Nowa generacja skafoldów na bazie kurdlanu i izolatu białka serwatkowego otrzymywanych metodą elektroprzędzenia do leczenia defektów chrzęstnych, kostnych i chrzęstno-kostnych

Effective treatment of cartilage, bone, and osteochondral defects still remains a challenge for modern medicine. These defects are the result of injuries, traffic accidents or pre-existing and existing diseases, and their frequency increases with the patient’s age. Although, autografts or alternative allografts are considered as gold standard in the treatment of these defects, they have many disadvantages, which restricts their use. To overcome limitations associated with traditional treatment methods, tissue engineering products (TEP) are increasingly being used. This modern approach includes application of artificial scaffold most often in combination with bioactive molecules (e.g., growth factors) and cells. Unfortunately, so far it has not been possible to develop biomaterials that meet all requirements, namely scaffolds that are at the same time biomimetic, porous, mechanically stable, and promote cell response as well as regeneration of surrounding tissues. Therefore, there is a need to work on new biomaterials that will have improved properties from the existing ones and will ensure the regeneration of mentioned tissues to a greater extent. This project is thus an attempt to respond to these needs and aims to develop a new generation of biomaterials based on two natural and non-toxic polymers, i.e., curdlan and whey protein isolate (WPI), using modern fabrication technique – electrospinning. In order to increase the biomimetic nature of designed biomaterials, they will be additionally enriched with ingredients that are of great importance in the regeneration of cartilage tissue (hyaluronic acid – HA or chondroitin sulfate - CS) and bone tissue (nanohydroxyapatite – nHAp, magnesium oxide – MgO or zinc oxide - ZnO nanoparticles). Moreover, osteochondral scaffolds will combine the best features of both cartilage and bone scaffolds, will have desired gradient structure, and will be additionally enriched with platelet-rich plasma (PRP), which is costeffective and an autologous source of various growth factors. Thus the novelty of this project includes the composition of biomaterials to increase their similarity to native tissues. Another originality of this project is the use of the electrospinning method for fabrication of scaffolds based on both curdlan and WPI. The use of this method will enable the fabrication of porous biomaterials that will more closely resemble the ECM of natural cartilage, bone, and osteochondral tissue. Within this project, newly designed biomaterials will be subjected to evaluation of their structural, physicochemical, and mechanical properties. Moreover, comprehensive biological characterization of the fabricated biomaterials will be also performed. For this purpose, it is planned to carry out a number of analyses, including: in vitro experiments, in vivo studies in the model of Danio rerio (zebrafish) larvae, ex ovo studies using chorioallantoic membrane (CAM) model, ex vivo tests, and in vivo studies on rats (but only on the best variants of biomaterials). This approach is motivated by compliance with the 3Rs principle (replacement, reduction, and refinement), which clearly indicates that the number of laboratory animals used in research should be limited. Therefore, it is worth underlining that this project fits into the standards of current research trends while maintaining the 3Rs principle. An advantage for the implementation of this project is research cooperation with several research units: Laboratory of Nanostructures, Institute of High Pressure Physics of the Polish Academy of Sciences, Poland; Center of Experimental Orthopaedics, Saarland University Medical Center, Saarland University, Germany; Department of Morphological Disciplines, University of Veterinary Medicine and Pharmacy in Kosice, Slovakia; and European Biomedical Institute, Poland. This interdisciplinary team, together with PI unit, will ensure the implementation of this project at a high, world-class level, as they have many years of knowledge and experience in specified fields. Considering the above, the implementation of this project will provide the answer whether new biomaterials based on curdlan and WPI, developed using nanotechnology have better properties than the existing ones and whether they are biosafe and have biomedical potential.