The bony remodeling observed in this model system appears to be a biological phenomena and not a result of altered mechanical loading, with the depth of the focal chondral defect (partial vs. full thickness) dictating the bony remodeling response. The type of cartilage injury should be carefully controlled in studies utilizing this model to evaluate TE approaches for cartilage repair.
Meniscal tears in the avascular zone have a poor self-healing potential, however partial meniscectomy predisposes the knee for early osteoarthritis. Tissue engineering with mesenchymal stem cells and a hyaluronan collagen based scaffold is a promising approach to repair meniscal tears in the avascular zone. 4 mm longitudinal meniscal tears in the avascular zone of lateral menisci of New Zealand White Rabbits were performed. The defect was left empty, sutured with a 5-0 suture or filled with a hyaluronan/collagen composite matrix without cells, with platelet rich plasma or with autologous mesenchymal stem cells. Matrices with stem cells were in part precultured in chondrogenic medium for 14 days prior to the implantation. Menisci were harvested at 6 and 12 weeks. The developed repair tissue was analyzed macroscopically, histologically and biomechanically. Untreated defects, defects treated with suture alone, with cell-free or with platelet rich plasma seeded implants showed a muted fibrous healing response. The implantation of stem cell-matrix constructs initiated fibrocartilage-like repair tissue, with better integration and biomechanical properties in the precultured stem cell-matrix group. A hyaluronan-collagen based composite scaffold seeded with mesenchymal stem cells is more effective in the repair avascular meniscal tear with stable meniscus-like tissue and to restore the native meniscus.
The biggest compartment of the musculoskeletal system is the tendons and ligaments. In particular, tendons are dense tissues connecting muscle to bone that are critical for the integrity, function and locomotion of this system. Due to the increasing age of our society and the overall rise in engagement in extreme and overuse sports, there is a growing prevalence of tendinopathies. Despite the recent advances in tendon research and due to difficult early diagnosis, a multitude of risk factors and vague understanding of the underlying biological mechanisms involved in the progression of tendon injuries, the toolbox of treatment strategies remains limited and non-satisfactory. This review is designed to summarize the current knowledge of triggers, trails and end state of tendinopathies.
BackgroundTendons are dense connective tissues and critical components for the integrity and function of the musculoskeletal system. Tendons connect bone to muscle and transmit forces on which locomotion entirely depends. Due to trauma, overuse and age-related degeneration, many people suffer from acute or chronic tendon injuries. Owing to their hypovascularity and hypocellularity, tendinopathies remain a substantial challenge for both clinicians and researchers. Surgical treatment includes suture or transplantation of autograft, allograft or xenograft, and these serve as the most common technique for rescuing tendon injuries. However, the therapeutic efficacies are limited by drawbacks including inevitable donor site morbidity, poor graft integration, adhesion formations and high rates of recurrent tearing. This review summarizes the literature of the past 10 y concerning scaffold-free and gel-based approaches for treating tendon injuries, with emphasis on specific advantages of such modes of application, as well as the obtained results regarding in vitro and in vivo tenogenesis.ResultsThe search was focused on publications released after 2006 and 83 articles have been analysed. The main results are summarizing and discussing the clear advantages of scaffold-free and hydrogels carriers that can be functionalized with cells alone or in combination with growth factors.ConclusionThe improved understanding of tissue resident adult stem cells has made a significant progress in recent years as well as strategies to steer their fate toward tendon lineage, with the help of growth factors, have been identified. The field of tendon tissue engineering is exploring diverse models spanning from hard scaffolds to gel-based and scaffold-free approaches seeking easier cell delivery and integration in the site of injury. Still, the field needs to consider a multifactorial approach that is based on the combination and fine-tuning of chemical and biomechanical stimuli. Taken together, tendon tissue engineering has now excellent foundations and enters the period of precision and translation to models with clinical relevance on which better treatment options of tendon injuries can be shaped up.
Total disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ. However, DAPS rapidly lost proteoglycan post-implantation and did not integrate into adjacent vertebrae. To address this, we modified the design to include polymer endplates to interface the DAPS with adjacent vertebrae, and showed that this modification mitigated in vivo proteoglycan loss while maintaining mechanical function and promoting integration. Together, these data demonstrate that cell-seeded engineered discs can replicate many characteristics of the native disc and are a viable option for total disc arthroplasty.
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