Objective To investigate the biomechanics of a novel injectable calcium phosphate cement (CPC) composited by poly (lactic-co-glycolic acid) (PLGA) combined with double-screw fixation in repairing Schatzker II type tibial plateau fracture, so as to provide the mechanical basis for the clinical minimally invasive treatment. Methods Ten matched pairs of proximal tibia specimens were harvested from 10 elderly cadavers to prepare Schatzker II type tibial plateau fracture model. Fracture was fixed by forcing injection of CPC (experimental group) or autologous cancellous bone (control group) combined with double-screw fixation. The samples underwent axial compression on MTS 858 material testing machine to measure the load-displacement, the maximum load, and compressive stiffness. Results The novel CPC had good injectable property at room temperature, which could fill in bone defect fully and permeated into the surrounding cancellous bone. The average bone mineral density of tibial metaphysis was (0.639 ± 0.081) g/cm2 in the experimental group and (0.668 ± 0.083) g/ cm2 in the control group, showing no significant difference (t=1.012, P=0.331). The maximum load in the experimental group [(4 101 ± 813) N] was significantly higher than that in the control group [(692 ± 138) N] (t=3.932, P=0.001). The compressive stiffness was (1 363 ± 362) N/mm in the experimental group and was (223 ± 54) N/mm in the control group, showing significant difference (t=3.023, P=0.013). Conclusion The novel CPC can effectively restore the biomechanical properties of tibilal plateau in repairing Schatzker II type tibial plateau fracture by means of forcing injection combining with double-screw fixation. It could be used as an effective bone substitute in the clinical application.
Objective To investigate the in vivo degradable properties of new calcium phosphate cement (CPC) containing poly lactic-co-glycolic acid (PLGA) so as to lay a foundation for the future clinical application. Methods A novel CPC containing PLGA (CPC/PLGA) was prepared according to a ratio of 45% dicalcium phosphate anhydrous ∶ 45% partially crystallized calcium phosphates ∶ 10% PLGA. Thirty-two adult New Zealand rabbits (weighing 2.2-3.0 kg, male or female in half) were divided into the experimental group (n=17) and the control group (n=15). The bone defect models of the bilateral femoral condyles (4.5 mm in diameter and 1.5 cm in depth) were made by drilling hole. Defect at the right side was repaired with CPC/ PLGA in the experimental group and with CPC in the control group, while defect at the left side was not treated as blank control. The general condition of rabbits was observed after operation; the histological observation and bone histomorphometric analysis were performed at 2, 4, 8, 16, and 24 weeks; and scanning electronic microscope (SEM) observation was performed at 8 and 16 weeks after operation. Results All rabbits survived to the end of experiment. The histological observation showed: CPC/PLGA degraded gradually, and the new-born bone trabecula ingrew; bone trabeculae became rough and b; and CPC/PLGA almost biodegraded at 24 weeks in the experimental group. The CPC degradation was much slower in the control group than in the experimental group. The total bone tissue percentage was 44.9% ± 23.7% in the experimental group, and 25.7% ± 10.9% in the control group, showing significant difference between 2 groups (t=3.302, P=0.001); and the bone tissue percentage showed significant difference between 2 groups at 8, 16, and 24 weeks (P lt; 0.05). The results of SEM observation showed that the pore size was 100-300 μm at 8 weeks after operation, new-born bone trabecula grew into the pores and combined bly with residual cement in the experimental group. Conclusion Novel CPC/PLGA has good in vivo degradable properties, and it can be an ideal bone substitute in future clinical application.
