Factor XIII Cross-Linked Hyaluronan Hydrogels for Cartilage Tissue Engineering

In this study, transglutaminase-cross-linked hyaluronan (HA-TG) hydrogels are investigated for their potential to treat cartilage lesions. We show the hydrogels fulfill key requirements: they are simultaneously injectable, fast-gelling, biocompatible with encapsulated cells, mitogenic, chondroinductive, and form a stable and strongly adhesive bond to native cartilage. Human chondroprogenitors encapsulated in HA-TG gels simultaneously show good growth and chondrogenesis. Strikingly, within soft gels (∼1 kPa), chondroprogenitors proliferate and deposit extracellular matrix to the extent that the hydrogels reach a modulus (∼0.3 MPa) approaching that of native cartilage (∼1 MPa) within 3 weeks. The combination of such an off-the-shelf human chondroprogenitor cell source with HA-TG hydrogels lays the foundation for a cell-based treatment for cartilage lesions which is based on a minimally invasive one-step procedure, with improved reproducibility due to the defined cells and with improved integration with the surrounding tissue due to the new hydrogel chemistry.