Current Trends in the Evaluation of Osteochondral Lesion Treatments: Histology, Histomorphometry, and Biomechanics in Preclinical Models

Abstract

Osteochondral lesions (OCs) are typically of traumatic origins but are also caused by degenerative conditions, in primis osteoarthritis (OA). On the other side, OC lesions themselves, getting worse over time, can lead to OA, indicating that chondral and OC defects represent a risk factor for the onset of the pathology. Many animal models have been set up for years for the study of OC regeneration, being successfully employed to test different treatment strategies, from biomaterials and cells to physical and biological adjuvant therapies. These studies rely on a plethora of post-explant investigations ranging from histological and histomorphometric analyses to biomechanical ones. The present review aims to analyze the methods employed for the evaluation of OC treatments in each animal model by screening literature data within the last 10 years. According to the selected research criteria performed in two databases, 60 works were included. Data revealed that lapine (50% of studies) and ovine (23% of studies) models are predominant, and knee joints are the most used anatomical locations for creating OC defects. Analyses are mostly conducted on paraffin-embedded samples in order to perform histological/histomorphometric analyses by applying semiquantitative scoring systems and on fresh samples in order to perform biomechanical investigations by indentation tests on articular cartilage. Instead, a great heterogeneity is pointed out in terms of OC defect dimensions and animal's age. The choice of experimental times is generally adequate for the animal models adopted, although few studies adopt very long experimental times. Improvements in data reporting and in standardization of protocols would be desirable for a better comparison of results and for ethical reasons related to appropriate and successful animal experimentation.

Long-term durable repaired cartilage induced by SOX9 in situ with bone marrow-derived mesenchymal stem cells

“…Here we used a surrogate to measure the quality of repaired cartilage - biomechanical property. Previous studies measuring cartilage biomechanical features involve separation of cartilage layer that are destructive 2 . Measurement of isolated cartilage suffers being destructive and inaccuracy in reflection of the property of articular cartilage in its native setting in the joint.…”

“…The technique employed in our study is a desirable measurement since it is nondestructive and measures cartilage biomechanical property with a subchondral bone as a single unit 9 . Indentation with a force to the intact cartilage surface in fresh tissue simulates in vivo situation 2 , 9 . It has been shown that indentation measurement of articular cartilage correlates with histological scores and biomechanical properties.…”

“…It has been shown that indentation measurement of articular cartilage correlates with histological scores and biomechanical properties. The measured electromechanical quantitative parameters are strongly related to the structure and organization of the collagen network and content of matrix protein such as proteoglycan 2 , 9 . Our results at both 12 and 24 weeks confirmed this correlation.…”

“…Quality articular cartilage repair remains an unmet need for treatment of cartilage injury to prevent progression into osteoarthritis (OA) 1 , 2 . Stimulating regeneration of articular cartilage by mobilizing bone marrow mesenchymal stem cells (MSCs) with microfracture has been a common procedure for treating cartilage injury in clinical practice in the expectation that hyaline cartilage will be regenerated.…”

Deep learning enables the automation of grading histological tissue engineered cartilage images for quality control standardization

“…J o u r n a l P r e -p r o o f chondrogenicity of engineered tissues, only qualitative manual scoring systems 8,11 . Today, deep learning methods are increasingly being used for biomedical image analysis and are widely available to researchers.…”