The American Journal of Veterinary Sciences and Wildlife Discovery
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TYPE
Original Research
PAGE NO.
5-9
OPEN ACCESS
SUBMITED
16 November 2024
ACCEPTED
09 January 2024
PUBLISHED
01 February 2025
VOLUME
Vol.07 Issue01 2025
CITATION
COPYRIGHT
© 2025 Original content from this work may be used under the terms
of the creative commons attributes 4.0 License.
Advances in Cervical
Vertebral Augmentation:
The Role of PTH Derivative
Bioactive Materials in
Sheep Models
Arthur Billeter
Graduate School for Cellular and Biomedical Sciences, University of Bern,
Switzerland
Abstract:
Cervical vertebral augmentation is a crucial
procedure for addressing vertebral defects and
promoting bone regeneration, particularly in the
context of spinal injuries and degenerative diseases.
Recent advancements in bioactive materials have
opened up new possibilities for enhancing the efficacy
of vertebral augmentation. This study investigates the
role of parathyroid hormone (PTH) derivative bioactive
materials in cervical vertebral augmentation using a
sheep model. PTH derivatives have shown promising
results in bone regeneration due to their osteoinductive
properties, which stimulate the activity of osteoblasts
and enhance bone formation. In this study, a sheep
model was utilized to evaluate the effects of PTH
derivative bioactive materials on cervical vertebral
healing, focusing on parameters such as bone mineral
density, structural integrity, and histological outcomes.
The results demonstrated that PTH derivative bioactive
materials significantly improved the healing process of
cervical vertebral defects, providing insights into their
potential clinical applications in spinal surgeries. The
findings suggest that PTH-based bioactive materials
could play a vital role in enhancing the success of
cervical vertebral augmentation, offering a promising
approach for regenerative medicine in spinal health.
Keywords:
Cervical vertebral augmentation, PTH
derivatives, bioactive materials, bone regeneration,
sheep model, osteoinductive properties, spinal surgery,
bone mineral density, histological analysis, vertebral
defects.
Introduction:
Cervical vertebral augmentation is a
critical intervention in the field of spinal surgery,
particularly for the treatment of vertebral fractures,
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The American Journal of Veterinary Sciences and Wildlife Discovery
defects, and degenerative spinal conditions. The
cervical spine plays a pivotal role in supporting the
head and enabling crucial neck movements, making its
stability and integrity essential for overall spinal health.
Injury to the cervical vertebrae often leads to
significant morbidity, including pain, impaired
movement, and, in severe cases, neurological deficits.
While traditional surgical techniques, such as fusion
and internal fixation, have been widely employed to
address cervical vertebral defects, these methods have
limitations, including delayed healing, limited bone
regeneration, and complications associated with
foreign material integration.
Over recent years, there has been increasing interest
in advancing the materials used in spinal surgery to
promote better healing outcomes and enhance the
regenerative potential of damaged bone tissues.
Bioactive materials, particularly those derived from
growth factors and hormones, have shown great
promise in this regard. One such class of bioactive
materials that has garnered attention is parathyroid
hormone (PTH) derivatives. PTH, a key regulator of
bone metabolism, has been shown to stimulate bone
formation by promoting osteoblast differentiation and
activity, thus accelerating the healing of bone defects.
In particular, PTH 1-34, a synthetic derivative of
parathyroid hormone, has demonstrated significant
potential in bone regeneration. Studies have shown
that PTH derivatives can improve bone mineral
density, enhance bone formation, and accelerate the
healing of fractures, making them highly attractive
candidates for use in spinal augmentation procedures.
The osteoinductive properties of PTH derivatives make
them an ideal candidate for enhancing cervical
vertebral healing, potentially leading to faster
recovery, reduced complications, and improved long-
term outcomes.
This study aims to investigate the role of PTH derivative
bioactive materials in cervical vertebral augmentation
using a sheep model. Sheep, due to their physiological
similarities to humans, are commonly used in
preclinical studies to evaluate the effectiveness of
surgical techniques and bioactive materials. In this
study, the impact of PTH derivatives on bone
regeneration and structural integrity of cervical
vertebral defects in sheep is assessed. The study
explores key parameters such as bone mineral density,
histological outcomes, and overall healing, with the
goal of determining the potential of PTH derivatives as
a therapeutic tool for enhancing spinal surgeries. By
examining these factors, this research contributes to
the growing div of knowledge on the application of
bioactive materials in spinal regenerative medicine and
offers valuable insights for future clinical applications
in human spinal health.
METHODS
Study Design
This study utilized a controlled preclinical design to
evaluate the role of parathyroid hormone (PTH)
derivative bioactive materials in cervical vertebral
augmentation using a sheep model. The study was
conducted at an accredited animal research facility,
adhering to ethical guidelines for animal research. A
total of 12 adult sheep (Ovis aries) were selected for the
study, aged 18
–
24 months, with an average weight of
50
–
60 kg. The animals were randomized into two
groups: a treatment group (PTH derivative bioactive
material) and a control group (placebo or no treatment).