【Abstract】 Objective To introduce a new method using calcium phosphate cement/Danshen drug del ivery systemfor avascular necrosis of femoral head and to evaluate its cl inical outcome. Methods From May 2000 to June 2005, 48 patients (54 hips) with avascular necrosis of femoral head were treated with calcium phosphate cement/Danshen drug del ivery system implantation in the involved femoral head. There were 32 males(36 hips) and 16 females(18 hips) with an average age of 38.7 years (26-62 years). Twenty-one cases had the history of drinking or smoking, 15 cases had the history of receiving hormonotherapy and 2 had the history of injury in hip joint. The disease course was 2-32 months. According to standard of Association Research Circulation Osseous (ARCO) staging, 9 hips were classified as stage I, 31 as stage II and 14 as stage III. The operation consisted of removal of necrotic bone under weight-loading cartilage and the implantation of calcium phosphate cement/Danshen drug del ivery system, all mani pulations were done through a bone tunnel in trochanter. The function of hi p joint were evaluated and X-ray films were taken pre- and post-operatively. Results No phlebothrombosis of leg and foreign body action occurred in all cases, and incision healed by first intention. The postoperative follow-up averaged 42.5 months, ranging from 22 to 73 months. According to the evaluation criterion of Dandong 1995 for adult avascular necrosis of femoral head, the results were excellent in 33 hi ps, good in 17, fair in 3 and poor in 1, the excellent and good rate was92.6 %. Conclusion This method is relatively simple with less invasion, it not only improves the microcirculation of femoral head by local appl ication of traditional Chinese medicine, but also provide mechanic buttress in the weight-loaded area, which is beneficial to repair and reconstruction of femoral head. It may be a choice of minimally invasion surgery for femoral head necrosis.
Objective To investigate the physicochemicalproperties of the calcium phosphate cement (CPC) containing Danshen composite injection and its drug release rate. Methods This experiment included 4 groups and each group contained 6 specimens. CPC (2 g) was mixed with the setting solution that served as thecontrol group; 0.1,0.5 and 1.0 ml of Danshen composites injection (concentration, 1 000 mg/ml; pH, 7.35) were respectively added to CPC (2 g), which were used as the experimental groups 1, 2 and 3. The resulting specimens were investigated by the X-ray diffraction (XRD), the fourier transformed infrared spectroscopy(FTIR), and the scanning electron microscope (SEM).ResultsThe XRD analysis showed that the control group had a typical diffraction pattern of the hydroxypatite (HAP), which was consistent with the standard patternof HAP. When more Danshen was added in the experimental groups, the diffractionpeaks of HAP gradually decreased; when the diffraction angle 2θ was about 25.92°, the HAP peaks disappeared. Based on the FTIR analysis, with an increase of the drug concentration, the absorption peak of the hydroxy groups decreased. The SEM showed that the size of the CPC particle was related to the drug concentration; with an increase of the drug concentration, the CPC particle increased in number, resulting in an increasing trend of coacervation. The elution test showed that the drugrelease rate and capacity varied with the different concentrationsof Danshen. The initial release rate was relatively great, but after 96 hours the rate slowed down, lasting for a long time. Conclusion The physicochemical properties of CPC do not change when a proper dose (0.1 ml/2 g) of Danshen isadded to CPC. The Danshen composite can be effectively released from CPC, and so CPCcan be used as an ideal drugdelivery carrier for Danshen composite.
Objective To investigate the biomechanical influence ofvertebroplasty using autosolidification calcium phosphate cement (CPC) on thoracolumbar osteoporotic fractures. Methods Four cadaver specimens with osteoporosiswere applied to make spine unit. There were 2 females and 2 males, whose average age was 69 years.All underwent flexion-axial loading to result in vertebral body fracture. Following reduction, the middle fractured vertebral body were strengthened by the method of vertebroplasty, using CPC. Before fracture and after vertebroplasty, all were conducted biomechanical test. Results After being packed- CPC to the space in the fractured vertebral body, the strength andstiffness in vertebroplastic group (2 285±34 N，427±10 N/mm) were significantly higher than that in osteoporotic group (1 954±46 N，349±18 N/mm) (Plt;0.05). The vertebral height changing in vertebroplastic group(5.35±0.60 mm) were significantly lower than that in osteoporotic group (5.60±0.70 mm) (Plt;0.05). And the fractured body increases its strength and stiffnessby 16.92% and 22.31% respectively in comparison with its initial situation. Conclusion After being injected CPC into bone trabecular interspaces, the fractured vertebral bodies can restore its strength and stiffness markedly.
