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Tissue engineering of functional articular cartilage: the current status.

Kock L, van Donkelaar CC, Ito K - Cell Tissue Res. (2011)

Bottom Line: The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area.In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation.In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.

ABSTRACT
Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The results of joint-preserving treatment protocols such as debridement, mosaicplasty, perichondrium transplantation and autologous chondrocyte implantation vary largely and the average long-term result is unsatisfactory. One reason for limited clinical success is that most treatments require new cartilage to be formed at the site of a defect. However, the mechanical conditions at such sites are unfavorable for repair of the original damaged cartilage. Therefore, it is unlikely that healthy cartilage would form at these locations. The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area. This review outlines the issues related to the composition and functionality of tissue-engineered cartilage. In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation. In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality.

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Related in: MedlinePlus

Sections of cultured periosteal explants, stained with Safranin-O (red, proteoglycans)/Fast Green (blue, collagen) (a–d, magnification ×40) and with antibodies for collagen types I and II (e–h, magnification ×40). Cartilage was produced by the explants between agarose layers, with and without addition of TGF-β1 (a, b) and collagen type II was synthesized in this cartilage (e–f). Only collagen type I was visible in explants that were cultured under tension by dynamic loading and no cartilage was formed (c, g). When dynamic loading was combined with TGF-β1 supplementation, cartilage formation was visible (d) and collagen type II could be seen in the chondrogenic area (h)
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Fig1: Sections of cultured periosteal explants, stained with Safranin-O (red, proteoglycans)/Fast Green (blue, collagen) (a–d, magnification ×40) and with antibodies for collagen types I and II (e–h, magnification ×40). Cartilage was produced by the explants between agarose layers, with and without addition of TGF-β1 (a, b) and collagen type II was synthesized in this cartilage (e–f). Only collagen type I was visible in explants that were cultured under tension by dynamic loading and no cartilage was formed (c, g). When dynamic loading was combined with TGF-β1 supplementation, cartilage formation was visible (d) and collagen type II could be seen in the chondrogenic area (h)

Mentions: The importance of the arcade-like collagen structure for the load-bearing properties of native cartilage is well-emphasized in literature (Korhonen and Herzog 2008; Owen and Wayne 2006; Wilson et al. 2007; Shirazi and Shirazi-Adl 2008; Shirazi et al. 2008; Bevill et al. 2010). It is logical to assume that this collagen architecture reproduced in engineered cartilage tissue would lead to superior mechanical properties. However, only a few studies have focused on the importance of depth-dependent material properties in engineered cartilage. However, using depth-dependent scaffold properties or cell sources did not lead to an arcade-like collagen structure (Kim et al. 2003; Malda et al. 2005; Ng et al. 2005, 2006; Klein et al. 2007; Moutos et al. 2007). Mechanical loading could be another stimulus for obtaining an anisotropic distribution of collagen in engineered cartilage. The rationale is that, at birth, cartilage contains a random collagen structure. However, a few months after animals start to walk, cartilage develops its arcade-like structure (van Turnhout et al. 2010). Radial confinement of self-assembled constructs increased collagen organization in the direction perpendicular to the articular surface, with no change in collagen or GAG content (Elder and Athanasiou 2008). Furthermore, using polarized light microscopy, it has been shown that unconfined compression aligns collagen fibers perpendicular to the compressive loading direction (Kelly et al. 2006), i.e. aligned with the direction in which it cyclically elongates due to Poissons effects and incompressibility of the tissue. The strain field generated by applying unconfined compression may be useful to generate a superficial zone with collagen fibers parallel to the surface or higher modulus near the surface (Kelly et al. 2006; Khoshgoftar et al. 2011). However, a physiological collagen network with additional vertical fibers in the deep zone may not be produced by this loading regime, since vertical strains are absent. A numerical study by Khoshgoftar et al. (2011) suggests that a loading regime involving indentation with subsequent sliding of the indenter can stimulate the formation of an appropriate superficial zone with parallel collagen fibers. Adding lateral compression to this loading regime may stimulate the formation of a deep zone with perpendicularly aligned fibers, creating an arcade-like collagen architecture. Currently, in our group, experiments are pending in which this loading regime is applied to chondrocyte-seeded agarose constructs in order to create a physiological collagen network in the engineered cartilage. This particular sliding indentation setup has already been shown to stimulate collagen synthesis in periosteum tissue (Fig. 1) (Kock et al. 2010). In that study, periosteal explants were embedded in between agarose layers, which induced cartilage formation, confirmed by synthesis of sGAG and collagen type II (Fig. 1a, e). Addition of TGF-β1 to the culture medium did not further enhance this chondrogenic response (Fig. 1b, f). Applying sliding indentation only to the periosteum inbetween agarose layers enhanced the production of collagen type I, leading to the formation of fibrous tissue without any evidence of cartilage formation (Fig. 1c, g). However, when stimulated by both TGF-β1 and sliding indentation, collagen production was still enhanced, but now it was collagen type II, while sGAG was found to be similar to TGF-β1 or unloaded samples (Fig. 1d, h).Fig. 1


Tissue engineering of functional articular cartilage: the current status.

