Hydrogel Containing Anti-CD44-Labeled Microparticles, Guide Bone Tissue Formation in Osteochondral Defects in Rabbits
Eva Filová,
Zbyněk Tonar,
Věra Lukášová,
Matěj Buzgo,
Andrej Litvinec,
Michala Rampichová,
Jiří Beznoska,
Martin Plencner,
Andrea Staffa,
Jana Daňková,
Miroslav Soural,
Jiří Chvojka,
Anna Malečková,
Milena Králíčková,
Evžen Amler
Affiliations
Eva Filová
Department of Tissue Engineering, Institute of Experimental Medicine of the Czech Academy of Science, Videnska 1083, 142 20 Prague 4, Czech Republic
Zbyněk Tonar
Institute of Histology and Embryology and Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Husova 3, 305 06 Pilsen, Czech Republic
Věra Lukášová
Department of Tissue Engineering, Institute of Experimental Medicine of the Czech Academy of Science, Videnska 1083, 142 20 Prague 4, Czech Republic
Matěj Buzgo
Department of Tissue Engineering, Institute of Experimental Medicine of the Czech Academy of Science, Videnska 1083, 142 20 Prague 4, Czech Republic
Andrej Litvinec
Department of Tissue Engineering, Institute of Experimental Medicine of the Czech Academy of Science, Videnska 1083, 142 20 Prague 4, Czech Republic
Michala Rampichová
Department of Tissue Engineering, Institute of Experimental Medicine of the Czech Academy of Science, Videnska 1083, 142 20 Prague 4, Czech Republic
Jiří Beznoska
Hospital of Rudolfa and Stefanie, a. s., Máchova 400, 256 30 Benešov, Czech Republic
Martin Plencner
Department of Tissue Engineering, Institute of Experimental Medicine of the Czech Academy of Science, Videnska 1083, 142 20 Prague 4, Czech Republic
Andrea Staffa
Department of Tissue Engineering, Institute of Experimental Medicine of the Czech Academy of Science, Videnska 1083, 142 20 Prague 4, Czech Republic
Jana Daňková
Department of Tissue Engineering, Institute of Experimental Medicine of the Czech Academy of Science, Videnska 1083, 142 20 Prague 4, Czech Republic
Miroslav Soural
Department of Organic Chemistry, Faculty of Science, Palacky University, 17. listopadu 12, 771 46 Olomouc, Czech Republic
Jiří Chvojka
Faculty of Textile Engineering, Technical University of Liberec, Studentská 2, 461 17 Liberec, Czech Republic
Anna Malečková
Institute of Histology and Embryology and Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Husova 3, 305 06 Pilsen, Czech Republic
Milena Králíčková
Institute of Histology and Embryology and Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Husova 3, 305 06 Pilsen, Czech Republic
Evžen Amler
Department of Tissue Engineering, Institute of Experimental Medicine of the Czech Academy of Science, Videnska 1083, 142 20 Prague 4, Czech Republic
Hydrogels are suitable for osteochondral defect regeneration as they mimic the viscoelastic environment of cartilage. However, their biomechanical properties are not sufficient to withstand high mechanical forces. Therefore, we have prepared electrospun poly-ε-caprolactone-chitosan (PCL-chit) and poly(ethylene oxide)-chitosan (PEO-chit) nanofibers, and FTIR analysis confirmed successful blending of chitosan with other polymers. The biocompatibility of PCL-chit and PEO-chit scaffolds was tested; fibrochondrocytes and chondrocytes seeded on PCL-chit showed superior metabolic activity. The PCL-chit nanofibers were cryogenically grinded into microparticles (mean size of about 500 µm) and further modified by polyethylene glycol–biotin in order to bind the anti-CD44 antibody, a glycoprotein interacting with hyaluronic acid (PCL-chit-PEGb-antiCD44). The PCL-chit or PCL-chit-PEGb-antiCD44 microparticles were mixed with a composite gel (collagen/fibrin/platelet rich plasma) to improve its biomechanical properties. The storage modulus was higher in the composite gel with microparticles compared to fibrin. The Eloss of the composite gel and fibrin was higher than that of the composite gel with microparticles. The composite gel either with or without microparticles was further tested in vivo in a model of osteochondral defects in rabbits. PCL-chit-PEGb-antiCD44 significantly enhanced osteogenic regeneration, mainly by desmogenous ossification, but decreased chondrogenic differentiation in the defects. PCL-chit-PEGb showed a more homogeneous distribution of hyaline cartilage and enhanced hyaline cartilage differentiation.