Songsong Zhu

The effect of strontium-substituted hydroxyapatite coating on implant fixation in ovariectomized rats

This study was designed to investigate the effects of strontium-substituted hydroxyapatite coatings with 10 mol% Ca(2+) replaced by Sr(2+) (10% SrHA) on implant fixation in ovariectomized (OVX) rats. Coatings of HA and 10% SrHA were prepared on the surface of titanium implant using sol-gel dip methods, and then characterized by Scanning Electron Microscope, Atomic Force Microscope, X-ray diffraction, X-ray Photoemission Spectroscopy, and an automatic scratch tester. Twelve weeks after bilateral ovariectomy, twenty OVX rats accepted implant insertion in the proximal tibiae, half with HA-coated implants and the other half with 10% SrHA coated implants. After 12-week healing period, 10% SrHA coated implants revealed improved osseointegration compared to HA, with the bone area ratio and bone-to-implant contact increased by 70.9% and 49.9% in histomorphometry, the bone volume ratio and percent osseointegration by 73.7% and 45.2% in micro-CT evaluation, and the maximal push-out force and ultimate shear strength by 107.2% and 132.9% in push out test. These results demonstrated that 10% SrHA coatings could enhance implant osseointegration in OVX rats, and suggested the feasibility of using SrHA coatings to improve implant fixation in osteoporotic bone.

Effect of combined local treatment with zoledronic acid and basic fibroblast growth factor on implant fixation in ovariectomized rats

Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone microarchitecture resulting in bone fragility, which impairs fixation of the implants. Zoledronic acid (ZOL) is a potential inhibitor of osteoclast-mediated bone resorption and basic fibroblast growth factor (bFGF) is a growth factor that stimulates osteoblast-mediated bone formation, and these drugs could enhance fixation of implants under osteoporotic conditions. In this study, 40 ovariectomized (OVX) rats were randomly divided into 4 groups (n=10 for each group) and underwent bilateral tibiae implantation using hydroxyapatite (HA)-coated titanium implant: Control group (distilled water immersing before implantation), ZOL group (1 mg/ml of ZOL immersing), bFGF group (20 microg/ml of bFGF immersing), and ZOL+bFGF group (1 mg/ml of ZOL and 20 microg/ml of bFGF immersing). At 3 months after implantation, all animal were sacrificed and the tibiae were harvested for histology, micro-CT examinations and biomechanical testing. Bone area and contact, determined by histomorphometric analysis, were 2.7-fold and 1.8-fold in the ZOL-treated implants, 1.9-fold and 1.8-fold in the bFGF-treated implants, 3.6-fold and 2.3-fold in the both-treated implants compared with controls (p<0.01). Such significant effects were further confirmed by microstructure parameters, the bone volume ratio and the percentage osteointegration were significantly increased by ZOL treatment (3.0-fold and 1.8-fold), bFGF treatment (1.2-fold and 1.9-fold) and ZOL+bFGF treatment (3.3-fold and 2.7-fold) (p<0.001). In addition, push-out test showed that the maximum force and the corresponding interfacial shear strength of the implants treated by ZOL, bFGF and ZOL+bFGF was 8.4-fold and 8.6-fold, 3.8-fold and 3.7-fold, 10.8-fold and 10.7-fold of the control levels, respectively (p<0.05). The combined treatment was better than either treatment alone for force, but was not different from ZOL alone for interfacial strength. The significant correlation between biomechanical and micro-CT parameters demonstrates the role of microstructure assessments in predicting mechanical fixation of implants (p<0.01). Our study suggests that locally applied ZOL or bFGF may improve implant fixation in the ovariectomized rats, and that combined treatment has more beneficial effects on osseointegration, peri-implant bone formation and maximum force than either intervention alone.

bFGF-Modified BMMSCs enhance bone regeneration following distraction osteogenesis in rabbits

