Research Program 5
Project 5 Development of Lignin Based Medicinal Active Ingredients and Formulations
Institution: The Center of Excellence for Functional Surfaces and interfaces for Nano diagnostics (EFSUN)
The Center of Excellence for Functional Surfaces and interfaces for Nano diagnostics (EFSUN) was established in September of 2016. The Center aims at the discovery of efficient tools for an early, efficient accurate, cheap and on-site diagnosis of important health problems using nanotechnology tools. Highly qualified local researchers in various fields, including medicine, molecular biology, genetics, pathology, chemistry, physics, engineering, nanotechnology and electronics were brought together in the center in order to generate original, innovative and patentable knowledge and produce high impact research. Moreover, interdisciplinary nature of the center facilitates coordinated interactions between members from different fields to reach a common goal of generation of high-tech nano-based diagnostic devices. The advisory board consists of outstanding and experienced researchers from the best institutes and universities in the US and in Europe. EFSUN is now a center of attraction in the fields of nanotechnology and medical diagnostics in Turkey as well as in the region, and it always welcomes motivated researchers who would like to join forces to reach this goal.
The Center was founded by 5 scientists and were soon joined by more scientists, who are world-class experts in their respective fields. 14 out of the 36 scientists are staff members of Sabanci University and Sabanci University Nanotechnology and Applications Center (SUNUM). Contributing members are recipients of various prestigious national and international awards. Collaborations with the industry are ongoing. More than 33 Ph.D. students (26 Ph.D. students from Sabanci University) and 34 M.S. students (22 M.S. students from Sabanci University) as well as more than 10 Post Doctoral Research Associates (8 Post Doctoral Research Associates from Sabanci University/SUNUM) are benefitting from the stimulating and collaborative environment of the Center.
Within a short time, the Center became a ‘Research Powerhouse’ at Sabanci University with extensive and collaborative efforts of the members. EFSUN made it possible for several of its members to join TÜBİTAK 1004 projects such as NANOSIS, LIGNONANO and MEMS in the period 2021-2023. The research efforts and collaborations in the Center has led to more than 100 journal publications in top journals (such as International Journal of Heat and Mass Transfer, Chemical Engineering Journal, Scientific Reports, Nanoscale, Journal of Materials Chemistry C and etc.) within the last 5 years. 9 joint patents applications were made, and 3 joint patent grants were obtained within 12 months. The ongoing project budget currently amounts to around 2M USD. EFSUN is fully self-sustaining its finances and provides high impact research results.
EFSUN has also been organizing the Nanotechnology School for high school students, a 2 week intense educational activity, since early 2019 in collaboration with SUNUM of Sabancı University, providing awareness and knowledge to more than 400 students in the past 4 years.
Project 5.1 Development of Modified Lignin Based Tissue Adhesives
Project 5.1 Summary
Closing and healing of the wound are crucial for the success of surgical operations. Currently, traditional methods such as stitches, staples, clips, and skin closure strips are used as the gold standard to ensure wound closure. However, these methods have drawbacks such as the possibility of infection, the risk of tissue damage from stitches, high precision requirements, and the need for trained personnel. One of the new approaches applied today is the use of tissue adhesives.
In today's world, commercial tissue adhesives are available for use both internally and externally. However, they have various problems such as toxicity, kidney failure, delayed degradation, allergic reactions, excessive swelling, and high cost. Despite the existence of numerous commercial tissue adhesives, there is a need for new tissue adhesives, especially to meet different clinical requirements and to address the aforementioned drawbacks, particularly in the context of internal organ injuries and diseases. Therefore, research in this area continues to increase.
In this project; lignin-based hydrogel tissue adhesives with superior adhesion properties, supporting tissue regeneration, and hemostatic effect for surgical applications are being developed. In the project, after modifying lignin, the most abundant natural polymer in nature after cellulose, tissue adhesive formulations are developed with two different approaches. One of them is tissue adhesives based on silk fibroin, and the other is based on tannic acid and polycation coacervation. Injectable tissue adhesives obtained in both approaches are designed to cure in the presence of UV light.
Additionally, process design is carried out with the aim of recycling the waste generated according to the zero-waste principle, isolating by-products, and determining their areas of use in the project. Recycling and reuse of the solutions used are ensured.
