I am the principal investigator of the musculoskeletal tissue engineering lab. at Foundation, a biomedical and biotechnology
center of excellence in Palermo, Italy. I have been a visiting research scientist at University of Pittsburgh and at Children's Hospital of Philadelphia, two of the top research institutions in the US. I initially graduated from Pharmacy School, then continued to complete my PhD in Biotechnology at University of Palermo working on bone tissue engineering and on drug delivery for cancer and Alzheimer's. During my first postdoc, I developed polymeric drug delivery systems (DDS) to treat maculopathy. Then I worked for two years as a senior scientist at Merck in Rome, developing an anti-cancer monoclonal antibody currently commercialized in the US as Bavencio. Then, I joined the University of Bologna working on electrospun DDS for spinal cord injuries. In I am engineering 3D in vitro models to study and treat musculoskeletal disorders.
Tissue engineering for tendon and ligament repair: Insights and advances Francesca Romano, Francesco Lopresti, Roberto Di Gesù, Vincenzo La Carrubba View, 2025 Diseases and injuries affecting tendons (Ts) and ligaments (Ls) are among the most frequently diagnosed musculoskeletal disorders. Although many of these are not life threatening, they can cause severe debilitation, ultimately leading to substantial reductions in the patients’ mobility and quality of life. Even though the relevant advances in surgical and rehabilitative approaches to treat T/Ls diseases, the incidence of complications associated with those approaches is still too high, making T/Ls diseases an unmet clinical need. Currently, there is no consensus on an effective therapeutic strategy able to promote a complete T/Ls healing process. Over the past decade, there has been a growing interest in developing tissue‐engineered T constructs as viable graft alternatives. In this review, we aim to delve into the latest advancements in the field of tissue engineering for T repair. The most advanced technologies such as electrospinning, 3D printing, melt electrowriting, and hybrid fabrication techniques have been discussed, adopting critical connections with biological and biomolecular aspects. Furthermore, this review provides comprehensive insights into current strategies, and future directions, of T/Ls regeneration using tissue engineering approaches, thus paving the way to the development of new effective approaches to T/Ls diseases.
Engineering a Human-Sized Common Bile Duct Prototype with Regenerative Potential: In Vitro Evaluation of Mechanics, Function, Degradation, and Immune Modulation Mattia Pasqua, Marianna Barbuto, Matteo Calligaris, Roberto Di Gesù, Duilio Pagano, et al. Advanced Healthcare Materials, 2025 Tissue engineering offers new hope for treating biliary defects. Several scaffolds have been proposed, but their properties have not been fully investigated. In this study, the design, fabrication, and characterization of a novel common bile duct (CBD)‐like prototype are described. This prototype combines two biocompatible biomaterials, methacrylated type I collagen (CollMA) and poly(ε‐caprolactone) (PCL), along with biliary epithelial cells. CollMA supports the organization of biliary epithelial cells into a functional biliary‐like epithelium, as shown by histological, functional, and proteomic assays, while PCL provides mechanical strength. The biological and mechanical phases of the prototype are integrated into a multiphasic tubular scaffold using molding and electrospinning techniques. The final CBD‐like prototype consists of three interpenetrating phases: from innermost to outermost, these are biliary epithelial cell‐laden CollMA, PCL, and CollMA. This design overcomes challenges seen in multilayer constructs, such as interlayer delamination and lack of homogeneity. The prototype remains stable under physiological conditions, enables bile flow without leakage, and exhibits bile acid transport and modification activities, warranting future in vivo preclinical evaluation. In an ex vivo human blood assay, the acellular prototype elicited a favorable immune response, limiting inflammation and promoting sustained release of epidermal growth factor (EGF), indicating its potential to support regenerative processes.
