scholarly journals Biological Effect of Single or Combined Pharmacological Therapy Using Alendronate and Simvastatin on Implant Osseointegration: An In Vivo Study in Healthy and Osteoporotic Rat Models

2020 ◽  
Vol 10 (12) ◽  
pp. 4298
Author(s):  
Amani M. Basudan ◽  
Marwa Y. Shaheen ◽  
Abdurahman A. Niazy ◽  
Jeroen J.J.P. van den Beucken ◽  
John A. Jansen ◽  
...  
Keyword(s):  
Bone Formation ◽  
Biomechanical Testing ◽  
Pharmacological Therapy ◽  
Histological Evaluation ◽  
Osteoporotic Bone ◽  
Implant Fixation ◽  
Superior Effect ◽  
Female Wistar Rats ◽  
Bone To Implant Contact

To evaluate peri-implant bone formation following single or combined systemic administration of alendronate and simvastatin in healthy and osteoporotic rats, eighty female Wistar rats were ovariectomized (n = 40) or sham-operated (n = 40). At six weeks, implants were placed in femoral condyles. Then, ovariectomized (OVX) and sham-operated (SHAM) animals received daily subcutaneous alendronate (50 µg/kg), simvastatin (5 mg/kg), or both, for three weeks. Control animals received subcutaneous saline. Thereafter, specimens were retrieved for biomechanical testing, histological evaluation, and bone area (BA%) and bone-to-implant contact (BIC%). In healthy and osteoporotic rats, similar (p > 0.05) push-out values were observed for all groups. For BA% analysis, control rats showed similar results for OVX (9.2% ± 2.4%) and SHAM (11.1% ± 3.5%) animals. In contrast, single or combined drug therapy significantly increased BA% compared to controls in both healthy and osteoporotic conditions (p < 0.05). In osteoporotic conditions, alendronate alone showed a superior effect on BA% compared to simvastatin alone, or their combination. Systemic alendronate, simvastatin, or both showed a similar BIC% compared to controls (p > 0.05). The present study demonstrates that single or combined systemic alendronate and simvastatin increases bone formation around implants (i.e., distance osteogenesis) in healthy and osteoporotic bone conditions. However, these drugs showed no beneficial effect on direct bone-to-implant contact or implant fixation.

scholarly journals Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Philipp S. Lienemann ◽  
Stéphanie Metzger ◽  
Anna-Sofia Kiveliö ◽  
Alain Blanc ◽  
Panagiota Papageorgiou ◽  
...  
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Bone Defects ◽  
Histological Evaluation ◽  
Biological Processes ◽  
Micro Ct ◽  
Pinhole Spect

Abstract Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.

A Biomechanical Comparison of Three Miniature Locking Plate Systems in a Rabbit Radial and Ulnar Fracture Model

2019 ◽  
Vol 32 (04) ◽  
pp. 297-304 ◽  
Author(s):  
Harue Takizawa ◽  
Muneki Honnami ◽  
Takamasa Sakai ◽  
Akari Sasaki ◽  
Ayumi Sakamoto ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Locking Plate ◽  
Healing Process ◽  
Biomechanical Testing ◽  
Histological Evaluation ◽  
Fracture Stabilization ◽  
Significant Difference ◽  
Ulnar Fracture ◽  
Fracture Models

Objective The aim of this study was to evaluate the biomechanical properties of three different miniature locking plate systems used to fixate radial and ulnar fractures in toy breed dogs. Implant size, shape, material and locking systems differ, and their influence on the fracture healing process is unknown. In the present study, we aimed to investigate this matter in vivo using rabbit radial and ulnar fracture models. Study Design Eighteen rabbits were randomly divided into three groups, and the left radius and ulna were osteotomized to create fracture models. The osteotomies were then fixated using either the TITAN LOCK 1.5, Fixin micro or LCP 1.5 system. Radiographs were obtained 2, 3 and 4 weeks after surgery. Four weeks after surgery, the radiuses were collected and used for biomechanical testing or histological examinations. Results During the 4 weeks of observation, no adverse effects due to the implants occurred. The radiographic scores in each group did not differ significantly at any time point. The maximum load in the LCP group was significantly higher than that in the TITAN and Fixin groups. There was no significant difference in bending stiffness or work to failure among the groups. Initial fracture healing via woven bone was evident at histological evaluation. Conclusions All three miniature locking plate systems provided adequate fracture stabilization 4 weeks after surgery, despite their differences, in rabbit models.

