scholarly journals Efficacy for Whitlockite for Augmenting Spinal Fusion

2021 ◽  
Vol 22 (23) ◽  
pp. 12875
Author(s):  
Su Yeon Kwon ◽  
Jung Hee Shim ◽  
Yu Ha Kim ◽  
Chang Su Lim ◽  
Seong Bae An ◽  
...  

Whitlockite (WH) is the second most abundant inorganic component of human bone, accounting for approximately 25% of bone tissue. This study investigated the role of WH in bone remodeling and formation in a mouse spinal fusion model. Specifically, morphology and composition analysis, tests of porosity and surface area, thermogravimetric analysis, an ion-release test, and a cell viability test were conducted to analyze the properties of bone substitutes. The MagOss group received WH, Group A received 100% beta-tricalcium phosphate (β-TCP), Group B received 100% hydroxyapatite (HAp), Group C received 30% HAp/70% β-TCP, and Group D received 60% HAp/40% β-TCP (n = 10 each). All mice were sacrificed 6 weeks after implantation, and micro-CT, hematoxylin and eosin (HE) staining, and Masson trichome (MT) staining and immunohistochemistry were performed. The MagOss group showed more homogeneous and smaller grains, and nanopores (<500 nm) were found in only the MagOss group. On micro-CT, the MagOss group showed larger fusion mass and better graft incorporation into the decorticate mouse spine than other groups. In the in vivo experiment with HE staining, the MagOss group showed the highest new bone area (mean: decortication group, 9.50%; A, 15.08%; B, 15.70%; C, 14.76%; D, 14.70%; MagOss, 22.69%; p < 0.0001). In MT staining, the MagOss group demonstrated the highest new bone area (mean: decortication group, 15.62%; A, 21.41%; B, 22.86%; C, 23.07%; D, 22.47%; MagOss, 26.29%; p < 0.0001). In an immunohistochemical analysis for osteocalcin, osteopontin, and CD31, the MagOss group showed a higher positive area than other groups. WH showed comparable bone conductivity to HAp and β-TCP and increased new bone formation. WH is likely to be used as an improved bone substitute with better bone conductivity than HAp and β-TCP.

RSC Advances ◽  
2018 ◽  
Vol 8 (22) ◽  
pp. 12484-12493 ◽  
Author(s):  
Bo Liang ◽  
Jinghuan Huang ◽  
Jianguang Xu ◽  
Xiaolin Li ◽  
Jingfeng Li

With the development of tissue engineering, bone defects, such as fractured long bones or cavitary lesions, may be efficiently repaired and reconstructed using bone substitutes.


2020 ◽  
Vol 35 (6) ◽  
pp. 681-695
Author(s):  
Yiqian Ying ◽  
Beibei Li ◽  
Changying Liu ◽  
Zuochun Xiong ◽  
Wei Bai ◽  
...  

The search for bone substitutes that are biodegradable, ensure space maintenance, and have osteogenic predictability, is ongoing in the field of sinus augmentation. We thus compared the bone regeneration potential of nanostructured sponges (NS-Sponge) with that of collagen-stabilized inorganic bovine bones (BO-Collagen), gelatin sponges (Gelatin), and blood clots (Cont) in sinus augmentation of rabbits. NS-Sponge was prepared by thermally induced phase separation with porogen leaching techniques. All the materials were non-hemolytic and cytocompatible. The porous and nanofibrous NS-Sponge showed better dimensional stability to support cell growth and osteogenic differentiation. In vivo, the sinus membrane collapsed in Cont and Gelatin, while BO-Collagen and NS-Sponge maintained the elevated height as assessed by come-beam computed tomography. Limited bone regeneration was observed in Cont and Gelatin. In the entire implanted area, histological analysis revealed a higher percentage of new bone area at 4 weeks of BO-Collagen treatment; however, a significantly greater increase in new bone area was observed after 12 weeks of NS-Sponge treatment. The 12-week remnant NS-Sponge material was significantly lower than the 4-week remnant material. Overall, NS-Sponge may be highly recommended for sinus augmentation, as it exhibits numerous advantages, including excellent operability, clear imaging characteristics, space maintenance, biodegradability, and superior osteogenic potential.


