To observe the clinical effect and safety of the nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite in repairing the bone defects due to benign bone tumors. Methods From January 2003 to May 2005, 38 patients (21 males, 16 females; age, 19-58 years, averaged 38.5 years) with the bone defects due to benign bone tumors were treated with the n-HA/PA66 grains. Among the 37 patients, 11 had fibrous dysplasia, 14 had bone cyst, 10 had giant cell tumor of the bone (Grade Ⅰ), and 2 had enchondroma. The tumors ranged in size from 1.0 cm×0.7 cm×0.4 cm to 10.0 cm×4.0 cm×3.0 cm, with the location of the proximal femur in 12 patients, the distal femur in 7, the proximal tibia in 9, the proximal humerus in 5, the phalanges of the finger in 2, the metacarpal bone in 1,and the calcaneus in 1. Allthe benign bone tumors underwent the curettage treatment, and then the tumor cavities were filled up with the n-HA/PA66 grains. The incision healing, local inflammatory reaction, rejection, toxic reaction, tumor cavity healing, and function recovery of the limbs were all observed after operation. Results All the patients were followed up for 5-33 months, and all the incisions healed by the first intention except 1 incision, which developed infection. The inflammatory reaction was mild, with no reection or general toxic reaction. At 3 to 5.5 months(mean 4 months) after operation, osteogenesis wasfound in the space filled with the n-HA/PA66 grains. Eight months after operation, the patients’ lower limbs could bear weights; 5 months after operation, the upper limbs could complete daily work. Conclusion The n-HA/PA66 grains have great biological safety, good biocompatibility, and good bone conduction, which aregood materials for the bone repair and reconstruction, and can be safely, andeffectively used for repairing the bone defects due to benign bone tumors．
Objective To develop the plastic nano-hydroxyapatite (nano-HA)/poly (3-hydroxybutyrate-hydroxyvalerate) polyethylene glycol(PHBV-PEG) gentamicin (GM) drug delivery system(DDS)(nano-HA/PHBV-PEG-GM-DDS) for treating osteomyelitis and find its releasing character in vivo. Methods The plastic nano-HA/PHBV- PEG-GM-DDS was prepared using nanoHAas the core carrier of GM, nano-HA with PHBV and PEG as coating and plastic fibrin glue(FG) as microsphere scaffold. The morphological features of nano-HA,drug loaded nano-HA and drug loaded nano-HA/PHBVPEG microsphere were examined by electron microscope.The GM concentration in blood, cortex bone and cancellousbone was detected at 12 different time points by the method of K-B after the plastic nano-HA/PHBV-PEGGM-DDS was implanted into the femora of 36 rabbits. Its GM releasing character was assayed in vivo. Results Nano-HA was similar to a blackjack, and its length was less than 60 nm. Drug loaded nano-HA appeared natural crystal condensate, of which surface adsorbed massive GM. The average grain diameter was 200.5 nm. Drug loaded nanoHA/PHBV-PEG microsphere had a shrinkable porous structure, of which surface configuration was consistent. The average grain diameter was 34.5 μm. The GM concentration and the antibacterial annulus was in the linear correlation. The correlation coefficient was 0.998. In cortex and cancellous bone tissue, the GM concentration was about 95.50±16.50 μg/ml and 80.20±13.80 μg/ml from the plastic nano-HA/PHBV-PEG-GM-DDS on the 1st day, then decreased gradually. After 56 days of operation, the GM concentration still exceeded the minimum inhibitory concentrationfor the staphylococcus aureus, but the peak level of serum GM concentration wasunder the nephrotoxicity concentration. Conclusion Plastic nano-HA/PHBV-PEG-GM-DDS was a good drug delivery system with sustained antibiotic effect in vivo. It was an effective method for the treatment of osteomyelitis.
Objective To investigate the effect of tissue engineering bone compounded in vitro by nanohydroxyapatite/collagen/ polylactic acid (nHAC/PLA) and recombinant human bone morphogenetic protein 2 (rhBMP-2) in repairing rabbit critical calvarial defects. Methods Forty eight New Zealand rabbits, weighting 2.0-2.5 kg, were made the models of critical cranial defects(15 mm in diameter) and divided into 4 groups randomly. Defects were repaired with autoflank bone in the positive control group; with no implant in the blank control group; with nHAC/PLA in the negative control; and with active nHAC/PLA(AnHAC/PLA) in the experimental group(the average quality of each AnHAC/PLA absorbed rhBMP-2 was 1.431 mg). The reapir results were observed through X-ray,HE dyeing and Masson’s trichrism dyeing after 8 and 16 weeks. Results The difference of bone formation was observed by X-ray block degree of skull defect area at 8 and 16 weeks. In the 8 th week and 16 th week, the radiopacities on cranial defect were 67.21%±2.06% and 86.48%±1.73% in the positive control group； 5.84%±1.92% and 9.48%±2.72% in the blank control group; 19.13%±2.51% and 35.67%±3.28% in the negative control group; and 58.84%±2.55% and 8561%±3.36% in the experimental group. There were significant differences between the negative control and the positive control group, and between the experimental group and the positive control group at 8 weeks(Plt;0.05) . There were significant differences between the negative control and blank group, and between the experiment and the blank group at 8 and 16 weeks(P＜0.05). The histology observation showed that the width of bone trabecula at 16 weeks was more than that at 8 weeks and bone defectwas full of bone tissue in positive control group. The bone defect was full of fibrous tissue at 8 and 16 weeks, and there was no new bone in the blank group. The bone defect was full of remnant material and fibrous tissue in the negative control group. The implanted area was replaced by the new bone at 8 weeks and the new bone was lamellar at 16 weeks in the experimental group; the residual material was less in defect area and there were more osteoblasts surrounding. Conclusion The nHAC/PLA is a good scaffoldmaterial of rhBMP-2 and AnHAC/PLA has agood ability in repairing bone defect. So it is hopeful to be applied in the clnical repair of large bone defect.
