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Bone formation and degradation behavior of nanocrystalline hydroxyapatite with
or without collagen-type 1 in osteoporotic bone defects
–
an experimental
study in osteoporotic goats
Volker Alt
a,b
, Wing Hoi Cheung
c
, Simon K.H. Chow
c
, Ulrich Thormann
b
, Edmond N.M. Cheung
c
, Katrin S. Lips
b
,
Reinhard Schnettler
a,b
, Kwok-Sui Leung
c,
*
a
Department of Trauma Surgery, University Hospital of Giessen-Marburg GmbH, Campus Giessen, 35385 Giessen, Germany
b
Laboratory of Experimental Trauma Surgery Giessen, Justus-Liebig-University Giessen, 35394 Giessen, Germany
c
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China
A B S T R A C T
The intention of the current work is to assess new bone formation and degradation behavior of nanocrystalline
hydroxyapatitewith (HA/col-1) or without collagen-type I (HA) in osteoporotic metaphyseal bone defects in goats.
After ovariectomy and special low-calcium diet for three months, 3 drill hole defects in the vertebrae of L3, L4, L5, 4
drill hole defects in the right and left iliac crest and 1 drill hole defect at the distal femur were created in three
Chinese mountain goats with a total of 24 defects. The defects were either filled with one of the biomaterials or left
empty (empty defect control group). After 42 days, the animals were euthanized and the samples were assessed
for new bone formation using high-resolution peripheral quantitative computed tomography (HR-pQCT) and
histomorphometry with 2 regions of interest. Detail histology, enzymehistochemistry and immunohistochemistry
as well as connexin-43 in situ hybridization and transmission electron microscopy were carried out for evaluation
of degradation behavior of the materials and cellular responses of the surrounding tissue in respect to the
implants. HR-pQCT showed the highest BV/TV ratio (
p
= 0.008) and smallest trabecular spacing (
p
= 0.005) for HA
compared to the other groups in the region of interest at the interface with 1 mm distance to the initially created
defect. The HA/col-1 yielded the highest connectivity density (Conn.D) (
p
= 0.034) and the highest number of
trabeculae (Tb.N) (
p
= 0.002) compared to the HA and the control group. Histomorphometric analysis for the core
region of the initially created defect revealed a statistically higher new bone formation in the HA (
p
= 0.001) and
HA/col-1 group (
p
= 0.001) compared to the empty defect group including all defect sites. This result was
confirmed for site specific analysis with significant higher new bone formation for the HA group for vertebral
defects compared to the empty defect group (
p
= 0.029). For the interface region, no statistically significant
differences were found between the three groups (
p
= 0.08). Histology revealed a good biocompatibility without
inflammatory reaction for the HA- and HA/col-1 implants with a higher fragmentation of the HA-implant
compared to the HA/col-1 biomaterial and formation of new bone in the region between the biomaterial
fragments by osteoblasts. Fragmentation was shown by transmission electron microscopy to be caused by
multinuclear osteoclast-like cells with degradation of the implant via intracellular incorporation of degraded
implant material particles. In conclusion, both nanoparticulate HA with and without collagen type-1 showed
better new bone formation compared to untreated drill hole defects in metaphyseal regions of this osteoporotic
Chinese mountain goat model with good biocompatibility.
© 2016 Elsevier Ltd. All rights reserved.
K E Y W O R D S
Hydroxyapatite
Collagen
Osteoporosis
Degradation
Biomaterial
*
Corresponding author at: Volker Alt, Department of Trauma Surgery Giessen, University
Hospital Giessen-Marburg GmbH, Campus Giessen, Rudolf-Buchheim-Strasse 7, 35385
Giessen, Germany. Tel.:
+49 (0)641 985 44
601; fax:
+49 (0)641 985 44
609.
E-mail address:
volker.alt@chiru.med.uni-giessen.de(Volker Alt).
Injury, Int. J. Care Injured 47S2 (2016) S58
–
S65
Contents lists available at ScienceDirect
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journal homepage: www.
elsevier.com/locate/Injury0020-1383 / © 2016 Elsevier Ltd. All rights reserved.