Syntheses of multifunctional polymers aim to engineer a wide range of material properties by adjusting the composition and positioning of functional groups. While manifold syntheses of side-chain-functionalized polymers are known, synthetic protocols for main-chain-functionalized polymers are less common. This work describes a general one-pot strategy to prepare polymers containing multiple functional moieties in their main-chain, e.g., azobenzene units separated by variable oligomers. The polymerization proceeds in two steps, starting from a single azobenzene initiator and commercially available monomers (lactones and cyclic carbonates). Various main-chain-functionalized polymers were obtained with a predictable and adjustable ratio of monomer units (5-20) to photoswitchable azobenzene groups. The thermal properties of these polymers were analyzed and rationalized with regard to the parent polymers' properties and the peculiarities arising from their segmented microstructure. Furthermore, the azobenzenes' ability to undergo light-induced cis/trans-isomerization is confirmed. High isomerization yields of up to 90% were observed for the polymers in solution with a half-life of several days for the cis-isomers in solution. When irradiated as solid films, the azobenzenes still undergo isomerization, but the cis-isomers are less stable compared to the liquid state.

Bi-functional organocatalysts constituted by a (thio-)urea moiety and an iminophosphorane moiety were synthesized and optimised for the ring-opening alternating co-polymerisation of phthalic anhydride with three different epoxides: cyclohexene oxide, propylene oxide and butylene oxide. The most effective catalyst featured a cyclohexyl urea moiety, an iminophosphorane moiety with three 2,4-dimethyl-3-methoxy phenyl substituents, and a short spacer length of two carbon atoms between them. All tested epoxides reached quantitative conversion within 24 hours with ester-selectivities up to >97%. NMR and DFT experiments reveal that the catalysts exist in solution as dimers that dissociate during the initiation of the polymerisation. During the polymerisation, the catalyst is coordinated to the growing chain and further modulates its reactivity through reversible protonation/deprotonation suppressing transesterification side reactions even at prolonged polymerisation times without the need for a co-catalyst. The rate-determining step of the polymerisation is the ring-opening of the epoxide by the carboxylate chain end, and accordingly, higher temperatures (up to 150 °C) and higher concentrations of epoxide and catalyst increase polymerisation rates.

The ring-opening copolymerization (ROcoP) of epoxides and anhydrides is exploited to afford 4 structurally diverse and functional copolyesters. Mixtures of 2 epoxides (allyl glycidyl ether and butylene oxide) with 1 anhydride (succinic, glutaric, phthalic and homo phthalic anhydride) are copolymerized in the presence of bis (triphenylphosphine)iminium chloride (PPNCl) as organocatalyst. All monomer combinations yield vinyl-functionalized materials with alternating epoxide-anhydride units, statistical incorporation of both epoxides along the polymer chain and molar masses up to 28.3 kg/mol. The copolyesters are amorphous with a Tg between -39 degrees C and 38 degrees C. Together with the molar mass, the anhydride dictates the thermal stability of the copolyesters with glutaric anhydride resulting in a remarkably high thermal stability up to 310 degrees C. In a post-polymerization step, the pendant double bonds are radically crosslinked to gels with swelling ratios above 1500 % and com-parable to enhanced thermal stability with respect to the non-crosslinked, parent copolyesters. The degradation of the 4 copolyesters (before and after crosslinking) is tested in abiotic and enzymatic conditions: The highest degradation rates are observed for the non-crosslinked materials in enzymatic conditions with a mass loss of up to 60 % after 27 d. After crosslinking, the gels are more stable against degradation under both conditions, although a decrease in the gel content and a decrease in mass indicates that degradation still takes place.

Synthetic, degradable macromonomers have been developed to serve as ink for 3D printing technologies based on direct-ink-writing. The macromonomers are purposely designed to be cross-linkable under the radical mechanism, to impart hydrophilicity to the final material, and to have rheological properties matching the printer's requirements. The suitable viscosity enables the ink to be printed at room temperature, in absence of organic solvents, and to be cross-linked to manufacture soft 3D scaffolds that show no indirect cytotoxicity and have a hydration capacity of up to 100% their mass and a compressive modulus in the range of 0.4-2 MPa.

