Engineering Tendon Assembloids to Probe Cellular Crosstalk in Disease and Repair

Tendons facilitate movement by transmitting forces from muscle to bone. Although tendon injury is common, these are quite difficult to treat and the outcome for patients is often poor. Currently, all treatments of tendon injury involve some kind of physiotherapy, and this reflects the fact that mechanical forces play such a central role in tendon biology.

Good experimental models for studying tendon damage and repair don't really exist, so my lab is actively developing new models that can better capture important features of tendon physiology and pathophysiology. In previous studies, we could show that the tendon core, which represents the load-bearing part of the tendon, has by itself a very limited repair capacity. Combined with other research in the field, we hypothesized that an injured core would recruit cells from the extrinsic tendon compartment to help it heal.

Tissue-engineered tendon model system may provide a loadable 3D environment but don't match the intricacies of an in vivo exocellular matrix. Explant model systems do, but they are often difficult to keep alive and mechanically load over longer periods of time or lack the extrinsic compartment that is central for the repair processes. Our unique model system combines the advantages of marine tail tendon-derived core explants with those of 3D hydrogel base systems.

It provides a loadable, in vivo-like core matrix, alongside an artificial extrinsic compartment. Its composition can be tuned to the research hypothesis and the biomimetic cross-compartmental barrier in between the two. Our hybrid hydrogel explant assembloids are in a prime position to study tendon core biology, matrix structure function interactions, and cross-compartmental interactions between specific cell populations in a fine-tunable micro environment.

Discoveries from the studies conducted with this system will guide in vivo research and treatment development.