Biodegradable aliphatic polyesters such as poly(lactide) and poly(ε-caprolactone), largely used in tissue engineering applications, lack suitable functional groups and biological cues to enable interactions with cells. Because of the ubiquity of thiol groups in the biological environment and the pliability of thiol chemistry, we aimed to design and synthesize poly(ester) chains bearing pendant thiol-protected groups. To achieve this, 3-methyl-6-(tritylthiomethyl)-1,4-dioxane-2,5-dione, a lactide-type monomer possessing a pendant thiol-protected group, was synthesized. This molecule, when used as a monomer in controlled ring-opening polymerization in combination with lactide and ε-caprolactone, appeared to be a convenient "building block" for the preparation of functionalized aliphatic copolyesters, which were easily modified further. A polymeric sample bearing pyridyl disulfide groups, able to bind a cysteine-containing peptide, was efficiently obtained from a two-step modification reaction. Porous scaffolds were then prepared by blending this latter copolymer sample with poly(L-lactide-co-ε-caprolactone) followed by salt leaching. A further disulfide exchange reaction performed in aqueous medium formed porous scaffolds with covalently linked arginine-glycine-aspartic acid sequences. The scaffolds were characterized by thermal and mechanical tests, and scanning electron microscopy surface images revealed a highly porous morphology. Moreover, a cytotoxicity test indicated good cell viability.

The dimethylaluminum compounds Al(CH 3 ) 2 [(O-2-{(C 6 F 5 )NCH}-4,6-R 2 C 6 H 2 )], R = H (1) or cumyl (2), were synthesized and tested as initiators in the homo-and copolymerization of rac-lactide and glycolide. These complexes resulted active for the production of PLGA copolymers with variable microstructure. All the copolymers were fully characterized by NMR, GPC, and DSC analysis. The copolymerization reactions were performed in bulk and in solution, by varying comonomers ratio, monomer/catalyst feed ratio, temperature, reaction time, and solvent. Interestingly, by changing the reaction conditions, copolymers from random, to blocky, to diblock were obtained, demonstrating the effectiveness and versatility of such systems in modulating the copolymers microstructure and the related thermal properties.

The homo and co-polymerization of a large ring size lactone afforded unsaturated poly(esters), further modified to functional thermoplastic materials.

Various 3D printing techniques currently use degradable polymers such as aliphatic polyesters to create well-defined scaffolds. Even though degradable polymers are influenced by the printing process, and this subsequently affects the mechanical properties and degradation profile, degradation of the polymer during the process is not often considered. Degradable scaffolds are today printed and cell–material interactions evaluated without considering the fact that the polymer change while printing the scaffold. Our methodology herein was to vary the printing parameters such as temperature, pressure, and speed to define the relationship between printability, polymer microstructure, composition, degradation profile during the process, and rheological behavior. We used high molecular weight medical-grade (co)­polymers, poly­(l-lactide-co-ε-caprolactone) (PCLA), poly­(l-lactide-co-glycolide) (PLGA), and poly­(d,l-lactide-co-glycolide) (PDLGA), with l-lactide content ranging from 25 to 100 mol %, for printing in an extrusion-based printer (3D Bioplotter). Optical microscopy confirmed that the polymers were printable at high resolution and good speed, until a certain degree of degradation. The results show also that printability can not be claimed just by optimizing printing parameters and highlight the importance of a careful analysis of how the polymer’s structure and properties vary during printing. The polymers thermally decomposed from the first processing minute and caused a decrease in the average block length of the lactide blocks in the copolymers and generated lower crystallinity. Poly­(l-lactide) (PLLA) and PCLA are printable at a higher molecular weight, less degradation before printing was possible, compared to PLGA and PDLGA, a result explained by the higher complex viscosity and more elastic polymeric melt of the copolymer containing glycolide (GA) and lactide (LA). In more detail, copolymers comprised of LA and ε-caprolactone (CL) formed lower molecular weight compounds over the course of printing, while the PLGA copolymer was more susceptible to intermolecular transesterification reactions, which do not affect the overall molecular weight, but cause changes in the copolymer microstructure. This results in a longer printing time for PLGA than PLLA and PCLA.

