Tissue engineering and future directions in regenerative medicine for knee cartilage repair: a comprehensive review.

This review evaluates the current landscape and future directions of regenerative medicine for knee cartilage repair, with a particular focus on tissue engineering strategies. In this context, scaffold-based approaches have emerged as promising solutions for cartilage regeneration. Synthetic scaffolds, while offering superior mechanical properties, often lack the biological cues necessary for effective tissue integration. Natural scaffolds, though biocompatible and biodegradable, frequently suffer from inadequate mechanical strength. Hybrid scaffolds, combining elements of both synthetic and natural materials, present a balanced approach, enhancing both mechanical support and biological functionality. Advances in decellularized extracellular matrix scaffolds have shown potential in promoting cell infiltration and integration with native tissues. Additionally, bioprinting technologies have enabled the creation of complex, bioactive scaffolds that closely mimic the zonal organization of native cartilage, providing an optimal environment for cell growth and differentiation. The review also explores the potential of gene therapy and gene editing techniques, including CRISPR-Cas9, to enhance cartilage repair by targeting specific genetic pathways involved in tissue regeneration. The integration of these advanced therapies with tissue engineering approaches holds promise for developing personalized and durable treatments for knee cartilage injuries and osteoarthritis. In conclusion, this review underscores the importance of continued multidisciplinary collaboration to advance these innovative therapies from bench to bedside and improve outcomes for patients with knee cartilage damage.

Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair.

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 Effects of Mechanical Load on Chondrogenic Responses of Bone Marrow Mesenchymal Stem Cells and Chondrocytes Encapsulated in Chondroitin Sulfate-Based Hydrogel.

Articular cartilage is vulnerable to mechanical overload and has limited ability to restore lesions, which leads to the development of chronic diseases such as osteoarthritis (OA). In this study, the chondrogenic responses of human bone marrow mesenchymal stem cells (BMMSCs) and OA cartilage-derived chondrocytes in 3D chondroitin sulfate-tyramine/gelatin (CS-Tyr)/Gel) hydrogels with or without experimental mechanical load have been investigated. Chondrocytes were smaller in size, had slower proliferation rate and higher level of intracellular calcium (iCa2+) compared to BMMSCs. Under 3D chondrogenic conditions in CS-Tyr/Gel with or without TGF-ß3, chondrocytes more intensively secreted cartilage oligomeric matrix protein (COMP) and expressed collagen type II (COL2A1) and aggrecan (ACAN) genes but were more susceptible to mechanical load compared to BMMSCs. ICa2+ was more stably controlled in CS-Tyr/Gel/BMMSCs than in CS-Tyr/Gel/chondrocytes ones, through the expression of L-type channel subunit CaV1.2 (CACNA1C) and Serca2 pump (ATP2A2) genes, and their balance was kept more stable. Due to the lower susceptibility to mechanical load, BMMSCs in CS-Tyr/Gel hydrogel may have an advantage over chondrocytes in application for cartilage regeneration purposes. The mechanical overload related cartilage damage in vivo and the vague regenerative processes of OA chondrocytes might be associated to the inefficient control of iCa2+ regulating channels.

Modeling the Effect of Annulus Fibrosus Stiffness on the Stressed State of a Vertebral L1 Body and Nucleus Pulposus.

The investigation examines the transference of stiffness from intervertebral discs (IVDs) to the lumbar body of the L1 vertebra and the interactions among adjacent tissues. A computational model of the vertebra was developed, considering parameters such as cortical bone thickness, trabecular bone elasticity, and the nonlinear response of the nucleus pulposus to external loading. A nonlinear dynamic analysis was performed, revealing certain trends: a heightened stiffness of the annulus fibrosus correlates with a significant reduction in the vertebral body's ability to withstand external loading. At a supplied displacement of 6 mm, the vertebra with a degenerative disc reached its yielding point, whereas the vertebrae with a healthy annulus fibrosus exhibited a strength capacity exceeding 20%. The obtained findings and proposed methodology are potentially useful for biomedical engineers and clinical specialists in evaluating the condition of the annulus fibrosus and predicting its influence on the bone components of the spinal system.

Menstrual Blood-Derived Stem Cell Paracrine Factors Possess Stimulatory Effects on Chondrogenesis In Vitro and Diminish the Degradation of Articular Cartilage during Osteoarthritis.

Articular cartilage is an avascular tissue with a limited capacity for self-regeneration, leading the tissue to osteoarthritis (OA). Mesenchymal stem cells (MSCs) are promising for cartilage tissue engineering, as they are capable of differentiating into chondrocyte-like cells and secreting a number of active molecules that are important for cartilage extracellular matrix (ECM) synthesis. The aim of this study was to evaluate the potential of easily accessible menstrual blood-derived MSC (MenSC) paracrine factors in stimulating bone marrow MSC (BMMSCs) chondrogenic differentiation and to investigate their role in protecting cartilage from degradation in vitro. MenSCs and BMMSCs chondrogenic differentiation was induced using four different growth factors: TGF-ß3, activin A, BMP-2, and IGF-1. The chondrogenic differentiation of BMMSCs was stimulated in co-cultures with MenSCs and cartilage explants co-cultured with MenSCs for 21 days. The chondrogenic capacity of BMMSCs was analyzed by the secretion of four growth factors and cartilage oligomeric matrix protein, as well as the release and synthesis of cartilage ECM proteins, and chondrogenic gene expression in cartilage explants. Our results suggest that MenSCs stimulate chondrogenic response in BMMSCs by secreting activin A and TGF-ß3 and may have protective effects on cartilage tissue ECM by decreasing the release of GAGs, most likely through the modulation of activin A related molecular pathway. In conclusion, paracrine factors secreted by MenSCs may turn out to be a promising therapeutical approach for cartilage tissue protection and repair.

Modeling the Impact of Meniscal Tears on von Mises Stress of Knee Cartilage Tissue.

The present study aims to explore the stressed state of cartilage using various meniscal tear models. To perform this research, the anatomical model of the knee joint was developed and the nonlinear mechanical properties of the cartilage and meniscus were verified. The stress-strain curve of the meniscus was obtained by testing fresh tissue specimens of the human meniscus using a compression machine. The results showed that the more deteriorated meniscus had greater stiffness, but its integrity had the greatest impact on the growth of cartilage stresses. To confirm this, cases of radial, longitudinal, and complex tears were examined. The methodology and results of the study can assist in medical diagnostics for meniscus treatment and replacement.