Matteo Gigli

Influence of chemical and architectural modifications on the enzymatic hydrolysis of poly(butylene succinate)

Copolymers of poly(butylene succinate) (PBS) containing diethylene succinate sequences (PBSPDGS) with different molecular architectures were prepared via reactive blending in the presence of a Ti-based catalyst. In particular, a block copolymer with long sequences and a random one with very short sequences were synthesized, characterized and investigated in terms of enzymatic biodegradability. For comparison, the parent homopolymer PBS has been also prepared by the usual two-stage melt polycondensation. Preliminary biodegradation tests based on the highly sensitive film opacity assay indicated that lipase from Candida cylindracea was the most effective among four different commercially available lipases (e.g., those from Candida rugosa, Candida cylindracea, Aspergillus niveus and hog pancreas) and a serine protease (α-chymotrypsin from bovine pancreas), and that optimal test conditions were 50 enzyme U mL−1, 30 °C and pH 7.0. Under such conditions, copolymers degraded to a much higher extent as compared to PBS. Moreover, the random copolymer degraded 100 times faster than the block one. ATRIR analysis and DSC measurements indicated that the enzyme attacked the amorphous phase first. Further, NMR analysis indicated that enzyme hydrolysis involved preferentially ester groups of DGS sequences, more hydrophilic than the others. These findings confirm previous evidence on the correlation between polymers biodegradation rate and their hydrophilic and amorphous degree. More importantly, they indicate (i) that dramatic increases in polyesters biodegradability can be obtained by introducing ether-oxygen atoms into the polymer chain and (ii) that biodegradability of oxygen etheroatom-containing copolyesters might be tuned within a wide range of rates through the modification of their molecular architecture.

Tailoring chemical and physical properties of fibrous scaffolds from block copolyesters containing ether and thio-ether linkages for skeletal differentiation of human mesenchymal stromal cells

Bioactive scaffolds for tissue engineering call for demands on new materials which can enhance traditional biocompatibility requirements previously considered for clinical implantation. The current commercially available thermoplastic materials, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(ε-caprolactone) (PCL) and their copolymers, have been used to fabricate scaffolds for regenerative medicine. However, these polymers have limitations including lacking of broadly tuning mechanical and degradable properties, and activation of specific cell-scaffold interactions, which limit their further application in tissue engineering. In the present study, electrospun scaffolds were successfully fabricated from a new class of block poly(butylene succinate)-based (PBS-based) copolyesters containing either butylene thiodiglycolate (BTDG) or butylene diglycolate (BDG) sequences. The polyesters displayed tunable mechanical properties and hydrolysis rate depending on the molecular architecture and on the kind of heteroatom introduced along the polymer backbone. To investigate their potential for skeletal regeneration, human mesenchymal stromal cells (hMSCs) were cultured on the scaffolds in basic, osteogenic and chondrogenic media. Our results demonstrated that PBS-based copolyesters containing thio-ether linkages (i.e. BTDG segments) were more favorable for chondrogenesis of hMSCs than those containing ether linkages (i.e. BDG sequences). In contrast, PBS-based copolyesters containing ether linkages showed enhanced mineralization. Therefore, these new functional scaffolds might hold potential for osteochondral tissue engineering applications.

Gas permeability, mechanical behaviour and compostability of fully-aliphatic bio-based multiblock poly(ester urethane)s

A family of poly(ester urethane)s obtained by chain extending hydroxyl-terminated polyester prepolymers has been studied. Poly(butylene cyclohexanedicarboxylate) has been coupled in different mass ratios with two poly(butylene succinate)-based random copolymers containing ether linkages. So, five high molecular weight bio-based poly(ester urethane)s have been designed. The effect of the chemical structure and of the mass ratio of the two blocks in the final polymer has been evaluated by characterizing the materials from a molecular, thermal and mechanical point of view. In addition, envisioning a food packaging application, biodegradation in compost and measurement of the gas barrier properties have been carried out and correlated to the polymer chemical structure. The activation energy of the gas permeation process has been calculated, too. The results highlight that through the adopted strategy it is possible to prepare a new class of promising materials whose properties can be easily tailored by acting on two parameters: the mass ratio between the two prepolymers in the final material and the chemical structure of each block.