Linear aliphatic polyesters are degradable thermoplastic polymers, which can be obtained by ring-opening polymerization (ROP) of cyclic esters through a coordination-insertion mechanism. Aluminum based organometallic complexes have a leading position as efficient catalysts for this polymerization process. Aluminumalkyl complexes bearing salicylaldiminato ligands, although less explored, have been shown to be efficient and versatile catalysts for the ROP of various cyclic esters. These species have the potential to function as active catalysts in the ROP because of their less coordinatively saturated nature with respect to analogous SALEN-type complexes. They have been used as efficient catalysts in the ROP of commercially available cyclic esters, such as ε-caprolactone, L-lactide, rac-lactide, and glycolide. Moreover, they resulted in efficient catalysts for the ROP of cyclic esters with large ring-size and for the ROP of functionalized lactide. Furthermore, they have been used in the co-and ter-polymerization of various cyclic esters affording well controlled polymerization and a plethora of microstructural architectures, ranging from random to block to multiblock.

We have developed a strategy for the preparation of redox-responsive PEG–PLA-based nanoparticles containing disulfide bonds that can be disassembled in the presence of cellular concentrations of glutathione. Functionalized poly­(lactide)­s were prepared by ring-opening copolymerization of l-lactide and 3-methyl-6-(tritylthio­methyl)-1,4-dioxane-2,5-dione, a monomer bearing a pendant trityl-thiol group, followed by the postpolymerization modification of trityl-thiol into pyridyl disulfide groups. Polymeric networks composed of PLA and PEG blocks linked by disulfide bonds were prepared by a disulfide exchange reaction between the functionalized PLAs and telechelic PEG having thiol groups at both ends, HS-PEG-SH, in DMF. When dialyzed against water, they assembled into dispersible nanoparticles, with a flowerlike structure having a hydrophobic core and a hydrophilic shell, with sizes in the range 167–300 nm that are suitable for drug delivery. The effects of the number of functional groups, molecular weight, and concentration on the nanoparticle size were evaluated. The stability of the nanoparticles after dilution and the redox-responsive behavior in the presence of different concentrations of glutathione were assessed. The hydrophobic molecule Nile red could be encapsulated in the nanoparticles and then released in the presence of glutathione at cellular concentration.

We have developed a straightforward strategy to obtain semicrystalline and random copolymers of εcaprolactone (CL) and p-dioxanone (DX) with thermal stabilities similar to poly(ε-caprolactone), PCL, but with a faster hydrolytic degradation rate. CL/DX copolymers are promising inks when printing scaffolds aimed for tissue engineering. Such copolymers behave similar to PCL and resorb faster. The copolymers were synthesized by bulk ringopening copolymerization, achieving a high yield; a molecular weight, M n , of 57−176 kg mol −1 ; and an inherent viscosity of 1.7−1.9 dL g −1 . The copolymer microstructure consisted of long CL blocks that are separated by isolated DX units. The block length and the melting point were a linear function of the DX content. The copolymers crystallize as an orthorhombic lattice that is typical for PCL, and they formed more elastic, softer, and less hydrophobic films with faster degradation rates than PCL. Relatively high thermal degradation temperatures (above 250 °C), similar to PCL, were estimated by thermogravimetric analysis, and copolymer filaments for three-dimensional printing and scaffolds were produced without thermal degradation.

The advancement of 3D printing technologies in the fabrication of degradable scaffolds for tissue engineering includes, from the standpoint of the polymer chemists, an urgent need to develop new materials that can be used as ink and are suitable for medical applications. Here, we demonstrate that a copolymer of ε-caprolactone (CL) with low amounts of p-dioxanone (DX) (15 mol %) is a degradable and printable material that suits the requirements of melt extrusion 3D printing technologies, including negligible degradation during thermal processing. It is therefore a potential candidate for soft tissue regeneration. The semicrystalline CL/DX copolymer is processed at a lower temperature than a commercial polycaprolactone (PCL), shaped as a filament for melt extrusion 3D printing and as porous and pliable scaffolds with a gradient design. Scaffolds have Young's modulus in the range of 60−80 MPa, values suitable for provision of structural support for damaged soft tissue such as breast tissue. SEM and confocal microscope indicate that the CL/DX copolymer scaffolds support adipose stem cell attachment, spreading, and proliferation.