Tissue Engineering and Cell Therapy for Cartilage Repair: Preclinical Evaluation Methods.

A chondral injury is a limiting disease that can affect the quality of life and be an economic burden due to the cost of immediate treatment and loss in work productivity. If left untreated, such an injury may progress to osteoarthritis, a degenerative and debilitating joint disease characterized by pain and functional impairment. Mesenchymal stromal cells (MSCs), which have immune-modulatory properties and the ability to differentiate into chondroblasts and osteoblasts, are a predictable source for the treatment of cartilage injuries. This article presents tools to evaluate cartilage restoration by tissue engineering and cell therapy treatment in a translational and preclinical large animal model. In this controlled experimental study with 14 miniature pigs, a scaffold-free tissue engineering construct (TEC) derived from dental pulp and synovial MSCs for cartilage therapy was tested. Total thickness cartilage defects were performed in both posterior knees. The defect was left empty in one of the knees, and the other received the TEC. The tissue repair was morphologically assessed by magnetic resonance imaging (MRI) using the three-dimensional double echo steady-state (3D-DESS) sequence, and compositional assessment was carried out based on the T2 mapping technique. The osteochondral specimens were fixed for histopathology, decalcified, subjected to standard histological processing, sectioned, and stained with hematoxylin and eosin. The sections stained for immunohistochemical detection of collagen types were digested with pepsin and chondroitinase and incubated with antibodies against them. The mechanical evaluation involved analysis of Young's modulus of the cartilage samples based on the indentation and maximum compression test. In addition, a finite element model was used to simulate and characterize properties of the osteochondral block. At 6 months after surgery, there were no complications with the animals and the MRI, histological, immunohistochemical, and biomechanical evaluations proved to be effective and qualified to differentiate good quality chondral repair from inadequate repair tissue. The proposed methods were feasible and capable to properly evaluate the defect filled with TEC containing stromal cells after 6 months of follow-up in a large animal model for articular cartilage restoration. Impact Statement Articular chondral injuries are prevalent and represent an economic burden due to the cost of treatment. The engineering of cartilage tissue can promote the repair of chondral injuries and is dependent on selecting appropriate cells and biocompatible frameworks. In this article, methods for evaluation of a scaffold-free cell delivery system made from mesenchymal stromal cells were present in a translational study that allows further clinical safety and efficacy trials.

Anatomic Risk Factors for Focal Cartilage Lesions in the Patella and Trochlea: A Case-Control Study.

BACKGROUND: Focal cartilage lesions in the patellofemoral (PF) joint are common. Several studies correlated PF risk factors with PF instability, anterior knee pain, and PF arthritis; however, there is a lack of evidence correlating those factors to PF focal cartilage lesions. PURPOSE: To evaluate the influence of the anatomic PF risk factors in patients with isolated focal PF cartilage lesions. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients with isolated PF focal cartilage lesions were included in the cartilage lesion group, and patients with other pathologies and normal PF cartilage were included in the control group. Multiple PF risk factors were accessed on magnetic resonance imaging scans: patellar morphology (patellar width, patellar thickness, and patellar angle), trochlear morphology (trochlear sulcus angle, lateral condyle index, and trochlear sulcus depth), patellar height (Insall-Salvati ratio and Caton-Deschamps index), axial patellar positioning (patellar tilt, angle of Fulkerson), and quadriceps vector (tibial tuberosity-trochlear groove distance). RESULTS: A total of 135 patients were included in the cartilage lesion group and 100 in the control group. As compared with the control group, the cartilage lesion group had a higher sulcus angle (P = .0007), lower trochlear sulcus depth (P < .0001), lower angle of Fulkerson (P < .0001), lower patellar width (P = .0003), and higher Insall-Salvati ratio (P < .0001). From the patients in the cartilage lesion group, 36% had trochlear dysplasia; 27.6%, patella alta; and 24.7%, abnormal patellar tilt. These parameters were more frequent in the cartilage lesion group (P < .0001). Trochlear lesions were more frequent in men, presented at an older age, and had fewer associated anatomic risk factors. Patellar lesions, conversely, were more frequent in women, presented at younger age, and were more closely associated with anatomic risk factors. CONCLUSION: PF anatomic abnormalities are significantly more common in patients with full-thickness PF cartilage lesions. Trochlear dysplasia, patella alta, and excessive lateral patellar tilt are the most common correlated factors, especially in patellar lesions.