Articular Cartilage Regeneration in Osteoarthritis

Abstract

There has been considerable advancement over the last few years in the treatment of osteoarthritis, common chronic disease and a major cause of disability in older adults. In this pathology, the entire joint is involved and the regeneration of articular cartilage still remains one of the main challenges, particularly in an actively inflammatory environment. The recent strategies for osteoarthritis treatment are based on the use of different therapeutic solutions such as cell and gene therapies and tissue engineering. In this review, we provide an overview of current regenerative strategies highlighting the pros and cons, challenges and opportunities, and we try to identify areas where future work should be focused in order to advance this field.

Keywords: cartilage; cell-based therapy; gene therapy; osteoarthritis; tissue-based therapy.

Figure 1

Representative micrographs of articular cartilage tissues representing healthy (a) and OA (b) stained with Safranin-O/Fast Green staining taken from the laboratory archive. Representation of typical healthy and OA features in the superficial, mid, deep, and calcified zones of articular cartilage. Scale bar: 100 µm; red staining: proteoglycan content; pinkish staining: depletion of proteoglycan content; green staining: collagen content. (a) Healthy articular cartilage, black arrows report: (i) the presence of flat cells in the ECM rich of collagen fibres in the superficial zone; (ii) the presence of round cells in the ECM rich of proteoglycans in the mid-zone; (iii) the presence of isogenic groups in the ECM rich of proteoglycans in the deep zone; and (iv) the presence of tidemark in the calcified zone. (b) OA articular cartilage, black arrow reports the presence of fibrillation in the superficial zone; red arrows report the presence of empty lacunae; blue arrow: tidemark interruptions; green arrow: trabecular spaces; # reports ECM release; * cluster clones.

Figure 2

Graphical representation of regenerative medicine strategies utilized to treat OA. Clockwise from the upper left: cell therapy, i.e., injection, grafting or implantation of cells previously manipulated ex vivo or non-manipulated (concentrates); tissue engineering, relying on the use of scaffolds which act as a template for cell attachment and reproduce as closely as possible cartilage ECM and can be produced by conventional or additive manufacturing procedures; growth factors, synthetic on naturals, to be used as adjuvants to favor tissue regeneration; gene therapy, with the aim to treat human diseases by correcting an existing abnormality or providing a new function by means of viral and non-viral (plasmids) vectors.

Figure 3

Schematic representation of the procedures needed to obtain (a) bone marrow aspirate (BMC) through a cell concentration step, from bone marrow; (b) stromal vascular fraction (SVF) from adipose tissue (enzymatic and mechanical procedures, followed by centrifugation).

Figure 4

Schematic representation of the bioprinting process. Cells and polymeric scaffolds are mixed together (bioink) and dispensed on a substrate in a layer-by-layer approach, in order to build a living structure mimicking native tissue.