Visible light-mediated crosslinked methacrylated gellan gum nanocomposite hydrogel: physicochemical characterization and in vivo safety Giorgia Codispoti, Diego Trucco, Melania Carniato, Lorenzo Vannozzi, Lucia Martini, Cristina Manferdini, Gina Lisignoli, Matilde Tschon, Milena Fini, Leonardo Ricotti Materials and Design, 2026 • Photocrosslinkable methacrylated gellan gum (GGMA)-based hydrogel for cartilage applications. • Comprehensive characterization and assessment of the in vitro and in vivo safety profile of the GGMA nanocomposite. • GGMA nanocomposite shows improved injectability, mechanical properties, and cartilage adhesion. • GGMA nanocomposite is fully biocompatible and exhibits translational potential. Methacrylated gellan gum (GGMA) injectable hydrogels have emerged as promising candidates for cartilage tissue engineering due to their structural similarity to cartilage glycosaminoglycans and the tunability enabled by visible-light photocrosslinking. Incorporating functional nanomaterials represents a promising approach to improve their functionality for cartilage repair. Although several studies have highlighted the in vitro potential of nanocomposite hydrogels, comprehensive evaluations of the in vivo safety of photocrosslinkable hydrogels for clinical use remain limited. Here, we demonstrated that the incorporation of graphene oxide nanoflakes and barium titanate nanoparticles into visible light–crosslinked GGMA hydrogels preserved their shear-thinning behavior while improving mechanical properties and adhesion to cartilage, without affecting lubrication or degradation. In vitro safety, evaluated according to ISO 10993 standards, confirmed the absence of cytotoxicity in human chondrocytes and genotoxic effects both in bacteria and human lymphoblasts. In vivo ISO 10993-compliant assessments (including skin irritation, delayed-type hypersensitivity, acute and subchronic systemic toxicity, and local effects after implantation) confirmed the biocompatibility of GGMA nanocomposites, with no local or systemic adverse effects in both animal sexes. Overall, GGMA-based nanocomposite hydrogels exhibited favorable mechanical and biological properties and a safe in vivo profile, supporting their potential for translational cartilage applications.
Correction: Electrospun polymeric scaffolds enable 3D tissue-like functionality and efficient photoinduced contraction Giulia Simoncini, Fabio Marangi, Ilaria Venturino, Vito Vurro, Andrea Bartolucci, Lorenzo Vannozzi, Ludovico Aloisio, Martina Rossi, Paola Moretti, Chiara Bertarelli, Giuseppe Maria Paternò, Guglielmo Lanzani Journal of Materials Chemistry B, 2026 Correction for ‘Electrospun polymeric scaffolds enable 3D tissue-like functionality and efficient photoinduced contraction’ by Giulia Simoncini et al. , J. Mater. Chem. B , 2026, 14 , 2832–2842, https://doi.org/10.1039/D5TB02640G.
Electrospun polymeric scaffolds enable 3D tissue-like functionality and efficient photoinduced contraction Giulia Simoncini, Fabio Marangi, Ilaria Venturino, Vito Vurro, Andrea Bartolucci, Lorenzo Vannozzi, Ludovico Aloisio, Martina Rossi, Paola Moretti, Chiara Bertarelli, Giuseppe Maria Paternò, Guglielmo Lanzani Journal of Materials Chemistry B, 2026 Free-standing, aligned electrospun PVA nanofiber membranes create a quasi-3D scaffold for C2C12 alignment. With Ziapin2 infiltration, visible light paces macroscopic contractions up to ∼460 µN (∼3.3 kPa) without genetics in vitro .
