Microbubble Injection Enhances Inhibition of Low-Intensity Pulsed Ultrasound on Debris-Induced Periprosthetic Osteolysis in Rabbit Model

Authors

Bin Hu, Xun-Zi Cai, Zhong-Li Shi, Yun-Lin Chen, Xiang Zhao, Han-Xiao Zhu, Shi-Gui Yan

Abstract

We determined whether the addition of microbubbles enhances the effect of low-intensity pulsed ultrasound (LIPUS) on bone–implant integration in an early-stage osteolysis model. The bone canals were injected with titanium particles before implantation to establish the periprosthetic osteolysis model. Before ultrasonic therapy, the microbubble-enhanced LIPUS group (GTi-Us-Mb) received an intra-articular injection of microbubbles. Biomechanical testing revealed that GTi-Us-Mb had significantly greater fixation strength than the LIPUS group (GTi-Us). Distal periprosthetic bone mineral density was also higher in GTi-Us than in the Ti group (GTi), but no significant increase was detected after administration of microbubbles. Histomorphometric analyses revealed that bone formation around the implant in GTi-Us was enhanced by the addition of microbubbles in GTi-Us-Mb. Taken together, our data indicate that microbubble injection enhances the inhibitory effect of LIPUS on debris-induced osteolysis and further strengthens the mechanical fixation of implants in an early-stage osteolysis model in vivo.

Link To Article

http://dx.doi.org/10.1016/j.ultrasmedbio.2014.08.016

Development of Injectable Citrate-Based Bioadhesive Bone Implants

Authors

Denghui Xie, Jinshan Guo, Reza Mehdizadeh, Richard T. Tran, Ruisong chen, Dawei Sun, Guoying Qian, Dadi Jin, Xiaochun Bai and Jian Yang

Abstract

Injectable bone implants have been widely used in bone tissue repairs including the treatment of comminuted bone fractures (CBF). However, most injectable bone implants are not suitable for the treatment of CBF due to their weak tissue adhesion strengths and minimal osteoinduction. Citrate has been recently reported to promote bone formation through enhanced bioceramic integration and osteoinductivity. Herein, a novel injectable citrate-based mussel-inspired bioadhesive hydroxyapatite (iCMBA/HA) bone substitute was developed for CBF treatment. iCMBA/HA can be set within 2-4 minutes and the as-prepared (wet) iCMBA/HA possess low swelling ratios, compressive mechanical strengths of up to 3.2±0.27 MPa, complete degradation in 30 days, suitable biocompatibility, and osteoinductivity. This is also the first time to demonstrate that citrate supplementation in osteogenic medium and citrate released from iCMBA/HA degradation can promote the mineralization of osteoblastic committed human mesenchymal stem cells (hMSCs). In vivo evaluation of iCMBA/HA in a rabbit comminuted radial fracture model showed significantly increased bone formation with markedly enhanced three-point bending strength compared to the negative control. Neovascularization and bone ingrowth as well as highly organized bone formation were also observed showing the potential of iCMBA/HA in treating CBF.

Link To Article

http://dx.doi.org/10.1039/C4TB01498G

Fracture healing using degradable magnesium fixation plates and screws

Authors

Amy Chaya, BS, Sayuri Yoshizawa, DDS, PhD, Kostas Verdelis, DDS, PhD, Sabrina Noorani, MS, B.J. Costello, MD, DMD, Charles Sfeir, DDS, PhD

Abstract

Purpose Internal bone fixation devices made with permanent metals are associated with numerous long-term complications and may require removal. We hypothesized that fixation devices made with degradable magnesium alloys could provide an ideal combination of strength and degradation, facilitating fracture fixation and healing, while eliminating the need for implant removal surgery.

Methods Fixation plates and screws were machined from 99.9% pure magnesium and compared to titanium devices in a rabbit ulna fracture model. Magnesium device degradation and effect on fracture healing and bone formation was assessed after four weeks. Fracture healing with magnesium device fixation was compared to that of titanium devices using qualitative histological analysis and quantitative histomorphometry.

Results Microcomputed tomography showed device degradation after four weeks in vivo. In addition, 2D microCT slices and histological staining showed that magnesium degradation did not inhibit fracture healing or bone formation. Histomorphology revealed no difference in bone bridging fractures fixed with magnesium and titanium devices. Interestingly, abundant new bone was formed around magnesium devices, suggesting a connection between magnesium degradation and bone formation.

Conclusion Our results demonstrate potential for magnesium fixation devices in a loaded fracture environment. Furthermore, these results suggest that magnesium fixation devices may enhance fracture healing by encouraging localized new bone formation.

