Bone apposition to titanium implants biocoated with recombinant human bone morphogenetic protein-2 (rhBMP-2). A pilot study in dogs

Becker, Jürgen; Kirsch, A; Schwarz, Frank; Chatzinikolaidou, Μaria; Rothamel, Daniel; Lekovic, Vojislav; Jennissen, H. P.

doi:10.1007/s00784-006-0049-0

Cited by 88 publications

(43 citation statements)

References 36 publications

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“…The covalent and non-covalent immobilization of growth factors such as recombinant human bone morphogenetic protein 2 (rhBMP-2) on metals [16] and bone replacement materials [17] in bioactive form [18,19] [21]) could be easily coated. In this paper the first results in the preparation of a poly-Tyr tagged rhBMP-2 which is to be converted into a poly-DOPA-tagged rhBMP-2 will be described.…”

Section: Introductionmentioning

confidence: 99%

Development of an universal affinity fusion tag (Poly‐DOPA) for immobilizing recombinant proteins on biomaterials

Jennissen

Laub

2007

Materialwissenschaft Werkst

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The covalent and non-covalent immobilization of growth factors such as recombinant human bone morphogenetic protein 2 (rhBMP-2) on metals and bone replacement materials in bioactive form is a recent development. Up to now the immobilization technology usually involved the chemical modification and activation of the biomaterial surface followed by attachment of the bioactive protein.Here we suggest an alternative method in which an affinity tag fused to an active protein will allow immobilization without additional chemistry. For biomaterials such as minerals, metals (titanium, steel, CoCrMo), glass ceramics, teflon and possibly bone and teeth ideal adhesion molecules would be the foot proteins (Mefps) of the mussel M. edulis which contain the rare amino acid dihydroxy phenylalanine (DOPA). Recently it could be shown by Messersmith's group that a single DOPA-molecule can be noncovalently bound to titanium dioxide surface with a dissociation energy of 22.2 kcal/mol (Lee, H.; Scherer, N. F.; Messersmith, P. B. Proc. Natl. Acad. Sci. U. S. A 2006, 103, 12999 -13003

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Section: Introductionmentioning

confidence: 99%

Development of an universal affinity fusion tag (Poly‐DOPA) for immobilizing recombinant proteins on biomaterials

Jennissen

Laub

2007

Materialwissenschaft Werkst

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“…The biological activity is reported as still evident [25] shown in cell culture by detection of alkaline phosphatase as an indicator of bone induction by BMP-2. Thus, the results of the present study can close the gap between in vitro and in vivo assessment together with preliminary studies with the same bioactive layer [40]. Sumner and coworkers made a study to analyze the influence of different dosage of BMP-2 on top of a HA/TCP.…”

Section: Discussionmentioning

confidence: 62%

“…It has already been shown that this has a positive effect on osseoinduction as well as on osseoconduction [10, 40]. This effect, however, appears to be higher after addition of BMP-2.…”

Section: Discussionmentioning

confidence: 91%

Osseointegrative effect of rhBMP-2 covalently bound on a titan-plasma-spray-surface after modification with chromosulfuric acid in a large animal bone gap-healing model with the Göttingen minipig

et al. 2018

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BackgroundBone morphogenetic proteins play an important role as osseointegrative factors. It is used widely in orthopedic research and surgery to enhance the osseointegrative potential of implants, e.g., in spinal fusion or alveolar socket augmentation. The aim of the present study was to investigate the benefit of rhBMP-2 on a titan plasma spray (TPS) layer after a special modification with chromosulfuric acid (CSA) at different postoperative times, regarding osseoconduction and osseoinduction.MethodsWe allocated 27 Göttinger minipigs into three groups consisting of nine animals each. They received four dumbbell-shaped implants in the metaphyseal parts of the femora. The implants had a TPS surface with (CSA group) and without a CSA treatment (TPS group). The former received an additional layer of BMP-2 (BMP-2 group). For the assessment of osseointegration after healing periods of 4, 8, and 12 weeks, histomorphometry was applied to undecalcified specimens after staining according to Masson-Goldner. An intravital labeling with different fluorochromes was used in the gap model. A multivariable analysis with repeated measurement design was performed for statistical evaluation.ResultsWe observed several statistical differences in a three-way ANOVA. The comparison between the BMP-2 and the TPS group (two-way ANOVA) showed statistically significant differences in terms of the osseoinduction (osteoid volume), and pronounced for the osseoconduction (bone and osteoid ongrowth), in favor of the BMP-2 group. In the pairwise comparison between BMP-2 and CSA (two-way ANOVA), no statistical significance occurred. The intravital staining with tetracycline, calcein green, and xylenol orange revealed no considerable differences between the groups.ConclusionBMP-2, covalently bound on a CSA-treated TPS surface, has positive effects on the osseointegration in the large animal bone gap-healing model over the observation period of 12 weeks.