Kock L, van Donkelaar CC, Ito K - Cell Tissue Res. (2011)

Sections of cultured periosteal explants, stained with Safranin-O (red, proteoglycans)/Fast Green (blue, collagen) (a–d, magnification ×40) and with antibodies for collagen types I and II (e–h, magnification ×40). Cartilage was produced by the explants between agarose layers, with and without addition of TGF-β1 (a, b) and collagen type II was synthesized in this cartilage (e–f). Only collagen type I was visible in explants that were cultured under tension by dynamic loading and no cartilage was formed (c, g). When dynamic loading was combined with TGF-β1 supplementation, cartilage formation was visible (d) and collagen type II could be seen in the chondrogenic area (h)
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3306561&req=5

Fig1: Sections of cultured periosteal explants, stained with Safranin-O (red, proteoglycans)/Fast Green (blue, collagen) (a–d, magnification ×40) and with antibodies for collagen types I and II (e–h, magnification ×40). Cartilage was produced by the explants between agarose layers, with and without addition of TGF-β1 (a, b) and collagen type II was synthesized in this cartilage (e–f). Only collagen type I was visible in explants that were cultured under tension by dynamic loading and no cartilage was formed (c, g). When dynamic loading was combined with TGF-β1 supplementation, cartilage formation was visible (d) and collagen type II could be seen in the chondrogenic area (h)
Mentions: The importance of the arcade-like collagen structure for the load-bearing properties of native cartilage is well-emphasized in literature (Korhonen and Herzog 2008; Owen and Wayne 2006; Wilson et al. 2007; Shirazi and Shirazi-Adl 2008; Shirazi et al. 2008; Bevill et al. 2010). It is logical to assume that this collagen architecture reproduced in engineered cartilage tissue would lead to superior mechanical properties. However, only a few studies have focused on the importance of depth-dependent material properties in engineered cartilage. However, using depth-dependent scaffold properties or cell sources did not lead to an arcade-like collagen structure (Kim et al. 2003; Malda et al. 2005; Ng et al. 2005, 2006; Klein et al. 2007; Moutos et al. 2007). Mechanical loading could be another stimulus for obtaining an anisotropic distribution of collagen in engineered cartilage. The rationale is that, at birth, cartilage contains a random collagen structure. However, a few months after animals start to walk, cartilage develops its arcade-like structure (van Turnhout et al. 2010). Radial confinement of self-assembled constructs increased collagen organization in the direction perpendicular to the articular surface, with no change in collagen or GAG content (Elder and Athanasiou 2008). Furthermore, using polarized light microscopy, it has been shown that unconfined compression aligns collagen fibers perpendicular to the compressive loading direction (Kelly et al. 2006), i.e. aligned with the direction in which it cyclically elongates due to Poissons effects and incompressibility of the tissue. The strain field generated by applying unconfined compression may be useful to generate a superficial zone with collagen fibers parallel to the surface or higher modulus near the surface (Kelly et al. 2006; Khoshgoftar et al. 2011). However, a physiological collagen network with additional vertical fibers in the deep zone may not be produced by this loading regime, since vertical strains are absent. A numerical study by Khoshgoftar et al. (2011) suggests that a loading regime involving indentation with subsequent sliding of the indenter can stimulate the formation of an appropriate superficial zone with parallel collagen fibers. Adding lateral compression to this loading regime may stimulate the formation of a deep zone with perpendicularly aligned fibers, creating an arcade-like collagen architecture. Currently, in our group, experiments are pending in which this loading regime is applied to chondrocyte-seeded agarose constructs in order to create a physiological collagen network in the engineered cartilage. This particular sliding indentation setup has already been shown to stimulate collagen synthesis in periosteum tissue (Fig. 1) (Kock et al. 2010). In that study, periosteal explants were embedded in between agarose layers, which induced cartilage formation, confirmed by synthesis of sGAG and collagen type II (Fig. 1a, e). Addition of TGF-β1 to the culture medium did not further enhance this chondrogenic response (Fig. 1b, f). Applying sliding indentation only to the periosteum inbetween agarose layers enhanced the production of collagen type I, leading to the formation of fibrous tissue without any evidence of cartilage formation (Fig. 1c, g). However, when stimulated by both TGF-β1 and sliding indentation, collagen production was still enhanced, but now it was collagen type II, while sGAG was found to be similar to TGF-β1 or unloaded samples (Fig. 1d, h).Fig. 1

Bottom Line: The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area.In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation.In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.

ABSTRACT
Osteoarthritis is a degenerative joint disease characterized by pain and disability. It involves all ages and 70% of people aged >65 have some degree of osteoarthritis. Natural cartilage repair is limited because chondrocyte density and metabolism are low and cartilage has no blood supply. The results of joint-preserving treatment protocols such as debridement, mosaicplasty, perichondrium transplantation and autologous chondrocyte implantation vary largely and the average long-term result is unsatisfactory. One reason for limited clinical success is that most treatments require new cartilage to be formed at the site of a defect. However, the mechanical conditions at such sites are unfavorable for repair of the original damaged cartilage. Therefore, it is unlikely that healthy cartilage would form at these locations. The most promising method to circumvent this problem is to engineer mechanically stable cartilage ex vivo and to implant that into the damaged tissue area. This review outlines the issues related to the composition and functionality of tissue-engineered cartilage. In particular, the focus will be on the parameters cell source, signaling molecules, scaffolds and mechanical stimulation. In addition, the current status of tissue engineering of cartilage will be discussed, with the focus on extracellular matrix content, structure and its functionality.

Show MeSH
Related in: MedlinePlus