UW Shoulder and Elbow Academy: Rotator cuff repair - can we improve healing with biologics?

In Vivo Evaluation of Adipose-Derived Stromal Cells Delivered with a Nanofiber Scaffold for Tendon-to-Bone Repair.

These authors note that rotator cuff tears and rotator cuff repair attempts are very common, yet the repair is prone to failure because the structural (e.g., aligned collagen) and compositional (e.g., a gradient in mineral) elements that produce a robust attachment in the healthy tissue are not regenerated during the healing of the repair. Specifically the repair response consists of poorly aligned scar tissue and loss of bone at the repair site.

The objective of their study in a rat cuff repair model was to improve tendon-to-bone healing by promoting aligned collagen deposition and increased bone formation using a biomimetic nanofibrous poly(lactic-co-glycolic acid) scaffold seeded with pluripotent adipose-derived stromal cells (ASCs) and implanted at the repair site.

The healing response was examined in four groups (suture only, acellular scaffold, cellular scaffold, and cellular scaffold in which the cells were transduced with the osteogenic factor bone morphogenetic protein 2 (BMP2).

Histologically, the healing interface was dominated by a fibrovascular scar response in all groups.

The acellular scaffold group showed a delayed healing response compared to the other groups.

Bone loss was evident in the cellular BMP2 group compared to other groups at 28 days.

The strength and modulus were decreased in the cellular BMP2 groups compared to other groups at 28 and 56 days.

They concluded that in this model tendon-to-bone healing was dominated by scar formation, that prevented any positive effects of the implanted biomimetic scaffold.

Cells transduced with the osteogenic factor BMP2 led to impaired healing, suggesting that this growth factor should not be used in the tendon-to-bone repair setting.

Comment: There is a great deal of academic and commercial interest in 'orthobiologics'. Stem cells, stromal cells, bone morphogenic proteins, platelet rich fibrin clots, biologic scaffolds have all been brought forth as possible means for enhancing the healing of a rotator repair. Because of the many factors that can affect the structural outcome in human cuff repairs, the authors' use of a standardized cuff repair in an animal model is appropriate. Their results indicate that none of the repairs remodeled into a normal-appearing tendon insertion and that the scaffold (whether with or without cells and with or without BMP) did not enhance the desired healing response. Specifically, regenerative strategies can be overwhelmed by the natural scar-mediated response and BMP2 is not an effective growth factor for improving tendon-to-bone healing.

In the normal cuff attachment, there is a transition from tendon to fibrocartilage to calcified fibrocartilage to bone. As shown in the photomicrographs of the normal baboon supraspinatus bone-tendon junction showing a) purple lines aligned perpendicularly to the direction of the insertion of the tendon which represent the tidemark (arrows) (haematoxylin and eosin), and b) the orientation of the fibres at the bone-tendon junction and Sharpey fibres crossing the tidemark (Picro Sirius Red). After a cuff repair in a primate model it took at least 15 weeks for this anatomy to be restored (see this link).

This arrangement not only provides strength but also a gradual transition in material properties from the flexible tendon to the stiff bone. The desirability of this transition is recognized in the design of a modern electrical plug in contrast to the old design.