Scientists from three universities in Istanbul have developed a 3D-bioprinted microneedle-based patch system that combines chemotherapy and photothermal therapy on the same platform for the treatment of melanoma, one of the most aggressive types of skin cancer.
Initiated within the Health Biotechnology Center of Excellence Joint Application and Research Center (SABİOTEK)—established in 2022 through a partnership between Yıldız Technical University (YTU), Marmara University, and Istanbul University-Cerrahpaşa (IUC)—the research focuses on a next-generation microneedle platform designed to deliver drugs directly to the target area.
Within the scope of projects supported by TÜBİTAK and the Presidency of the Health Institutes of Turkey (TÜSEB), a microneedle-based patch system for melanoma treatment was developed under the leadership of Prof. Dr. Cem Bülent Üstündağ, a faculty member in the YTU Department of Bioengineering and SABİOTEK Director, with the participation of researchers from Marmara University and IUC.
As part of the study titled "3D-Printed Microneedle Patch for the Treatment of Melanoma via Synergistic Chemotherapy and Photothermal Therapy," hydrogel-based microneedles were produced utilizing 3D bioprinting technology.
In the system, which brings together chemotherapy and photothermal therapy on the same platform, the goal is to deliver the chemotherapeutic agent directly to the target area via microneedles and release it in a controlled manner. The photothermal component, on the other hand, converts light energy into heat, creating a localized temperature increase in the tumor region.
The combined use of these two mechanisms aims to increase the local efficacy of the treatment and reduce systemic side effects associated with the spread of the chemotherapeutic drug to other parts of the body.
While laboratory studies of the developed microneedle patch system on cancer cells have been completed, preclinical studies are planned for the subsequent phases of the research.
In a statement to the AA correspondent, Prof. Dr. Cem Bülent Üstündağ said that the foundation of their work on microneedle technology dates back to a TÜBİTAK project supported in 2021.
Stating that in the early stages of the project they compared gelatins produced from bovine skin in Turkey with a commercially available product widely used on an international scale, Üstündağ noted that they found the domestic gelatins exhibited similar properties.
Emphasizing that following these results, they used gelatins sourced from domestic resources in the development of microneedle-based drug delivery systems, Üstündağ explained that the work progressed with different applications and was subsequently advanced into a platform for melanoma treatment through projects supported by TÜBİTAK and TÜSEB.
Noting that they combined two different treatment mechanisms for melanoma in the TÜSEB-supported project, Üstündağ said, "We developed a microneedle-based patch that allows the combined use of chemotherapy and photothermal therapy, aiming to create a synergistic effect."
Stating that the microneedle system they developed consists of two distinct functional zones, Üstündağ noted that they utilized "graphene quantum dots" to create a photothermal effect.
Conveying that these dots, measuring approximately 5-10 nanometers, can generate heat when stimulated by light, Üstündağ stated that they placed these structures in the base section of the microneedle system, while placing 5-fluorouracil (5-FU)—used as the chemotherapeutic agent—in the tip section of the microneedles.
Explaining that the microneedles are produced from sodium alginate and gelatin-based biomaterials, Üstündağ continued as follows:
"Our aim is to stimulate the system externally with light after the microneedles penetrate the skin, thereby creating a controlled temperature increase in the target area. The local temperature rise, reaching approximately 42 degrees, can disrupt cellular processes in cancer cells and trigger programmed cell death mechanisms. At the same time, the generated heat contributes to the controlled release of the chemotherapeutic agent loaded into the microneedles. Thus, we present a dual-action approach that combines the photothermal effect and the chemotherapeutic effect within the same system."
Emphasizing that this method aims to administer the chemotherapeutic agent directly to the target area, Üstündağ noted that reducing the amount of drug entering the systemic circulation could provide a potential advantage in terms of limiting chemotherapy-related side effects.
Stating that the project outputs have also been exhibited on international platforms, Üstündağ said that the developed "3D-Printed Microneedle Patch for Melanoma" technology was awarded a gold medal and the World Intellectual Property Associations (WIIPA) Special Award at an international competition.
Stating that they have applied for two separate patents within the scope of the studies—one regarding the microneedle-based system and the other concerning a test platform they developed to evaluate the mechanical performance of the microneedles—Üstündağ said, "We developed a test system that evaluates to what extent the microneedle can penetrate the skin, the forces generated during application, and whether the microneedles reach the targeted skin layers."
Next stage: Preclinical studies
Prof. Dr. Üstündağ emphasized that experiments on cell culture for the developed system have been completed, and that more comprehensive preclinical and clinical research is required for it to reach clinical use.
Üstündağ said, "In the next stage, preclinical studies involving animal experiments need to be completed. If successful results are achieved, it will be possible to move on to clinical research phases. However, preclinical and clinical studies require long-term and high-budget research processes."
Stating that TÜBİTAK's and TÜSEB's supports for the development of health technologies reaching certain technology readiness levels are important, Üstündağ said that in order for academic research to transform into products, public support must be reinforced by industry cooperation.
Drawing attention to the significant projects carried out in the field of health technologies at universities, Üstündağ expressed, "We expect our industrialists to provide more support not only for our project, but also for innovative health technologies developed at universities. A strong university-industry collaboration is needed for scientific studies to transform from the laboratory to the product."
Stating that the technology development ecosystem created in the defense industry should also be strengthened in the field of health, Üstündağ noted that reducing foreign dependency in health technologies is important both strategically and economically.
Domestic raw material used in the study
Stating that gelatin, one of the main biomaterials used in the production of microneedles, was procured from a manufacturer operating in Turkey, Üstündağ said the domestic product was compared with a reference product from an international supplier and similar results were obtained.
Pointing out that following these results, they continued their work using domestic gelatin, Üstündağ stated that the developed approach has the potential to be evaluated as a local complementary method to surgical treatment in the future.
Üstündağ made the following assessment: "One of the long-term goals of our approach is to develop a local and complementary treatment option against cancer cells that may remain in the region following the surgical removal of the tumor. By combining the photothermal effect with the chemotherapeutic effect, we aim to create a synergistic strategy to eliminate remaining tumor cells. In order for this to be demonstrated clinically, preclinical and clinical studies must be completed."