In the project, 10 researchers competent in the fields of chemistry, engineering, and medicine from 3 different institutions contribute.
Project 5.2 Development of Lignin-Based Biocomposite Surgical Patches
Project 5.2 Summary: Hernia formation in the abdominal area after surgical operations is frequently seen around the world and can cause pain and infection in the patient after surgery. Approximately 50,000 postoperative hernias are repaired every year in Germany and 100,000 in the USA. The hernia repair market was valued at US$4.09 Billion in 2018, reaching a value of US$4.3 Billion in 2020, and going forward, IMARC Group estimates the market to reach a value of US$4.9 Billion by 2026. Accordingly, while the global hernia repair devices market was valued at US$ 3.49 billion in 2020, this market is expected to expand at a compound annual growth rate (CAGR) of 5.65% from 2021 to 2028.
Surgical patches are used quite frequently in the treatment of incisional hernias that may occur after open abdominal surgery, and it has been determined that the risk of recurrence of the disease in patients when using patches is 40% less compared to the use of standard sutures. Due to these advantages, hernia patches have become widely used, and thus the patches dominated the market with a revenue share of 76.1% in 2020.
Although the use of synthetic patches in hernia treatment has become widespread, it has been stated in the literature that such patches cause complications such as chronic infection, pain, and breakage or premature degradation of the patch. Along with these post-treatment complications, side effects such as bloating and intestinal disorders are also observed. In addition, biological patches should be used, especially in high-risk patients and those with the possibility of contamination in the surgery area. For these reasons, studies on the use of biodegradable, biocompatible materials and/or bio-synthetic composite patches recommended instead of synthetic patches have increased in recent years. However, studies on the use of biomaterials obtained from sustainable sources in surgical patches have not yet become widespread in the literature.
Lignin is one of the most widely used biocompatible, biodegradable natural polymers worldwide and is used in drug delivery and tissue engineering studies. In addition to its biocompatibility and biodegradability properties, lignin also exhibits antimicrobial and antioxidant properties. Although lignin is a potential material suitable for hernia patches thanks to all these properties, its use for hernia patches has not been found in the literature In this study, for the first time, it is aimed to design and produce lignin-based, drug-releasing, double-layered biocomposite patches for the purpose of preventing or treating postoperative hernia formation.
The project consists of 4 main work packages and will be carried out in cooperation with researchers competent in the field of materials and mechatronics engineering and medicine from 3 different institutions, and BETATECH MEDİKAL, a company operating in the commercialization of surgical patches.
Within the scope of the first work package, "Preparation of lignin-based biocomposite surgical patches", lignin-based patches will be produced and performance tests will be carried out in cooperation with Sabancı University and Betatech Medikal. The biocomposite patch to be produced has a two-layer structure, absorbable and non-absorbable. The non-absorbable layer will form the surface of the patch that will touch the internal organs, while the absorbable layer will be coated so as not to stick to the viscera. Within the scope of the second work package, "Simulation-based analysis and design studies", the SAbancı University team will carry out design studies based on computational analysis, and the designs obtained from this work package will be used in the synthesis of patches in the first work package. In this way, the composite surgical patches to be produced will be able to provide the mechanical properties required by the region where they are implanted, through their new material-based and numerical analysis-based design. Within the scope of the third work package, "Controlled agent release from patches", Koç University and SUNUM researchers will synthesize drug-loaded lignin-based nanoparticles, and the nanoparticles will be integrated into the patches with the joint work of IP 1 and IP 3 teams. In this way, different functions will be added to the patch. The most important of these are accelerating tissue integration and wound healing, reducing the risk of infection and post-operative pain control. Within the scope of the last work package, the fourth work package "In vitro/in vivo biocompatibility tests of surgical patches", KOÇ University and SUNUM researchers will conduct in vitro and in vivo studies of the developed surgical patches and nanoparticles and examine the biocompatibility of the patches.
At the end of the project, it is aimed to produce a prototype of lignin-based double-layer surgical patches that provide controlled drug release. Although there is no study in the literature on lignin-based surgical patch production, targeted agent release and computational analysis-based design ability increase the originality of the project. In this project, it is aimed to reach Technology Readiness Level-6 from the current Technology Readiness Level-3 with the prototype patches to be developed.