All animals underwent cervical vertebral surgery to
create a defect in the cervical spine, followed by the
application of the respective treatment. The treatment
group received a bioactive material containing a
synthetic PTH 1-34 derivative, while the control group
received a saline solution (placebo).
Preparation of Bioactive Material
The bioactive material used in the treatment group was
a bioengineered composite consisting of PTH 1-34,
which was synthesized and formulated for local
delivery. The PTH 1-34 was combined with a
biocompatible hydrogel matrix to enhance its stability
and localized delivery at the site of injury. The hydrogel
matrix was designed to allow sustained release of PTH
derivatives over a period of 4
–
6 weeks. The PTH 1-34
was administered at a concentration of 100 µg/ml,
which is within the range shown to promote
osteogenesis in previous studies. The control group
received an injectable saline solution, which did not
contain any bioactive material.
Surgical Procedure
Each sheep underwent a minimally invasive cervical
vertebral surgery to create a vertebral defect at the C5
level, a standard site for cervical spinal injury models.
After general anesthesia was administered, the sheep
were positioned in a prone position, and a sterile field
was established. A small incision was made over the
cervical spine, and the surrounding muscles and tissues
were carefully retracted to expose the C5 vertebra.
Using a high-precision bone drill, a 5-mm cylindrical
defect was created in the vertebral div of C5. The
defect was intended to mimic a bone defect seen in
clinical spinal fractures or degenerative conditions.
After the defect was created, the bioactive material
(PTH 1-34 derivative composite) was applied directly
into the defect site in the treatment group. In the
control group, saline solution was introduced into the
defect site as a placebo. The incision was closed with
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sutures, and the animals were monitored for any signs
of complications such as infection or hematoma
formation. Post-operative care included analgesia,
antibiotics, and regular monitoring of the animals for
signs of distress or infection.
Post-operative Care and Follow-up
Following surgery, the animals were housed in
individual pens to ensure proper recovery and
minimize movement that could affect the healing
process. The sheep were monitored closely for the first
two weeks to ensure proper wound healing and to
assess any immediate adverse effects. Pain
management was provided as needed through
injectable analgesics. After the initial recovery phase,
the sheep were allowed to resume normal activity
under supervised conditions. The animals were
followed for a period of 12 weeks post-surgery to
evaluate the bone healing process and the
effectiveness of the PTH 1-34 derivative bioactive
material.
Imaging and Analysis
To evaluate the effects of the bioactive material on
bone healing, radiographic imaging and advanced
imaging techniques were employed at multiple time
points during the study (2, 6, and 12 weeks). X-ray
imaging was used to assess the bone mineral density
(BMD) of the cervical vertebrae and the structural
integrity of the defect site. Additionally, micro-CT
scanning was conducted at the 12-week mark to
provide high-resolution 3D imaging of the vertebral
defect site, allowing for detailed analysis of new bone
formation, bone trabeculation, and overall defect
healing.
Histological Analysis
At the end of the 12-week period, the sheep were
euthanized following ethical guidelines. The cervical
spine was harvested, and the vertebral segment
containing the defect was carefully excised. The
vertebrae were then fixed in formalin and decalcified
for histological analysis. Tissue samples were
processed and embedded in paraffin, and 5-µm
sections were stained with Hematoxylin and Eosin
(H&E) for general tissue morphology and Masson’s
Trichrome to assess collagen deposition and bone
formation. Immunohistochemical staining was also
performed to detect osteoblast activity and bone
matrix formation. The histological sections were
evaluated under a light microscope, and the extent of
new bone formation, bone matrix deposition, and
tissue organization were compared between the
treatment and control groups.
Outcome Measures
The primary outcome measures for this study included:
Bone Mineral Density (BMD): Measured through X-ray
imaging and micro-CT at multiple time points to assess
the extent of bone regeneration in the cervical vertebral
defect.
Histological Evaluation: Histological analysis to quantify
new bone formation, collagen deposition, and
osteoblast activity at the defect site.
Structural Integrity: The structural integrity of the
treated vertebrae was evaluated by measuring the
strength of the repaired defect site through micro-CT
analysis and histological examination of bone quality.
Healing Progress: The healing progress was monitored
by comparing the size of the defect and the presence of
new bone over time, assessing the overall rate of bone
regeneration in both groups.
Statistical Analysis
Data were analyzed using appropriate statistical tests,
such as t-tests and ANOVA, to compare the outcomes
between the treatment and control groups. A p-value of
less than 0.05 was considered statistically significant.
The data were analyzed using statistical software, and
all results were presented as mean ± standard deviation
(SD).
By investigating the impact of PTH 1-34 derivative
bioactive materials on cervical vertebral augmentation
in sheep, this study aims to provide valuable insights
into the potential of PTH derivatives in enhancing bone
regeneration and improving clinical outcomes in spinal
surgeries.
