Bone augmentation by recombinant human BMP-2 and collagen on adult rat parietal bone

Murata, Masaru; Huang, Bingzhen; Shibata, Toshiyuki; Imai, Sawako; Nagai, Noriyuki; Arisue, Makoto

doi:10.1016/s0901-5027(99)80144-1

Cited by 71 publications

(24 citation statements)

References 30 publications

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“…Such a result suggests that the periosteum may act as a source of osteoprogenitor elements as well as a mineralization front. This is consistent with previous reports of sub-periosteal bone formation in onlay grafts covered with native periosteum [3940] and highlights the importance of periosteal preservation in bone regenerative procedures.…”

Section: Discussionsupporting

confidence: 93%

“Over-inlay” block graft and differential morphometry: a novel block graft model to study bone regeneration and host-to-graft interfaces in rats

Ghiacci

Graiani

Ravanetti

et al. 2016

J Periodontal Implant Sci

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PurposeThe aim of this study was to present new a model that allows the study of the bone healing process, with an emphasis on the biological behavior of different graft-to-host interfaces. A standardized “over-inlay” surgical technique combined with a differential histomorphometric analysis is presented in order to optimize the use of critical-size calvarial defects in pre-clinical testing.MethodsCritical-size defects were created into the parietal bone of 8 male Wistar rats. Deproteinized bovine bone (DBBM) blocks were inserted into the defects, so that part of the block was included within the calvarial thickness and part exceeded the calvarial height (an “over-inlay” graft). All animals were sacrificed at 1 or 3 months. Histomorphometric and immunohistochemical evaluation was carried out within distinct regions of interest (ROIs): the areas adjacent to the native bone (BA), the periosteal area (PA) and the central area (CA).ResultsThe animals healed without complications. Differential morphometry allowed the examination of the tissue composition within distinct regions: the BA presented consistent amounts of new bone formation (NB), which increased over time (24.53%±1.26% at 1 month; 37.73%±0.39% at 3 months), thus suggesting that this area makes a substantial contribution toward NB. The PA was mainly composed of fibrous tissue (71.16%±8.06% and 78.30%±2.67%, respectively), while the CA showed high amounts of DBBM at both time points (78.30%±2.67% and 74.68%±1.07%, respectively), demonstrating a slow remodeling process. Blood vessels revealed a progressive migration from the interface with native bone toward the central area of the graft. Osterix-positive cells observed at 1 month within the PA suggested that the periosteum was a source of osteoprogenitor elements. Alkaline phosphatase data on matrix deposition confirmed this observation.ConclusionsThe present model allowed for a standardized investigation of distinct graft-to-host interfaces both at vertically augmented and inlay-augmented sites, thus possibly limiting the number of animals required for pre-clinical investigations.

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Section: Discussionsupporting

confidence: 93%

“Over-inlay” block graft and differential morphometry: a novel block graft model to study bone regeneration and host-to-graft interfaces in rats

Ghiacci

Graiani

Ravanetti

et al. 2016

J Periodontal Implant Sci

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“…This suggests that the bone had formed directly without any endochondral process. It has been shown in similar models that direct bone formation predominates if high doses of BMP are given (Murata et al 1999). Thus, our results may not be valid for endochondral bone formation during fracture repair.…”

Section: Discussionmentioning

confidence: 99%

Etanercept does not impair healing in rat models of tendon or metaphyseal bone injury

et al. 2012

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Background and purposeShould blockade of TNF-α be avoided after orthopedic surgery? Healing of injuries in soft tissues and bone starts with a brief inflammatory phase. Modulation of inflammatory signaling might therefore interfere with healing. For example, Cox inhibitors impair healing in animal models of tendon, ligament, and bone injury, as well as in fracture patients. TNF-α is expressed locally at increased levels during early healing of these tissues. We therefore investigated whether blocking of TNF-α with etanercept influences the healing process in established rat models of injury of tendons and metaphyseal bone.MethodsRats were injected with etanercept, 3.5 mg/kg 3 times a week. Healing of transected Achilles tendons and bone healing around screws implanted in the tibial metaphysis were estimated by mechanical testing. Tendons were allowed to heal either with or without mechanical loading. Ectopic bone induction following intramuscular BMP-2 implants has previously been shown to be stimulated by etanercept in rodents. This was now tested as a positive control.ResultsTendon peak force after 10 days was not significantly influenced by etanercept. Changes exceeding 29% could be excluded with 95% confidence. Likewise, screw pull-out force was not significantly influenced. More than 25% decrease or 18% increase could be excluded with 95% confidence. However, etanercept treatment increased the amount of bone induced by intramuscular BMP-2 implants, as estimated by blind histological scoring.InterpretationEtanercept does not appear to impair tendon or metaphyseal bone healing to any substantial degree.

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“…The bone formations in the skeleton are made from atclocollagen 41. There was a report of using a combination of atelocollagen and rhBMP‐2 as an onlay beneath the cranial periosteum 42. Consequently, we chose atelocollagen.…”

Section: Discussionmentioning

confidence: 99%

“…The entire procedure is extremely simple. The ease of handling this material could be an important factor for numerous clinical applications 42. In this study, rhBMP‐2 composites were manually changed to arbitrary shapes.…”

Section: Discussionmentioning

confidence: 99%

Regeneration of rat auditory ossicles using recombinant human BMP‐2/collagen composites

Takeda

Tsujigiwa

Nagatsuka

et al. 2005

J Biomedical Materials Res

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Tympanoplasty operations to improve hearing impairment require a wide middle ear cavity and reconstruction of columellar formations. There is no specific material for use in the reconstruction of columellar formations. Tissue response to BMP has been employed as regenerative material. To our knowledge, however, there are no reports of the reconstruction of columellar formations using recombinant human bone morphogenetic protein-2/bovine collagen composites in the middle ear. The purpose of this study is to investigate whether recombinant human bone morphogenetic protein-2/bovine collagen composites (rhBMP-2 composites) are appropriate for use as regenerative material for tympanoplasty. In the form of pellets, rhBMP-2 composites were implanted as columellae into the tympanic cavity. At 2, 4, 6, 8, and 12 weeks after surgery, the middle ear of the animals (n = 4 at each week) was stained with hematoxylin-eosin for light microscopic observation. All composites were in the process of ossification or had ossified according to their developmental stages and were covered with a single layer of squamous or cuboidal epithelium. The new bone formed in these composites was persistently stable and displayed some columellar conditions assessed by histological examination. This study led to the conclusion that rhBMP-2 composites make excellent regenerative material for auditory ossicles.

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Bone augmentation by recombinant human BMP-2 and collagen on adult rat parietal bone

Cited by 71 publications

References 30 publications

“Over-inlay” block graft and differential morphometry: a novel block graft model to study bone regeneration and host-to-graft interfaces in rats

“Over-inlay” block graft and differential morphometry: a novel block graft model to study bone regeneration and host-to-graft interfaces in rats

Etanercept does not impair healing in rat models of tendon or metaphyseal bone injury

Regeneration of rat auditory ossicles using recombinant human BMP‐2/collagen composites

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