Shchotkina N. Bioengineering foundations of obtaining lyophilized tissue-modified biocompatible matrix for use in cardiac surgery

Around 275,000 surgical operations are performed worldwide each year for the implantation of heart valve prostheses, both mechanical and biological. However, their use has several drawbacks, such as the risk of thromboembolism, the need for lifelong anticoagulant therapy (mechanical prostheses), short lifespan, and the need for prosthesis replacement (biological prostheses). An alternative is bioimplants created based on xenotissues (for example, horses, pigs, cattles), which have mechanical and biological properties similar to human tissue. Implants, which are based on decellularized extracellular matrix tissue (bioengineering transformation), are increasingly used in reconstructive and regenerative medicine since they ensure repopulation by the recipient's own cells, rapid growth and regeneration. In addition, such bioimplants are considered less prone to calcification and provide better hemodynamic parameters. With its biomechanical properties, the extracellular matrix differs little from native pericardial tissue, making it suitable for replacing heart valves in adults and correcting congenital heart defects in children. Commercial xenotransplants for cardiothoracic surgery, decellularized by various methods, are available on the European and American markets. However, there are several factors that limit their use. Firstly, the manufacturing methods mostly involve the use of cytotoxic aldehydes, which can, in rare cases, cause rejection of the transplant. Additionally, the cost of glutaraldehyde-free matrices has increased three to four times. Besides the economic component, an important aspect is the lengthy certification process of foreign medical products in Ukraine, which is particularly complicated during epidemiological restrictions and a state of war. According to the current urgent need for medicine for high-quality biological material, domestic scientists have developed a unique method for decellularization of the tissue-modified matrix of the bovine pericardium, which has already successfully passed the stage of preclinical trials. However, the aim for further certification of the product is to establish an economically viable production process that complies with standards and legislative requirements. At the same time, the impact of sterilization and lyophilization on the properties of newly created transplants requires further research, which determines the relevance of defining optimal technology parameters, as both sterilization and lyophilization can significantly affect tissue stability. Thus, the relevance of this research is driven by the need to optimize the parameters of the tissue-modified matrix manufacturing process and ensure long-term storage of the product without loss of functional features. Creating a unique technological roadmap for manufacturing will allow certification of the medical device and speed up its use in cardiac surgical practice. The aim of the work was to justify the bioengineering approaches to obtain a lyophilized tissue-modified biocompatible matrix based on the pericardium of cattle suitable for use in cardio surgery. To achieve the goal, the following tasks were necessary: 1. Improve the scheme for obtaining tissue-modified matrix from cattle pericardium based on the analysis of critical points of the technology to improve the qualitative and techno-economic characteristics of the xenogeneic bioimplant; 2. Improve the scheme for sterilization of tissue-modified matrix based on cattle pericardium; 3. Develop a technological process to ensure the stability of the tissue-modified matrix based on cattle pericardium under conditions of long-term storage using lyophilization technology; 4. Develop hardware and technological schemes for the production of lyophilized tissue-modified biocompatible matrix based on cattle pericardium. For the first time, the hardware and technological schemes for obtaining a lyophilized tissue-modified biocompatible matrix of the cattle pericardium have been substantiated and developed based on a highly effective method of decellularization of xenogenic biomaterial, which provides technological and bioengineering equipment for the manufacturing of a bioimplant. For the first time, the algorithm for sterilization and lyophilization of tissue-modified matrix while preserving the architecture of the collagen-elastin framework has been scientifically substantiated and developed, which makes it possible to use it as a bioimplant in cardiovascular surgery.