2020 ◽  
Author(s):  
Tetsutaro Abe ◽  
Masashi Miyazaki ◽  
Toshinobu Ishihara ◽  
Shozo Kanezaki ◽  
Yuhta Tsubouchi ◽  
...  

Abstract Background: Both bone morphogenetic protein 2 (BMP-2) and teriparatide (parathyroid hormone [PTH] 1-34) are used to enhance bone healing. There is still no established opinion regarding the optimum dose and administration method. We investigated the optimal dose and administration method for the combination of BMP-2 and PTH 1-34 in a rat spinal fusion model. Methods: Group I was implanted with a control carrier. Groups II, III, and IV were implanted with a carrier containing 3μg of recombinant human BMP-2 (rhBMP-2). In addition, following implantation, PTH 1-34 injections were administered to Group III thrice a week (total, 180 μg/kg/week) and Group IV six times a week (total, 180 µg/kg/week). The rats were euthanized after 8 weeks, and their spines were explanted; assessed by manual palpation, radiographs, and high-resolution micro-computed tomography (micro-CT); and subjected to histological analysis. Serum markers of bone metabolism were also analyzed. Results: Manual palpation tests showed that the fusion rates in Groups III and IV were considerably higher than those in Group I. They also had higher radiographic scores than Group I. Micro-CT analysis revealed enhanced bone marrow density expressed as bone volume/tissue volume in Group IV versus Group I. Serum marker analysis revealed that Group IV had higher osteocalcin and lower tartrate-resistant acid phosphatase-5b than Group III. Histological analysis indicated that Group IV had enhanced remodeling. Conclusions: The rhBMP-2 and PTH combination enhanced bone fusion and remodeling of newly formed bone in the rat spinal fusion model. More frequent administration may be superior in terms of bone fusion and bone metabolism.


2020 ◽  
Vol 11 ◽  
pp. 204173142096759
Author(s):  
Tarek M. Bedair ◽  
Chang Kyu Lee ◽  
Da-Seul Kim ◽  
Seung-Woon Baek ◽  
Hanan M. Bedair ◽  
...  

Spinal fusion has become a common surgical technique to join two or more vertebrae to stabilize a damaged spine; however, the rate of pseudarthrosis (failure of fusion) is still high. To minimize pseudarthrosis, bone morphogenetic protein-2 (BMP2) has been approved for use in humans. In this study, we developed a poly(lactide-co-glycolide) (PLGA) composite incorporated with magnesium hydroxide (MH) nanoparticles for the delivery of BMP2. This study aimed to evaluate the effects of released BMP2 from BMP2-immobilized PLGA/MH composite scaffold in an in vitro test and an in vivo mice spinal fusion model. The PLGA/MH composite films were fabricated via solvent casting technique. The surface of the PLGA/MH composite scaffold was modified with polydopamine (PDA) to effectively immobilize BMP2 on the PLGA/MH composite scaffold. Analyzes of the scaffold revealed that using PLGA/MH-PDA improved hydrophilicity, degradation performance, neutralization effects, and increased BMP2 loading efficiency. In addition, releasing BMP2 from the PLGA/MH scaffold significantly promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells. Furthermore, the pH neutralization effect significantly increased in MC3T3-E1 cells cultured on the BMP2-immobilized PLGA/MH scaffold. In our animal study, the PLGA/MH scaffold as a BMP2 carrier attenuates inflammatory responses and promotes BMP2-induced bone formation in posterolateral spinal fusion model. These results collectively demonstrate that the BMP2-immobilized PLGA/MH scaffold offers great potential in effectively inducing bone formation in spinal fusion surgery.


2020 ◽  
Vol 35 (4-5) ◽  
pp. 532-543
Author(s):  
Juliane D Glaeser ◽  
Khosrowdad Salehi ◽  
Linda EA Kanim ◽  
Derek G Ju ◽  
Jae Hyuk Yang ◽  
...  

