dc.contributor.author
Jonscher, Sebastian
dc.date.accessioned
2018-06-07T19:15:03Z
dc.date.available
2010-08-16T08:46:17.335Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/5909
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-10108
dc.description.abstract
In der vorliegenden in vivo Studie wurden an 34 Merino-Schafen zwei neue
Knochenersatzmaterialien, Calciumalkaliorthophosphatkeramiken eine mit der
Hauptkristallphase Ca10[K/Na](PO4)7 (325i) und eine mit der Hauptkristallphase
Ca2KNa(PO4)2 (GB14), im Vergleich mit Tricalciumphosphat (β-TCP), autologem
Knochen als derzeitigem Goldstandard und einem kollagenschwammgefüllten Defekt
als Leerdefekt zur Kontrolle, verglichen. Nach jeweils 1, 4, 12, und 24 Wochen
Liegezeit wurden die augmentierten Knochendefekte lichtmikroskopisch,
immunhistologisch und histomorphometrisch untersucht. Hierzu wurden vorher im
Unterkiefer beidseits Critical Size Defekte angelegt die dann mit den
genannten Materialien augmentiert wurden. Die lichtmikroskopische Auswertung
belegte die Biokompatibilität, Bioaktivität, Degradierbarkeit und Löslichkeit
der verwendeten KEM, die jedoch in differierender Quantität und auch Qualität
auftraten. 325i zeigte in Bezug auf die Degradierbarkeit und Knochenneubildung
die schlechtesten Ergebnisse. Bei β-TCP ergaben sich nach anfänglich
mangelhaften Ergebnissen dann doch ausreichend gute Werte nach 24 Wochen, die
denen anderer Studien vergleichbar sind. Als in dieser Studie herausragendes
Material präsentierte sich GB14 über alle untersuchten Liegezeiten.
Partikelresorption, Partikel-Osteoidkontakt, Knochenneubildung und Partikel-
Knochenkontakt waren im Vergleich zu den anderen untersuchten Materialien
(β-TCP, 325i) überzeugend und größtenteils von signifikanten Unterschieden (p
< 0,001) geprägt. Als besonders interessant ist hierbei die gemessene
prozentuale Knochenfläche nach 24 Wochen Liegezeit im augmentierten Bereich
von 82,3% im Vergleich zu 75,6% beim autologen Knochen festzuhalten. Es
handelt sich dabei nicht um einen signifikanten Unterschied, jedoch um ein
bemerkenswertes Ergebnis. Bei vergleichender Auswertung der osteogenen Marker
zwischen dem autologen Material und GB14 zeigten sich ähnliche Kurvenverläufe
in den Diagrammen die den Schluss zulassen, dass GB14 im Hinblick auf die
Knochenneubildung in zeitlicher und molekularer Hinsicht nahezu dieselben
Prozesse durchlaufen. GB14 ist daher als vielversprechendes, bioaktives
Material anzusehen, dessen Einsatz im Bereich präimp87 lantologischer
Augmentationen vorteilhaft zu sein scheint. Weiterführende klinische Studien
zur Bestätigung dieser Ergebnisse erscheinen demzufolge sinnvoll, ebenso
Forschungsvorhaben zur Entwicklung weiterer Applikationsformen.
de
dc.description.abstract
Among the various techniques to reconstruct or enlarge a deficient alveolar
ridge, the concept of guided bone regeneration (GBR) has become a predictable
and well-documented surgical approach. At present, autogenous bone grafts are
preferably combined with barrier membranes. Using synthetic biodegradable bone
substitute materials, however, is advantageous, since it avoids second-site
surgery for autograft harvesting. A bone substitute for alveolar ridge
augmentation must be rapidly resorbable and should undergo complete
substitution by newly formed functional bone tissue in view of placing dental
implants in such augmented sites. Compared to the bone substitutes which are
currently clinically available, there is a significant need for bone
substitutes which degrade more rapidly, but still stimulate osteogenesis at
the same time. This has led to the development of novel, bioactive, rapidly
resorbable glassy crystalline calcium-alkali-orthophosphate materials. This in
vivo study evaluates the effect of two novel bioactive particulate calcium-
alkali-phosphate bone substitute materials as compared to the currently
clinically used material β-tricalcium phosphate (β-TCP) on bone regeneration
and expression of osteogenic markers after implantation in the sheep mandible.