Objective To find out an effective technique torepair large segmental infected bony defect.Methods Calcium phosphate cement(CPC) incorporated with bone morphogenetic protein and gentamycin was embedded in the massive reconstituted bovine xenograft(MRBX), then CPC-MRBX was obtained after CPC’s solidification. In vivo test was applied to test the drug delivery capability of CPC-MRBX, in which it was implanted in the dorsal muscle pouch of 18 rabbits. The drug concentration of animal blood and surrounding soft tissue of the CPC-MRBX in the muscle pouch was measured 1, 2, 5, 10, 15, 20, 25, 30 and 35 d after operation, 2 rabbits each time. Large segmental infected femur defect in the rabbit model was created to test the repairing capability of CPC-MRBX. External fixation was done 1.5~2.0 cm above the knee, the most adjacent nail to fracture site was 0.5～0.8 cm away, and proper pressure was applied to the graft. In experimental group(n=25), the bony defect was replaced by CPC-MRBX, while in the control group(n=15) dissected bone block was re-implanted in original position. The animal was subjected to radiographic, histological examination at 4, 8, 16 and 24 weeks. The general condition was observed after the operation.Results CPC-MRBX was easily made under normal temperature and pressure. In viro drug delivery test showed that the drug concentration of the tissue remainedabove the minimal inhibitory concentration of staphylococcus 30 d after operation and no significant increase of blood drug concentration was observed. In experimental group, no adverse influence was observed. Four weeks after operation, the animal could bear load, bony callus around the graft was observed by X-ray, and abundant chondral tissues that grew into CPC-MRBX were observed by histological method. Eight weeks after operation, progressively increasing bony callus around the graft was observed, external fixation could be removed, normal function was restored, and CPC was degenerated dramatically while new bone tissues were growing. Sixteen weeks after the operation, more new bone tissues grew and CPC was degenerated furtherly while marrow tissues were taking shape. Twenty-four weeks after the operation, femur healed completely and CPC was degenerated completely. In the control group, the autograft remained unhealedon X-ray at 4 weeks, and osteomyelitis manifestation such as inflammatory cells infiltration and osteolysis was detected at 4 weeks. All the animals in the control group died before the 8th week, 4 of which showed positive hemoculture. Conclusion CPC-MRBX is readily available and can be applied to repairing large segmental infected bony defect.30 d after operation and no significant increase of blood drug concentration was observed. In experimental group, no adverse influence was observed. Four weeks after operation, the animal could bear load, bony callus around the graft was observed by X-ray, and abundant chondral tissues that grew into CPCMRBX were observed by histological method. Eight weeks after operation, progressively increasing bony callus around the graft was observed, external fixation could be removed, normal function was restored, and CPC was degenerated dramatically while new bone tissues were growing. Sixteen weeks after the operation, more new bone tissues grew and CPC was degenerated furtherly while marrow tissues were taking shape. Twenty-four weeks after the operation, femur healed completely and CPC was degenerated completely. In the control group, the autograft remained unhealedon X-ray at 4 weeks, and osteomyelitis manifestation such as inflammatory cells infiltration and osteolysis was detected at 4 weeks. All the animals in the control group died before the 8th week, 4 of which showed positive hemoculture.Conclusion CPC-MRBX is readily available and can be applied to repairing large segmental infected bony defect.
