Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: a biomechanical and histological study in rats

Schmidmaier, Gerhard; Wildemann, Britt; Cromme, F.; Kandziora, Frank; Haas, Norbert; Raschke, M.

doi:10.1016/s8756-3282(02)00740-8

Cited by 116 publications

(70 citation statements)

References 25 publications

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“…Taking into account the results of our in vivo study 2 weeks postoperatively, this supports the hypothesis that non-union formation is due to a reduced expression of osteogenic growth factors such as e.g. BMP-2/-4/-6/-7 during the early stage of bone healing (Mi et al, 2013;Cheng et al, 2003;Tsuij et al, 2006;Schmidmaier et al, 2002;Garcia et al, 2012;Schwabe et al, 2014). Although we do not have any data on BMP-2 release from MCM in vivo, our study demonstrates for the first time that the release of BMP-2 from MCM generates healing in a challenging non-union model.…”

Section: Orth Et Al Bmp-2-coated MCM and Bone Repairsupporting

confidence: 84%

“…The animals of the group MCM + BMP (n = 16) received also by direct injection MCM coated with approximately 13.7 µg BMP-2/ mg MCM. The dosage of BMP-2 was chosen based upon pre-experiments and an extensive literature search (Saito et al, 2003;Schmidmaier et al, 2002;Suárez-González et al, 2014;Kanczler et al, 2010). Finally, wound closure completed the surgical procedure.…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…The fact that MCM + BMP showed a reduced total callus area and total bone volume at 10 weeks compared to 2 weeks may be interpreted as adequate bone healing, including the process of remodelling, which is characteristic for the late stage of bone repair (Schindeler et al, 2008;Hankenson et al, 2014). The dosage of BMP-2 used in rodent animal models varies (Saito et al, 2003;Schmidmaier et al, 2002;Kanczler et al, 2010). However, the dosage necessary to improve bone repair is not elucidated yet and may depend on the route of application and the use of the carrier system.…”

Section: Orth Et Al Bmp-2-coated MCM and Bone Repairmentioning

confidence: 99%

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BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions

Orth

Kruse²,

Braun³

et al. 2017

eCM

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Atrophic non-unions are a major clinical problem. Mineral coated microparticles (MCM) are electrolyte-coated hydroxyapatite particles that have been shown in vitro to bind growth factors electrostatically and enable a tuneable sustained release. Herein, we studied whether MCM can be used in vivo to apply Bone Morphogenetic Protein-2 (BMP-2) to improve bone repair of atrophic non-unions. For this purpose, atrophic non-unions were induced in femurs of CD-1 mice (n = 48). Animals either received BMP-2-coated MCM (MCM + BMP; n = 16), uncoated MCM (MCM; n = 16) or no MCM (NONE; n = 16). Bone healing was evaluated 2 and 10 weeks postoperatively by micro-computed tomographic (µCT), biomechanical, histomorphometric and immunohistochemical analyses. µCT revealed more bone volume with more highly mineralised bone in MCM + BMP femurs. Femurs of MCM + BMP animals showed a significantly higher bending stiffness compared to other groups. Histomorphometry further demonstrated that the callus of MCM + BMP femurs was larger and contained more bone and less fibrous tissue. After 10 weeks, 7 of 8 MCM + BMP femurs presented with complete osseous bridging, whereas NONE femurs exhibited a non-union rate of 100 %. Of interest, immunohistochemistry could not detect macrophages within the callus, indicating a good biocompatibility of MCM. In conclusion, the local application of BMP-2-coated MCM improved bone healing in a challenging murine non-union model and, thus, should be of clinical interest in the treatment of non-unions.

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Section: Orth Et Al Bmp-2-coated MCM and Bone Repairsupporting

confidence: 84%

Section: Surgical Proceduresmentioning

confidence: 99%

Section: Orth Et Al Bmp-2-coated MCM and Bone Repairmentioning

confidence: 99%

See 1 more Smart Citation

BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions

Orth

Kruse²,

Braun³

et al. 2017

eCM

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“…The most common osteogenic growth factors used for biomedical purposes are the members of the TGF-β superfamily, including the BMP family (126). In particular BMP-2, BMP-7 and TGF-β1 are promising growth factors for enhanced bone formation around the implant (127)(128)(129)(130)(131)(132)(133). Growth factors can be adsorbed or covalently bound to the titanium surface (129,134), but are commonly added to CaP or collagen-coated implants (103,132,(135)(136)(137).…”

Section: Growth Factor Immobilizationmentioning

confidence: 99%

“…This may be due to a sustained delivery profile or a higher stability of the growth factor (103,141). Overall, loading implants with growth factors has shown to accelerate bone formation (129,131,142,143) and to facilitate the bridging of small gaps between implant and surrounding bone (130,144,145). In summary, coating implants with locally acting growth factors can improve the remodelling process at the tissue-implant interface, and is therefore a promising option for establishing an improved integration of implants into healing bone.…”

Section: Growth Factor Immobilizationmentioning

confidence: 99%

Organic–Inorganic Surface Modifications for Titanium Implant Surfaces

et al. 2008

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Abstract. This paper reviews current physicochemical and biochemical coating techniques that are investigated to enhance bone regeneration at the interface of titanium implant materials. By applying coatings onto titanium surfaces that mimic the organic and inorganic components of living bone tissue, a physiological transition between the non-physiological titanium surface and surrounding bone tissue can be established. In this way, the coated titanium implants stimulate bone formation from the implant surface, thereby enhancing early and strong fixation of bone-substituting implants. As such, a continuous transition from bone tissue to implant surface is induced. This review presents an overview of various techniques that can be used to this end, and that are inspired by either inorganic (calcium phosphate) or organic (extracellular matrix components, growth factors, enzymes, etc.) components of natural bone tissue. The combination, however, of both organic and inorganic constituents is expected to result into truly bone-resembling coatings, and as such to a new generation of surface-modified titanium implants with improved functionality and biological efficacy.

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Enhanced bone morphogenetic protein‐2 performance on hydroxyapatite ceramic surfaces

Schuessele

Mayr

Teßmar

et al. 2008

J Biomedical Materials Res

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The immobilization of biomolecules on biomaterial surfaces allows for the control of their localization and retention. In numerous studies, proteins have been simply adsorbed to enhance the biological performance of various materials in vivo. We investigated the potential of surface modification techniques on hydroxyapatite (HA) ceramic discs in an in vitro approach. A novel method for protein immobilization was evaluated using the aminobisphosphonates pamidronate and alendronate, which are strong Ca chelating agents, and was compared with the established silanization technique. Lysozyme and bone morphogenetic protein-2 (BMP-2) were used to assess the suitability of the two surface modification methods with regard to the enzymatic activity of lysozyme and to the capacity of BMP-2 to stimulate the osteoblastic differentiation of C2C12 mouse myoblasts. After immobilization, a 2.5-fold increase in enzymatic activity of lysozyme was observed compared with the control. The alkaline phosphatase activity per cell stimulated by immobilized BMP-2 was 2.5-fold higher [9 x 10(-6) I.U.] than the growth factor on unmodified surfaces [2-4 x 10(-6) I.U.]. With regard to the increase in protein activity, both procedures lead to equivalent results. Thus, the bisphosphonate-based surface modification represents a safe and easy alternative for the attachment of proteins to HA surfaces.

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Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: a biomechanical and histological study in rats

Cited by 116 publications

References 25 publications

BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions

BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions

Organic–Inorganic Surface Modifications for Titanium Implant Surfaces

Enhanced bone morphogenetic protein‐2 performance on hydroxyapatite ceramic surfaces

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