This was in addition to examining the biodegradability. Test materials were
two glassy crystalline calcium-alkali-orthophosphates: first, a material with
a crystalline phase Ca2KNa(PO4)2 and with a small amorphous portion containing
magnesium potassium phosphate (material denominated GB14) and second, a
material with a novel crystalline phase Ca10[K/Na](PO4)7 (material denominated
352i). These materials (grain size 300-350 µm) were implanted in the sheep
mandible for 1, 4 , 12 and 24 weeks to regenerate membrane protected critical
size defects and were compared to β-TCP particles of the same grain size as
well as autogenous bone chips. Empty defects, in which collagen sponges were
utilized for stabilization of the blood clot, served as control. In this study
a total of 34 sheep were used. In order to generate chronicle defects, the
premolars and one molar were extracted bilaterally in the sheep mandible and
critical-size defects 14 mm in width and 1 cm in height were created. After 8
weeks a reentry was performed, and the defects were augmented with the various
bone grafting materials and covered with a titanium membrane. At implant
retrieval the tissue samples were fixed in an alcohol based fixative. The
specimens were then embedded in a resin which facilitated performing
immunohisto-chemical analysis on hard tissue sections. 50 µm-sections were cut
in a buccal - lingual direction using a Leitz 1600 sawing microtome. Sections
were then deacrylized and immunohistochemical staining was performed using
primary antibodies specific to collagen type I, alkaline phosphatase,
osteocalcin, bone sialoprotein, osteopontin and osteonectin in combination
with the DAKO EnVision+TM Dual link System Peroxidase. Mayer's haematoxylin
was used as a counterstain. Semi-quantitative analysis of the sections was
performed. A scoring system quantified the amount of staining observed using
light microscopy. A score of (+++), (++) and (+) corresponded to strong,
moderate or mild, whereas a score of (0) correlated with no staining.
Furthermore, histomorphometrical evaluation of the sections was performed. The
bone area fraction, the particle area fraction as well as the bone-particle
contact and the osteoid-particle contact was measured using a light microscope
in combination with a digital camera and SIS Analysis software (Olympus,
Germany). Additional specimens were prepared to scanning electron microscopy.
Of the various grafting materials studied, GB14 had the greatest stimulatory
effect on bone formation and expression of osteogenic markers and displayed
the best bone bonding behaviour, while exhibiting the highest
biodegradability. This was true for all time points studied. At 24 weeks, GB
14 even facilitated greater bone formation (82.3%) than the autogenous bone
chips (75.6%), which is a remarkable result, since autogenous bone is
generally regarded as the gold standard. The material 352i showed poor bone
bonding behaviour and the lowest biodegradability thereby yielding a
disadvantageous result. The TCP particles displayed a lower biodegradability
than the GB14 particles. Both bone bonding behaviour and biodegrability
increased at the later time points. Overall, TCP displayed good
osteoconductivity and facilitated regeneration of the critical-size defects,
which is in agreement with other studies reported in the literature. The
diagram displaying the results for the osteogenic marker expression shows that
the curve for GB 14 has a similar shape compared to that for autogenous bone.
Hence, it can be concluded that the process of new bone formation with GB14 is
comparable to that with autogenous bone chips with respect to molecular
mechanisms and temporal pattern, i.e. time-dependent course of the respective
diagram. Therefore, GB14 can be regarded as a promising bone substitute
material for pre-implantology alveolar ridge augmentation. In order to take
this bone grafting material to the clinical arena, controlled clinical studies
need to be performed. Application for CE approval is currenty underway.
en
dc.rights.uri
http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen
dc.subject
bone substitute
dc.subject
calcium-alkali-orthophosphate
dc.subject
histostmorphometry
dc.subject
immunhistochemistry
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Untersuchung zum Einfluss schnell resorbierbarer bioaktiver
Knochenersatzmaterialien auf die osteoblastische Zelldifferenzierung in vivo
dc.contributor.firstReferee
Prof. Dr. G. Gómez-Román
dc.contributor.furtherReferee
PD Dr. Dr. M. Stiller
dc.contributor.furtherReferee
PD Dr. med.dent. Christine Knabe
dc.date.accepted
2010-09-03
dc.identifier.urn
urn:nbn:de:kobv:188-fudissthesis000000018410-6
dc.title.translated
Investigation of novel bioactive rapidly resorbable bone substitute materials
and their influence on osteoblastic cell differentiation in vivo
de
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDISS_thesis_000000018410
refubium.mycore.derivateId
FUDISS_derivate_000000007963
dcterms.accessRights.dnb
free
dcterms.accessRights.openaire
open access