Objective To investigate the clinical application of self-settingcalcium phosphate cement (CPC) in bone defect repair of extremities. Methods From May 1998 to January 2000, 32 cases of bone defect, in 36 sites, were repairedand reviewed, aged from 4 to 59 years old (24.7 years old on average), with bone defect 2 to 125 cm2 in size (13.1 cm2 on average). The causes of the bone defect werefracture, bone cyst, iliac bone harvesting, fibrous dysplasia, enchondroma and bone tuberculosis, which involved femur, iliac, tibia, humerus, phalanx, fibula, calcaneus, talus and acetabulum. All of the cases were followed up for 1 to 23 months, 15.3 months on average, before radiographic examination. Results All operations were successful and no general response was observed in all of the cases. X-ray examination showed an integrity interface between CPC and bone. And CT showed no gap existed. There was no increase of serum calcium and phosphate levels. Conclusion CPC is applicable in the low- or non-weight-bearing site of the extremities.
Objective To investigate the effect of a porous calcium phosphate/bone matrix gelatin (BMG) composite cement (hereinafter referred to as the " porous composite cement”) for repairing lumbar vertebral bone defect in a rabbit model. Methods BMG was extracted from adult New Zealand rabbits according to the Urist’s method. Poly (lactic-co-glycolic) acid (PLGA) microsphere was prepared by W/O/W double emulsion method. The porous composite cement was developed by using calcium phosphate cement (CPC) composited with BMG and PLGA microsphere. The physicochemical characterizations of the porous composite cement were assessed by anti-washout property, porosity, and biomechanical experiment, also compared with the CPC. Thirty 2-month-old New Zealand rabbits were used to construct vertebral bone defect at L3 in size of 4 mm×3 mm×3 mm. Then, the bone defect was repaired with porous composite cement (experimental group, n=15) or CPC (control group, n=15). At 4, 8, and 12 weeks after implantation, each bone specimen was assessed by X-ray films for bone fusion, micro-CT for bone mineral density (BMD), bone volume fraction (BVF), trabecular thickness (Tb. Th.), trabecular number (Tb.N.), and trabecular spacing (Tb. Sp.), and histological section with toluidine blue staining for new-born bone formation. Results The study demonstrated well anti-washout property in 2 groups. The porous composite cement has 55.06%±1.18% of porosity and (51.63±6.73) MPa of compressive strength. The CPC has 49.38%±1.75% of porosity and (63.34±3.27) MPa of compressive strength. There were significant differences in porosity and compressive strength between different cements (t=4.254, P=0.006; t=2.476, P=0.034). X-ray films revealed that the zone between the cement and host bone gradually blurred with the time extending. At 12 weeks after implantation, the zone was disappeared in the experimental group, but clear in the control group. There were significant differences in BMD, BVF, Tb. Th., Tb. N., and Tb. Sp. between 2 groups at each time point (P<0.05). Histological observation revealed that there was new-born bone in the cement with the time extending in 2 groups. Among them, bony connection was observed between the new-born bone and the host in the experimental group, which was prior to the control group. Conclusion The porous composite cement has dual bioactivity of osteoinductivity and osteoconductivity, which are effective to promote bone defect healing and reconstruction.
Objective To explore the clinical efficiency of vancomycin-loaded calcium phosphate cement (CPC) in the treatment of chronic osteomyelitis (CO). Methods From December 1st 2014 to December 1st 2015, 98 patients with CO were randomly divided into the research group and the control group, with 49 in each group. The patients in the research group were primarily implanted with vancomycin-loaded CPC after debridement, while the ones in the control group were placed with irrigation and drainage device to take continous irrigation with antibiotics after debridement. The treatment effect and the recurrence rate in the two groups were observed. Results The patients in the two groups were followed up for 12 months. In the research group, 30 patients were cured, 16 were improved, and 3 were not improved with the total effective rate of 93.9%; no systemic adverse reactions and recurrence took place after the operation; X-ray results showed well CPC tamponade and partially degenerated osteogenesis. In the control group, 16 patients were cured, 20 were improved and 13 were not improved, with the total effective rate of 73.5%; 11 had recurrent inflammation in 2–6 months after operation and were reoperated again. Conclusion The primary implantation of vancomycin-loaded CPC in CO lesions can fill the dead space, resist infection persistently, induce osteogenesis in bone defect area, and reduce the recurrence of CO, which is an effective method for the treatment of CO.