scholarly journals Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Rasmus Hestehave Pedersen ◽  
Marina Rasmussen ◽  
Søren Overgaard ◽  
Ming Ding
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Volume Fraction ◽  
Structure Type ◽  
Osteoporotic Bone ◽  
Bone Volume Fraction ◽  
Defect Repair ◽  
Paired Design ◽  
Tibia Defect

This study assessed the efficacy of anorganic bone mineral coated with P-15 peptide (ABM/P-15) on tibia defect repair longitudinally in both normal and osteoporotic rats in vivo. A paired design was used. 24 Norwegian brown rats were divided into normal and osteoporotic groups. 48 cylindrical defects were created in proximal tibias bilaterally. Defects were filled with ABM/P-15 or left empty. Osteoporotic status was assessed by microarchitectural analysis. Microarchitectural properties of proximal tibial defects were evaluated at 4 time points. 21 days after surgery, tibias were harvested for histology and histomorphometry. Significantly increased bone volume fraction, surface density, and connectivity were seen in all groups at days 14 and 21 compared with day 0. Moreover, the structure type of ABM/P-15 group was changed toward typical plate-like structure. Microarchitectural properties of ABM/P-15 treated newly formed bones at 21 days were similar in normal and osteoporotic rats. Histologically, significant bone formation was seen in all groups. Interestingly, significantly increased bone formation was seen in osteoporotic rats treated with ABM/P-15 indicating optimized healing potential. Empty defects showed lower healing potential in osteoporotic bone. In conclusion, ABM/P-15 accelerated bone regeneration in osteoporotic rats but did not enhance bone regeneration in normal rats.

scholarly journals Effect of Cervus and Cucumis Peptides on Osteoblast Activity and Fracture Healing in Osteoporotic Bone

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ai-Yuan Wang ◽  
Yue Tian ◽  
Mei Yuan ◽  
Li Zhang ◽  
Ji-Feng Chen ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Callus Formation ◽  
Biomechanical Testing ◽  
Physiological Saline ◽  
Osteoporotic Bone ◽  
Sprague Dawley ◽  
Matrix Mineralization ◽  
Osteoblast Activity

Osteoporosis is associated with delayed and/or reduced fracture healing. As cervus and cucumis are the traditional Chinese treatments for rheumatoid arthritis, we investigated the effect of supplementation of these peptides (CCP) on bone fracture healing in ovariectomized (OVX) osteoporotic ratsin vitroandin vivo. CCP enhanced osteoblast proliferation and increased alkaline phosphatase activity, matrix mineralization, and expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 4 (BMP4), and osteopontin.In vivo, female Sprague-Dawley rats underwent ovariectomy and the right femora were fractured and fixed by intramedullary nailing 3 months later. Rats received intraperitoneal injections of either CCP (1.67 mg/kg) or physiological saline every day for 30 days. Fracture healing and callus formation were evaluated by radiography, micro-CT, biomechanical testing, and histology. At 12 weeks after fracture, calluses in CCP-treated bones showed significantly higher torsional strength and greater stiffness than control-treated bones. Bones in CCP-treated rats reunified and were thoroughly remodeled, while two saline-treated rats showed no bone union and incomplete remodeling. Taken together, these results indicate that use of CCP after fracture in osteoporotic rats accelerates mineralization and osteogenesis and improves fracture healing.

Cell-Free Book-Shaped Decellularized Tendon Matrix Graft Capable of Controlled Release of BMP-12 to Improve Tendon Healing in a Rat Model

2021 ◽  
pp. 036354652199455
Author(s):  
Han Xiao ◽  
Yang Chen ◽  
Muzhi Li ◽  
Qiang Shi ◽  
Yan Xu ◽  
...  
Keyword(s):  
Rat Model ◽  
Biomechanical Testing ◽  
Tendon Healing ◽  
Biomechanical Properties ◽  
The Other ◽  
Histological Evaluation ◽  
Sprague Dawley ◽  
A Cell