In vivo efficacy of an injectable piezoelectric nanocomposite hydrogel and low-intensity pulsed ultrasound in two preclinical models of osteoarthritis Matilde Tschon, Giorgia Codispoti, Paolo Cabras, Andrea Cafarelli, Diego Trucco, Lorenzo Vannozzi, Cristina Manferdini, Melania Carniato, Giorgio Cassiolas, Lucia Martini, Milena Fini, Giovanni D'Atri, Carsten Jost, Yirij Fedutik, Gilbert Daniel Nessim, Erik Dumont, Gina Lisignoli, Leonardo Ricotti Biomaterials, 2026 Smart hydrogels embedding mesenchymal stromal cells are receiving increasing attention as a potential solution for preventing articular cartilage degeneration in knee osteoarthritis (OA). In this work we demonstrate that an injectable piezoelectric hydrogel embedding autologous adipose tissue-derived mesenchymal stromal cells (ASCs), stimulated by low-intensity pulsed ultrasound (LIPUS), is effective in reducing knee OA in two preclinical surgically induced OA models. A medium-sized rabbit model was used to evaluate sex differences in treatment efficacy, while a large-sized sheep model was employed to assess the translatability of this innovative approach to a scenario with similarities to human conditions. We developed computational models to ensure reliable and precise delivery of a specific ultrasound dose to the target, modelling wave propagation through tissues and considering the anatomy of the two experimental animal models. Sex-based differences in therapy effectiveness were observed in rabbits, with better macroscopic and microscopic outcomes in counteracting OA in female animals. Furthermore, we found that the combination of ASC-laden piezoelectric hydrogel and LIPUS can be scaled in a large-sized sheep model, proving effective in counteracting OA.
Towards Real-Time Monitoring of Soft Robotic Systems in Endoscopic Application With Ultra-Flexible Organic Transistor-Based Strain Sensors Usama Mahmood, Andrea Bartolucci, Giulia Casula, Antonello Mascia, Lorenzo Vannozzi, Stefano Lai Advanced Electronic Materials, 2026 The development of sensing elements capable of direct and real‐time monitoring is fundamental to the actual exploitation of soft robotic systems in real application scenarios. In this paper, the integration of an electronic strain sensor based on an ultra‐flexible, all‐organic field‐effect transistor on a soft structure, conceived for future application as a soft robotic catheter in drug delivery, is reported. The device, entirely fabricated by means of cost‐effective, large area processes, is developed over a sub‐micrometrical, biocompatible substrate, with mechanical properties compatible with soft robotic production. Electrical performance of the transistor is characterized, showing the suitability of the device parameters to the envisaged application in terms of low power consumption and reproducibility. A successful integration of the ultra‐flexible transistor platform into the soft robotic system is demonstrated. A thorough electromechanical characterization of the sensorized system is provided, showing a programmable sensitivity to mechanical deformation in the range 5°–30°, based on the overthreshold conditions imposed by the transistor gate voltage. The results pave the way for the effective exploitation of organic flexible electronics as a valuable solution for the development of sensorized soft robots, toward a complete observability and controllability of their actuation in operation scenarios.
Development of an electrical current stimulator for controlling biohybrid machines Riccardo Collu, Judith Fuentes, Florencia Lezcano, Maria Crespo-Cuadraro, Andrea Bartolucci, Leonardo Ricotti, Lorenzo Vannozzi, Samuel Sánchez, Stefano Lai, Massimo Barbaro Scientific Reports, 2025 Soft and flexible robotics is an emerging field that attracts a huge interest due to its ability to produce bioinspired devices that are easily adaptable to the environment. Biohybrid Machines (BHM) represent a category of soft robots that integrate biological tissues, such as engineered muscle tissues, as actuating systems. Although these devices present several advantages in some applications, their proper actuation still represents a challenge for researchers. This paper focuses on the development of a portable and programmable electrical stimulator designed to control muscle fiber-based biohybrid actuators. The stimulator, made using off-the-shelf components, was designed as a stacking of three independent printed circuit boards (PCBs), connected vertically in order to result in a final device with compact dimensions of 59 mm $$\times$$ 28 mm $$\times$$ 25 mm. The stimulation circuit is capable of delivering currents up to 18 mA with a voltage compliance of ± 90 V, and a power consumption of approximately 1.3 W. The device’s ability to induce twitch and tetanic contractions in a biohybrid actuator is demonstrated in different stimulation conditions. A practical application was also explored through a test case involving a flexible catheter prototype controlled by a biohybrid actuator, demonstrating its potential utility in a BHMs.
