with a compatibilizer is a common strategy for increasing miscibility between polymers. In this study, PBSeT polyester was synthesized, and poly(lactic acid) (PLA) was blended with 25 wt% PBSeT by melt processing with 3-6 phr PLA-grafted maleic anhydride (PLA-g-MAH) compatibilizers. PLA-g-MAH enhanced the interfacial adhesion of the PLA/PBSeT blend, and their mechanical and morphological properties confirmed that the miscibility also increased. Adding more than 6 phr of PLA-g-MAH significantly improved the mechanical properties and accelerated the cold crystallization of the PLA/PBSeT blends. Furthermore, the thermal stabilities of the blends with PLA-g-MAH were slightly enhanced. PLA/PBSeT blends with and without PLA-g-MAH were not significantly different after 120 h, whereas all blends showed a more facilitated hydrolytic degradation rate than neat PLA. These findings indicate that PLA-g-MAH effectively improves PLA/PBSeT compatibility and can be applied in the packaging industry.

Evaluation and Characterization of Ultrathin Poly(3-hydroxybutyrate) Fibers Loaded with Tetraphenylporphyrin and Its Complexes with Fe(III) and Sn(IV).

The effect of small additions (1-5 wt.%) of tetraphenylporphyrin (TPP) and its complexes with Fe (III) and Sn (IV) on the structure and properties of ultrathin fibers based on poly(3-hydroxybutyrate) (PHB) has been studied. A comprehensive study of biopolymer compositions included X-ray diffraction (XRD), differential scanning calorimetry (DSC), spin probe electron paramagnetic resonance method (EPR), and scanning electron microscopy (SEM). It was demonstrated that the addition of these dopants to the PHB fibers modifies their morphology, crystallinity and segmental dynamics in the amorphous regions. The annealing at 140 °C affects crystallinity and molecular mobility in the amorphous regions of the fibers, however the observed changes exhibit multidirectional behavior, depending on the type of porphyrin and its concentration in the fiber. Fibers exposure to an aqueous medium at 70 °C causes a nonlinear change in the enthalpy of melting and challenging nature of a change of the molecular dynamics.

Micropatterned Poly(D,L-Lactide-Co-Caprolactone) Conduits With KHI-Peptide and NGF Promote Peripheral Nerve Repair After Severe Traction Injury.

Severe traction injuries after stretch to peripheral nerves are common and challenging to repair. The nerve guidance conduits (NGCs) are promising in the regeneration and functional recovery after nerve injuries. To enhance the repair of severe nerve traction injuries, in this study KHIFSDDSSE (KHI) peptides were grafted on a porous and micropatterned poly(D,L-lactide-co-caprolactone) (PLCL) film (MPLCL), which was further loaded with a nerve growth factor (NGF). The adhesion number of Schwann cells (SCs), ratio of length/width (L/W), and percentage of elongated SCs were significantly higher in the MPLCL-peptide group and MPLCL-peptide-NGF group compared with those in the PLCL group in vitro. The electromyography (EMG) and morphological changes of the nerve after severe traction injury were improved significantly in the MPLCL-peptide group and MPLCL-peptide-NGF group compared with those in the PLCL group in vivo. Hence, the NGCs featured with both bioactive factors (KHI peptides and NGF) and physical topography (parallelly linear micropatterns) have synergistic effect on nerve reinnervation after severe traction injuries.

Poly(Glycerol Sebacate) in Biomedical Applications-A Review of the Recent Literature.

Poly(glycerol sebacate) (PGS) continues to attract attention for biomedical applications owing to its favorable combination of properties. Conventionally polymerized by a two-step polycondensation of glycerol and sebacic acid, variations of synthesis parameters, reactant concentrations or by specific chemical modifications, PGS materials can be obtained exhibiting a wide range of physicochemical, mechanical, and morphological properties for a variety of applications. PGS has been extensively used in tissue engineering (TE) of cardiovascular, nerve, cartilage, bone and corneal tissues. Applications of PGS based materials in drug delivery systems and wound healing are also well documented. Research and development in the field of PGS continue to progress, involving mainly the synthesis of modified structures using copolymers, hybrid, and composite materials. Moreover, the production of self-healing and electroactive materials has been introduced recently. After almost 20 years of research on PGS, previous publications have outlined its synthesis, modification, properties, and biomedical applications, however, a review paper covering the most recent developments in the field is lacking. The present review thus covers comprehensively literature of the last five years on PGS-based biomaterials and devices focusing on advanced modifications of PGS for applications in medicine and highlighting notable advances of PGS based systems in TE and drug delivery.

