Solvent-triggered shape change in gradient-based 4D printed bilayers: case study on semi-crystalline polymer networks.

We propose an approach to 4D print solvent-triggered, gradient-based bilayers made of semi-crystalline crosslinked polymer networks. Out-of-plane bending is obtained after immersion in the solvent, exploiting the different swelling degrees of the layers resulting from crosslinking gradients. Lastly, a beam model of the shape transformation is applied and experimentally validated.

Thermoactive Smart Electrospun Nanofibers.

The recent burst of research on smart materials is a clear evidence of the growing interest of the scientific community, industry, and society in the field. The exploitation of the great potential of stimuli-responsive materials for sensing, actuation, logic, and control applications is favored and supported by new manufacturing technologies, such as electrospinning, that allows to endow smart materials with micro- and nanostructuration, thus opening up additional and unprecedented prospects. In this wide and lively scenario, this article systematically reviews the current advances in the development of thermoactive electrospun fibers and textiles, sorting them, according to their response to the thermal stimulus. Hence, several platforms including thermoresponsive systems, shape memory polymers, thermo-optically responsive systems, phase change materials, thermoelectric materials, and pyroelectric materials, are described and critically discussed. The difference in active species and outputs of the aforementioned categories is highlighted, evidencing the transversal nature of temperature stimulus. Moreover, the potential of novel thermoactive materials are pointed out, revealing how their development could take to utmost interesting achievements.

Hybrid Core-Shell Polymer Scaffold for Bone Tissue Regeneration.

A great promise for tissue engineering is represented by scaffolds that host stem cells during proliferation and differentiation and simultaneously replace damaged tissue while maintaining the main vital functions. In this paper, a novel process was adopted to develop composite scaffolds with a core-shell structure for bone tissue regeneration, in which the core has the main function of temporary mechanical support, and the shell enhances biocompatibility and provides bioactive properties. An interconnected porous core was safely obtained, avoiding solvents or other chemical issues, by blending poly(lactic acid), poly(ε-caprolactone) and leachable superabsorbent polymer particles. After particle leaching in water, the core was grafted with a gelatin/chitosan hydrogel shell to create a cell-friendly bioactive environment within its pores. The physicochemical, morphological, and mechanical characterization of the hybrid structure and of its component materials was carried out by means of infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and mechanical testing under different loading conditions. These hybrid polymer devices were found to closely mimic both the morphology and the stiffness of bones. In addition, in vitro studies showed that the core-shell scaffolds are efficiently seeded by human mesenchymal stromal cells, which remain viable, proliferate, and are capable of differentiating towards the osteogenic phenotype if adequately stimulated.

Advances in chemoselective intermolecular cross-benzoin-type condensation reactions.

The intermolecular cross-benzoin and acyloin condensation reactions are powerful approaches to α-hydroxy carbonyls in a single step. However, their potentiality suffers from the occurrence of side reactions including self-condensation and the formation of the undesired cross-acyloin. The broad range of azolium salt precatalysts available confers high tunability to NHC mediated benzoin condensation, assuring a good level of selectivity to the direct coupling between two non-equivalent aldehydes. Many efforts have also been devoted to the design of strategies that expand the range of suitable reaction partners beyond the traditional aldehydes and to the discovery of novel umpolung catalytic systems. The synthesis of both racemic and enantiomerically enriched acyloins is reviewed.

Synthesis and Biological Evaluation of New Natural Phenolic (2E,4E,6E)-Octa-2,4,6-trienoic Esters.

In the present study the esterification of the OH groups of resveratrol, caffeic acid, ferulic acid, and ß-sitosterol with an antioxidant polyconjugated fatty acid, (2E,4E,6E)-octa-2,4,6-trienoic acid, was achieved. As the selective esterification of OH groups of natural compounds can affect their biological activity, a selective esterification of resveratrol and caffeic acid was performed by an enzymatic approach. The new resulting compounds were characterized spectroscopically (FT-IR, NMR mono, and bidimensional techniques); when necessary the experimental data were integrated by quantum chemical calculations. The antioxidant, anti-inflammatory and proliferative activity was evaluated. The good results encourage the use of these molecules as antioxidant and/or anti-inflammatory agents in dermocosmetic application.

Hydrogel-chitosan and polylactic acid-polycaprolactone bioengineered scaffolds for reconstruction of mandibular defects: a preclinical in vivo study with assessment of translationally relevant aspects.

Background: Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction. Methods: In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly ( ε -caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses. Results: The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group. Conclusion: Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.

