Osteochondral tissue cultures: Between limits and sparks, the next step for advanced in vitro models

Abstract

The increasing demand for reliable preclinical models and to reduce, refine and, if possible, replace animal studies have brought forth the development of complex tissue cultures in different research areas, including the musculoskeletal field. In this paper, we review the literature within last 10 years on the state of progress for in vitro models of osteochondral tissue cultures, taking into account the clinical relevance of the management and treatment of osteochondral lesions. According to the selected research criteria, 35 works, 27 of which with animal tissues and 8 with human tissues, resulted to be relevant for the purposes of this review. Data analyzed revealed a great heterogeneity among the proposed tissue culture models. The anatomical harvesting sites resulted to be mainly the knee stifle joint, both for animal (prevalently bovines) and human tissues derived from joint replacement surgery, and significant heterogeneity among culture conditions and media were found. To date, very few papers have focused on the set up of a reproducible in vitro model, applicable to a variety of studies, thus suggesting a relevant gap to fill in the development of advanced three-dimensional osteochondral culture models. K E Y W O R D S graft, in vitro culture, osteochondral, review, three-dimensional organ culture, tissue model 1 | INTRODUCTION The first observations of a pathological condition of the articular osteochondral district date back to at least three centuries. Over time, many authors have published works with assessment of lesions, characterized by damages of cartilage and subchondral bone (Laffenêtre, 2010). The current definition of "osteochondral lesion" (OCL) identifies a widespread condition which affects joints of different anatomical sites, mainly knee, followed by ankle and elbow and, less frequently, shoulder and hip. The etiology, which is still not completely understood, includes, among genetic factors and ischemic events, repetitive trauma, which is the most reported cause at time of diagnosis (Durur-Subasi, Durur-Karakaya & Yildirim, 2015). It is estimated that more than half of knee arthroscopy surgeries in the United States leads to the detection of OCL (Katagiri, Mendes & Luyten, 2017), reflecting the great prevalence of this pathological condition. Considering also the related decrease in patient quality of life and the costs for the NationalHealth System, it is intuitive that many preclinical in vivo studies are performed and are nowadays applied for the study of OCL treatments.Animal models for the study of OCL have been developed for years, being successfully used to test a plethora of treatment strategies, from biomaterials of different composition to physical therapies as pulsed electromagnetic fields (PEMFs;Benazzo et al., 2008;Kon et al., 2010;Veronesi et al., 2015). Animal models remain to be irreplaceable models in these studies given that, presently, alternative models (in vitro, in silico, and robotic) cannot recreate the complete biological setting of a complex organism in a trau...

Ex vivo Bone Models and Their Potential in Preclinical Evaluation

“…Osteoarthritis is a disease that is characterized by cartilage degeneration as well as changes in the subchondral bone with a close interrelationship between osteoblasts, osteoclasts, and chondrocytes [94]. Therefore, a clinically relevant preclinical model for osteoarthritis would involve explant tissue consisting of articular cartilage and subchondral bone, the so-called osteochondral unit, which can be obtained from distal femoral condyles or femoral heads [95][96][97]. However, osteochondral cultures were primarily optimized to investigate cartilage regeneration without considering the optimal culture conditions for bone [95,97,98].…”

“…Therefore, a clinically relevant preclinical model for osteoarthritis would involve explant tissue consisting of articular cartilage and subchondral bone, the so-called osteochondral unit, which can be obtained from distal femoral condyles or femoral heads [95][96][97]. However, osteochondral cultures were primarily optimized to investigate cartilage regeneration without considering the optimal culture conditions for bone [95,97,98]. Recently, a culture platform with two separated media compartments was established, which achieved a better reproduction of the in vivo situation because signaling between the cartilage and bone could only happen through the subchondral bone plate [99].…”

Biosensors for real‐time monitoring of physiological processes in the musculoskeletal system: A systematic review

“…None of the included studies evaluated biosensors by culturing them with other cell types of the musculoskeletal apparatus, such as osteoclasts, chondrocytes or ligament cells. After a preliminary screening in a 2D culture systems, it would be notably of interest the study of such biosensors with other relevant and more complex in vitro systems, as co and tri-cultures or ex vivo chondral, osteochondral, or bone explants (Forte et al, 2017;Maglio, Tschon, Sicuro, Lolli, & Fini, 2019;Pagani et al, 2018). The present review highlighted that the in vitro scenario pertaining to developing biosensors is undoubtedly still at an early phase and limited for what concerns both the type of bioanalyte to be measured and for the type of system detector used.…”

Human tissue culture of osteochondral defect: An advanced <em>in vitro</em> model

“…To date, as regards the study of osteochondral regeneration, the models present in literature are few, variable and difficult to compare with each other, creating an important gap in this research field. 1 Aim of the present study is to set up an in vitro 3D tissue models simulating osteochondral defects using human osteochondral tissue, in order to assess the best protocol to perform a long tissue culture for possible evaluation of the regenerative potential of biomaterials/bank products, cells, growth factors or combination of them.…”