rhBMP-12 Accelerates Healing of Rotator Cuff Repairs in a Sheep Model
ABSTRACT 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.
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ABSTRACT: The clinical superiority of the double-row technique is still a subject of controversial debate in rotator cuff repair. We hypothesised that the expression of different collagen types will differ between double-row and single-row rotator cuff repair indicating a faster healing response by the double-row technique. Twenty-four mature female sheep were randomly assembled to two different groups in which a surgically created acute infraspinatus tendon tear was fixed using either a modified single- or double-row repair technique. Shoulder joints from female sheep cadavers of identical age, bone maturity, and weight served as untreated control cluster. Expression of type I, II, and III collagen was observed in the tendon-to-bone junction along with recovering changes in the fibrocartilage zone after immunohistological tissue staining at 1, 2, 3, 6, 12, and 26 weeks postoperatively. Expression of type III collagen remained positive until 6 weeks after surgery in the double-row group, whereas it was detectable for 12 weeks in the single-row group. In both groups, type I collagen expression increased after 12 weeks. Type II collagen expression was increased after 12 weeks in the double-row versus single-row group. Clusters of chondrocytes were only visible between week 6 and 12 in the double-row group. The study demonstrates differences regarding the expression of type I and type III collagen in the tendon-to-bone junction following double-row rotator cuff repair compared to single-row repair. The healing response in this acute repair model is faster in the double-row group during the investigated healing period.Archives of Orthopaedic and Trauma Surgery 11/2014; DOI:10.1007/s00402-014-2118-1 · 1.31 Impact Factor
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ABSTRACT: ➤ Tendon-to-bone healing is vital to the ultimate success of the various surgical procedures performed to repair injured tendons.➤ Achieving tendon-to-bone healing that is functionally and biologically similar to native anatomy can be challenging because of the limited regeneration capacity of the tendon-bone interface.➤ Orthopaedic basic-science research strategies aiming to augment tendon-to-bone healing include the use of osteoinductive growth factors, platelet-rich plasma, gene therapy, enveloping the grafts with periosteum, osteoconductive materials, cell-based therapies, biodegradable scaffolds, and biomimetic patches.➤ Low-intensity pulsed ultrasound and extracorporeal shockwave treatment may affect tendon-to-bone healing by means of mechanical forces that stimulate biological cascades at the insertion site.➤ Application of various loading methods and immobilization times influence the stress forces acting on the recently repaired tendon-to-bone attachment, which eventually may change the biological dynamics of the interface.➤ Other approaches, such as the use of coated sutures and interference screws, aim to deliver biological factors while achieving mechanical stability by means of various fixators.➤ Controlled Level-I human trials are required to confirm the promising results from in vitro or animal research studies elucidating the mechanisms underlying tendon-to-bone healing and to translate these results into clinical practice.The Journal of Bone and Joint Surgery 03/2014; 96(6):513-21. DOI:10.2106/JBJS.M.00009 · 4.31 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the efficiency of biologic augmentation of rotator cuff repair with iliac crest bone marrow-derived mesenchymal stem cells (MSCs). The prevalence of healing and prevention of re-tears were correlated with the number of MSCs received at the tendon-to-bone interface.International Orthopaedics 06/2014; 38(9). DOI:10.1007/s00264-014-2391-1 · 2.02 Impact Factor