Francesca Agostinacchio

The metastable β-Ti21S alloy exhibits a lower elastic modulus than Ti-6Al-4V ELI while maintaining high mechanical strength and ductility. To address stress shielding, this study explores the integration of lattice structures within prosthetics, which is made possible through additive manufacturing. Continuous adhesion between the implant and bone is essential; therefore, auxetic bow-tie structures with a negative Poisson’s ratio are proposed for regions under tensile stress, while Triply Periodic Minimal Surface (TPMS) structures with a positive Poisson’s ratio are recommended for areas under compressive stress. This research examines the manufacturability and quasi-static mechanical behaviour of two auxetic bow-tie (AUX 2.5 and AUX 3.5) and two TPMS structures (TPMS 2.5 and TPMS 1.5) in β-Ti21S alloy produced via laser powder bed fusion. Micro-CT reveals printability issues in TPMS 1.5, affecting pore size and reducing fatigue resistance compared to TPMS 2.5. AUX 3.5’s low stiffness matches cancellous bone but shows insufficient yield strength and fatigue resistance for femoral implants. Biological tests confirm non-toxicity and enhanced cell activity in β-Ti21S structures. The study concludes that the β-Ti21S alloy, especially with TPMS 2.5 structures, demonstrates promising mechanical and biological properties for femoral implants. However, challenges like poor printability in TPMS 1.5 are acknowledged and should be addressed in future research.

Magnetically responsive soft biomaterials are at the forefront of bioengineering and biorobotics. We have created a magnetic hybrid material by coupling silk fibroin─i.e., a natural biopolymer with an optimal combination of biocompatibility and mechanical robustness─with the FeCo alloy, the ferromagnetic material with the highest saturation magnetization. The material is in the form of a 6 μm-thick silk fibroin film, coated with a FeCo layer (nominal thickness: 10 nm) grown by magnetron sputtering deposition. The sputtering deposition technique is versatile and eco-friendly and proves effective for growing the magnetic layer on the biopolymer substrate, also allowing one to select the area to be decorated. The hybrid material is biocompatible, lightweight, flexible, robust, and water-resistant. Electrical, structural, mechanical, and magnetic characterization of the material, both as-prepared and after being soaked in water, have provided information on the adhesion between the silk fibroin substrate and the FeCo layer and on the state of internal mechanical stresses. The hybrid film exhibits a high magnetic bending response under a magnetic field gradient, thanks to an ultralow fraction of the FeCo component (less than 0.1 vol %, i.e., well below 1 wt %). This reduces the risk of adverse health effects and makes the material suitable for bioactuation applications.

The shortage of tissues and organs for transplantation is an urgent clinical concern. In situ 3D printing is an advanced 3D printing technique aimed at printing the new tissue or organ directly in the patient. The ink for this process is central to the outcomes, and must meet specific requirements such as rapid gelation, shape integrity, stability over time, and adhesion to surrounding healthy tissues. Among natural materials, silk fibroin exhibits fascinating properties that have made it widely studied in tissue engineering and regenerative medicine. However, further improvements in silk fibroin inks are needed to match the requirements for in situ 3D printing. In the present study, silk fibroin-based inks were developed for in situ applications by exploiting covalent crosslinking process consisting of a pre-photo-crosslinking prior to printing and in situ enzymatic crosslinking. Two different silk fibroin molecular weights were characterized and the synergistic effect of the covalent bonds with shear forces enhanced the shift in silk secondary structure toward β-sheets, thus, rapid stabilization. These hydrogels exhibited good mechanical properties, stability over time, and resistance to enzymatic degradation over 14 days, with no significant changes over time in their secondary structure and swelling behavior. Additionally, adhesion to tissues in vitro was demonstrated.