Biofabrication of an in situ hypoxia-delivery scaffold for cartilage regeneration R Di Gesù, A Palumbo Piccionello, G Vitale, S Buscemi, S Panzavolta, et al. Biofabrication, 2025 Osteoarthritis (OA) is a debilitating joint condition affecting millions of people worldwide, triggering painful chondral defects (CDs) that ultimately compromise the overarching patients’ quality of life. Currently, several reconstructive cartilage techniques (RCTs) (i.e.: matrix-assisted autologous chondrocytes implantation has been developed to overcome the total joint replacement limitations in the treatment of CDs. However, there is no consensus on the effectiveness of RCTs in the long term, as they do not provide adequate pro-regenerative stimuli to ensure complete CDs healing. In this study, we describe the biofabrication of an innovative scaffold capable to promote the CDs healing by delivering pro-regenerative hypoxic cues at the cellular/tissue level, to be used during RCTs. The scaffold is composed of a gelatin methacrylate (GelMA) matrix doped with hypoxic seeds of GelMA functionalized with a fluorinated oxadiazole (GelOXA), which ensures the delivery of hypoxic cues to human articular chondrocytes (hACs) embedded within the scaffold. We found that the GelMA/GelOXA scaffold preserved hACs viability, maintained their native phenotype, and significantly improved the production of type II collagen. Besides, we observed a reduction in type I and type X collagen, characteristic of unhealthy cartilage. These findings pave the way for the regeneration of healthy, hyaline-like cartilage, by delivering hypoxic cues even under normoxic conditions. Furthermore, the GelMA/GelOXA scaffold’s ability to deliver healing signals directly to the injury site holds great potential for treating OA and related CDs, and has the potential to revolutionize the field of cartilage repair and regenerative medicine.
Engineered collagen-coated scaffolds for tendon repair: a novel drug delivery system Convegno Nazionale Di Bioingegneria, 2025
A High-Throughput Mechanical Activator for Cartilage Engineering Enables Rapid Screening of in vitro Response of Tissue Models to Physiological and Supra-Physiological Loads Elisa Capuana, Davide Marino, Roberto Di Gesù, Vincenzo La Carrubba, Valerio Brucato, et al. Cells Tissues Organs, 2023 Articular cartilage is crucially influenced by loading during development, health, and disease. However, our knowledge of the mechanical conditions that promote engineered cartilage maturation or tissue repair is still incomplete. Current in vitro models that allow precise control of the local mechanical environment have been dramatically limited by very low throughput, usually just a few specimens per experiment. To overcome this constraint, we have developed a new device for the high throughput compressive loading of tissue constructs: the High Throughput Mechanical Activator for Cartilage Engineering (HiT-MACE), which allows the mechanoactivation of 6 times more samples than current technologies. With HiT-MACE we were able to apply cyclic loads in the physiological (e.g., equivalent to walking and normal daily activity) and supra-physiological range (e.g., injurious impacts or extensive overloading) to up to 24 samples in one single run. In this report, we compared the early response of cartilage to physiological and supra-physiological mechanical loading to the response to IL-1β exposure, a common but rudimentary in vitro model of cartilage osteoarthritis. Physiological loading rapidly upregulated gene expression of anabolic markers along the TGF-β1 pathway. Notably, TGF-β1 or serum was not included in the medium. Supra-physiological loading caused a mild catabolic response while IL-1β exposure drove a rapid anabolic shift. This aligns well with recent findings suggesting that overloading is a more realistic and biomimetic model of cartilage degeneration. Taken together, these findings showed that the application of HiT-MACE allowed the use of larger number of samples to generate higher volume of data to effectively explore cartilage mechanobiology, which will enable the design of more effective repair and rehabilitation strategies for degenerative cartilage pathologies.
Generation of hepatobiliary cell lineages from human induced pluripotent stem cells: Applications in disease modeling and drug screening Mattia Pasqua, Roberto Di Gesù, Cinzia Maria Chinnici, Pier Giulio Conaldi, Maria Giovanna Francipane International Journal of Molecular Sciences, 2021 The possibility to reproduce key tissue functions in vitro from induced pluripotent stem cells (iPSCs) is offering an incredible opportunity to gain better insight into biological mechanisms underlying development and disease, and a tool for the rapid screening of drug candidates. This review attempts to summarize recent strategies for specification of iPSCs towards hepatobiliary lineages —hepatocytes and cholangiocytes—and their use as platforms for disease modeling and drug testing. The application of different tissue-engineering methods to promote accurate and reliable readouts is discussed. Space is given to open questions, including to what extent these novel systems can be informative. Potential pathways for improvement are finally suggested.
