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.

4D printing is an innovative manufacturing approach that combines 3D printing and stimuli- responsive abilities to produce objects with complex geometry and capable of shapeshifting over time (the fourth dimension). To pursue such an approach this paper proposes to develop re-entrant honeycomb auxetic grids with tunable shape reconfigurable behavior. Particularly, the work combines 3D printing and a photopolymer exhibiting the so-called temperature memory effect (TME), a peculiar shape memory behavior expressing the capability of the material to remember not only the original shape but also the deformation temperature. A thorough experimental activity was carried out on single auxetic unit cells, chosen as representative of the whole auxetic grid, to properly highlight and assess their response upon heating after single-step and multiple-step deformation histories and to describe the recovery process as a function of time and temperature. Results demonstrate the possibility to achieve an easily controlled TME and to successfully exploit it for autonomous, complex hierarchical transformations over a large range of temperatures. As a proof-of-concept, the study of the sequential recovery of an entire auxetic grid subjected to double-step programming allowed highlighting a decoupled in-plane elongation and out-of-plane bending. The behavior of the 4D-printed auxetic structures was simulated by means of finite element (FE) analysis, using a thermoviscoelastic model of the photopolymer and viscoelastic experimental data obtained by time-temperature superposition analysis applied to multifrequency dynamic mechanical tests and to isothermal recovery tests. A good correspondence between experiments and simulations was obtained for all shape memory tests, demonstrating that the proposed FE approach is a suitable tool to support the design of these structures. The combination of 3D printing and TME opens new perspectives to achieve dynamic tunability in mechanical metamaterials, that is a key ingredient in several application fields.

This work presents a new method for 4D fabrication of two‐way shape memory materials that are capable of reversible shapeshifting right after manufacturing, upon application of proper heating and cooling cycles. The innovative solution presented here consists in the combination of highly stretched electrospun shape memory polymer (SMP) nanofibers with a melt electrowritten elastomer. More specifically, the stretched nanofibers are made of a biocompatible thermoplastic polyurethane (TPU) with crystallizable soft segments, undergoing melt‐induced contraction and crystallization‐induced elongation upon heating and cooling, respectively. Reversible actuation during crystallization becomes possible due to the elastic recovery of the elastomer component, obtained by melt electrowriting of a commercial TPU filament. Thanks to the design freedom offered by additive manufacturing, the elastomer structure also has the role of guiding the shape transformation. Electrospinning and melt electrowriting process parameters are set up so to obtain smart 4D objects capable of two‐way shape memory effect (SME), and the possibility of reversible and repeatable actuation is demonstrated. The two components are then combined in different proportions with the aim of tailoring the two‐way SME, taking into account the effect of design parameters such as the SMP content, the elastomer pattern, and the composite thickness.

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.

Motivated by the enormous potential of hydrogels in regenerative medicine, new biocompatible gelatin-based hybrid hydrogels were developed through a green process using poly(ethylene glycol) diglycidyl ether as a cross-linking agent, adding carrageenan and chitosan polysaccharides to the network to better mimic the hybrid composition of native extracellular matrix. Overall, the hydrogels show suitable structural stability, high porosity and pore interconnectivity, good swellability, and finally, biocompatibility. Their mechanical behavior, investigated by tensile and compression tests, appears to be characterized by nonlinear elasticity with high compliance values, fast stress-relaxation, and good strain reversibility with no sign of mechanical failure for compressive loading–unloading cycles at relatively high deformation levels of 50%. Degradation tests confirm the hydrogel bioresorbability by gradual hydrolysis, during which the structural integrity of both materials is maintained, while their mechanical behavior becomes more and more compliant. Human Umbilical Cord-derived Mesenchymal Stem Cells (hUC-MSCs) were used to test the hydrogels as potential carriers for cell delivery in tissue engineering. hUC-MSCs cultured inside the hydrogels show a homogenous distribution and maintain their growth and viability for at least 21 days of culture, with an increasing proliferation trend. Hence, this study contributes to a further understanding of the potential use of hybrid hydrogels and hUC-MSCs for a wide range of biomedical applications, particularly in soft tissue engineering.

The optimal performance of scaffolds for tissue engineering relies on a proper combination of their constituent biomaterials and on the design of their structure. In this work, composite scaffolds with a core-shell architecture are realized by grafting a gelatin-chitosan hydrogel onto a 3D-printed polylactic acid (PLA) core, aiming in particular at bone regeneration. This hydrogel was recently found to sustain osteogenic differentiation of mesenchymal stromal cells, leading to new bone tissue formation. Here, the integration with rigid PLA lattice structures provides improved mechanical support and finer control of strength and stiffness. The core is prepared by fused deposition modeling with the specific aim to study several lattice structures and thereby better tune the scaffold mechanical properties. In fact, the core architecture dictates the scaffold strength and stiffness, which are seen to match those of different types of bone tissue. For all lattice types, the hydrogel is found to penetrate throughout the entire core and to present highly interconnected pores for cell colonization. By varying the void volume fraction in the core it is possible to significantly change the bioactive shell content, as well as the mechanical properties, over a wide range of values. Looking for design guidelines, relationships between stiffness/strength and density are here outlined for scaffolds featuring different lattice parameters. Moreover, by acting on the core strut arrangement, scaffolds are reinforced along specific directions, as evaluated under compressive and bending loading conditions.