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Growth of Cartilage and Bone Tissue01:27

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Chondrocytes form a temporary cartilaginous model by dividing and secreting a thick gel-like extracellular matrix. Once the chondrocytes undergo programmed cell death, osteoblasts enter the site of the cartilaginous model. The process of replacing the temporary cartilaginous model with bone in an ordered manner is called endochondral ossification. In endochondral ossification, not all of the cartilage is replaced by bone tissue. Some cartilage that performs a protective and supportive function...
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Optimizing nutrient channel spacing and revisiting TGF-beta in large engineered cartilage constructs.

Alexander D Cigan1, Robert J Nims1, Gordana Vunjak-Novakovic1

  • 1Departments of Mechanical Engineering, Biomedical Engineering and Medicine, Columbia University, New York, NY 10027, United States.

Journal of Biomechanics
|June 4, 2016
PubMed
Summary

Optimizing nutrient channel spacing in cartilage tissue engineering is crucial for creating clinically relevant constructs. Channels enhance nutrient transport, but their effectiveness depends on transforming growth factor-beta (TGF-β) presence.

Keywords:
AgaroseCartilageChondrocytesGrowth factorsNutrient transportTissue engineering

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Area of Science:

  • Biomedical Engineering
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • Cartilage tissue engineering aims to treat osteoarthritis but faces limitations in producing clinically relevant construct sizes.
  • Nutrient transport limitations in large constructs can be addressed using engineered channels.
  • Optimal channel spacing for recapitulating native cartilage properties remains unidentified.

Purpose of the Study:

  • To optimize nutrient channel spacing in engineered cartilage constructs.
  • To investigate the role of transforming growth factor-beta (TGF-β) in conjunction with nutrient channels.
  • To determine ideal parameters for creating articular layer-sized cartilage constructs.

Main Methods:

  • Engineered cartilage constructs (10mm diameter) were cultured with varying numbers of nutrient channels (0, 12, 19, 27) and TGF-β dosages (0, 1, 10 ng/mL).
  • Constructs were analyzed for mechanical properties (Young's modulus), biochemical composition (GAG, collagen content), and histology.
  • The study evaluated the interplay between channel density and TGF-β concentration.

Main Results:

  • Constructs with 12 or 19 channels demonstrated favorable growth, achieving a Young's modulus of 344±113 kPa and significant GAG and collagen content.
  • Higher channel density (27 channels) resulted in reduced GAG deposition.
  • Nutrient channels were effective only in the presence of TGF-β, with similar outcomes observed for 1 and 10 ng/mL TGF-β dosages.

Conclusions:

  • Channel spacing equivalent to 12 channels in 10mm constructs, combined with TGF-β, can yield desirable mechanical and compositional properties.
  • These findings suggest that optimized channel designs can facilitate the development of larger, clinically relevant cartilage constructs.
  • Reduced TGF-β dosages may be sufficient when utilizing optimized nutrient channel configurations.