Skip to main content
CTOS 2023 Main banner
Final Program


Schedule at a Glance
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Back

Preclinical Models & Translational Research

(P 253) THE EFFICACY OF MEDICATED PATCHES IN SOFT TISSUE SARCOMAS: IN-VITRO AND EX-VIVO VALIDATION.

Location: The Liffey, Level 1

    Co-Author(s)

  • Alessandro De Vita, PhD (he/him/his)

    Senior Researcher
    Istituto Scientifico Romagnolo per lo studio dei Tumori "Dino Amadori", Preclinic and Osteoncology Unit, Meldola, Italy
    Meldola, Emilia-Romagna, Italy

  • Claudia Cocchi, PhD (she/her/hers)

    Researcher
    Istituto Scientifico Romagnolo per lo studio dei Tumori "Dino Amadori", Preclinic and Osteoncology Unit, Meldola, Italy
    Meldola, Emilia-Romagna, Italy

  • EL

    Enrico Lucarelli, M. Sc, PhD

    Istituto Ortopedico Rizzoli IRCCS, Osteoncology- Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • Chiara Bellotti, M. Sc. (she/her/hers)

    Researcher
    Istituto Ortopedico Rizzoli IRCCS, Osteoncology- Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • Ania Naila Guerrieri, M. Sc, PhD (she/her/hers)

    Health researcher
    Istituto Ortopedico Rizzoli IRCCS, Osteoncology- Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • CL

    Chiara Liverani, PhD

    Researcher
    Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" IRST IRCCS, Preclinic and Osteoncology Unit, Meldola, Italy
    Bologna, Emilia-Romagna, Italy

  • GS

    Giulia Sbanchi, n/a

    Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" IRST IRCCS, Preclinic and Osteoncology Unit, Meldola, Italy
    Bologna, Emilia-Romagna, Italy

  • Maria Letizia Focarete, PhD (she/her/hers)

    Full Professor
    Department of Chemistry "Giacomo Ciamician", University of Bologna, 40126 Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • AL

    Anna Liguori, n/a

    Department of Chemistry "Giacomo Ciamician", University of Bologna, 40126 Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • LO

    Luna Oliveti, MSc

    Department of Chemistry "Giacomo Ciamician", University of Bologna, 40126 Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • CG

    Chiara Gualandi, PhD

    Department of Chemistry "Giacomo Ciamician", University of Bologna, 40126 Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • Tommaso Frisoni, PhD

    Consultant, Orthopaedic & Traumatology
    Istituto Ortopedico Rizzoli IOR IRCCS, SC Third Orthopaedic Clinic and Traumatology, Bologna Italy
    Bologna, Emilia-Romagna, Italy

  • DD

    Davide Maria M. Donati, MD

    Professor
    Istituto Ortopedico Rizzoli IOR IRCCS, SC Third Orthopaedic Clinic and Traumatology, Bologna Italy
    Bologna, Emilia-Romagna, Italy

  • GM

    Giacomo Miserocchi, MSc

    Researcher
    Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" IRST IRCCS, Preclinic and Osteoncology Unit, Meldola, Italy
    Bologna, Emilia-Romagna, Italy

  • Silvia Vanni, PhD (she/her/hers)

    Researcher
    Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" IRST IRCCS, Preclinic and Osteoncology Unit, Meldola, Italy
    Meldola, Emilia-Romagna, Italy

  • Chiara Spadazzi, PhD

    Researcher
    Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" IRST IRCCS, Preclinic and Osteoncology Unit, Meldola, Italy
    Meldola, Emilia-Romagna, Italy

  • CC

    Chiara Calabrese, MSc

    Researcher
    Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" IRST IRCCS, Preclinic and Osteoncology Unit, Meldola, Italy
    Bologna, Emilia-Romagna, Italy

  • SG

    Sofia Gabellone, n/a

    MsC
    Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" IRST IRCCS, Preclinic and Osteoncology Unit, Meldola, Italy
    Meldola, Emilia-Romagna, Italy

  • FP

    Federica Pieri, n/a

    Pathology Unit, "Morgagni-Pierantoni" Hospital, 47121 Forlì, Italy
    Bologna, Emilia-Romagna, Italy

  • rC

    roberto Casadei, MD

    Medical Doctor
    Orthopedic Unit, Morgagni-Pierantoni Hospital, 47121 Forli, Italy
    Forlì, Emilia-Romagna, Italy