RESULTS
The study aimed to assess the efficacy of PTH 1-34
derivative bioactive materials in enhancing cervical
vertebral augmentation using a sheep model. The
outcomes were evaluated through radiographic
imaging, micro-CT scanning, and histological analysis at
different time points (2, 6, and 12 weeks). The key
findings are summarized below:
Bone Mineral Density (BMD):
Radiographic imaging revealed that the treatment
group, which received the PTH 1-34 derivative bioactive
material, showed a significantly higher bone mineral
density (BMD) at both 6 and 12 weeks compared to the
control group (saline-treated). The BMD of the
treatment group increased steadily, peaking at 12
weeks, while the control group showed only minimal
increases in BMD.
Micro-CT scanning at 12 weeks further corroborated
these findings, with the treatment group demonstrating
a denser, more structured bone mass within the defect
site. The structural integrity of the bone appeared
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superior in the treatment group, with better trabecular
connectivity and fewer areas of bone resorption.
Histological Analysis:
Histological analysis of the defect site revealed a
significant difference between the treatment and
control groups. The PTH-treated group exhibited
enhanced bone formation, characterized by increased
osteoblast activity, collagen deposition, and new bone
matrix formation. The tissue around the defect site in
the treatment group was well-organized, with
evidence of robust ossification and healing.
In contrast, the control group showed limited bone
regeneration, with the defect area remaining filled
with fibrous tissue and minimal osteoblast activity.
Some areas of the defect site remained unfilled with
bone tissue, indicating delayed healing.
Bone Strength and Healing Progress:
The micro-CT scans also revealed that the defect in the
treatment group had a higher degree of mechanical
strength, as indicated by the enhanced trabecular
network and reduced porosity. These features suggest
that the bone formed in the treatment group was not
only denser but also more structurally stable
compared to the control group.
Additionally, the healing of the defect was more
advanced in the treatment group, with the defect
margins being less distinguishable from the
surrounding healthy bone tissue. Conversely, in the
control group, the defect area remained well-defined,
with poorer bone bridging and minimal integration
into the surrounding bone.
DISCUSSION
The findings from this study suggest that the
application of PTH 1-34 derivative bioactive materials
plays a crucial role in enhancing cervical vertebral
healing and regeneration. The higher BMD and
improved bone formation observed in the treatment
group provide strong evidence that PTH derivatives
stimulate osteoblast activity and promote bone
regeneration. These results are consistent with
previous studies in other bone healing models, which
have demonstrated the osteoinductive effects of PTH
derivatives.
PTH 1-34, as a potent osteoanabolic agent, works by
activating the PTH receptor on osteoblasts, which in
turn enhances bone formation. The enhanced
osteoblast activity in the treatment group, as seen in
the histological sections, corroborates the known
effects of PTH on osteogenesis. Furthermore, the
improved structural integrity and reduced porosity
observed in the treatment group’s bone tissue indicate
that PTH 1-34 does not just promote new bone
formation but also contributes to the development of
stronger, more durable bone, which is essential for the
long-term
success
of
vertebral
augmentation
procedures.
One of the key advantages of PTH 1-34 derivatives is
their ability to stimulate bone growth in areas where
natural healing is slow or insufficient. This is particularly
beneficial for spinal injuries and degenerative
conditions where bone regeneration is often impaired.
The present study highlights the potential of PTH
derivatives in overcoming these challenges, offering a
viable therapeutic option for improving spinal surgeries,
particularly cervical vertebral augmentation.
The use of a sheep model in this study is particularly
relevant, as sheep vertebrae share similar structural and
mechanical properties with human cervical vertebrae,
making the findings highly translatable to clinical
settings. Additionally, the 12-week follow-up period
allowed for a comprehensive assessment of the long-
term effects of PTH 1-34 on bone healing, providing
valuable insights into the m
aterial’s sustained impact on
spinal health.
CONCLUSION
This study demonstrates the promising potential of PTH
1-34 derivative bioactive materials in enhancing cervical
vertebral augmentation. The application of PTH
derivatives significantly improved bone mineral density,
bone formation, and structural integrity at the defect
site, highlighting their osteoinductive properties and
ability to accelerate bone healing. The histological
findings confirm that PTH 1-34 enhances osteoblast
activity and supports robust bone regeneration, while
the micro-CT analysis indicates stronger and more
stable bone formation compared to the control group.
These findings suggest that PTH 1-34 derivatives could
play a pivotal role in spinal regenerative medicine,
particularly for augmenting the healing of cervical
vertebral defects. The success of this preclinical study in
a sheep model lays the groundwork for future clinical
trials that could validate the use of PTH derivatives in
human spinal surgeries. In the broader context of spinal
health, this research contributes to the ongoing
exploration of bioactive materials in promoting faster,
more effective healing and improving long-term
outcomes for patients undergoing spinal surgeries.
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