Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

Abstract

One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by fully understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products.

Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair

“…ACI involves cell seeding in the defect depth and scaffold-based approaches, e.g., NOVOCART 3D ® , Bioseed ® , or MACI, are often associated with limited penetration of seeded chondrocytes into the scaffold (Huang et al, 2016). Although scaffold-based approaches show promising results, incomplete and moderate defect filling was reported in patients treated with NOVOCART 3D ® (Niethammer et al, 2016) or Bioseed ® (Kreuz et al, 2011) and MACI (Meyerkort et al, 2014), respectively.…”

“…The findings of this study may impact on cell-based cartilage repair strategies currently used in the clinic, as the majority of these do not provide homogeneous spatially distributed chondrocytes (Huang et al, 2016). ACI involves cell seeding in the defect depth and scaffold-based approaches, e.g., NOVOCART 3D ® , Bioseed ® , or MACI, are often associated with limited penetration of seeded chondrocytes into the scaffold (Huang et al, 2016).…”

“…Current clinical therapies are based on the introduction of a dense cell layer in the defect depth, e.g., by means of microfracture or application of ACI (Huang et al, 2016). Although the initial situation is different with MACI, as the chondrocytes are Chondrocytes were seeded at the bottom of the defect (A, 20x10 6 cells/ml), homogeneously in the hydrogel (B, 20x10 6 cell/ml), both at the bottom of the defect and in the hydrogel (C, 10x10 6 cell/ml + 10x10 6 cell/ml, respectively; D, 20x10 6 cell/ml + 20x10 6 cell/ml, respectively).…”

“…Contrarily, new hydrogel-based repair strategies allow homogeneous chondrocyte encapsulation and delivery into the defect, representing an alternative chondrocyte delivery approach. In order to optimize hydrogel-based therapies for clinical use, it is crucial to better understand the associated repair mechanisms (Huang et al, 2016) and to optimize the spatial chondrocyte distribution for cartilage repair. This study aimed to investigate the effect of spatial variations in chondrocyte distribution within a hydrogel construct on cartilage repair and to investigate the effect of the ex vivo OC plug model on tissue formation within the hydrogel, as well as to assess the contribution of endogenous and delivered cells to the formation of repair tissue.…”

Hydrogels and bioreactors for cartilage research and functional tissue engineering

“…The majority of autologous cellular products utilize cells which are derived from a tissue or blood biopsy and propagated in the laboratory before re-implantation with or without a scaffold, while others aim to create more mature cartilage constructs through extended ex vivo 3D tissue culture [396]. Regulation and approval of such products is overseen by the Center for Ham's F-12 media, either serum-free or supplemented with foetal bovine, autologous, or allogeneic serum [399]. Once a sufficient cell number is obtained, chondrocytes are either directly injected into the defect site (traditional ACI), or seeded onto 3D matrices and cultured for 3-35 days before implantation to allow for chondrocyte redifferentiation and construct maturation.…”