Monolithic Biohybrid Flexure Mechanism Actuated by Bioengineered Skeletal Muscle Tissue Andrea Bartolucci, Judith Fuentes, Daniele Guarnera, Florencia Lezcano, Maria Crespo‐Cuadrado, Lorena Guachi‐Guachi, Francesco Iacoponi, Carlotta Salvatori, Riccardo Collu, Massimo Barbaro, Stefano Lai, Leonardo Ricotti, Samuel Sánchez, Lorenzo Vannozzi Advanced Intelligent Systems, 2025 Skeletal muscle tissue represents an attractive powering component for biohybrid robots, as traditional actuators used in the soft robotic context often rely on complex mechanisms and lack scalability at small dimensions. This article proposes a monolithic biohybrid flexure mechanism actuated by a bioengineered skeletal muscle tissue. The design leverages the contractile properties of a bioengineered skeletal muscle to produce a bending motion in a monolithic, tubular mechanism made of a soft and biocompatible silicone blend. This structure integrates two cylindrical pillars that facilitate force transmission from the bioengineered muscle tissue. Performance assessments reveal excellent contractile and stable behavior upon electrical stimulation, compared to current biohybrid actuation systems, with enhanced performance as the mechanism's internal and external diameters decrease. Finite‐element simulations further reveal distinct force–displacement responses in mechanisms with different flexural rigidity. This innovative, scalable, and easy‐to‐fabricate design represents a significant step forward in the development of novel biohybrid machines.
Nanoscale piezoelectric patches preserve electrical integrity of infarcted hearts Luís M. Monteiro, Pedro J. Gouveia, Francisco Vasques-Nóvoa, Susana Rosa, Ifigeneia Bardi, Rita N. Gomes, Simão Correia-Santos, Leonardo Ricotti, Lorenzo Vannozzi, Daniele Guarnera, Liliana Costa, André M. Leite-Moreira, Pedro Mendes-Ferreira, Adelino F. Leite-Moreira, Filippo Perbellini, Cesare M. Terracciano, Perpétua Pinto-do-Ó, Lino Ferreira, Diana S. Nascimento Materials Today Bio, 2025 implantation of Piezo patches in porcine hearts revealed to be electrically safe as no major effects in its electrophysiology were detected. Overall, the results presented here endorse Piezo patches as a promising therapeutic strategy to improve post-myocardial infarction structural and electrical remodeling.
Micropatterned Styrene-Butadiene-Styrene Thin Films Doped with Barium Titanate Nanoparticles: Effects on Myoblast Differentiation Leonardo Boccoli, Elena Drago, Andrea Cafarelli, Lorenzo Vannozzi, Angelo Sciullo, Federica Iberite, Sajedeh Kerdegari, Toshinori Fujie, Emanuele Gruppioni, Claudio Canale, Leonardo Ricotti ACS Biomaterials Science and Engineering, 2025 Biohybrid actuators exploit the contraction of biological components (muscle cells) to produce a force. In particular, bottom-up approaches use tissue engineering techniques, by coupling cells with a proper scaffold to obtain constructs undergoing contraction and guaranteeing actuation in biohybrid devices. However, the fabrication of actuators able to recapitulate the organization and maturity of native muscle is not trivial. In this field, quasi-two-dimensional (2D) substrates are raising interest due to their high surface/thickness ratio and the possibility of functionalizing their surface. In this work, we fabricated micropatterned thin films made of poly(styrene–butadiene–styrene) (SBS) doped with barium titanate nanoparticles (BTNPs) for fostering myogenic differentiation. We investigated material concentrations and fabrication process parameters to obtain thin microgrooved films with an average thickness below 1 μm, thus featured by a relatively low flexural rigidity and with an anisotropic topography to guide cell alignment and myotube formation. The embodiment of BTNPs did not significantly affect the film’s mechanical properties. Interestingly, the presence of BTNPs enhanced the expression of myogenic differentiation markers (i.e., MYH1, MYH4, MYH8, and ACTA1). The results show the promising potential of SBS thin films doped with BTNPs, opening avenues in the fields of biohybrid actuation and skeletal muscle tissue engineering.