Distraction osteogenesis (DO), which induces new bone formation along the vector of pull without requiring the use of bone graft, has become a valuable surgical method for patients with limb discrepancy or craniofacial microsomia. However, the long treatment period and possible fibrous union or nonunion hampers its further clinical application. Bone marrow mesenchymal stem cells (BMMSCs) have been widely used as a source of cell therapy or a vector for gene transfer. Basic fibroblast growth factor (bFGF) has high potential for promotion of bone regeneration. However, bFGF has a short half value period in vivo. In this study, osteodistraction was applied in craniofacial bone of rabbit to observe the effects of BMMSCs with or without bFGF gene transfected on bone regeneration in the distracted zone. Mandibular lengthening (10 mm) was performed in 42 New Zealand white rabbits using a rapid distraction rate (2 mm/day). The animals were then randomly divided into group A, group B and group C (n=14 for each group). At the end of distraction, physiological saline, autologous BMMSCs and BMMSCs transfected with bFGF were injected into the distraction gaps in groups A, B, and C, respectively. Eight weeks after DO, the rabbits were sacrificed, and the distracted mandibles were harvested and processed for radiography, dual energy x-ray absorptiometry (DXA), micro-CT, histology and three-point bend testing. Under a rapid distraction, immature or poor bone healing was observed in the distracted callus from group A. However, better bone formation and higher bone mineral density (BMD) and bone mineral content (BMC) in the distracted callus were observed in group B and group C, the latter showed excellent bone formation and highest BMD and BMC. Such finding was confirmed by histological and micro-CT examinations. The values of BT/TV in group C were highest and the micro-architecture presented more mature characteristics. The mechanical strength in group C was 1.63-fold and 1.28-fold greater than that in group A and B by three-point bending testing. The results of this study suggest that BMMSCs transplantation can promote bone formation in DO, and bFGF-modified BMMSCs were more effective in this enhancement.

Alendronate protects against articular cartilage erosion by inhibiting subchondral bone loss in ovariectomized rats.

Osteoporosis (OP) and osteoarthritis (OA) are major health problems in the increasing elderly population, particularly in postmenopausal women, but their relationship remains unclear. The present study investigated whether alendronate (ALN), a potent inhibitor of bone resorption, could protect articular cartilage from degeneration in a combined animal model of OP and OA induced by ovariectomy (OVX). Seventy-eight seven-month-old female Sprague-Dawley rats were assigned into five experimental groups: (1) sham-operated with vehicle treatment, (2) sham-operated with ALN treatment, (3) OVX with vehicle treatment, (4) ALN treatment starting at OVX, and (5) ALN treatment starting at eight weeks after OVX. Histological and micro-CT analyses, together with urine collagen degradation markers, indicated that early ALN treatment completely prevented both subchondral bone loss and cartilage surface erosion induced by OVX. Although late ALN treatment also inhibited subchondral bone loss and significantly reduced cartilage erosion in the OVX rats, these tissues did not completely recover even after 10-weeks of ALN treatment. Quantitative RT-PCR analyses showed that the protective effect of ALN correlated with increased ratio of OPG/RANKL in both subchondral bone and cartilage. Moreover, whereas OVX caused upregulation of expression of matrix metalloproteinases MMP-13 and MMP-9 in the articular cartilage and chondrocytes in the interface between the articular cartilage and subchondral bone, respectively, early ALN treatment blocked whereas late ALN treatment attenuated the upregulation of these catabolic enzymes in the corresponding tissues. Together, these data indicate that the subchondral bone loss plays an important role in OA pathogenesis in the combined OP and OA model and suggest that treatment timing is an important factor for the effectiveness of anti-resorptive drug therapy of combined OP and OA.

Effects of strontium on proliferation and differentiation of rat bone marrow mesenchymal stem cells

Strontium ranelate (SrR) was an effective anti-osteoporotic drug to increase bone formation and decrease bone resorption. However, reports about the effect of SR on osteoblastic and adipocytic differentiation from bone marrow mesenchymal stem cells (BMMSCs) are limited. The purpose of this study is to evaluate whether SrR affects the ability of BMMSCs to differentiate into osteoblasts or adipocytes. Rat BMMSCs were identified by flow cytometry and exposed to SR (0.1 and 1.0mMSr(2+)) under osteogenic or adipogenic medium for 1 and 2weeks. The proliferation and differentiation of BMMSCs were analyzed by MTT, alkaline phosphatase (ALP), Oil red O staining, quantitative real-time RT-PCR and Western blot assays. SrR significantly inhibited the proliferation, increased osteoblastic but decreased adipocytic differentiation of rat BMMSCs dose-dependently. In osteogenic medium, SrR increased the expression of ALP, the mRNA levels of Cbfa1/Runx2, bone sialoprotein, and osteocalcin by RT-PCR, and the protein levels of Cbfa1/Runx2 by Western blot. In adipogenic medium, SrR decreased the mRNA levels of PPARγ2, adipocyte lipid-binding protein 2 (aP2/ALBP), and lipoprotein lipase (LPL) by RT-PCR, and the protein expression of PPARγ in Western blot analysis. These results indicated that the effects of SrR to promote osteoblastic but inhibit adipocytic differentiation of BMMSCs might contribute to its effect on osteoporosis treatment.

