Bioprinting personalized cartilage implants
MatriChem, an innovative Bulgarian startup and a leader in the development and production of bioinks and bioresins for 3D bioprinting, in collaboration with Boxcol, an innovative Bulgarian startup and a leader in the production of FDM 3D printers, and the Medical University of Plovdiv, a leader in the construction and validation of bioprinted tissue models, was awarded an innovation grant by the National Innovation Fund, Bulgaria. The awarded project is titled “A comprehensive approach for the development of personalized bioprinted autologous cartilage implants“. The decision was announced on 30 November 2022 while the funding contract was signed in the beginning of December 2022. The funded project has a duration of 18 months.
Problem Statement
The hyaline cartilage is a type of connective tissue found in the joints, trachea, and nose. It has a smooth, shiny appearance, but it is uniquely important for its ability to absorb shock and enable smooth movement.
As we age, the ability of the hyaline cartilage to regenerate becomes limited, and in some cases, the cartilage may become damaged beyond the body's ability to repair it. This can lead to a range of problems, including pain, stiffness, and difficulty moving. Available treatments often have a very limited effect. As the cartilage wears away, the bones in the joint rub against each other, exacerbating the symptoms and resulting in osteoarthritis (OA). OA is a common condition that affects mostly middle-aged and older adults. However, younger individuals can also experience problems with hyaline cartilage, particularly if they engage in activities that put a lot of stress on their joints, such as high-impact sports.
OA is one of the leading causes of disability in Europe, where it is estimated to affect approximately 20% of adults, according to the European League Against Rheumatism. This number is expected to grow significantly with the expected increase of the median age of the European population by 4.5 years to 48.2 in the next 20 years.
There are several treatment options available for individuals with OA. These include non-surgical treatments, such as physical therapy, medications, and injections, as well as surgical procedures, such as joint replacement or cartilage repair surgery, e.g., microfracture (MF). MF is the most common regenerative therapy for damaged cartilage in joints, particularly the knee. MF relies on the body's own ability to repair. During it, a "microfracture" in the bone is introduced, which allows the skeletal stem cells inside to flow into the damaged area. They, in turn, transform into cartilage cells, repairing the joint. However, the formed tissue is fibrocartilage, which cannot entirely reproduce the function of the original hyaline cartilage. Thus, in the context of the lengthy process required to develop and approve the clinical use of medicinal products, the creation of an effective treatment for OA and/or prerequisites for such is highly urgent.
The primary goal of the project is the bioprinting and validation of a high fidelity biomimetic cartilage implant that reproduces the histomorphology and mechanical characteristics of articular cartilage.
Key Project Objectives
Development of a prototype of a high precision smart bioprinter.
Development of a chondrogenic ink with molecular, rheological and mechanical characteristics optimized for four-dimensional bioprinting a hyaline cartilage tissue.
Development of protocols for the processing of donor adipose tissue and optimization of the differentiation of multipotent cells into chondrocytes and their bioprinting.
Development of a biomimetic personalized cartilage implant reproducing the histomorphology and biochemistry of a hyaline cartilage.
The Partners
MatriChem develops universal and tissue-specific bioinks capable of reproducing tissue histomorphology with high fidelity. We validate the bioinks by cost-effective in vitro human tissue models.
MatriChem's team has multiyear experience in the field of bioprinting. This includes numerous achievements, such as the supervision of the first thesis on bioprinting defended in Bulgaria, as well as publishing the first peer-reviewed publication describing a locally developed bioprinted cancer model. The team's expertise is focused on the physical chemistry of polymers, but it is crucially complemented by key expertise in microbiology, molecular and cell biology, as well as experimental medicine. The team consists of experienced scientists, including professors, PhDs, and young researchers. In total, they have been involved in over 20 successful research projects, which have been reported at national and international scientific conferences.
Having obtained in 2021 the first-of-its-kind permission in Bulgaria for handling animal by-products to develop collagen for R&D purposes, in accordance with European Regulation and the principles of Good Laboratory Practices, MatriChem is in a unique position to develop and realize truly innovative products for tissue engineering.
BOXCOL is the first Bulgarian manufacturer of commercial FDM 3D printers and offers a wide spectrum of 3D printing products and services.
The team at BOXCOL has deep expertise in software and hardware engineering, including proficiency in modeling and designing 3D objects in CAD software. This expertise is complemented by their developed production and quality control processes in additive manufacturing. Their previous experience in the design and development of an extrusion bioprinter, as well as in research projects, is decisive for the successful completion of the current project. The team's software engineering competence, which includes the development, integration, and validation of a management control and automation system, adds to their uniquely tuned engineering mix.
Medical University of Plovdiv is the leading Bulgarian academic institution in the construction and validation of bioprinted tissue models.
MU-Plovdiv has rich research experience and deep biomedical expertise, essential for formulating effective and safe products and protocols that are suitable for validation in clinical applications. The wide expertise of the team includes specialists in medical biology, molecular and regenerative medicine, cell biology, reconstructive plastic surgery, and autologous adipose grafting. For the current project, the state of the art laboratory research infrastructure, the advanced skills in the isolation and cultivation of primary cells, as well as a variety of molecular biology techniques for characterisation and validation of different types of cell/tissue, are also indispensable for this project.
The team has authored pioneering for Bulgaria peer-reviewed publications on bioprinting. Furthermore, they have built an effective partnership with a successful French bioprinting company, creating 3D tissue models for the needs of the cosmetic industry, which also includes researcher exchanges for effective transfer of know-how.
The team consists of experienced scientists, including professors, MDs, PhDs, and talented young researchers. In total, they have been involved in tens of successful research projects, including the development of a bioprinted colorectal cancer model, which have been reported at national and international scientific conferences. The team is a member of TEDD (Tissue Engineering for Drug Development and Substance Testing), which is one of the largest bioengineering competence centres and as well as a unique education, R&D and networking platform, and the team's leading scientist represents Bulgaria at the Innovative Medicines Initiative, funded by the European Commission. Thereby, MU-Plovdiv and particularly the research group participating in this project stand at the forefront of 3D biofabrication and can deliver highly competitive scientific and biomedical outputs.