  • Valentina Fausti, MD

    Medical Doctor
    Clinical and Experimental Oncology, Immunotherapy, Rare Cancers and Biological Resource Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy
    Meldola, Emilia-Romagna, Italy

  • LG

    Lorena Gurrieri, MD

    Medical Doctor
    Clinical and Experimental Oncology, Immunotherapy, Rare Cancers and Biological Resource Center, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy
    Meldola, Emilia-Romagna, Italy

  • MP

    Micaela Pannella, M.Sc, PhD

    Istituto Ortopedico Rizzoli IRCCS, Osteoncology- Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • MS

    Massimo Serra, MSc

    Istituto Ortopedico Rizzoli IRCCS, Osteoncology- Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • CH

    Claudia Hattinger, PhD

    Istituto Ortopedico Rizzoli IRCCS, Osteoncology- Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • Simona Paglia, PhD (she/her/hers)

    Project Manager
    Istituto Ortopedico Rizzoli IRCCS, Osteoncology- Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, Bologna, Italy
    Bologna, Emilia-Romagna, Italy

  • Toni Ibrahim, BSc, MSc, MD, PhD

    Director
    Istituto Ortopedico Rizzoli IRCCS, Osteoncology- Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, Bologna, Italy
    Bologna, Emilia-Romagna, Italy

    • Author(s)

  • Laura Mercatali, PhD (she/her/hers)

    Senior Researcher
    Istituto Ortopedico Rizzoli IRCCS, Osteoncology- Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, Bologna, Italy ; Istituto Scientifico Romagnolo per lo studio dei Tumori "Dino Amadori", Preclinic and Osteoncology Unit, Meldola, Italy
    Bologna, Emilia-Romagna, Italy

Objective: Soft Tissue sarcomas (STS) are a heterogeneous group of rare tumors with a set of specific clinical challenges, such as tumor recurrence and wound complications. To improve patients’ outcomes, innovative therapeutic strategies must be settled. Biomimetic materials with both, antitumor and regenerative agents could be used after surgery to induce the death of the residual cancer cells and restore the damaged tissue. To this purpose, we have developed a device designed for the treatment of patients with STS, and here we report its functional characterization.

Methods: The device was developed as a bioabsorbable, flexible and suturable patch. The patch consists of multiple layers of medicated materials, each with different functionality. The two outer layers consist of a biodegradable polymer (poly(L)lactic acid containing pluronic acid), while the inner layer is a methacrylate gelatin hydrogel. The anti-inflammatory drug Diclofenac (DICL) was added to both outer layers to ensure controlled release over 7 days, while the anticancer drug Epirubicin (EPI) was added to the inner hydrogel layer to obtain sustained release over 3 days. Drug release was assessed through HPLC-MS. The effect of single or combined (EPI-DCIL) drugs was evaluated in vitro and ex-vivo using commercial and patient-derived STS cell lines. Co-culture with normal fibroblasts was used to mimic soft tissue tumour microenvironment. Cell viability, growth, and necrosis were assessed. Immunofluorescence and confocal microscopy were also carried out to evaluate viability on STS cell-fibroblast co-culture.

Results: First, differential drug release from the devices was assessed. Results confirmed that EPI and DICL were released in a sustained manner over a period of 3 and 7 days, respectively.
Using the epithelioid sarcoma cell line (VA-ES-BJ), it was confirmed that functionalized EPI had the same cytotoxic effect on both 2D-grown and patch-grown tumor cells. In the murine embryonic fibroblast cell line (3T3), DICL decreased fibroblast survival. Co-culture showed no further effects of DICL on tumor cells and confirmed the pharmacological effect of EPI.
In ex-vivo analyses, only samples from patients diagnosed with myxofibrosarcoma were included in order to reduce variability due to different histotypes. In particular, primary cultures and a patient-derived myxofibrosarcoma cell line (MF-R3) were used. Both models showed a decrease in cell viability for EPI-medicated patches, although this was more evident in the patient-derived cell line, where a significantly reduced proliferation was also observed for DICL and EPI-DICL. LDH release, monitored as a sign of necrosis, was higher than unmedicated samples for DICL at day 3 and for EPI at day 7 in primary cultures. In the patient-derived cell line, a significant higher necrosis was observed at the end of the treatment for all the drug-medicated devices.

Conclusion: These results provide an in-vitro and ex-vivo proof of the efficacy of medicated patches in STS, establishing the basis for the application of these materials to control tumor growth. Further preclinical studies will be conducted to test whether they induce soft tissue regeneration as well.