Reinforcement of injectable hydrogels through melt electro-written structures: Influence of shape and pore size on the injection force Diego Trucco, Rory Gibney, Lorenzo Vannozzi, Gina Lisignoli, Daniel J. Kelly, Leonardo Ricotti Journal of Materials Research and Technology, 2025 Hydrogels are commonly used for tissue engineering applications due to their high water content, biocompatibility, injectability, and ability to mimic the extracellular matrix of native tissues. However, their weak mechanical properties limit their use, especially in load-bearing applications. In this study, we developed fibrous architectures with a pre-defined shape using melt electro-writing (MEW) to strengthen injectable hydrogels. We assessed the injection forces required to successfully extrude the hydrogel reinforced with MEW-printed structures, varying their geometry (square/hexagonal pores) and pore sizes (0.6, 0.8, 1.0 mm) through needles having a size compatible with clinical applications. Our findings indicate that MEW structures with hexagonal pores exhibit a higher tensile modulus than those with square pores. Additionally, the injection forces required to extrude hydrogels embedding MEW structures through needles were greater for hexagonal pores. Thinner pores and smaller needle diameters resulted in higher injection forces; a few conditions among the ones tested were compatible with the limits defined by the EU ISO 7886–1:2018 standard. After injection and crosslinking, hydrogels reinforced with MEW structures showed improved mechanical properties (up to 6.34-fold), particularly when structures with hexagonal pores were used.
Integration of Organic Field-Effect Transistor-based Strain Sensors and Soft Robotic Catheters for Drug Delivery Convegno Nazionale Di Bioingegneria, 2025
Potassium sodium niobate piezoelectric nanoparticles: a platform for wireless cell modulation in tissue engineering Convegno Nazionale Di Bioingegneria, 2025
The MioPRO2 project: a novel regenerative peripheral nerve interface for prostheses control based on an engineered piezoelectric skeletal muscle construct Convegno Nazionale Di Bioingegneria, 2025
Ultrasound Stimulation of Piezoelectric Nanocomposite Hydrogels Boosts Chondrogenic Differentiation in Vitro, in Both a Normal and Inflammatory Milieu Leonardo Ricotti, Andrea Cafarelli, Cristina Manferdini, Diego Trucco, Lorenzo Vannozzi, Elena Gabusi, Francesco Fontana, Paolo Dolzani, Yasmin Saleh, Enrico Lenzi, Marta Columbaro, Manuela Piazzi, Jessika Bertacchini, Andrea Aliperta, Markys Cain, Mauro Gemmi, Paola Parlanti, Carsten Jost, Yirij Fedutik, Gilbert Daniel Nessim, Madina Telkhozhayeva, Eti Teblum, Erik Dumont, Chiara Delbaldo, Giorgia Codispoti, Lucia Martini, Matilde Tschon, Milena Fini, Gina Lisignoli ACS Nano, 2024
Technologies for the Automation of Anatomic Pathology Processes: A Review Sabrina Ciancia, Lorenzo Vannozzi, Aliria Poliziani, Lorena Guachi-Guachi, Denise Amram, Dario Lunni, Alessandra Zucca, Marco Bellini, Luigi Spagnoli, Gian Andrea Pedrazzini, Andrea Cavazzana, Leonardo Ricotti IEEE Transactions on Medical Robotics and Bionics, 2024
Integration of Organic Field-Effect Transistor-based strain sensors to soft robotic devices and systems Usama Mahmood, Giulia Casula, Judith Llanos, Ignazio Niosiline, Carlotta Salvatori, Andrea Bartolucci, Florencia Lezcano, Maria Crespo, Leonardo Ricotti, Piero Cosseddu, Maria Guix, Lorenzo Vannozzi, Samuel Sanchez, Stefano Lai 6th IEEE International Flexible Electronics Technology Conference Ifetc 2024 Proceedings, 2024
Soft Perfusable Device to Culture Skeletal Muscle 3D Constructs in Air Federica Iberite, Marco Piazzoni, Daniele Guarnera, Francesco Iacoponi, Silvia Locarno, Lorenzo Vannozzi, Giacomo Bolchi, Federica Boselli, Irini Gerges, Cristina Lenardi, Leonardo Ricotti ACS Applied Bio Materials, 2023
Microgrooved ultra-thin films as building blocks of future bio-hybrid actuators Lorenzo Vannozzi, Leonardo Ricotti, Shaikha Alyassi, Claudia Bearzi, Cesare Gargioli, Roberto Rizzi, Kinda Khalaf, Paolo Dario, Arianna Menciassi Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society EMBS, 2015