Introduction Synthetic bone grafts are often used to achieve a well-consolidated fusion mass in spinal fusion procedures. These bone grafts function as scaffolds, and ideally support cell function and facilitate protein binding. Objective The aim was to characterize an electrospun, synthetic bone void filler (Reb) for its bone morphogenetic protein (BMP)-2 release properties and support of human mesenchymal stem cell (hMSC) function in vitro, and its efficacy in promoting BMP-2-/bone marrow aspirate-(BMA)-mediated posterolateral spinal fusion (PLF) in vivo. Methods BMP-2 release kinetics from Reb versus standard absorbable collagen sponge (ACS) was determined. hMSC adhesion and proliferation on Reb was tested using cell counting, fluorescence microscopy and MTS. Cell osteogenic differentiation was quantified via cellular alkaline phosphatase (ALP) activity. For in vivo analysis, 18 Lewis rats were treated during PLF surgery with the following groups: (I) Reb + BMA, (II) Reb + BMA + BMP-2 and (III) BMA. A safe, minimally effective dose of BMP-2 was used. Fusion consolidation was followed for 3 months using radiography and micro-CT. After sacrifice, fusion rate and biomechanical stiffness was determined using manual palpation, biomechanical tests and histology. Results In vitro, BMP-2 release kinetics were similar between Reb versus ACS. MSC proliferation and differentiation were increased in the presence of Reb. At 3 months post-surgery, fusion rates were 29% (group I), 100% (group II), and 0% (group III). Biomechanical stiffness was higher in group II versus I. Micro-CT showed an increased bone volume and connectivity density in group II. Trabecular thickness was increased in group I versus II. H&E staining showed newly formed bone in group II only. Conclusions Reb possesses a high protein binding affinity and promotes hMSC function. Combination with BMA and minimal dose BMP-2 allowed for 100% bone fusion in vivo. This data suggests that a minimally effective dose of BMP-2 can be used when combined with Reb.


2021 ◽  
Author(s):  
Yu Kang ◽  
Chao Liu ◽  
Ming Wang ◽  
Cheng Wang ◽  
Yi-Guo Yan ◽  
...  

Abstract Background: Rats have been widely used as experimental animals when performing fundamental research because they are economical, rapidly reproducing, and heal quickly. While the rat interbody fusion model has been applied in basic studies, existing rat models generally have shortcomings, such as insufficiently simulating clinical surgery. The purpose of this study was to develop a novel rat model of interbody fusion which more closely represents clinical surgery.Methods: The internal fixation was designed based on physical measurements of the rats’ lumbar spine. Then, ten rats divided into two groups (A and B) underwent anterior lumbar corpectomy and fusion of the L5 vertebrae. Groups A and B were sacrificed four and eight weeks post-surgery, respectively. Micro-CT and histological examination were used to evaluate the model. Fusion rate, bone volume fraction (BV/TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), and the area ratio of newly formed bone (NB) were calculated for quantitative analysis.Results: Based on the L5 body dimensions of individual rats, 3D-printed titanium cage of the appropriate size were printed. The operations were successfully completed in all ten rats, and X-ray confirmed that internal fixation was good without migration. Micro-CT suggested that fusion rates in group B (100%) were greater than group A (40%, P<0.05). The BV/TV (B: 42.20±10.50 vs. A: 29.02±3.25, P<0.05) and Tb.N (B: 4.66±1.23 vs. A: 1.97±0.40, P<0.05) were greater in group B than A, and the Tb.Th in group B was lower than group A (B: 0.10±0.04 vs. A: 0.15±0.02, P<0.05). Histomorphometry results demonstrated that the area ratio of NB in group B were greater than group A (B: 35.72±12.80 vs. A: 12.36±16.93, P<0.05).Conclusion: A rat interbody fusion model based on anterior lumbar corpectomy and fusion has successfully been constructed and verified. It could provide a new choice for fundamental research using animal models of spinal fusion.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yu Kang ◽  
Chao Liu ◽  
Ming Wang ◽  
Cheng Wang ◽  
Yi-Guo Yan ◽  
...  

