TGF-beta Delivery in Cartilage Tissue Engineering

TGFbeta Delivery_Constructs.jpg
  • Transforming growth factor beta (TGF-beta) is an essential anabolic mediator for cartilage tissue engineering (TE), enabling accelerated recapitulation of neocartilage with a native-matched composition and functional mechanical properties.

  • TGF-beta can be delivered to constructs via culture media supplementation or scaffold delivery platforms.

  • A significant challenge remains dosing optimization—low doses give rise to insufficient growth and high doses can induce pathology (e.g., fibrosis, hypertrophy, hyperplasia).

TGFbeta Delivery_Optimization Dose.jpg

TGF-beta Reaction-Diffusion Modeling

TGFbeta Delivery_Reaction Cartoon.jpg
  • TGF-beta transport in TE cartilage is influenced by an assortment of chemical reactions (e.g., reversible binding to scaffold/ECM, cell-mediated internalization, enzyme-mediated degradation. 

  • Delivery of TGF-beta to cells can be predicted by reaction-diffusion frameworks, allowing for optimization of delivery platforms.

TGFbeta Delivery_Equations.jpg

Modeling TGF-beta: In Vitro Delivery

  • Reaction-diffusion modeling frameworks depict the pronounced influence of chemical reactions in hindering media-supplemented TGF-beta uptake into TE cartilage

  • For cellularized TE cartilage (binding + internalization present), TGF-beta is unable to penetrate beyond 0.3 mm into tissues.

  • Illustrates challenges encountered with conventional media-supplementation delivery strategies and the need for advanced scaffold-based TGF-beta delivery platforms for cartilage regeneration.

TGFbeta Delivery_Uptake Model.jpg

Modeling TGF-beta: In Vivo Delivery

  • TGF-beta delivery scaffolds (heparin affinity domains) are developed to prolong TGF-beta delivery to construct embedded cells after in vivo implantation.

  • Reaction-diffusion models illustrate pronounced influence of chemical reactions on TGF-beta retention kinetics.

  • Heparin affinity domains are unable to compete with cell-mediated TGF-beta internalization kinetics--cells deplete sequestered TGF-beta faster than anticipated,

  • Models can be used to optimize next-generation biomaterials-based scaffold delivery platforms to achieve sustained TGF-beta delivery for improving clinical cartilage regeneration outcomes.

TGFbeta Delivery_Scaffold Delivery Model.jpg