Hydrogel Containing Anti-CD44-Labeled Microparticles, Guide Bone Tissue Formation in Osteochondral Defects in Rabbits

Abstract

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.

Microcarriers in application for cartilage tissue engineering: Recent progress and challenges

“… Polymer type Polymer name Targeted diseases Fabrication techniques Advantages Limitations Refs. Synthetic polymers Polysaccharides PLGA Osteochondral defect Osteoarthritis Acute arthritis Emulsion-solidcation Good biocompatibility Ease of functionalization Low bioactivity [ [85] , [86] , [87] , [88] , 92 , [212] , [213] , [214] , [215] , [216] , [217] , [218] , [219] , [220] , [221] , [222] , [223] , [224] ] PCL Endochondral defect Osteochondral Defects Emulsion-solidcation Biodegradability Good processability and compatibility Long-term mechanical stability Low bioactivity Hydrophobicity [ 93 , 95 , 225 , 226 ] PLA Osteochondral defect Cartilage defects Osteoarthritis Degeneration of articular cartilage Emulsion-solidcation Electrostatic spraying Good bioco...…”

Advances in Electrospun Hybrid Nanofibers for Biomedical Applications

“…The system showed functional proteins on the surface and controlled degradation based on functionalization degree. Similarly, chitosan nanofibers prepared by needleless spinning were functionalized by anti-CD44 antibodies, resulting in enhanced osteogenesis in vivo [ 211 ]. Thus, needleless electrospinning can produce nanofibers on an industrial scale, and helps with the translation of the functionalization system to clinical practice.…”

Progress of Platelet Derivatives for Cartilage Tissue Engineering

“…The release of GFs varied from material to material, while all prolonged to more than 35 days. In some strategies with particle materials involved as previously mentioned, platelet derivatives are not only used as bioactive agent sources for biological promotion but also as a material to establish links between the particles and provide at least part of the mechanical support ( Santo et al, 2015 ; Filova et al, 2020 ; Wu et al, 2021 ).…”