Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair

Abstract

The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.

The Effect of CaV1.2 Inhibitor Nifedipine on Chondrogenic Differentiation of Human Bone Marrow or Menstrual Blood-Derived Mesenchymal Stem Cells and Chondrocytes

“…Previously published studies showed the chondrogenic potential of BMMSCs being high enough to be used for the cartilage regeneration purpose in vitro [ 43 , 44 ]. Our recently published findings also confirmed the higher chondrogenic potential of BMMSCs than other MSCs and their suitability for the investigation of chondrogenic differentiation mechanisms in model systems in vitro [ 41 , 45 ]. Human BMMSCs recruitment to the IL-8- and MIP-3α-containing scaffolds enhanced tissue regeneration of an osteochondral defect site in beagle knee articular cartilage [ 46 ].…”

“…The various types of the multipotent and pluripotent stem cells, tissue engineering technologies, including scaffolds or hydrogels, have been investigated for the cartilage tissue regenerating purposes [ 40 , 41 ]. The multipotent MSCs derived from the adipose [ 20 ], human synovial membrane [ 21 ], autologous and allogeneic bone marrow [ 22 , 23 ] and chondrocytes [ 24 , 25 ], umbilical cord [ 26 ] and other tissues in patients and animal models have been investigated for the OA regeneration purposes.…”

Role of hydrogels in osteoarthritis: A comprehensive review

“…However, adding the CS-Tyr/Gel/BM-MSCs composite downregulated the release of COMP and GAGs. 17 Interestingly, synovial cells from OA mice treated with glycosaminoglycan-based hydrogel incorporated with hyaluronic acid, chondroitin sulfate E disaccharide, and thermosensitive Pluronic F127 (PF-HA-diSE), indicating decreased expression of C5a, C8, C9, and SC5b-9. 18 SW1353 cells stimulated with IL-1β showed increased expression of NF-κB p65 and cyclooxygenase-2 (COX-2), but reduced levels of collagen II.…”

“…When OA patients' cartilage explants were incubated in chondrogenic condition and applied stronger mechanical load, the expression of extracellular matrix (ECM) components glycosaminoglycans (GAGs) and proteoglycans was reduced, and cartilage components (cartilage oligomeric matrix protein (COMP) and (GAGs)) were released as compared with not‐compressed OA cartilage explants. However, adding the CS‐Tyr/Gel/BM‐MSCs composite downregulated the release of COMP and GAGs 17 . Interestingly, synovial cells from OA mice treated with glycosaminoglycan‐based hydrogel incorporated with hyaluronic acid, chondroitin sulfate E disaccharide, and thermosensitive Pluronic F127 (PF‐HA‐diSE), indicating decreased expression of C5a, C8, C9, and SC5b‐9 18 .…”

“…Bone marrow mesenchymal stem cells were encapsulated in a chondroitin sulfate-tyramine-gelatin hydrogel (CS-Tyr/Gel/ BM-MSCs composite) and then treated under chondrogenic differentiation condition and applied mild mechanical load, showing increased expression of collagen II. 17 When OA patients' cartilage explants were incubated in chondrogenic condition and applied stronger mechanical load, the expression of extracellular matrix (ECM) components glycosaminoglycans (GAGs) and proteoglycans was reduced, and cartilage components (cartilage oligomeric matrix protein (COMP) and (GAGs)) were released as compared with not-compressed OA cartilage explants. However, adding the CS-Tyr/Gel/BM-MSCs composite downregulated the release of COMP and GAGs.…”