Abstract Background Rats have been widely used as experimental animals when performing fundamental research because they are economical, rapidly reproducing, and heal quickly. While the rat interbody fusion model has been applied in basic studies, existing rat models generally have shortcomings, such as insufficiently simulating clinical surgery. The purpose of this study was to develop a novel rat model of interbody fusion which more closely represents clinical surgery. Methods The internal fixation was designed based on physical measurements of the rats’ lumbar spine. Then, ten rats divided into two groups (A and B) underwent anterior lumbar corpectomy and fusion of the L5 vertebrae. Groups A and B were sacrificed four and 8 weeks post-surgery, respectively. Micro-CT and histological examination were used to evaluate the model. Fusion rate, bone volume fraction (BV/TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), and the area ratio of newly formed bone (NB) were calculated for quantitative analysis. Results Based on the L5 body dimensions of individual rats, 3D-printed titanium cage of the appropriate size were printed. The operations were successfully completed in all ten rats, and X-ray confirmed that internal fixation was good without migration. Micro-CT suggested that fusion rates in group B (100%) were greater than group A (40%, P < 0.05). The BV/TV (B: 42.20 ± 10.50 vs. A: 29.02 ± 3.25, P < 0.05) and Tb.N (B: 4.66 ± 1.23 vs. A: 1.97 ± 0.40, P < 0.05) were greater in group B than A, and the Tb.Th in group B was lower than group A (B: 0.10 ± 0.04 vs. A: 0.15 ± 0.02, P < 0.05). Histomorphometry results demonstrated that the area ratio of NB in group B were greater than group A (B: 35.72 ± 12.80 vs. A: 12.36 ± 16.93, P < 0.05). Conclusion A rat interbody fusion model based on anterior lumbar corpectomy and fusion has successfully been constructed and verified. It could provide a new choice for fundamental research using animal models of spinal fusion.


2021 ◽  
Vol 11 (1) ◽  
pp. 86
Author(s):  
Chenglei Fan ◽  
Carmelo Pirri ◽  
Caterina Fede ◽  
Diego Guidolin ◽  
Carlo Biz ◽  
...  

Background: Muscle spindles (MSs) play a crucial role in proprioception and locomotor coordination. Although the elasticity and viscosity of the extracellular matrix (ECM) within which MSs are embedded may play a key role in MS function, the impact of aging on ECM components is unclear. The aim of the current study was to investigate the age-related physiological changes of the ECM and to verify if these could be due to alterations of the environment directly surrounding MSs. Methods: Hematoxylin Eosin and picrosirius-red staining was carried out; collagen types I (COLI) and III (COLIII) were assessed, and biotinylated hyaluronan binding protein (HABP) immunohistochemical analysis was undertaken to evaluate alterations of the ECM in the intramuscular connective tissue (IMCT) of the hindlimbs of C57BL/6J male mice. Assessments were carried out on 6-week-old (Group A), 8-month-old (Group B), and 2-year-old (Group C) laboratory mice. Results: The capsule’s outer layer became progressively thicker with aging (it was 3.02 ± 0.26 μm in Group A, 3.64 ± 0.31 μm in Group B, and 5.81 ± 0.85 μm in Group C). The collagen in IMCT around and within the MSs was significantly higher in Group C, but there were no significant differences between Groups A and B. The MS capsules and continuous IMCT were primarily made up of COLI and COLIII. The average optical density (AOD) values of COLI in IMCT surrounding MS were significantly higher after aging (p < 0.05), but there were no significant differences in COLIII in the three groups (p > 0.05). HA was present in IMCT and filled the MSs capsule. The AOD of HABP of MS showed that there were lower HA levels in Group C with respect to Group A (p = 0.022); no significant differences were noted neither between Groups A and B nor between Groups B and C (p > 0.05). Conclusion: Age-related collagen accumulation and lower HA in the ECM in which the MSs were embedded may probably cause more stiffness in the ECM in vivo, which could help to partly explain the peripheral mechanisms underlying the age-related decline in functional changes related to MSs.


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