UW Shoulder and Elbow Academy: scaffold

Friday, November 30, 2018

Are PRP, stem cells, or biomaterials of value in rotator cuff repair?

Biologics for Rotator Cuff Repair A Critical Analysis Review

In their introduction, the authors state that "Despite an increase in the number of operations performed and enhanced surgical techniques, unacceptably high rates of failure of up to 94% still occur." They point out that this has driven intense scientific and commercial interest in "biologics" (platelet-rich plasma, stem cells, and biomaterials) as a possible means for enhancing the healing of attempted cuff repairs.

In their review, these authors note that

(1) among the many types of biologic augmentation, there is considerable heterogeneity of the content, quality, and quantity of growth factors used in platelet-rich plasma and bone marrow aspirate concentrate, and conclusions from individual studies may not necessarily be generalizable to other formulations within the group.

(2) current Level-I evidence suggests that universal use of platelet-rich plasma provides no significant clinical benefit in rotator cuff repair.
(3) although some evidence exists for the use of stem cells from bone marrow aspirate concentrate and the use of biologic grafts, results from Level-I studies are lacking and

(4) level-I trials focused on the evaluation of clinical outcomes (i.e. using the Simple Shoulder Test, the American Shoulder and Elbow Surgeons score, the University of California at Los Angeles shoulder score, or the Constant score) should be performed to help to determine the appropriate use of biologic augmentation in rotator cuff surgical procedures.

Comment: As these authors indicate, all of the scientific and commercial interest in biologics needs to be evaluated in terms of well controlled studies showing that clinical outcomes are better for patients receiving biologics in comparison to comparable patients not receiving them. These studies need to be carried out in recognition of the observation that over 10 million individuals are living with cuff tears and at most 4% of them get surgery each year. It is commonly observed that patients with cuff tears can respond to physical therapy. Furthermore, patients are commonly clinically improved after cuff repair surgery whether or not the surgery is successful in restoring the integrity of the cuff. From a clinical standpoint, therefore, biologics are going to need to make a big difference in order to justify their cost.

For a perspective on cuff repair as well as a Robert Frost poem, readers are invited to visit this post:

Rotator cuff repair - failure with continuity

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Tuesday, December 1, 2015

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.