Background Age-driven immune signals cause a state of chronic low-grade inflammation and in consequence affect bone healing and cause challenges for clinicians when repairing critical-sized bone defects in elderly patients. Methods Poly(l-lactide-co-e-caprolactone) (PLCA) scaffolds are functionalized with plant-derived nanoparticles from potato, rhamnogalacturonan-I (RG-I), to investigate their ability to modulate inflammation in vitro in neutrophils and macrophages at gene and protein levels. The scaffolds' early and late host response at gene, protein and histological levels is tested in vivo in a subcutaneous rat model and their potential to promote bone regeneration in an aged rodent was tested in a critical-sized calvaria bone defect. Significant differences were tested using one-way ANOVA, followed by a multiple-comparison Tukey's test with a p value <= 0.05 considered significant. Results Gene expressions revealed PLCA scaffold functionalized with plant-derived RG-I with a relatively higher amount of galactose than arabinose (potato dearabinated (PA)) to reduce the inflammatory state stimulated by bacterial LPS in neutrophils and macrophages in vitro. LPS-stimulated neutrophils show a significantly decreased intracellular accumulation of galectin-3 in the presence of PA functionalization compared to Control (unmodified PLCA scaffolds). The in vivo gene and protein expressions revealed comparable results to in vitro. The host response is modulated towards anti-inflammatory/ healing at early and late time points at gene and protein levels. A reduced foreign body reaction and fibrous capsule formation is observed when PLCA scaffolds functionalized with PA were implanted in vivo subcutaneously. PLCA scaffolds functionalized with PA modulated the cytokine and chemokine expressions in vivo during early and late inflammatory phases. PLCA scaffolds functionalized with PA implanted in calvaria defects of aged rats downregulating pro-inflammatory gene markers while promoting osteogenic markers after 2 weeks in vivo. Conclusion We have shown that PLCA scaffolds functionalized with plant-derived RG-I with a relatively higher amount of galactose play a role in the modulation of inflammatory responses both in vitro and in vivo subcutaneously and promote the initiation of bone formation in a critical-sized bone defect of an aged rodent. Our study addresses the increasing demand in bone tissue engineering for immunomodulatory 3D scaffolds that promote osteogenesis and modulate immune responses.

Polymers containing ester bonds undergo abiotic degradation independently from the surrounding environment as long as the hydrolytic conditions are provided. The hydrolysis of the ester bonds leads a bulk degradation of the polymeric matrix which, contrary to surface erosion, is unpredictable. The enchainment of diverse degradability functions was sought to expand the scope of the degradation mechanism and achieve a more predictable profile of the mass loss.The copolymerization of trimethylene carbonate and p-dioxanone enabled the synthesis of one class of copolymers with controllable erosion rate and susceptible to three degradation pathways depending on the surrounding environment. The synthetic strategy used organocatalysts and allowed the synthesis at room temperature of both random and block copolymers in high yield and with molar mass, Mn, in the range 12-22 kg mol- 1. The composition and microstructure of the random copolymers were regulated by varying the monomers' ratio. Diverse cleavable groups, i.e., ester/ether and carbonate bonds, were statistically incorporated along the same polymer chain to yield materials able to degrade under hydrolytic, oxidative and enzymatic conditions. Bulk degradation was the mechanism that took place under hydrolytic conditions, while the oxidative and enzymatic environments lead to surface erosion. The rate of mass loss of the random copolymers was regulated by varying the composition. These results showed how the statistical incorporation of different degradable bonds could pave the way to diverse and more predictable degradation pathways than simple hydrolysis by taking advantages of the surrounding environment to trigger surface erosion.

We have developed an innovative methodology to overcome the lack of techniques for real-time assessment of degradable biomedical polymers at physiological conditions. The methodology was established by combining polymer characterization techniques with electrochemical sensors. The in vitro hydrolytic degradation of a series of aliphatic polyesters was evaluated by following the molar mass decrease and the mass loss at different incubation times while tracing pH and L-lactate released into the incubation media with customized miniaturized electrochemical sensors. The combination of different analytical approaches provided new insights into the mechanistic and kinetics aspects of the degradation of these biomedical materials. Although molar mass had to reach threshold values for soluble oligomers to be formed and specimens' resorption to occur, the pH variation and L-lactate concentration were direct evidence of the resorption of the polymers and indicative of the extent of chain scission. Linear models were found for pH and released L-lactate as a function of mass loss for the Llactide-based copolymers. The methodology should enable the sequential screening of degradable polymers at physiological conditions and has potential to be used for preclinical material's evaluation aiming at reducing animal tests.

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.

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 the 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. 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. 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.

We present a solution to regenerate adipose tissue using degradable, soft, pliable 3D-printed scaffolds made of a medical-grade copolymer coated with polydopamine. The problem today is that while printing, the medical grade copolyesters degrade and the scaffolds become very stiff and brittle, being not optimal for adipose tissue defects. Herein, we have used high molar mass poly(L-lactide-co-trimethylene carbonate) (PLATMC) to engineer scaffolds using a direct extrusion-based 3D printer, the 3D Bioplotter (R). Our approach was first focused on how the printing influences the polymer and scaffold's mechanical properties, then on exploring different printing designs and, in the end, on assessing surface functionalization. Finite element analysis revealed that scaffold's mechanical properties vary according to the gradual degradation of the polymer as a consequence of the molar mass decrease during printing. Considering this, we defined optimal printing parameters to minimize material's degradation and printed scaffolds with different designs. We subsequently functionalized one scaffold design with polydopamine coating and conducted in vitro cell studies. Results showed that polydopamine augmented stem cell proliferation and adipogenic differentiation owing to increased surface hydrophilicity. Thus, the present research show that the medical grade PLATMC based scaffolds are a potential candidate towards the development of implantable, resorbable, medical devices for adipose tissue regeneration.