Biocompatible multiblock aliphatic polyesters containing ether-linkages: influence of molecular architecture on solid-state properties and hydrolysis rate

In this study, we propose a new class of multiblock copolyesters containing butylene 1,4-cyclohexanedicarboxylate (BCE) and diethylene glycol 1,4-cyclohexanedicarboxylate (DGCE) sequences. The two parent homopolymers were prepared by the usual two-stage melt polycondensation. On the other hand, the multiblock copolyesters, characterized by the same chemical composition but different block lengths, were synthesized by reactive blending. Physicochemical characterization (DSC, WAXS, tensile tests, WCA, hydrolysis experiments) demonstrated that the block length controls the polymer crystallinity, the thermal and mechanical properties, the wettability and the degradation rate. The copolymers displayed different stiffnesses, mainly depending on the crystallinity degree and macromolecular chain flexibility, a tunable range of degradation rates, and different surface hydrophilicity. Biocompatibility assays showed the absence of potentially cytotoxic products released into the culture medium by the investigated samples, and demonstrated that our substrates support a physical environment where cells can adhere and proliferate, confirming their potential for biomedical applications.

Processing and characterization of nanocomposite based on poly(butylene/triethylene succinate) copolymers and cellulose nanocrystals

A new class of biodegradable materials developed by a combination of random eco-friendly copolyesters containing butylene succinate (BS) and triethylene succinate (TES) sequences with cellulose nanocrystals (CNC), is proposed and studied. Polymers and nanocomposite films were prepared by an optimized extrusion process to improve the processability and mechanical response for flexible film manufacturing. Poly(butylene succinate) (PBS) homopolymer and two random copolyesters containing different amounts of TES co-units, P(BS85TES15) and P(BS70TES30), were synthesized by melt polycondensation. The effect of TES and CNC presence and content on the microstructure, tensile properties, thermal characteristics and disintegration under composting conditions, as well as on the toughening mechanism of the blends was investigated. Material properties were modulated by varying the chemical composition. CNC were used as reinforcement additive and their effect is modulated by the interaction with the three polymeric matrices. The extruded films displayed tunable degradation rates, mechanical properties and wettability, and showed promising results for different industrial applications.

Structural Investigation of Poly(ethylene furanoate) Polymorphs

α and β crystalline phases of poly(ethylene furanoate) (PEF) were determined using X-ray powder diffraction by structure resolution in direct space and Rietveld refinement. Moreover, the α’ structure of a PEF sample was refined from data previously reported for PEF fiber. Triclinic α-PEF a = 5.729 Å, b = 7.89 Å, c = 9.62 Å, α = 98.1°, β = 65.1°, γ = 101.3°; monoclinic α’-PEF a = 5.912 Å, b = 6.91 Å, c = 19.73 Å, α = 90°, β = 90°, γ = 104.41°; and monoclinic β-PEF a = 5.953 Å, b = 6.60 Å, c = 10.52 Å, α = 90°, β = 107.0°, γ = 90° were determined as the best fitting of X-ray diffraction (XRD) powder patterns. Final atomic coordinates are reported for all polymorphs. In all cases PEF chains adopted an almost planar configuration.

Influence of the nanofiber chemistry and orientation of biodegradable poly(butylene succinate)-based scaffolds on osteoblast differentiation for bone tissue regeneration

