Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints: from bench to clinic

Abstract

Osteoarthritis is a degenerative joint disease, typified by the loss in the quality of cartilage and bone at the interface of a synovial joint, resulting in pain, stiffness and reduced mobility. The current surgical treatment for advanced stages of the disease is joint replacement, where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective. These are major surgical procedures which have a substantial impact on patients' quality of life and lifetime risk of requiring revision surgery. Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints. In this approach, 3-dimensional scaffolds (with or without cells) are employed to provide support for tissue growth. However, none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects. Herein, we discuss the current regenerative treatment options for cartilage and osteochondral (cartilage and underlying subchondral bone) defects in the articulating joints. We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues. The evolution of the osteochondral scaffolds - from monophasic to multiphasic constructs - is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices. Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge. Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements.

Keywords: cartilage injury; osteoarthritis; osteochondral scaffold; regenerative medicine; subchondral defect; tissue engineering.

Figure 1. Changes in the osteochondral unit in osteoarthritic joints. Cartilage thinning, blood vessels infiltration into cartilage and subchondral plate thickening with the progress of osteoarthritis (OA). Created with BioRender.com.

Figure 2. Osteoarthritis (OA) progression and treatment options: non-pharmacological and pharmacological therapies can be used for the treatment of mild and non-acute OA; when the cartilage and bone loss at the joint has significantly impacted the quality of life of the patient, and non-surgical treatments are no longer effective the current state of the art in terms of surgical intervention is a joint replacement operation. Osteochondral (OC) scaffold (with or without addition of cells, such as chondrocytes or stem cells and growth factors such as transforming growth factor-β) seeks to repair and regenerate the local cartilage defects at an early stage to stop or delay the progression of OA to avoid the use of joint replacements. Adapted from Tamaddon et al.

Figure 3. A literature search on scaffolds for cartilage repair was performed using Science Direct Databases from their inception to date for publications in English. The literature search showing: (A) the increasing number of researches on scaffolds for cartilage and osteochondral defects, and (B) in vivo performance evaluation of osteochondral scaffolds using animal models.

Figure 4. Cartilage/OCD treatment algorithm according to the condition and size of the defect. ACI: autologous chondrocyte implantation; MACI: matrix-assisted autologous chondrocyte implantation; MF: microfracture; OATS: osteochondral autograft transfer system.

Figure 5. Evolution of osteochondral scaffolds from monophasic to bi- and multi-phasic states seek to recapitulate the zonal property of osteochondral tissue, concept adapted from Jeon et al. with permission from Elsevier.

Figure 6. The novel multilayer osteochondral scaffold developed at University College London has achieved improved stable fixation via good bone integration which provides a strong support to the overlying cartilage healthy growth. Six months in vivo studies showed a hyaline-like cartilage formation, over 90% cartilage fill, and improved subchondral bone regeneration in a large OCD of sheep knee. OCD: osteochondral defect; PLA: polylactic acid; PLGA: polylactic acid; pQCT: peripheral quantitative computed tomography; Ti: titanium.