Link To Article

http://dx.doi.org/10.1016/j.joms.2014.09.007

In vivo assessment of guided neural stem cell differentiation in growth factor immobilized chitosan-based hydrogel scaffolds

Authors

Hang Li, Andrew M. Koenig, Patricia Sloan, Nic D. Leipzig

Abstract

In this study, we demonstrate that a unique growth factor-biomaterial system can offer spatial control of growth factors with sustained signaling to guide the specific lineage commitment of neural stem/progenitor cells (NSPCs) in vivo. First, recombinant fusion proteins incorporating an N-terminal biotin tag and interferon-γ (IFN-γ), platelet derived growth factor-AA (PDGF-AA), or bone morphogenic protein-2 (BMP-2) were immobilized to a methacrylamide chitosan (MAC) based biopolymer via a streptavidin linker to specify NSPC differentiation into neurons, oligodendrocytes, or astrocytes, respectively. MAC was mixed with growth factors (immobilized or adsorbed), acrylated laminin, NSPCs, and crosslinked within chitosan conduits. This system mimics regenerative aspects of the central nervous system ECM, which is largely composed of a crosslinked polysaccharide matrix with cell-adhesive regions, and adds the new functionality of protein sequestration. We demonstrated that these growth factors are maintained at functionally significant levels for 28 d in vitro. In the main study, immobilized treatments were compared to absorbed and control treatments after 28 d in vivo (rat subcutaneous). Masson's Trichrome staining revealed that small collagen capsules formed around the chitosan conduits with an average acceptable thickness of 153.07 ± 6.02 μm for all groups. ED-1 staining showed mild macrophage clustering around the outside of chitosan conduits in all treatments with no macrophage invasion into hydrogel portions. Importantly, NSPC differentiation staining demonstrated that immobilized growth factors induced the majority of cells to differentiate into the desired cell types as compared with adsorbed growth factor treatments and controls by day 28. Interestingly, immobilized IFN-γ resulted in neural rosette-like arrangements and even structures resembling neural tubes, suggesting this treatment can lead to guided dedifferentiation and subsequent neurulation.

Link To Article

http://dx.doi.org/10.1016/j.biomaterials.2014.07.038

Bone formation in peri-implant defects grafted with microparticles: a pilot animal experimental study

Authors

Tobias Moest, Franz Koehler, Christopher Prechtl, Christian Schmitt, Georg Watzek and Karl Andreas Schlegel

Abstract

Aim This study aimed to evaluate the healing of peri-implant defects grafted with microparticles (MPs).

Material and Methods Six domestic pigs received nine standardized defects at the calvaria, and an implant was inserted in the middle of each defect. The space between the implant and lateral bone portion was filled with MP pellets (n = 18) or MP supernatant (n = 18) or left unfilled (n = 18). After 14 and 28 days, three animals were sacrificed and specimens removed for further processing. Samples were microradiographically and histologically analysed. In addition, we immunohistochemically stained for anti-vWF as a marker of angiogenesis.

Results In the case of bone regeneration and vessel formation, the null hypothesis can be partially rejected. After 14 and 28 days, no significant difference was observed within groups regarding de novo bone formation, bone density and osseointegration. However, superior vessel formation was found at both time points.

Conclusion Microparticles represent a promising treatment option to accelerate peri-implant vessel formation. Further studies are needed to investigate the regenerative properties of MPs more precisely.

Link To Article

http://dx.doi.org/10.1111/jcpe.12295

Comparative study of the osseous healing process following three different techniques of bone augmentation in the mandible: an experimental study

Authors

M.E. Benlidayi, A. Gaggl, H. Buerger, O.E. Kahraman, L. Sencar, C. Brandtner, M. Kurkcu, S. Polat, F. Borumandi

Abstract

The aim of this study was to evaluate the osseointegration of three different bone grafting techniques. Forty-eight mature New Zealand rabbits were divided randomly into three groups of 16 each. Horizontal augmentation was performed on the corpus of the mandible using three different techniques: free bone graft (FBG), free periosteal bone graft (PBG), pedicled bone flap (BF). The animals were sacrificed at postoperative weeks 1, 3, or 8. Specimens were decalcified for histological examination, and histomorphometric measurements were performed. The histological evaluation demonstrated bony fusion between the grafts and the augmented mandibular bone after 8 weeks in all groups. At week 8, the bone volume was significantly greater in the BF group than in the FBG (P<0.001) and PBG (P=0.001) groups, and also the trabecular thickness was significantly greater than in the FBG (P=0.015) and PBG (P=0.015) groups. Trabecular separation was significantly lower in the BF group than in the FBG group at week 8 (P=0.015). BF demonstrated greater osseous healing capacity compared to FBG and PBG. The preserved vascularization in BF improves the bone quality in mandibular bone augmentations.

Link To Article

http://dx.doi.org/10.1016/j.ijom.2014.07.004