Broguiere Nicolas, Cavalli Emma, Salzmann Gian M, Applegate Lee Ann, Zenobi-Wong Marcy
ETH Zürich, Cartilage Engineering and Regeneration Laboratory, HPL J20, Otto-Stern-Weg 7, 8093 Zürich, Switzerland.
Schulthess Klinik, Lengghalde 2, 8008 Zürich, Switzerland.
ACS Biomater Sci Eng. 2016 Dec 12;2(12):2176-2184. doi: 10.1021/acsbiomaterials.6b00378. Epub 2016 Nov 7.
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.
在本研究中，对转谷氨酰胺酶交联透明质酸（HA-TG）水凝胶治疗软骨损伤的潜力进行了研究。我们表明，该水凝胶满足关键要求：它们同时具有可注射性、快速凝胶化、与包封细胞具有生物相容性、有促有丝分裂作用、具有软骨诱导性，并且能与天然软骨形成稳定且强力的黏附结合。包封在HA-TG凝胶中的人软骨祖细胞同时表现出良好的生长和软骨形成能力。令人惊讶的是，在软凝胶（约1千帕）中，软骨祖细胞增殖并沉积细胞外基质，以至于水凝胶在3周内达到接近天然软骨（约1兆帕）的模量（约0.3兆帕）。这种现成的人软骨祖细胞来源与HA-TG水凝胶的结合，为基于细胞的软骨损伤治疗奠定了基础，该治疗基于微创一步法，由于细胞明确而具有更高的可重复性，并且由于新的水凝胶化学性质而与周围组织具有更好的整合性。