Advances in multidrug delivery from electrospun nanomaterials Roberto Di Gesù, Andrea Merlettini, Chiara Gualandi, Maria Letizia Focarete Core Shell Nanostructures for Drug Delivery and Theranostics Challenges Strategies and Prospects for Novel Carrier Systems, 2018
Tissue engineering for tendon and ligament repair: Insights and advances F Romano, F Lopresti, RD Gesù, V La Carrubba View 6 (6), 20250063 , 2025 2025 Citations: 1
TUNABLE SMART BIOMATERIAL FOR CARTILAGE REGENERATION (ULTRACART REGENERA) R Di Gesù, G Burriesci, F Lopresti, F Romano, S Di Leonardo, ... Orthopaedic Proceedings 107 (SUPP_8), 13-13 , 2025 2025
INNOVATIVE ELECTROSPUN SCAFFOLDS FOR TENDON REGENERATION: A NOVEL APPROACH TO PREVENT POST-SURGICAL FIBROSIS F Romano, F Lopresti, C Di Marco, V La Carrubba, R Di Gesù Orthopaedic Proceedings 107 (SUPP_6), 100-100 , 2025 2025
Engineering a Human‐Sized Common Bile Duct Prototype with Regenerative Potential: In Vitro Evaluation of Mechanics, Function, Degradation, and Immune Modulation M Pasqua, M Barbuto, M Calligaris, R Di Gesù, D Pagano, R Busà, ... Advanced Healthcare Materials 14 (21), 2501660 , 2025 2025 Citations: 1
Biofabrication of an in situ hypoxia-delivery scaffold for cartilage regeneration R Di Gesù, A Palumbo Piccionello, G Vitale, S Buscemi, S Panzavolta, ... Biofabrication 17 (2), 025025 , 2025 2025 Citations: 6
Engineered collagen-coated scaffolds for tendon regeneration: a multifunctional drug delivery approach F Di Marco, C., Romano, F Lopresti, S Campora, A Comelli, R Di Gesù, ... International Journal of Biological Macromolecules 315 (144445) , 2025 2025 Citations: 4
Scaffold for cartilage regeneration R Di Gesù, A Palumbo Piccionello, R Gottardi IT Patent P024171IT-01 , 2024 2024
Peptide direct growth on poly (acrylic acid)/poly (vinyl alcohol) electrospun fibers coated with branched poly (ethylenimine): A solid-phase approach for scaffolds … A Liguori, J Zhao, R Di Gesù, R De Marco, C Gualandi, N Calonghi, ... Colloids and Surfaces B: Biointerfaces 241, 114052 , 2024 2024 Citations: 3
Novel half Salphen cobalt(III) complexes: synthesis, DNA binding and anticancer studies BG Bonsignore R., Trippodo E., Di Gesù R., Carreca A.P., Rubino S., Spinello ... Dalton Transaction , 2024 2024 Citations: 14
Implantable composition for use in cartilage defects repair in post-surgery rehabilitation R Di Gesù, R Gottardi US Patent WO2024251364, P023293WO-01 , 2023 2023
BIOFABRICATION OF A TRIPHASIC VASCULO-OSSEOUS-CHONDRAL CONSTRUCT TO MODEL THE OSTEOCHONDRAL COMPLEX IN VITRO I Chiesa, C De Maria, A Lapomarda, GM Fortunato, PM Geheret, ... TISSUE ENGINEERING PART A 28, S156-S157 , 2022 2022
A mesoscale 3D culture system for native and engineered biphasic tissues: application to the osteochondral unit I Chiesa, R Di Gesù, KJ Overholt, R Gottardi Organ-on-a-Chip: Methods and Protocols, 267-281 , 2021 2021 Citations: 3
Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo M Bulati, R Busà, C Carcione, G Iannolo, G Di Mento, N Cuscino, ... Microorganisms 9 (6), 1317 , 2021 2021 Citations: 36
Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System BML Dolci L.S., Perone R.C., Di Gesù R., Kurakula M., Gualandi C., Zironi E ... https://doi.org/10.3390/pharmaceutics13060848 13 (6), 848-867 , 2021 2021 Citations: 17
Generation of Hepatobiliary Cell Lineages from Human Induced Pluripotent Stem Cells: Applications in Disease Modeling and Drug Screening M Pasqua, R Di Gesù, CM Chinnici, PG Conaldi, MG Francipane International Journal of Molecular Sciences 22 (15), 8227 , 2021 2021 Citations: 8
A High-Throughput Mechanical Activator for Cartilage Engineering Enables Rapid Screening of in vitro Response of Tissue Models to Physiological and Supra-physiological Loads GR Capuana E., Marino D., Di Gesù R., La Carrubba V., Brucato V., Rocky S.T. Cells, Tissues, Organs , 2021 2021 Citations: 24
Application of a Hyperelastic 3D Printed Scaffold for Mesenchymal Stem Cell-based Fabrication of a Bizonal Tendon Enthesis-like Construct R Gottardi, K Moeller, R Di Gesù, RS Tuan, M van Griensven, ... Frontiers in Materials 8, 21 , 2021 2021 Citations: 22
Endothelial cells support osteogenesis in an in vitro vascularized bone model developed by 3D bioprinting I Chiesa, C De Maria, A Lapomarda, GM Fortunato, F Montemurro, ... Biofabrication 12 (2), 025013 , 2020 2020 Citations: 127
Biodegradable electrospun fibers enriched with struvite crystal seeds for the recovery of phosphorous and nitrogen R Di Gesù, C Gualandi, A Zucchelli, A Liguori, L Paltrinieri, ML Focarete European Polymer Journal 122, 109389 , 2020 2020 Citations: 10
Biofabrication and characterization of a biphasic construct to study osteochondral tissue in vitro I Chiesa, C De Maria, A Lapomarda, GM Fortunato, F Montemurro, ... Convegno Nazionale di Bioingegneria, 155-158 , 2020 2020
MOST CITED SCHOLAR PUBLICATIONS
Endothelial cells support osteogenesis in an in vitro vascularized bone model developed by 3D bioprinting I Chiesa, C De Maria, A Lapomarda, GM Fortunato, F Montemurro, ... Biofabrication 12 (2), 025013 , 2020 2020 Citations: 127
Lipid nanoparticles for drug targeting to the brain ML Bondì, R Di Gesù, EF Craparo Methods in enzymology 508, 229-251 , 2012 2012 Citations: 68
3D Printing for Tissue Engineering in Otolaryngology R Di Gesù, A Acharya, I Jacobs, R Gottardi Connective Tissue Research 60 , 2019 2019 Citations: 50
Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo M Bulati, R Busà, C Carcione, G Iannolo, G Di Mento, N Cuscino, ... Microorganisms 9 (6), 1317 , 2021 2021 Citations: 36
Entrapment of an EGFR inhibitor into nanostructured lipid carriers (NLC) improves its antitumor activity against human hepatocarcinoma cells (vol 12, 21, 2014) R Di Gesu, ML Bondi, A Azzolina, EF Craparo, C Botto, E Amore, ... JOURNAL OF NANOBIOTECHNOLOGY 16 , 2018 2018 Citations: 32
A High-Throughput Mechanical Activator for Cartilage Engineering Enables Rapid Screening of in vitro Response of Tissue Models to Physiological and Supra-physiological Loads GR Capuana E., Marino D., Di Gesù R., La Carrubba V., Brucato V., Rocky S.T. Cells, Tissues, Organs , 2021 2021 Citations: 24
Application of a Hyperelastic 3D Printed Scaffold for Mesenchymal Stem Cell-based Fabrication of a Bizonal Tendon Enthesis-like Construct R Gottardi, K Moeller, R Di Gesù, RS Tuan, M van Griensven, ... Frontiers in Materials 8, 21 , 2021 2021 Citations: 22
