Abstract
Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP) were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies). Cartilage regeneration was expressed on an absolute 0–100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.
Highlights
Articular cartilage facilitates joint loading and movement by resisting compressive and shear forces (Swieszkowski et al, 2007)
In a previous systematic review and meta-analysis on animal models, we showed that acellular biomaterials in addition to bone marrow stimulation was more effective in regenerating cartilage in vivo than bone marrow stimulation alone, which was further improved by use of biologics (Pot et al, 2016)
Searching PubMed and EMBASE databases for references regarding cartilage regeneration by implantation of cellular and acellular biomaterials in the knee and ankle joint in combination with bone marrow stimulation resulted in a total of 11,248 references (Pubmed 4,743, Embase 6,505)
Summary
Articular cartilage facilitates joint loading and movement by resisting compressive and shear forces (Swieszkowski et al, 2007). Localized cartilage defects can have detrimental long term effects such as joint dysfunction, pain, and degenerative osteoarthritis. Clinical treatments for full-thickness cartilage defects and osteochondral lesions include bone marrow stimulation techniques, e.g., microfracture and subchondral drilling, and autologous chondrocyte implantation. Defect size generally determines treatment, where microfracture and autologous chondrocyte implantation are used to treat small (2.5 cm2), respectively (Cucchiarini et al, 2014). The formed blood clot consists of bone marrow-derived mesenchymal stem cells (BM-MSCs), growth factors and other proteins, supporting cartilage formation (Steadman, Rodkey & Rodrigo, 2001). Microfracture results in temporary clinical improvement only (Saris et al, 2014), and the demand for improved cartilage regeneration persists
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