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“…In later work lower contact angles in the ultra-hydrophilic range were also reported for SLA surfaces [17] which can be stored similarly in NaCl but not in methanol. Surfaces displaying contact angles < 10 8 on titanium implants have lead to a significant increase of bone apposition versus controls in minipigs and dogs respectively [17,18]. Recently we discovered the conservation of ultra-hydrophilic surfaces in the dry state and reported this for the first time in the form of an invention [19,20].…”

Section: Introductionmentioning

confidence: 98%

Stabilizing ultra‐hydrophilic surfaces by an exsiccation layer of salts and implications of the Hofmeistereffect

Jennissen¹

2010

Materialwissenschaft Werkst

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Ultra-hydrophilic titanium surfaces can be prepared in a variety of ways by acid etching. However such surfaces are unstable in air and in water so that a storage for several years, as is necessary for clinical use, is a major problem. Ultrahydrophilic surfaces on miniplates prepared by chromosulfuric acid (CSA) enhancement showing dynamic advancing and receding contact angles of 0 8 (no hysteresis) can be easily stabilized and stored at room temperature in the dry state in air atmosphere. After evaporation of the aqueous phase of a salt containing solution (e. g. PBS) an exsiccation layer composed of specific ions is formed on the dry metal oxide surface exerting the stabilizing effect. The mechanism involved in this stabilizing effect of salts appears to be governed by the Hofmeister Effect. Ultra-hydrophilic CSA (chromsulfuric acid) etched surfaces can be stabilized by an exsiccation layer for over 3 years without loss of hydrophilicity.Keywords: Hydrophilic / ultra-hydrophilic / osteophilic / nanostructures / titanium / contact angles / exsiccation layer / Ultra-hydrophile Titanoberflächen können auf verschiedenen Wegen gewonnen werden. Diese Oberflächen verlieren jedoch sowohl in der Luft als auch in Wasser ihre ultra-hydrophilen Eigenschaften, wodurch die Lagerung über mehrere Jahre, wie sie für Implantate notwendig ist, zum Problem wird. Ultrahydrophile Oberflächen auf Titanplättchen, die mit Chromschwefelsäure (CSA) veredelt wurden und dynamische Vorrück-und Rückzugswinkel von 0 Grad (keine Hysterese) aufweisen, können leicht im trockenen Zustand bei Zimmertemperatur in Luftatmosphäre stabilisiert und gelagert werden. Nach Evaporierung der wässrigen Phase einer Salzlösung (z. B. PBS) bildet sich auf der Metalloberfläche eine Exsikkationsschicht bestehend aus einer spezifischen Ionenzusammensetzung, die den stabilisierenden Effekt hervorruft. Der zugrunde liegende Mechanismus für die Stabilisierung von Exsikkationsschichten scheint im Hofmeister-Effekt zu liegen. Ultra-hydrophile CSA (Chromschwefelsäure) geätzte Oberflächen können durch eine Exsikkationsschicht für 3 Jahre stabilisiert und gelagert werden ohne Hydrophilizitätsverlust.

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Bone apposition to titanium implants biocoated with recombinant human bone morphogenetic protein-2 (rhBMP-2). A pilot study in dogs

Cited by 88 publications

References 36 publications

Development of an universal affinity fusion tag (Poly‐DOPA) for immobilizing recombinant proteins on biomaterials

Development of an universal affinity fusion tag (Poly‐DOPA) for immobilizing recombinant proteins on biomaterials

Osseointegrative effect of rhBMP-2 covalently bound on a titan-plasma-spray-surface after modification with chromosulfuric acid in a large animal bone gap-healing model with the Göttingen minipig

Stabilizing ultra‐hydrophilic surfaces by an exsiccation layer of salts and implications of the Hofmeistereffect

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