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The clever one‐pot combination of two macromolecular concepts, ring‐opening polymerization (ROP) and step‐growth polymerization (SGP), is demonstrated to be a simple, yet powerful tool to design a library of sequence‐controlled polymers with diverse and spatially regulated degradability functions. ROP and SGP occur sequentially at room temperature when the organocatalytic conditions are switched from basic to acidic, and each allows the encoding of specific degradable bonds. ROP controls the sequence length and position of the degradability functions, while SGP between the complementary vinyl ether and hydroxyl chain‐ends enables the formation of acetal bonds and high‐molar‐mass copolymers. The result is the rational combination of cleavable bonds prone to either bulk or surface erosion within the same macromolecule. The strategy is versatile and offers higher chemical diversity and level of control over the primary structure than current aliphatic polyesters or polycarbonates, while being simple, effective, and atom‐economical and having potential for scalability., A dual polymerization approach creates new possibilities to access polymeric materials with sequence‐controlled primary structure and diverse degradable bonds. The methodology is overall simple and effective and involves an in situ organocatalyst switch, which leads to different polymerization mechanisms, and as a consequence, specific degradability functions are encoded.

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 e-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.

We have developed a straightforward strategy to obtain semicrystalline and random copolymers of e-caprolactone (CL) and p-dioxanone (DX) with thermal stabilities similar to poly(e-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 ring-opening copolymerization, achieving a high yield; a molecular weight, Mn, 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.

We consider optimal sensor scheduling with unknown communication channel statistics. We formulate two types of scheduling problems with the communication rate being a soft or hard constraint, respe ...

Aliphatic polyesters are the synthetic polymers most commonly used in the development of resorbable medical implants/devices. Various three-dimensional (3D) scaffolds have been fabricated from these polymers and used in adipose tissue engineering. However, their systematic evaluation altogether lacks, which makes it difficult to select a suitable degradable polymer to design 3D resorbable implants and/or devices able to effectively mimic the properties of adipose tissue. Additionally, the impact of sterilization methods on the medical devices, if any, must be taken into account. We evaluate and compare five different medical-grade resorbable polyesters with l-lactide content ranging from 50 to 100 mol% and exhibiting different physiochemical properties depending on the comonomer (d-lactide, ε-caprolactone, glycolide, and trimethylene carbonate). The salt-leaching technique was used to prepare 3D microporous scaffolds. A comprehensive assessment of physical, chemical, and mechanical properties of the scaffolds was carried out in PBS at 37 °C. The cell-material interactions and the ability of the scaffolds to promote adipogenesis of human adipose tissue-derived stem cells were assessed in vitro. The diverse physical and mechanical properties of the scaffolds, due to the different composition of the copolymers, influenced human adipose tissue-derived stem cells proliferation and differentiation. Scaffolds made from polymers which were above their glass transition temperature and with low degree of crystallinity showed better proliferation and adipogenic differentiation of stem cells. The effect of sterilization techniques (electron beam and ethylene oxide) on the polymer properties was also evaluated. Results showed that scaffolds sterilized with the ethylene oxide method better retained their physical and chemical properties. Overall, the presented research provides (i) a detailed understanding to select a degradable polymer that has relevant properties to augment adipose tissue regeneration and can be further used to fabricate medical devices/implants; (ii) directions to prefer a sterilization method that does not change polymer properties. publishedVersion

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-e-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 e-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.

Polyester-based scaffolds covalently functionalized with arginine-glycine-aspartic acid-cysteine (RGDC) peptide sequences support the proliferation and osteogenic differentiation of stem cells. The aim is to create an optimized 3D niche to sustain human bone marrow stem cell (hBMSC) viability and osteogenic commitment, without reliance on differentiation media. Scaffolds consisting of poly(lactide-co-trimethylene carbonate), poly(LA-co-TMC), and functionalized poly(lactide) copolymers with pendant thiol groups are prepared by salt-leaching technique. The availability of functional groups on scaffold surfaces allows for an easy and straightforward method to covalently attach RGDC peptide motifs without affecting the polymerization degree. The strategy enables the chemical binding of bioactive motifs on the surfaces of 3D scaffolds and avoids conventional methods that require harsh conditions. Gene and protein levels and mineral deposition indicate the osteogenic commitment of hBMSC cultured on the RGDC functionalized surfaces. The osteogenic commitment of hBMSC is enhanced on functionalized surfaces compared with nonfunctionalized surfaces and without supplementing media with osteogenic factors. Poly(LA-co-TMC) scaffolds have potential as scaffolds for osteoblast culture and bone grafts. Furthermore, these results contribute to the development of biomimetic materials and allow a deeper comprehension of the importance of RGD peptides on stem cell transition toward osteoblastic lineage.

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. QC 20160518

We have designed photocurable, telechelic macromonomers consisting of random oligo(e-caprolactone-co-p-dioxanone), oligo(CL-co-DX), and demonstrated their suitability for preparing pliable polyester networks whose properties resemble those of gels. A versatile and effective metal-free co-oligomerization, catalyzed by diphenyl phosphate, was developed in bulk and at room temperature. A high rate of conversion of monomers was achieved and oligo(CL-co-DX)s with different composition and topology were obtained with controlled molar mass, approx. 2000 g mol−1, low dispersity and a random distribution of the two monomeric units. Kinetics analysis of the reaction disclosed a faster incorporation rate for the p-dioxanone (DX) than e-caprolactone (CL). The extrapolated rate constant, kDX, was 0.030 min−1 against a kCL of 0.013 min−1. The reactivity ratios were respectively 2.7 (rDX) and 0.28 (rCL). A detailed NMR analysis was performed to elucidate the structure of the co-oligomers, which could be precisely controlled by varying the monomer feed ratio and initiator. Depending on the composition, amorphous to semicrystalline oligomers with melting points close to room temperature were obtained, which after acrylation of the chain-end gave polyester networks with high swelling capacity up to 700%, and water uptake up to 70%.

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.

Although 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 mole ...