ObjectiveTo investigate the mechanical properties of the novel compound calcium phosphate cement (CPC) biological material as well as the biological activity and osteogenesis effects of induced pluripotent stem cells (iPS) seeding on scaffold and compare their bone regeneration efficacy in cranial defects in rats.MethodsAc- cording to the different scaffold materials, the experiment was divided into 4 groups: pure CPC scaffold group (group A), CPC∶10%wt chitosan as 2∶1 ratio mixed scaffold group (group B), CPC∶10%wt chitosan∶whisker as 2∶1∶1 ratio mixed scaffold group (group C), and CPC∶10%wt chitosan∶whisker as 2∶1∶2 ratio mixed scaffold group (group D). Mechanical properties (bending strength, work-of-fracture, hardness, and modulus of elasticity) of each scaffold were detected. The scaffolds were cultured with fifth generation iPS-mesenchymal stem cells (MSCs), and the absorbance (A) values of each group were detected at 1, 3, 7, and 14 days by cell counting kit 8 (CCK-8) method; the alkaline phosphatase (ALP) activity, Live/Dead fluorescence staining and quantitative detection, ALP, Runx2, collagen typeⅠ, osteocalcin (OC), and bone morphogenetic protein 2 (BMP-2) gene expressions by RT-PCR were detected at 1, 7, and 14 days; and the alizarin red staining were detected at 1, 7, 14, and 21 days. Twenty-four 3-month-old male Sprague Dawley rats were used to establish the 8 mm-long skull bone defect model, and were randomly divided into 4 groups (n=6); 4 kinds of scaffold materials were implanted respectively. After 8 weeks, HE staining was used to observe the repair of bone defects and to detect the percentage of new bone volume and the density of neovascularization.ResultsThe bending strength, work-of-fracture, hardness, and modulus of elasticity in groups B, C, and D were significantly higher than those in group A, and in groups C, D than in group B, and in group D than in group C (P<0.05). CCK-8 assay showed that cell activity gradually increased with the increase of culture time, theA values in groups B, C, and D at 3, 7, 14 days were signifiantly higher than those in group A, and in groups C, D than in group B (P<0.05), but no significant difference was found between groups C and D (P>0.05). Live/Dead fluorescence staining showed that the proportion of living cells in groups B, C, and D at 7 and 14 days was significantly higher than that in group A (P<0.05), and in groups C, D at 7 days than in group B (P<0.05); but no significant difference was found between groups C and D (P>0.05). RT-PCR showed that the relative expressions of genes in groups B, C, and D at 7 and 14 days were significantly higher than those in group A, and in groups C, D than in group B (P<0.05); but no significant difference was found between groups C and D (P>0.05). Alizarin red staining showed that the red calcium deposition on the surface of scaffolds gradually deepened and thickened with the prolongation of culture time; theA values in groups B, C, and D at 14 and 21 days were significantly higher than those in group A (P<0.05), and in groups C and D than in group B (P<0.05), but no significant difference was found between groups C and D (P>0.05).In vivo repair experiments in animals showed that the new bone in each group was mainly filled with the space of scaffold material. Osteoblasts and neovascularization were surrounded by new bone tissue in the matrix, and osteoblasts were arranged on the new bone boundary. The new bone in groups B, C, and D increased significantly when compared with group A, and the new bone in groups C and D was significantly higher than that in group B. The percentage of new bone volume and the density of neovascularization in groups B, C, and D were significantly higher than those in group A, and in groups C and D than in group B (P<0.05); but no significant difference was found between groups C and D (P>0.05).ConclusionThe mechanical properties of the new reinforced composite scaffold made from composite chitosan, whisker, and CPC are obviously better than that of pure CPC scaffold material, which can meet the mechanical properties of cortical bone and cancellous bone. iPS-MSCs is attaching and proliferating on the new reinforced composite scaffold material, and the repair effect of bone tissue is good. It can meet the biological and osteogenic activity requirements of the implant materials in the bone defect repair.