Computer-assisted surgical planning and simulation for condylar reconstruction in patients with osteochondroma

We describe the use of computer-assisted three-dimensional surgical planning in condylar reconstruction by vertical ramus osteotomy for patients with osteochondroma, and its clinical effects. Seventeen patients with osteochondroma of the mandibular condyle who were seen from March 2005 to March 2009 were divided into 2 groups treated by condylectomy and condylar reconstruction using vertical sliding osteotomy of the mandibular ramus with and without three-dimensional simulation using Surgicase CMF Materialise software. Clinical examination, radiographs, photographs, and details of operation and outcome were used postoperatively to evaluate the clinical effects of the technique. Satisfactory mouth opening was achieved in all cases. Mean (SD) osteotomy and fixation time, duration of intermaxillary fixation, and degree of postoperative numbness of the lower lip were considerably reduced among patients who had three-dimensional simulation. The combined use of computer-assisted three-dimensional surgical planning and simulation with vertical ramus osteotomy to reconstruct the condyle for patients with osteochondroma after excision of the tumour makes the operation more accurate and more convenient, and avoids damage to vital structures.

Combined effects of recombinant human BMP-2 and Nell-1 on bone regeneration in rapid distraction osteogenesis of rabbit tibia

Distraction osteogenesis (DO) has been accepted as an effective technique for bone lengthening. However, the long treatment period and possible fibrous union or nonunion hampers its further clinical application. Bone regeneration in DO involves multiple stages of repair and coordinated action of multiple cell types. Consequently, it may be possible to enhance bone regeneration through treatment strategies that target more than one repair process or cell types. The goal of this study was to determine the combined effects of recombinant human bone morephogenetic protein 2 (rhBMP-2) and NEL-like molecule-1 (NELL-1) on bone formation in DO. Unilateral tibiae in 48 rabbits were lengthened for 7days at a rate of 2mm/day after 3-day lag. At the end of distraction, the animals were randomly divided into four groups (n=12) and received phosphate-buffered saline, 50μg rhNell-1 or 50μg rhBMP-2, or both 25μg rhBMP-2 and 25μg rhNell-1 at the lengthened segment, respectively. After 4-week consolidation bony healing was assessed using histology, radiography, dual energy X-ray absorptiometry, micro-CT, and three-point bend testing. Treatment with rhNell-1 and/or rhBMP-2 resulted in better bone formation and higher BMD and BMC than the saline group, whilst excellent bone formation and the highest BMD and BMC was observed in the combined treatment group. Both rhNell-1 and rhBMP-2 groups presented more mature characteristics in the micro-architecture than the saline group, whereas the combined treatment group presented the highest BV/TV, Tb.Th and Tb.N as well as the lowest Tb.Sp. The peak load of the lengthened tibia increased by 71% in the combined treatment group, 54% in the rhBMP-2 group, and 25% in the rhNell-1 group compared to the control group, respectively. This work suggests that BMP-2 and Nell-1 enhance each others ability and dual delivery of two agents can significantly improve bony healing in tibial DO.

The effect of tranexamic acid on blood loss in orthognathic surgery: a meta-analysis of randomized controlled trials

OBJECTIVE The objective of this article was to evaluate the efficacy of tranexamic acid on blood loss in orthognathic surgery. A meta-analysis was performed. STUDY DESIGN The PubMed and EMBASE electronic databases were searched until June 30, 2012. Eligible studies were restricted to randomized controlled trials (RCTs). RESULTS Four RCTs with 183 patients were included. The results showed that intraoperative blood loss in the tranexamic acid group was statistically reduced (weighted mean difference [WMD] = -93.56, 95% CI = -132.59-54.52, P < .00001). However, the postoperative levels of hemoglobin (Hb) and hematocrit (Hct) have no significant difference compared with placebo groups (WMD = 0.50, 95% CIs = -0.43-1.43, P = .29 and WMD = 0.18, 95% CIs = -1.64-1.99, P = .85, respectively). CONCLUSIONS This meta-analysis confirms that tranexamic acid can effectively reduce intraoperative blood loss in orthognathic surgery, especially by intravenous administration. But, tranexamic acid cannot affect postoperative levels of Hb and Hct.