Innovative nanofibrous scaffolds have attracted considerable attention in bone tissue engineering, due to their ability to mimic the hierarchical architecture of an extracellular matrix. Aiming at investigating how the polymer chemistry and fiber orientation of electrospun scaffolds (ES) based on poly(butylene succinate) (PBS) and poly(butylene succinate/diglycolate) (P(BS80BDG20)) affect human osteoblast differentiation, uniaxially aligned (a-) and randomly (r-) distributed nanofibers were produced. Although human osteoblastic SAOS-2 cells were shown to be viable and adherent onto all ES materials, a-P(BS80BDG20) exhibited the best performance both in terms of cellular phosphorylated focal adhesion kinase expression and in terms of alkaline phosphatase activity, calcified bone matrix deposition and quantitative gene expression of bone specific markers during differentiation. It has been hypothesized that the presence of ether linkages may lead to an increased density of hydrogen bond acceptors along the P(BS80BDG20) backbone, which, by interacting with cell membrane components, can in turn promote a better cell attachment on the copolymer mats with respect to the PBS homopolymer. Furthermore, although displaying the same chemical structure, r-P(BS80BDG20) scaffolds showed a reduced cell attachment and osteogenic differentiation in comparison with a-P(BS80BDG20), evidencing the importance of nanofiber alignment. Thus, the coupled action of polymer chemical structure and nanofiber alignment played a significant role in promoting the biological interaction.

Gas Barrier and Thermal Behavior of Long Chain Aliphatic Polyesters after Stressed Treatments

ABSTRACT Poly(hexane dodecanoate)-based random copolyesters containing ether linkages have been subjected to contact with food simulant liquids and thermal and photoageing. Gas permeability, thermal and mechanical properties have been analyzed after each treatment, and the results obtained have been compared with low-density polyethylene films. The results showed that the gas barrier behavior was highly influenced by the polymer chemical composition. The contact with simulant liquids and the ageing treatments induced an increase in the crystallinity degree, together with a decrease in the molecular weight. This caused an increment of the elastic modulus and a decrement of the elongation at break. GRAPHICAL ABSTRACT

Characterization of Active Edible Films based on Citral Essential Oil, Alginate and Pectin

Thermal, structural and physico-chemical properties of different composite edible films based on alginate and pectin with the addition of citral essential oil (citral EO) as an agent to improve barrier properties, were investigated. The obtained films were clear and transparent, with a yellow hue that increased with citral EO addition. All the films displayed good thermal stability up to 160 °C, with a slight improvement observed by increasing the amount of citral EO in the composites. Gas transmission rate (GTR) strongly depended on the polymer structure, gas type and temperature, with improvement in barrier performance for composite samples. Also, citral EO did not exert any weakening action on the tensile behavior. On the contrary, an increase of the elastic modulus and of the tensile strength was observed. Lastly, water contact angle measurements demonstrated the dependence of the film wettability on the content of citral EO.

Ether-Oxygen Containing Electrospun Microfibrous and Sub-Microfibrous Scaffolds Based on Poly(butylene 1,4-cyclohexanedicarboxylate) for Skeletal Muscle Tissue Engineering

We report the study of novel biodegradable electrospun scaffolds from poly(butylene 1,4-cyclohexandicarboxylate-co-triethylene cyclohexanedicarboxylate) (P(BCE-co-TECE)) as support for in vitro and in vivo muscle tissue regeneration. We demonstrate that chemical composition, i.e., the amount of TECE co-units (constituted of polyethylene glycol-like moieties), and fibre morphology, i.e., aligned microfibrous or sub-microfibrous scaffolds, are crucial in determining the material biocompatibility. Indeed, the presence of ether linkages influences surface wettability, mechanical properties, hydrolytic degradation rate, and density of cell anchoring points of the studied materials. On the other hand, electrospun scaffolds improve cell adhesion, proliferation, and differentiation by favouring cell alignment along fibre direction (fibre morphology), also allowing for better cell infiltration and oxygen and nutrient diffusion (fibre size). Overall, C2C12 myogenic cells highly differentiated into mature myotubes when cultured on microfibres realised with the copolymer richest in TECE co-units (micro-P73 mat). Lastly, when transplanted in the tibialis anterior muscles of healthy, injured, or dystrophic mice, micro-P73 mat appeared highly vascularised, colonised by murine cells and perfectly integrated with host muscles, thus confirming the suitability of P(BCE-co-TECE) scaffolds as substrates for skeletal muscle tissue engineering.