Growth Factor Delivery in Tissue Engineering

Transforming growth factor beta (TGF-β) serves as the most widely utilized mediator of engineered cartilage growth. Conventionally, TGF-β is supplied to engineered tissues at highly supraphysiologic levels in an attempt to quickly grow tissue. However, a growing body of evidence brings to light a central paradox with this strategy. The conventional supplementation of highly supraphysiologic TGF-β levels induces signs of pathology (e.g. fibrosis, cellular hypertrophy). Alternatively, the supplementation of moderate, near-physiologic levels of TGF-β mitigate pathology, but exhibits severely limited transport into tissues.

In contrast, the natural TGF-β delivery process in cartilage occurs quite differently, where chondrocytes are surrounded by large stores of TGF-β that are sequestered in an inactive form, termed latent TGF-β. Chondrocytes activate latent stores when needed, leading to highly advantageous, regulated activity. This achieves essential biosynthesis while avoiding pathology. 

 

An exciting new project in the Growth Factor Mechanobiology Lab is the recreation of this native regulatory mechanism in tissue engineering systems. Chondrocytes are encapsulated in hydrogel scaffolds conjugated with large stores of latent TGF-β, akin to the native developmental process. Chondrocytes can activate these stores, giving rise to highly desirable, controlled activity in tissues, and subsequent improvements in the quality of tissue formation. We anticipate that this strategy will lead to a paradigm shift in tissue engineering technology and become a gold standard for musculoskeletal tissue regeneration.

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