TGF-beta Delivery in Cartilage Tissue Engineering
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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.
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TGF-beta can be delivered to constructs via culture media supplementation or scaffold delivery platforms.
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A significant challenge remains dosing optimization—low doses give rise to insufficient growth and high doses can induce pathology (e.g., fibrosis, hypertrophy, hyperplasia).
TGF-beta Reaction-Diffusion Modeling
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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.
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Delivery of TGF-beta to cells can be predicted by reaction-diffusion frameworks, allowing for optimization of delivery platforms.
Modeling TGF-beta: In Vitro Delivery
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Reaction-diffusion modeling frameworks depict the pronounced influence of chemical reactions in hindering media-supplemented TGF-beta uptake into TE cartilage
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For cellularized TE cartilage (binding + internalization present), TGF-beta is unable to penetrate beyond 0.3 mm into tissues.
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Illustrates challenges encountered with conventional media-supplementation delivery strategies and the need for advanced scaffold-based TGF-beta delivery platforms for cartilage regeneration.
Modeling TGF-beta: In Vivo Delivery
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TGF-beta delivery scaffolds (heparin affinity domains) are developed to prolong TGF-beta delivery to construct embedded cells after in vivo implantation.
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Reaction-diffusion models illustrate pronounced influence of chemical reactions on TGF-beta retention kinetics.
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Heparin affinity domains are unable to compete with cell-mediated TGF-beta internalization kinetics--cells deplete sequestered TGF-beta faster than anticipated,
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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.