Despite the tremendous technological advances that metal additive manufacturing (AM) has made in the last decades, there are still some major concerns guaranteeing its massive industrial application in the biomedical field. Indeed, some main limitations arise in dealing with their biological properties, specifically in terms of osseointegration. Morphological accuracy of sub-unital elements along with the printing resolution are major constraints in the design workspace of a lattice, hindering the possibility of manufacturing structures optimized for proper osteointegration. To overcome these issues, the authors developed a new hybrid multifunctional composite scaffold consisting of an AM Ti6Al4V lattice structure and a silk fibroin/gelatin foam. The composite was realized by combining laser powder bed fusion (L-PBF) of simple cubic lattice structures with foaming techniques. A combined process of foaming and electrodeposition has been also evaluated. The multifunctional scaffolds were characterized to evaluate their pore size, morphology, and distribution as well as their adhesion and behavior at the metal–polymer interface. Pull-out tests in dry and hydrated conditions were employed for the mechanical characterization. Additionally, a cytotoxicity assessment was performed to preliminarily evaluate their potential application in the biomedical field as load-bearing next-generation medical devices.

Silk fibroin precise cleavage on specific amino acid sites using collagenase type G enzyme leads to precise silk fibroin fragmentation and, thus, lower molecular weight materials whose length and properties can be tuned with the enzyme concentration.

Biogenic calcium carbonates naturally contain ions that can be beneficial for bone regeneration and therefore are attractive resources for the production of bioactive calcium phosphates. In the present work, cuttlefish bones, mussel shells, chicken eggshells and bioinspired amorphous calcium carbonate were used to synthesize hydroxyapatite nano-powders which were consolidated into cylindrical pellets by uniaxial pressing and sintering 800–1100 °C. Mineralogical, structural and chemical composition were studied by SEM, XRD, inductively coupled plasma/optical emission spectroscopy (ICP/OES). The results show that the phase composition of the sintered materials depends on the Ca/P molar ratio and on the specific CaCO₃ source, very likely associated with the presence of some doping elements like Mg²⁺ in eggshell and Sr²⁺ in cuttlebone. Different CaCO₃ sources also resulted in variable densification and sintering temperature. Preliminary in vitro tests were carried out (by the LDH assay) and they did not reveal any cytotoxic effects, while good cell adhesion and proliferation was observed at day 1, 3 and 5 after seeding through confocal microscopy. Among the different tested materials, those derived from eggshells and sintered at 900 °C promoted the best cell adhesion pattern, while those from cuttlebone and amorphous calcium carbonate showed round-shaped cells and poorer cell-to-cell interconnection.

The fabrication of multifunctional materials that interface with living environments is a problem of great interest. A variety of structural design concepts have been integrated with functional materials to form biodevices and surfaces for health monitoring. In particular, approaches based on kirigami-inspired cuts can engineer flexibility in materials through the creation of patterned defects. Here, the fabrication of a biodegradable and biofunctional “silk kirigami” material is demonstrated. Mechanically flexible, free-standing, optically transparent, large-area biomaterial sheets with precisely defined and computationally designed microscale cuts can be formed using a single-step photolithographic process. Using modeling techniques, it is shown how cuts can generate remarkable “self-shielding” leading to engineered elastic behavior and deformation. As composites with conducting polymers, flexible, intrinsically electroactive sheets can be formed. Importantly, the silk kirigami sheets are biocompatible, can serve as substrates for cell culture, and be proteolytically resorbed. The unique properties of silk kirigami suggest a host of applications as transient, “green”, functional biointerfaces, and flexible bioelectronics.

Thin polymeric films are being explored for biomedical uses such as drug delivery, biofiltration, biosensors, and tissue regeneration. Of specific interest is the formation of mechanically flexible sheets, which can be formed with controllable thickness for sealing wounds, or as biomimetic cellular constructs. Flexible substrates with precise micro‐ and nanopatterns can function as supports for cell growth with conformal contact at the biointerface. To date, approaches to form free‐standing, thin sheets are limited in the ability to present patterned architectures and micro/nanotextured surfaces. Other materials have a lack of degradability, precluding their application as cellular scaffolds. An approach is suggested using biocompatible and biodegradable films fabricated from silk fibroin. This work presents the fabrication and characterization of flexible, micropatterned, and biodegradable 2D fibroin sheets for cell adhesion and proliferation. A facile and scalable technique using photolithography is shown to fabricate optically transparent, strong, and flexible fibroin substrates with tunable and precise micropatterns over large areas. By controlling the surface architectures, the control of cell adhesion and spreading can be observed. Additionally, the base material is fully degradable via proteolysis. Through mechanical control and directing the adherent cells, it is possible to explore interactions of cells and the microscale geometric topography.