Synthesis, Characterization and Properties of Biodegradable Poly(Butylene Sebacate-Co-terephthalate).

In this study, poly(butylene sebacate-co-terephthalate) (PBSeT) was successfully synthesized using various ratios of sebacic acid (Se) and dimethyl terephthalate (DMT). The synthesized PBSeT showed a high molecular weight (Mw, 88,700-154,900 g/mol) and good elastomeric properties. In particular, the PBSeT64 (6:4 sebacic acid/dimethyl terephthalate mole ratio) sample showed an elongation at break value of over 1600%. However, further increasing the DMT content decreased the elongation properties but increased the tensile strength due to the inherent strength of the aromatic unit. The melting point and crystallization temperature were difficult to observe in PBSeT64, indicating that an amorphous copolyester was formed at this mole ratio. Interestingly, wide angle X-ray diffraction (WAXD) curves was shown in the cases of PBSeT46 and PBSeT64, neither the crystal peaks of PBSe nor those of poly(butylene terephthalate) (PBT) are observed, that is, PBSeT64 showed an amorphous form with low crystallinity. The Fourier-transform infrared (FT-IR) spectrum showed C-H peaks at around 2900 cm-1 that reduced as the DMT ratio was increased. Nuclear magnetic resonance (NMR) showed well-resolved peaks split by coupling with the sebacate and DMT moieties. These results highlight that elastomeric PBSeT with high molecular weight could be synthesized by applying DMT monomer and showed promising mechanical properties.

Synthesis and Properties of Bioresorbable Block Copolymers of l-Lactide, Glycolide, Butyl Succinate and Butyl Citrate.

The paper presents the course of synthesis and properties of a series of block copolymers intended for biomedical applications, mainly as a material for forming scaffolds for tissue engineering. These materials were obtained in the polymerization of l-lactide and copolymerization of l-lactide with glycolide carried out using a number of macroinitiators previously obtained in the reaction of polytransesterification of succinic diester, citric triester and 1,4-butanediol. NMR, FTIR and DSC were used to characterize the materials obtained; wettability and surface free energy were assessed too. Moreover, biological tests, i.e., viability and metabolic activity of MG-63 osteoblast-like cells in contact with synthesized polymers were performed. Properties of obtained block copolymers were controlled by the composition of the polymerization mixture and by the composition of the macroinitiator. The copolymers contained active side hydroxyl groups derived from citrate units present in the polymer chain. During the polymerization of L-lactide in the presence of polyesters with butylene citrate units in the chain, obtained products of the reaction held a fraction of highly branched copolymers with ultrahigh molecular weight. The reason for this observed phenomenon was strong intermolecular transesterification directed to lactidyl side chains, formed as a result of chain growth on hydroxyl groups related to the quaternary carbons of the citrate units. Based on the physicochemical properties and results of biological tests it was found that the most promising materials for scaffolds formation were poly(l-lactide-co-glycolide)-block-poly(butylene succinate-co-butylene citrate)s, especially those copolymers containing more than 60 mol % of lactidyl units.

Facile Preparation of Stereoblock PLA From Ring-Opening Polymerization of rac-Lactide by a Synergetic Binary Catalytic System Containing Ureas and Alkoxides.

Ring-opening polymerization (ROP) of cyclic esters/lactones by efficient catalysts is a powerful method for synthesis of biodegradable and biocompatible polyesters with well-defined structures. To develop catalytic systems that are fast, selective and controlled is a persistent effort of chemists. In this contribution, we report a binary urea/alkoxide catalytic system that could catalyze ROP of rac-LA in a fast (over 90% conversion within 1-2 min), stereoselective (P i up to 0.93) and controlled manner, indicated by narrow MW distributions, linear relationship between the monomer conversions and M ns, end-group fidelity, and chain extension experiments. Remarkably, the catalytic system described here is simple, easily prepared, and structurally tunable and thus has versatile catalytic performances.

Mechanisms of interaction of biodegradable polyester nanocapsules with non-phagocytic cells.