Background: Achilles tendon (AT) defects often occur in traumatic and chronic injuries. Currently, no graft can satisfactorily regenerate parallel tendinous tissue at the defect site to completely restore AT function. Purpose: To develop a cell-free functional graft by tethering bone morphogenetic protein 12 (BMP-12) on a book-shaped decellularized tendon matrix (BDTM) and to determine whether this graft is more beneficial for AT defect healing than an autograft. Study Design: Controlled laboratory study. Methods: Canine patellar tendon was sectioned into a book shape and decellularized to fabricate a BDTM. The collagen-binding domain (CBD) was fused into the N-terminus of BMP-12 to synthesize a recombinant BMP-12 (CBD-BMP-12), which was tethered to the BDTM to prepare a cell-free functional graft (CBD-BMP-12/BDTM). After its tensile resistance, tenogenic inducibility, and BMP-12 release dynamics were evaluated, the efficacy of the graft for tendon regeneration was determined in a rat model. A total of 140 mature male Sprague-Dawley rats underwent AT tenotomy. The defect was reconstructed with reversed AT (autograft group), native BMP-12 tethered to an intact decellularized tendon matrix (IDTM; NAT-BMP-12/IDTM group), native BMP-12 tethered to a BDTM (NAT-BMP-12/BDTM group), CBD-BMP-12 tethered on an IDTM (CBD-BMP-12/IDTM group), and CBD-BMP-12 tethered on a BDTM (CBD-BMP-12/BDTM group). The rats were sacrificed 4 or 8 weeks after surgery to harvest AT specimens. Six specimens from each group at each time point were used for histological evaluation; the remaining 8 specimens were used for biomechanical testing. Results: In vitro CBD-BMP-12/BDTM was noncytotoxic, showed high biomimetics with native tendons, was suitable for cell adhesion and growth, and had superior tenogenic inducibility. In vivo the defective AT in the CBD-BMP-12/BDTM group regenerated more naturally than in the other groups, as indicated by more spindle-shaped fibroblasts embedded in a matrix of parallel fibers. The biomechanical properties of the regenerated AT in the CBD-BMP-12/BDTM group also increased more significantly than in the other groups. Conclusion: CBD-BMP-12/BDTM is more beneficial than autograft for healing AT defects in a rat model. Clinical Relevance: The findings of this study demonstrate that CBD-BMP-12/BDTM can serve as a practical graft for reconstructing AT defects.

scholarly journals Biomechanical Evaluation of a Novel Loop Retention Mechanism for Cortical Graft Fixation in ACL Reconstruction

2020 ◽  
Vol 8 (2) ◽  
pp. 232596712090432
Author(s):  
Tobias Götschi ◽  
George Rosenberg ◽  
Xiang Li ◽  
Chen Zhang ◽  
Elias Bachmann ◽  
...  
Keyword(s):  
Fatigue Testing ◽  
Fatigue Behavior ◽  
Cruciate Ligament ◽  
Statistical Significance ◽  
Biomechanical Testing ◽  
Retention Mechanism ◽  
Cyclic Testing ◽  
Implant Fixation ◽  
Fixed Length

Background: Implant fixation by means of a cortical fixation device (CFD) has become a routine procedure in anterior cruciate ligament reconstruction. There is no clear consensus whether adjustable-length CFDs are more susceptible to loop lengthening when compared with pretied fixed-length CFDs. Purpose: To assess biomechanical performance measures of 3 types of CFDs when subjected to various loading protocols. Study Design: Controlled laboratory study. Methods: Three types of CFDs underwent biomechanical testing: 1 fixed length and 2 adjustable length. One of the adjustable-length devices is based on the so-called finger trap mechanism, and the other is based on a modified sling lock mechanism. A device-only test of 5000 cycles (n = 8 per group) and a tendon-device test of 1000 cycles (n = 8 per group) with lower and upper force limits of 50 and 250 N, respectively, were applied, followed by ramp-to-failure testing. Adjustable-length devices then underwent further cyclic testing with complete loop unloading (n = 5 per group) at each cycle, as well as fatigue testing (n = 3 per group) over a total of 1 million cycles. Derived mechanical parameters were compared among the devices for statistical significance using Kruskal-Wallis analysis of variance followed by post hoc Mann-Whitney U testing with Bonferroni correction. Results: All CFDs showed elongation <2 mm after 5000 cycles when tested in an isolated manner and withstood ultimate tensile forces in excess of estimated peak in vivo forces. In both device-only and tendon-device tests, differences in cyclic performance were found among the devices, favoring adjustable-length fixation devices over the fixed-length device. Completely unloading the suspension loops, however, led to excessive loop lengthening of the finger trap device, whereas the modified sling lock device remained stable throughout the test. The fixed-length device displayed superior ultimate strength over both adjustable-length devices. Both adjustable-length devices showed adequate fatigue behavior during high-cyclic testing. Conclusion: All tested devices successfully prevented critical construct elongation when tested with constant tension and withstood ultimate loads in excess of estimated in vivo forces during the rehabilitation phase. The finger trap device gradually lengthened excessively when completely unloaded during cyclic testing. Clinical Relevance: Critical loop lengthening may occur if adjustable-length devices based on the finger trap mechanism are repeatedly unloaded in situ.

scholarly journals Osteoconductive and electroactive carbon nanofibers/hydroxyapatite nanocomposite tailored for bone tissue engineering: in vitro and in vivo studies