Autogenous coronoid process pedicled on temporal muscle grafts for reconstruction of the mandible condylar in patients with temporomandibular joint ankylosis

OBJECTIVE The aim of this study was to investigate the feasibility of autogenous coronoid process pedicled on temporal muscle grafts (ACPTMG) for reconstruction of the mandible condyle, and to compare the differences in clinical effects with autogenous free coronoid process grafts (AFCPG) in patients with temporomandibular joint (TMJ) ankylosis. STUDY DESIGN From 2003 to 2005, 48 patients who were diagnosed with uni- or bilateral TMJ ankylosis were randomly divided into 2 groups: group A(24 cases, 28 joints) and group B(24 cases, 30 joints). All patients underwent operations for resection of condyle and surrounding bony masses and simultaneous recreation of the glenoid fossa, which was followed with, for group A, condylar reconstruction using ACPTMG and, for group B, AFCPG, as well as interposition of temporal muscle myofascial flaps or native articular disc. The pre- and postoperative interinsicial opening values and mouth-opening deviation were measured, and decrease in height of mandible ramus was analyzed by panoramic radiographs. RESULTS All patients showed apparent improved joint function except 1 patient of group B, who showed signs of reankylosis of the joint (<20 mm mouth opening). Radiographic examination and 3-dimensional computerized tomography both showed the grafts to be well attached to the ramus in their original positions and adaptive remodeling in both groups, but relatively more evident bony resorption was noted in group B. The mean measurement of mouth-opening deviation and postoperative decrease in height of mandible ramus in group B were significantly higher than in group A. CONCLUSIONS Satisfactory clinical outcomes show that both ACPTMG and AFCPG seem to be alternative and promising methods in the treatment of TMJ bony ankylosis. Compared with AFCPG, the advantages of ACPTMG include less bony resorption and better long-term clinical outcomes.

Combined Effects of Connective Tissue Growth Factor-Modified Bone Marrow-Derived Mesenchymal Stem Cells and NaOH-Treated PLGA Scaffolds on the Repair of Articular Cartilage Defect in Rabbits:

In cartilage tissue engineering using stem cells, it is important to stimulate proliferation and control the differentiation of stem cells to specific lineages. Here we reported a combined technique for articular cartilage repair, consisting of bone marrow mesenchymal stem cells (BMMSCs) transfected with connective tissue growth factor (CTGF) gene and NaOH-treated poly(lactic-co-glycolic) acid (PLGA) scaffolds. In the present study, BMMSCs or CTGF-modified BMMSCs seeded on PLGA or NaOH-treated PLGA scaffolds were incubated in vitro and NaOH-treated PLGA significantly stimulated proliferation of BMMSCs, while CTGF gene transfer promoted chondrogenic differentiation. The effects of the composite on the repair of cartilage defects were evaluated in rabbit knee joints in vivo. Full-thickness cartilage defects (diameter: 5 mm; depth: 3 mm) were created unilaterally in the patellar groove. Defects were either left empty (n = 18) or implanted with BMMSCs/ PLGA (n = 18), BMMSCs/NaOH-treated PLGA (n = 18), or CTGF-modified BMMSCs/NaOH-treated PLGA (n = 18). The defect area was examined grossly, histologically, and mechanically at 6, 12, and 24 weeks post-operatively. Implanted cells were tracked using adeno-LacZ labeling at 6 weeks after implantation. Overall, the CTGF-modified BMMSCs/NaOH-treated PLGA group showed successful hyaline-like cartilage regeneration similar to normal cartilage, which was superior to the other groups using gross examination, qualitative and quantitative histology, and mechanical assessment. The in vivo viability of the implanted cells was demonstrated by their retention for 6 weeks after implantation. These findings suggested that a combination of CTGF-modified BMMSCs and NaOH-treated PLGA may be an alternative treatment for large osteochondral defects in high-loading sites.