Osteochondral tissue engineering‑based subchondral bone plate repair (Review)

Abstract

Osteochondral defects are a series of pathological changes from the chondral surface to the deeper trabecular bone caused by trauma or degenerative changes; they typically induce serious joint dysfunction. Over the past few decades, various techniques have been attempted to repair these defects. Tissue‑engineered osteochondral grafts (TEOGs) with sophisticated architecture have been extensively explored for osteochondral regeneration. However, controversies persist regarding standards for clinical application of TEOGs. The present review focused on the design of TEOGs, emphasizing their capacity to repair the subchondral bone plate (SBP). The effect of animal models on techniques to repair osteochondral defects was also reviewed. To improve the evaluation of SBP regeneration, four typical histological characteristics (abnormal height, uneven surface, poor integration and loose internal structure) are summarized based on cases of unsatisfactory SBP regeneration. Incorporating mesenchymal stem cells with appropriate growth factors into trilayer or multilayer tissue‑engineered scaffolds is a promising strategy to avoid unsatisfactory SBP regeneration. Large animal models are recommended for translation to the clinic and there is a need to establish detailed and comprehensive osteochondral defect models in the future.

Keywords: osteochondral defect; osteochondral regeneration; subchondral bone plate; tissue engineering strategy; translational animal.

Figure 1.

Schematic of osteochondral unit structure and osteochondral defect definition. (A) The osteochondral unit is composed with articular cartilage and subchondral bone, (B) Schematic diagram of defect is exhibited and the different type of collagens are shown in the figure. As the depth of the defect deepens, the changes in the contents of water, oxygen and proteoglycan are also shown in the figure. Col, collagen.

Figure 2.

Overview of composition of tissue engineering osteochondral graft and clinical treatments for osteochondral lesion. (A) Graphical illustration of tissue engineering graft, including seeding cells, scaffolds and growth factors. Moreover, the cells are divided into two types, stem cells and somatic cells. Scaffolds are also divided into composite scaffolds and biomaterial scaffolds. (B) Summary of the development history of clinically utilized methods for the repair or/and regeneration of osteochondral lesions. PDCs, periosteum-derived cells; hiPSCs, human-induced pluripotent stem cells; ADSCs, adipose-derived stem cells; BMSCs, bone marrow stem cells; ACs, articular cells; PCL-PLGA, polycaprolactone-poly lactic-co-glycolic acid; SK-CS, silk-chitosan; GelMA, gelatin methacryloyl; ACM, acellular cartilage matrix; ECM, extracellular matrix; GDF, growth differentiation factor; FGF, fibroblast growth factor; IGF, insulin-like growth factor; BMP, bone morphogenetic protein; TGF, transforming growth factor.

Figure 3.

Natural history and typical schematic of unsatisfied subchondral bone plate regeneration in osteochondral defect repair. The following poor repair outcomes may occur after implantation of the graft into the defect, including abnormal height, uneven surface, poor integration and loose subchondral bone structure. These poor repair outcomes may eventually lead to serious problems, including fractures, osteochondritis, osteoporosis and bone necrosis. ACI, autologous chondrocyte implantation; MACI, matrix-induced autologous chondrocyte implantation.

Figure 4.

Diagram of seeding cells for tissue engineering osteochondral strategy. A schematic listing of the most commonly used seeding cell types, divided into stem cells and somatic cells, briefly simulates how they promote cartilage and/or subchondral bone regeneration in tissue engineered grafts. BMSCs, bone marrow stem cells; ADSCs, adipose-derived stem cells; PDCs, periosteum-derived cells.

Figure 5.

Preparation methods, materials types, structures and modifications of scaffolds for osteochondral repair. The illustration of preparation methods including 3D-printing, freeze-drying and electrospinning, scaffold designs including single, double, triple/multilayer and gradient and the main materials used in them respectively, as well as the functional modifications including growth factors, cells and exosomes. ECM, extracellular matrix; ACM, acellular cartilage matrix; HAp, hydroxyapatite; CCL, calcified cartilage layer; PCL/HA, polycaprolactone/hyaluronic acid; PLGA, poly lactic-co-glycolic acid.