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hadi Samadian ◽  
Hamid Mobasheri ◽  
Mahmoud Azami ◽  
Reza Faridi-Majidi
Keyword(s):  
Tissue Engineering ◽  
Bone Formation ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Carbon Nanofibers ◽  
In Vivo Studies ◽  
Histological Evaluation ◽  
Control Group

Abstract In this study, we aimed to fabricate osteoconductive electrospun carbon nanofibers (CNFs) decorated with hydroxyapatite (HA) crystal to be used as the bone tissue engineering scaffold in the animal model. CNFs were derived from electrospun polyacrylonitrile (PAN) nanofibers via heat treatment and the carbonized nanofibers were mineralized by a biomimetic approach. The growth of HA crystals was confirmed using XRD, FTIR, and EDAX analysis techniques. The mineralization process turned the hydrophobic CNFs (WCA: 133.5° ± 0.6°) to hydrophilic CNFs/HA nanocomposite (WCA 15.3° ± 1°). The in vitro assessments revealed that the fabricated 24M-CNFs nanocomposite was biocompatible. The osteoconductive characteristics of CNFs/HA nanocomposite promoted in vivo bone formation in the rat’s femur defect site, significantly, observed by computed tomography (CT) scan images and histological evaluation. Moreover, the histomorphometric analysis showed the highest new bone formation (61.3 ± 4.2%) in the M-CNFs treated group, which was significantly higher than the negative control group (the defect without treatment) (< 0.05). To sum up, the results implied that the fabricated CNFs/HA nanocomposite could be considered as the promising bone healing material.

scholarly journals Biomimetic vascularized adipose-derived mesenchymal stem cells bone-periosteum graft enhances angiogenesis and osteogenesis in a rabbit spine fusion model

2021 ◽  
Author(s):  
Tsai-Sheng Fu ◽  
Wei-Chuan Chen ◽  
Ying-Chih Wang ◽  
Chia-Wei Chang ◽  
Tung-Yi Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Blood Vessels ◽  
Critical Role ◽  
Cell Sheet ◽  
Biomechanical Testing ◽  
Bone Grafts ◽  
Vascularized Bone

Abstract BackgroundSeveral artificial bone grafts have been developed for bone reconstruction but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity. Besides, periosteum plays an essential role in the neovascularization process in bone formation and healing. The aim of this study was to develop a cell-based biomimetic vascularized bone-periosteum construct (VBPC) to provide better neovascularization for osteogenesis and bone regeneration.MethodsTwenty-four male New Zealand white rabbits were divided into four groups according to the experimental materials. We first cultured adipose-derived mesenchymal stem cells (AMSCs) and seeded them evenly in the collagen/chitosan sheet to form an AMSCs-sheet-engineered periosteum. Simultaneously, the AMSCs were seeded onto alginate scaffolds and were cultured to differentiate to endothelial-like cells to form vascularized bone constructs (VBC). The success of endothelial differentiation was confirmed by real-time polymerase chain reaction and immunofluorescence staining analysis. The AMSCs-sheet-engineered periosteum was wrapped onto VBC to create biomimetic VBPC, which was then implanted in bilateral L4-5 intertransverse space of rabbit. The acellular alginate-sheet construct, VBC, and non-vascularized AMSCs-alginate-periosteum construct were used as controls. At 12 weeks after implantation, the bone-forming capacities of the constructs were determined by computed tomography, biomechanical testing, histology, and immunohistochemistry staining analyses.ResultsTwelve weeks after implantation, the VBPC group significantly increased new bone formation volume than the control groups. Biomechanical testing demonstrated a higher torque strength in the VBPC group, and suggested that the cell sheet played a critical role for mechanical support. Notably, the hematoxylin and eosin, Masson’s trichrome, and immunohistochemistry stained histologic results revealed that the VBPC group promoted the formation of blood vessels and new bones in the L4-5 intertransverse fusion areas.ConclusionsThe tissue-engineered biomimetic VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. The VBPC may overcome the deficits of traditional bone grafts. These findings suggest a novel approach to improve the timely formation of blood vessels from bone substitutes and provide an ideal source for bone regeneration.

Oral in vivo Bactofection in Dextran Sulfate Sodium Treated Female Wistar Rats

2010 ◽  
Vol 58 (3) ◽  
pp. 171-176 ◽  
Author(s):  
Roland Pálffy ◽  
Michal Behuliak ◽  
Roman Gardlík ◽  
Peter Jáni ◽  
L'udevít Kádaši ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Female Wistar Rats
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