rhBMP-12 Accelerates Healing of Rotator Cuff Repairs in a Sheep Model

ArticleinThe Journal of Bone and Joint Surgery 90(10):2206-19 · November 2008with6 Reads
Impact Factor: 5.28 · DOI: 10.2106/JBJS.G.00742 · Source: PubMed

The success rate of rotator cuff repairs is variable. This study was performed to evaluate the ability of recombinant human bone morphogenetic protein-12 (rhBMP-12), administered in several carriers, to accelerate healing in a sheep model of rotator cuff repair. Local retention of tracer amounts of radiolabeled rhBMP-12, added to non-radiolabeled rhBMP-12 delivered in buffer, hyaluronan paste or sponges, or Type-I or Type-I/III collagen sponges was first evaluated with use of gamma scintigraphy in a pilot study of a rat intramuscular implant model. The rhBMP-12/paste and sponge combinations were then evaluated in eight sheep each with unilateral complete detachment and subsequent double-row reattachment of the infraspinatus tendon to the proximal part of the humerus. Contralateral, normal shoulders from sixteen sheep and shoulders in which a repair had been done without administration of rhBMP-12 in fourteen sheep were also evaluated. The rhBMP-12/Type-I and Type-I/III collagen sponge combinations were each evaluated in eight additional sheep on the basis of superior efficacy. The Type-I/III collagen sponge alone was evaluated in ten sheep to examine the effect of a collagen carrier. Ultrasound imaging was performed at four and eight weeks. Radiographic evaluation, mechanical testing, and biochemical evaluation were performed at eight weeks. Histological evaluation was performed on specimens from the sites of selected repairs following mechanical testing. The sponge carriers had longer local retention of rhBMP-12 than did the buffer or paste carriers in the rat models. All of the sheep shoulder-repair groups demonstrated ultrasound evidence of a gap between the tendon and the humeral insertion. The gap length and the cross-sectional area of the repair tissue decreased with time. The mechanical properties of the repairs treated with rhBMP-12 and hyaluronan paste were similar to those of the untreated repairs. The maximum loads for the rhBMP-12/hyaluronan sponge and rhBMP-12/collagen sponge-treated repairs were 2.1 and 2.7 times greater, respectively, than the loads for the untreated repairs and were 33% and 42% of the value for the normal tendon at eight weeks. The maximum loads for the repairs treated with rhBMP-12 and a Type-I or Type-I/III collagen sponge were 2.1 times greater than those for the repairs treated with the Type-I/III collagen sponge alone. Changes in maximum stiffness followed a similar pattern. Histological evaluation demonstrated accelerated healing of the rhBMP-12-treated repairs compared with the untreated repairs. Bone formation was observed in all repairs, and biochemical measurements were not equivalent to those of normal tendon at eight weeks. Delivery of rhBMP-12 in a collagen or hyaluronan sponge resulted in accelerated healing of acute full-thickness rotator cuff repairs in a sheep model. Delivery of rhBMP-12 in several sponge carriers has the potential to accelerate healing of rotator cuff repairs. Accelerated repair may allow shorter rehabilitation and an earlier return to occupational and recreational activities.

