Summary
Bio-hydrogels composed of tandem repeats of particular proteins of extracellular matrix (ECM), which have the capability to be “self-organized”, “self-assembled” as well as cross-linked, and which carry specific peptides for cell binding, with the aim to promote chondrogenesis.
The project ArthroMicroPerMed combines personalized medical treatment for joint damage (Arthro) with the simultaneous injection of new “intelligent” biomaterials and homologous stem cells isolated from hip or knee for “arthro-neo-genesis” as well as the study of the effect of Microbe metabolites (Micro) in the origin of osteoarthritis.
In particular, bio-scaffolds that combine the elasticity and mechanical strength of elastin and fibroin of silk, respectively will be constructed with protein engineering methodologies. The proposed “intelligent” biomaterials are porous interconnected hydrogels composed of repetitive motifs of specific regions of above mentioned proteins (“recombinamer”), capable of “self-organizing” and fusion with α. peptides of BMP7 (Bone Morphogenetic Protein-7) and TgFb (Transforming Growth Factor b) that promote chondrogenesis (unpublished current results of the Laboratory of Biochemistry, AUTH) and b. collagen and laminin peptides – known from the international literature – that attract stem cells. This material is injectable and has additional heparin interaction sites, an essential component of the extracellular matrix (ECM).
The innovation of these “intelligent” materials also lies in their ability to “alert” bacterial infections by changing the color of the hydrogel. More specifically, its function is attributed to the change of color from blue to red when secreted bacterial toxins enter through the pores of the hydrogel, penetrate the lipid phase of the nanoparticles and change the structure of the polymer, which absorbs at a different wavelength. These innovative scaffolds will be co-injected with the personalized mesenchymal cells – they will be prepared by the participating company BioHellenika- in animal knee / hip cartilage and will be evaluated with specific cartilage components and immunohistochemical stains.
Another important novelty of this proposal is to study the effect of the microbiome both in the new biomimetic materials and in the prevention / “personalized treatment” of osteoarthritis (OA). The appropriateness and the effectiveness of the bio- scaffolds will be studied also with in vivo planned clinical trials in small animals with osteoarthritis by injecting the innovative material and monitoring / studying the follow up of treatment (abruption of chondrocyte apoptosis, formation of vitreous cartilage).