The interaction of polymer nanocapsules (NC) prepared from four biodegradable polyesters with variable polymer hydrophobicity (PCL, PLA, PLGA and PLA-PEG) was investigated in the non-phagocytic Vero, Caco-2 and HepG2 cell lines. The NC, labeled with the highly lipophilic fluorescent indocarbocyanine dye DIL, had very similar sizes (approx. 140 nm) and negative zeta-potentials. Asymmetric flow field-flow fractionation evidenced NC colloidal stability and negligible transfer of the dye to serum proteins in the incubation medium. The cytotoxicity of the NC was evaluated via MTT assay over a large polymer concentration range (1-1000 µg/mL) and time of exposure (2, 24 and 48 h). The NC were safe in vitro up to a concentration of approx. 100 µg/mL or higher, depending on the cell line and nature of the polymer. Vero cells were more sensitive to the NC, in particular NC of the more hydrophobic polymer. The cells were exposed to endocytosis inhibitors, incubated with NC, and the cell-associated fluorescence was quantified by spectrofluorometry. HepG2 cells presented a 1.5-2-fold higher endocytic capacity than Caco-2 and Vero cells. The main mechanism of NC uptake was caveolin-mediated endocytosis in HepG2 and Vero cells, and macropinocytosis in Caco-2 cells. Polymer hydrophobicity had an effect on the level of NC associated to HepG2 cells and to a lesser extent on the endocytosis mechanisms in Vero and Caco-2 cells. The NC uptake levels and endocytosis mechanisms differed significantly between cell lines tested.

Biosynthesis and Characteristics of Aromatic Polyhydroxyalkanoates.

Polyhydroxyalkanoates (PHAs) are polyesters synthesized by bacteria as a carbon and energy storage material. PHAs are characterized by thermoplasticity, biodegradability, and biocompatibility, and thus have attracted considerable attention for use in medical, agricultural, and marine applications. The properties of PHAs depend on the monomer composition and many types of PHA monomers have been reported. This review focuses on biosynthesized PHAs bearing aromatic groups as side chains. Aromatic PHAs show characteristics different from those of aliphatic PHAs. This review summarizes the types of aromatic PHAs and their characteristics, including their thermal and mechanical properties and degradation behavior. Furthermore, the effect of the introduction of an aromatic monomer on the glass transition temperature (Tg) of PHAs is discussed. The introduction of aromatic monomers into PHA chains is a promising method for improving the properties of PHAs, as the characteristics of aromatic PHAs differ from those of aliphatic PHAs.

Microwave-assisted facile fabrication of porous poly (glycerol sebacate) scaffolds.

The biodegradable elastomeric polyester poly(glycerol sebacate) (PGS) was developed for soft-tissue engineering. It has been used in various research applications such as wound healing, cartilage tissue engineering, and vascular grafting due to its biocompatibility and elastomeric properties. However conventional PGS manufacture is generally limited by the laborious reaction conditions needed for curing which requires elevated reaction temperatures, high vacuum and multi-day reaction times. In this study, we developed a microwave irradiation methodology to fabricate PGS scaffolds under milder conditions with curing times that are 8 times faster than conventional methods. In particular, we determined microwave reaction temperatures and times for maximum crosslinking of PGS elastomers, demonstrating that PGS is fully crosslinked using gradual heating up to 160 °C for 3 h. Porosity and mechanical properties of these microwave-cured PGS elastomers were shown to be similar to PGS elastomers fabricated by the conventional polycondensation method (150 °C under 30 Torr for 24 h). To move one step closer to clinical application, we also examined the biocompatibility of microwave-cured PGS using in vitro cell viability assays with primary baboon arterial smooth muscle cells (SMCs). These combined results show microwave curing of PGS is a viable alternative to conventional curing.

Synthesis of E7 peptide-modified biodegradable polyester with the improving affinity to mesenchymal stem cells.

As the most promising stem cell, bone marrow-derived mesenchymal stem cells (BMSCs) has attracted many attentions and applied widely in regenerative medicine. A biodegradable polyester with tunable affinity to BMSCs plays critical role in determining the properties of the BMSCs-based constructs. In this study, maleimide functionalized biodegradable polyester (P(MTMC-LA)) was synthesized through ring-opening copolymerization between l-lactide (LA) and furan-maleimide functionalized trimethylene carbonate (FMTMC) and a subsequent retro Diels-Alder reaction. P(MTMC-LA) was modified by different amounts of BMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry to investigate the effect on BMSCs. The E7 peptide modified P(MTMC-LA) was casted into films on glass slides and BMSCs were seeded onto the films. In vitro study showed that E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation compared to unmodified P(MTMC-LA) film. Besides, the adhesion and proliferation were enhanced by the increasing peptide grafting ratio. These results indicated that the novel biodegradable polyester can serve as a biomaterial with great potential application in tissue engineering and regenerative medicine.