Rotator cuff tendon healing to bone is a clinically important topic that many of us have tried to understand in order to optimize long-term results in patients undergoing rotator cuff repair surgery. The study by Li et al. is a basic-science evaluation of the ability of prevascularization of bone marrow-derived mesenchymal stem cell (BMSC) sheets implanted at the tendon-bone interface (TBI) of the rotator cuff to promote integration in a rabbit model. The authors studied TBI healing, immunohistochemistry, gene expression, and biomechanical properties at 6 weeks after infraspinatus detachment and repair using either BMSC sheets or prevascularized BMSC (PBMSC) sheets in this animal model. They demonstrated that PBMSC sheet implantation yielded greater vascularization, based on a higher density of α-smooth muscle actin-positive vessels. Immunohistochemistry demonstrated greater type-II collagen deposition at the TBI and increased interleukin-10 expression. Biomechanically, PBMSC sheets yielded greater ultimate failure load and stiffness of the repair site. The authors conclude that prevascularization of BMSC sheets promotes angiogenesis and improves histological structure and biomechanical properties in bone-tendon healing. Clinically, PBMSC sheets could therefore represent a biological adjunct to enhance bone-tendon healing in rotator cuff repair surgery. I congratulate the authors for their contribution to helping us better understand techniques and basic science that may improve TBI healing in patients undergoing rotator cuff repair surgery. Their work addresses an important research question with clinical importance, in my opinion. Many of us have worked to improve our surgical techniques, and we now have identified those risk factors that may decrease surgical outcomes that are affected by rotator cuff healing capacity1. The biological milieu of the rotator cuff TBI remains a common interest not only for basic scientists but for many clinician scientists who perform rotator cuff repair. One important limitation in rotator cuff TBI healing is poor vascularity at this interface, and this probably remains a major contributor to the limited healing that we see. Surgical techniques, such as bone marrow stimulation, to improve the bleeding environment during rotator cuff repair have been described and are commonly performed today2,3. Nevertheless, recent systematic reviews have suggested limited effectiveness of such techniques4. I believe that Wei et al. take a methodical approach to studying this problem with the use of tissue engineering strategies involving not only bone-marrow sheets but also prevascularization of these sheets. As they point out, prevascularization can be an effective tissue engineering strategy to overcome oxygen and nutrient limitation in 3-dimensional constructs5,6. In their animal model, rotator cuff repairs were made and supplemented with BMSC sheets or PBMSC sheets. One limb per animal was assigned for biomechanical testing and the contralateral limb, for histological or gene expression analysis. One could argue that there was no group representing a sham operation or rotator cuff repair without scaffold placement. It still would have been interesting to see the immunohistochemistry, gene expression, and biomedical properties in a repair without any augmentation as a comparison, instead of the historical controls cited. Furthermore, it would have been of interest to have seen whether preloading the sheet would have increased cytokine activity of the cells they implanted on the sheet or demonstrated better-aligned collagen fibrils. Others have shown that in vitro mechanical stimulation can yield better alignment of collagen fibrils on scaffolds7. I do appreciate that the postoperative evaluations were short-term (6 weeks) and agree that this short time frame may represent a transition between the early stages of healing with inflammation and proliferation, but it would be interesting to see how these data change over a longer time period and whether these PBMSC sheets develop a more robust regenerative/remodeling phase of healing that could potentially result in a TBI such as is seen in the intact native state8,9. This research has, for me, created some excitement regarding the understanding of the basic science of healing of the TBI. I remain hopeful that this work will stimulate others to be innovative in thought and to create future studies in this area. It will remain important that these products be technically easy to surgically place, be readily available for health-care systems, and be affordable for our patients, in order for us to optimize long-term outcomes for our patients undergoing rotator cuff repair surgery.
Keith Kenter (Thu,) studied this question.