New Poly(lactic acid)-Hydrogel Core-Shell Scaffolds Highly Support MSCs' Viability, Proliferation and Osteogenic Differentiation.

Scaffolds for tissue engineering are expected to respond to a challenging combination of physical and mechanical requirements, guiding the research towards the development of novel hybrid materials. This study introduces innovative three-dimensional bioresorbable scaffolds, in which a stiff poly(lactic acid) lattice structure is meant to ensure temporary mechanical support, while a bioactive gelatin-chitosan hydrogel is incorporated to provide a better environment for cell adhesion and proliferation. The scaffolds present a core-shell structure, in which the lattice core is realized by additive manufacturing, while the shell is nested throughout the core by grafting and crosslinking a hydrogel forming solution. After subsequent freeze-drying, the hydrogel network forms a highly interconnected porous structure that completely envelops the poly(lactic acid) core. Thanks to this strategy, it is easy to tailor the scaffold properties for a specific target application by properly designing the lattice geometry and the core/shell ratio, which are found to significantly affect the scaffold mechanical performance and its bioresorption. Scaffolds with a higher core/shell ratio exhibit higher mechanical properties, whereas reducing the core/shell ratio results in higher values of bioactive hydrogel content. Hydrogel contents up to 25 wt% could be achieved while maintaining high compression stiffness (>200 MPa) and strength (>5 MPa), overall, within the range of values displayed by human bone tissue. In addition, mechanical properties remain stable after prolonged immersion in water at body temperature for several weeks. On the other hand, the hydrogel undergoes gradual and homogeneous degradation over time, but the core-shell integrity and structural stability are nevertheless maintained during at least 7-week hydrolytic degradation tests. In vitro experiments with human mesenchymal stromal cells reveal that the core-shell scaffolds are biocompatible, and their physical-mechanical properties and architecture are suitable to support cell growth and osteogenic differentiation, as demonstrated by hydroxyapatite formation. These results suggest that the bioresorbable core-shell scaffolds can be considered and further studied, in view of clinically relevant endpoints in bone regenerative medicine.

Expandable Drug Delivery Systems Based on Shape Memory Polymers: Impact of Film Coating on Mechanical Properties and Release and Recovery Performance.

Retentive drug delivery systems (DDSs) are intended for prolonged residence and release inside hollow muscular organs, to achieve either local or systemic therapeutic goals. Recently, formulations based on shape memory polymers (SMPs) have gained attention in view of their special ability to recover a shape with greater spatial encumbrance at the target organ (e.g., urinary bladder or stomach), triggered by contact with biological fluids at body temperature. In this work, poly(vinyl alcohol) (PVA), a pharmaceutical-grade SMP previously shown to be an interesting 4D printing candidate, was employed to fabricate expandable organ-retentive prototypes by hot melt extrusion. With the aim of improving the mechanical resistance of the expandable DDS and slowing down relevant drug release, the application of insoluble permeable coatings based on either Eudragit® RS/RL or Eudragit® NE was evaluated using simple I-shaped specimens. The impact of the composition and thickness of the coating on the shape memory, swelling, and release behavior as well as on the mechanical properties of these specimens was thoroughly investigated and the effectiveness of the proposed strategy was demonstrated by the results obtained.

Expandable drug delivery system for gastric retention based on shape memory polymers: Development via 4D printing and extrusion.

Several diseases would benefit from prolonged drug release provided by systems retained in the stomach for extended time periods. Expandable gastroretentive devices are administered in a collapsed configuration enabling swallowing and regain in situ their native shape having larger spatial encumbrance, thus hindering voidance through the wide open pylorus. An expandable system for gastric retention was here proposed relying on the shape memory behavior of pharmaceutical-grade poly(vinyl alcohol). Different original configurations to be recovered upon exposure to aqueous fluids at 37 °C, potentially enabling gastric retention, were conceived. Prototypes containing allopurinol were directly manufactured by fused deposition modeling or shaped by purposely-designed templates from hot melt extruded rods immediately after production. Various temporary shapes, in principle suitable for administration, were programmed by manual deformation of samples by means of specific templates, under defined temperature conditions. In 0.1 N hydrochloric solution at 37 °C, the prototypes recovered their original shape, reaching the desired spatial encumbrance within few minutes. Release from the samples, although of relatively short duration, was independent of the original shape and processing undergone, and was noticeably slowed down by application of Eudragit® RS/RL-based coatings.