    • "Despite the current literature [1, 6, 10, 21] describing the importance of biologic abnormalities in RCT and the biologic strategies [2, 5,30313233 to improve tendon to bone healing, the association between biological abnormalities and RCT has not been investigated previously and is poorly defined. In this study, we evaluated the MSC content in the tuberosities of the humeral head of patients with and without rotator cuff tear. "
    [Show abstract] [Hide abstract] ABSTRACT: While the use of bone marrow concentrate (BMC) has been described in the treatment of rotator cuff tears, the impact of a rotator cuff injury on the mesenchymal stem cells (MSCs) content present in the human shoulder has not been determined, especially with regard to changes in the levels of MSCs at the tendon-bone interface. With the hypothesis that there was a decreased level of MSCs at the tendon-bone interface tuberosity in patients with rotator cuff tear, we assessed the level of MSCs in the tuberosity of the shoulder of patients undergoing a rotator cuff repair. We analysed the data of 125 patients with symptomatic rotator cuff tears and of 75 control patients without rotator cuff injury. We recorded the following data: size of tear, number of torn tendons, aetiology of the tear, lag time between onset of shoulder symptoms/injury and repair, and also fatty infiltration of muscles. Mesenchymal stem cell content at the tendon-bone interface tuberosity was evaluated by bone marrow aspiration collected in the humeral tuberosities of patients at the beginning of surgery. A significant reduction in MSC content (from moderate, 30-50 %, to severe >70 %) at the tendon-bone interface tuberosity relative to the MSC content of the control was observed in all rotator cuff repair study patients. Severity of the decrease was statistically correlated to a number of factors, including the delay between onset of symptoms and surgery, number of involved tendons, fatty infiltration stage and increasing patient age. This study demonstrates that the level of MSCs present in the greater tuberosity of patients with a rotator cuff tear decreases as a function of a number of clinical factors, including lag time from tear onset to treatment, tear size, number of tears and stage of fatty infiltration, among others. This information may help the practices in using biologic augmentation of a rotator cuff repair.
    Full-text · Article · Mar 2015 · International Orthopaedics
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    • "However, the biomechanical properties did not show a significant improvement compared to single-row repairs using modified suture con- figurations7273747576. Furthermore, the potential benefit of improved footprint coverage could not be transferred in the clinical setting as the clinical results of double-row repairs are still comparable to single-row repairs concerning clinical scores as well as failure rates [15, 18, 34, 44, 68, 116]. Only a potential benefit concerning the structural results in rotator cuff healing is described. "
    [Show abstract] [Hide abstract] ABSTRACT: High initial fixation strength, mechanical stability and biological healing of the tendon-to-bone interface are the main goals after rotator cuff repair surgery. Advances in the understanding of rotator cuff biology and biomechanics as well as improvements in surgical techniques have led to the development of new strategies that may allow a tendon-to-bone interface healing process, rather than the formation of a fibrovascular scar tissue. Although single-row repair remains the most cost-effective technique to address a rotator cuff tear, some biological intervention has been recently introduced to improve tissue healing and clinical outcome of rotator cuff repair. Animal models are critical to ensure safety and efficacy of new treatment strategies; however, although rat shoulders as well as sheep and goats are considered the most appropriate models for studying rotator cuff pathology, no one of them can fully reproduce the human condition. Emerging therapies involve growth factors, stem cells and tissue engineering. Experimental application of growth factors and platelet-rich plasma demonstrated promising results, but has not yet been transferred into standardized clinical practice. Although preclinical animal studies showed promising results on the efficacy of enhanced biological approaches, application of these techniques in human rotator cuff repairs is still very limited. Randomized controlled clinical trials and post-marketing surveillance are needed to clearly prove the clinical efficacy and define proper indications for the use of combined biological approaches. The following review article outlines the state of the art of rotator cuff repair and the use of growth factors, scaffolds and stem cells therapy, providing future directions to improve tendon healing after rotator cuff repair. Level of evidence Expert opinion, Level V.
    Full-text · Article · Jan 2015 · Knee Surgery Sports Traumatology Arthroscopy
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    • "Also, the low voltage in the gamma band during sedation, ~0.5 uVrms, would be difficult to achieve with high electrode impedance, so the impedance was likely low. Sheep heal quickly so eight weeks was assumed to be adequate [10] but longer studies are now expected for neural electrodes [11]. The methodology of this study assumed high correlation of the EEG from the left and right hemispheres of sheep [12]. "
    [Show abstract] [Hide abstract] ABSTRACT: An implanted electroencephalogram (EEG) recorder would help diagnose infrequent seizure-like events. A proof-of-concept study quantified the electrical characteristics of the electrodes planned for the proposed recorder. The electrodes were implanted in an ovine model for eight weeks. Electrode impedance was less than 800 Ohms throughout the study. A frequency-domain determination of sedation performed similarly for surface versus implanted electrodes throughout the study. The time-domain correlation between an implanted electrode and a surface electrode was almost as high as between two surface electrodes (0.86 versus 0.92). EEG-certified clinicians judged that the implanted electrode quality was adequate to excellent and that the implanted electrodes provided the same clinical information as surface electrodes except for a noticeable amplitude difference. No significant issues were found that would stop development of the EEG recorder.
    Full-text · Article · Aug 2014
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