title: Stimulation of Rotator Cuff Repair by Sustained Release of Bone Morphogenetic Protein-7 Using a Gelatin Hydrogel Sheet.
abstract: Bone morphogenetic protein-7 (BMP-7) promotes not only osteogenesis but also matrix production in chondrocytes and tenocytes. However, because of its short half-life, maintaining local concentrations of BMP-7 is difficult. We examined the use of a gelatin hydrogel sheet (GHS) for the sustained release of BMP-7 in stimulating rotator cuff repair at the tendon-to-bone insertion. Twelve-week-old male Sprague-Dawley rats were used. Radiolabeled BMP-7 ((125)I-BMP-7) was injected into the subacromial bursa in the (125)I-BMP-7 group, whereas a GHS impregnated with (125)I-BMP-7 was implanted on the tendon attached to the tendon-to-bone insertion in the (125)I-BMP-7+GHS group. Levels of (125)I-BMP-7 in the tendon-to-bone insertion were assessed at 1, 3, 7, 14, and 21 postoperative days. The BMP-7 concentrations were significantly higher in the (125)I-BMP-7+GHS group than in the (125)I-BMP-7 group. Next, the bilateral supraspinatus tendons were resected and sutured to the greater tuberosity of the humerus using the Mason-Allen technique. Treatment groups were created as follows: either phosphate-buffered saline (PBS) or BMP-7 was injected into the subacromial bursa in the PBS and BMP-7 groups, whereas a GHS impregnated with either PBS or BMP-7 was implanted on the repaired tendon attached to the tendon-to-bone insertion in the PBS+GHS and BMP-7+GHS groups. The resected specimens were stained at 2, 4, and 8 postoperative weeks with hematoxylin and eosin as well as Safranin O, and tissue repair was evaluated histologically by using the tendon-to-bone maturing score. Tissue repair was assessed biomechanically at 4 and 8 postoperative weeks. The BMP-7+GHS group at 8 postoperative weeks demonstrated a favorable cartilage matrix production and tendon orientation; moreover, the tendon-to-bone maturing score and the ultimate force-to-failure were the highest in this group. The ability of GHS to provide controlled release of various growth factors has been previously reported. We confirmed that the GHS releases BMP-7 in a sustained manner in the rat shoulder joint. At 8 postoperative weeks, the repaired tissue was mostly restored, both histologically and biomechanically, in the BMP-7+GHS group. We therefore conclude that the sustained release of BMP-7 from a GHS can stimulate rotator cuff repair.
authors.affiliation: 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Kabuto
authors.affiliation: 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Toru
authors.initials: T
authors.lastname: Morihara
authors.affiliation: 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sukenari
authors.affiliation: 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kida
authors.affiliation: 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Ryo
authors.initials: R
authors.lastname: Oda
authors.affiliation: 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Yuji
authors.initials: Y
authors.lastname: Arai
authors.affiliation: 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Koshiro
authors.initials: K
authors.lastname: Sawada
authors.affiliation: 2 Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: 2 Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawata
authors.affiliation: 3 Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University , Kyoto, Japan .
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine , Kyoto, Japan .
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects; D003692:Delayed-Action Preparations; D005780:Gelatin / Q000494:pharmacology*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D008297:Male; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology* / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D055419:Bone Morphogenetic Protein 7; D003692:Delayed-Action Preparations; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin
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