Curcumin entrapped into lipid nanosystems inhibits neuroblastoma cancer cell growth and activates Hsp70 protein ML Bondì, EF Craparo, P Picone, MD Carlo, RD Gesu, G Capuano, ... Current Nanoscience 6 (5), 439-445 , 2010 2010 Citations: 21
Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System BML Dolci L.S., Perone R.C., Di Gesù R., Kurakula M., Gualandi C., Zironi E ... https://doi.org/10.3390/pharmaceutics13060848 13 (6), 848-867 , 2021 2021 Citations: 17
Novel half Salphen cobalt(III) complexes: synthesis, DNA binding and anticancer studies BG Bonsignore R., Trippodo E., Di Gesù R., Carreca A.P., Rubino S., Spinello ... Dalton Transaction , 2024 2024 Citations: 14
Lipid nanoparticles as delivery vehicles for the Parietaria judaica major allergen Par j 2 ML Bondì, G Montana, EF Craparo, R Di Gesù, G Giammona, A Bonura, ... International Journal of Nanomedicine, 2953-2962 , 2011 2011 Citations: 14
Advances in multidrug delivery from electrospun nanomaterials R Di Gesù, A Merlettini, C Gualandi, ML Focarete Core-Shell Nanostructures for Drug Delivery and Theranostics, 405-430 , 2018 2018 Citations: 13
Biodegradable electrospun fibers enriched with struvite crystal seeds for the recovery of phosphorous and nitrogen R Di Gesù, C Gualandi, A Zucchelli, A Liguori, L Paltrinieri, ML Focarete European Polymer Journal 122, 109389 , 2020 2020 Citations: 10
Electrospun Scaffolds in Tendons Regeneration: a review. R Di Gesù, G Amato, R Gottardi Muscles, Ligaments & Tendons Journal (MLTJ) 9 (4) , 2019 2019 Citations: 10
Lipid nanocarriers containing ester prodrugs of flurbiprofen preparation, physical-chemical characterization and biological studies ML Bondì, EF Craparo, P Picone, G Giammona, R Di Gesù, M Di Carlo Journal of Biomedical Nanotechnology 9 (2), 238-246 , 2013 2013 Citations: 9
Generation of Hepatobiliary Cell Lineages from Human Induced Pluripotent Stem Cells: Applications in Disease Modeling and Drug Screening M Pasqua, R Di Gesù, CM Chinnici, PG Conaldi, MG Francipane International Journal of Molecular Sciences 22 (15), 8227 , 2021 2021 Citations: 8
Biofabrication of an in situ hypoxia-delivery scaffold for cartilage regeneration R Di Gesù, A Palumbo Piccionello, G Vitale, S Buscemi, S Panzavolta, ... Biofabrication 17 (2), 025025 , 2025 2025 Citations: 6
Engineered collagen-coated scaffolds for tendon regeneration: a multifunctional drug delivery approach F Di Marco, C., Romano, F Lopresti, S Campora, A Comelli, R Di Gesù, ... International Journal of Biological Macromolecules 315 (144445) , 2025 2025 Citations: 4
Controlled and sustained release of a corticosteroid drug from block copolymers synthetized by ATRP P Valenti, G., La Carta, S., Mazzotti, G., Rapisarda, M., Perna, S., Di Gesù ... Polymer Engineering and Science , 2017 2017 Citations: 4
Peptide direct growth on poly (acrylic acid)/poly (vinyl alcohol) electrospun fibers coated with branched poly (ethylenimine): A solid-phase approach for scaffolds … A Liguori, J Zhao, R Di Gesù, R De Marco, C Gualandi, N Calonghi, ... Colloids and Surfaces B: Biointerfaces 241, 114052 , 2024 2024 Citations: 3