An injectable biomimetic hydrogel with tethered TGFβ3 for treatment in a rat growth plate injury model

Injury to the growth plate, a cartilage tissue found at the ends of children's long bones that is responsible for bone elongation, can result in bony repair tissue (or bony bar). The bony bar connects bone on both sides of the growth plate, preventing normal bone elongation. This can lead to abnormal growth and if severe, complete growth arrest. While surgical resection of this bar is performed clinically, the interpositional materials used to replace it are susceptible to bony bar reformation. Here, we developed a novel interpositional material based on a biodegradable,in situphotopolymerizable, biomimetic hydrogel with tethered TGFβ3.In vitrostudies with rat mesenchymal stromal cells (MSCs) encapsulated in the hydrogel and cultured for 9 weeksin vitroshowed that tethered TGFβ3 led to a hyaline-like cartilage with collagen type II, while soluble TGFβ3 produced tissue characteristic of fibrocartilage, confirmed by collagen type I. Treatment of a rat growth plate injury with the TGFβ3-tethered hydrogel with or without MSCs decreased bony bar formation and showed evidence of cartilage-like tissue after four weeks, while addition of MSCs promoted limb lengthening. This hydrogel with tethered TGFβ3 offers an innovative treatment for growth plate injuries by acting as an interpositional material that resists bony bar formation and restores growth.