Tissue-Engineered Cartilage Products

Autologous and Allogeneic Cytotherapies for Large Knee (Osteo)Chondral Defects: Manufacturing Process Benchmarking and Parallel Functional Qualification

“…In order to meet increasing clinical needs, important translational efforts are being allocated toward the optimization of existing ACI protocols or the creation of novel approaches [ 11 , 12 , 72 , 73 , 74 , 75 , 76 ]. Several generations of ACI have been clinically investigated and shown to yield positive impacts for treated patients [ 1 , 2 , 3 , 11 , 12 , 13 , 14 , 15 ]. Importantly, extensive, long-term, and large-scale clinical human data are available for ACI [ 15 , 22 , 29 , 30 ].…”

“…The aim of this study was to durably restore tissular structures and functions following lesion debridement and the creation of an optimal local environment for the cell-based product. Good clinical outcomes were obtained, yet a major cause of failure was the development of periosteal hypertrophy, requiring new surgical interventions [ 8 , 13 , 14 ]. Additionally, the surgery requires an open-joint procedure and the harvest of a periosteal flap, which is fragile and can tear during suturing.…”

“…However, articular cartilage is characterized by poor self-healing potential due to low vascularity and a limited supply of adjacent cells able to migrate to the lesion and mediate a healing response [ 2 , 3 , 6 ]. Therefore, various therapeutic approaches have been developed for the treatment of moderate knee chondropathies, such as microfracture (MFx) or osteochondral autografts and allografts, yet their use and efficacy are limited by the lesion type, size, and grade [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Importantly, the onset of severe OA often leads to the need to replace the arthritic surface with a synthetic prosthesis.…”

The place of Shi’i clerics in the first Iranian constitution

“…Further, this Ottoman article contained a provision for the protection of religious minorities, which affirmed that the Ottoman state would ''protect the free exercise of faiths professed in the empire.'' 13 Similarly, Article 37 of the Bulgarian Constitution stated that Eastern Orthodox Christianity was the state religion. Here again, provisions were added to safeguard the rights of religious minorities.…”

“…17 Under the Ottoman Constitution (Articles 4 and 11), the sultan retained the functions of both king and caliph, and was responsible for carrying out the shari'a as well as other laws. 13 Afary 331…”