Objective To investigate the safety of nano-hydroxyapatite/polyamide 66 (n-HA/PA66) bioactive support in bone grafting and fusion for elderly patients with lumbar tuberculosis, and to analyze its effectiveness and advantages by comparing with autologous iliac bone grafting. Methods A retrospective analysis was performed on 48 elderly patients with lumbar tuberculosis who met the selection criteria between January 2017 and January 2020. The patients all underwent one-stage posterior pedicle screw internal fixation combined with anterior lesion removal and bone grafting and fusion, of which 23 cases applied n-HA/PA66 bioactive support+allogeneic bone graft (n-HA/PA66 group) and 25 cases applied autologous iliac bone graft (autologous iliac bone group). There was no significant difference between the two groups in gender, age, bone density, disease duration, lesion segment, and preoperative pain visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and Cobb angle (P>0.05). The operation time, intraoperative blood loss, and postoperative complications, as well as the VAS score, JOA score, American Spinal Injury Association (ASIA) spinal cord injury grading, Cobb angle, and bone fusion were recorded and compared between the two groups. Results The operations were completed successfully in both groups. n-HA/PA66 group had significantly less operation time and intraoperative blood loss than the autologous iliac bone group (P<0.05). All patients were followed up 12-24 months, with an average of 15.7 months. And the difference in follow-up time between the two groups was not significant (P>0.05). Postoperative complications occurred in 3 cases (13%) in the n-HA/PA66 group and 10 cases (40%) in the autologous iliac group, and the difference in the incidence of complications between the two groups was significant (χ2=4.408, P=0.036). The postoperative VAS scores and JOA scores significantly improved when compared with the preoperative scores in both groups (P<0.05), and the difference was significant (P<0.05) between 2 weeks after operation and the last follow-up. The difference in VAS score at 2 weeks after operation was significant between the two groups (P<0.05), and there was no significant difference (P>0.05) at the other time points. At last follow-up, according to the ASIA grading, the effective improvement rate was 86% (18/21) in the n-HA/PA66 group and 90% (18/20) in the autologous iliac group, with no significant difference (χ2=0.176, P=0.675). Imaging review showed that grade Ⅰ bony fusion was obtained in both groups, and the fusion time of bone graft in the n-HA/PA66 group was significantly longer than that in the autologous iliac bone group (P<0.05). There was no significant difference in the Cobb angle at each time point between the two groups (P>0.05). No recurrence of tuberculosis, loosening or fracture of the internal fixator, or displacement of the bone graft was observed during follow-up. Conclusion In elderly patients with lumbar spine tuberculosis, the n-HA/PA66 bioactive support combined with allogeneic bone graft can effectively restore and maintain the fusion segment height and physiological curvature of the lumbar spine, and the fusion rate of bone graft is similar to that of autologous iliac bone, which can achieve better effectiveness.
ObjectiveTo explore the effectiveness of nano-hydroxyapatite/polyamide-66 (n-HA/PA66) Cage in interbody fusion for degenerative lumbar scoliosis.MethodsA retrospective analysis was designed and conducted for 43 patients, who underwent posterior decompression and n-HA/PA66 Cage interbody fusion with correction of deformity between January 2013 and June 2016. Eighteen cases were single-level fusion (single-level group) and 25 cases were double-level fusion (double-level group). There was no significant difference in gender, age, body mass index, direction of convex, degree of apical rotation, fusion level, the number of osteoporotic patients, pre-operative intervertebral height of fusion segments, coronal Cobb angle, visual analogue score (VAS), and modified Oswestry Disability Index (ODI) between 2 groups (P>0.05). The operation time, intraoperative blood loss, postoperative drainage, hospital stay, and complications of the operation were recorded. Modified ODI, VAS score, and MacNab criteria were adopted to assess clinical outcomes. Radiographic indexes, including intervertebral height of fusion segments, coronal Cobb angle, disc insertion depth, and the bone graft fusion rate, were also evaluated.ResultsThere was no significant difference in operation time, intraoperative blood loss, postoperative drainage, and hospital stay between 2 groups (P>0.05). All patients were followed up 18-62 months (mean, 30.9 months). Wound complications, postoperative delirium, and Cage retropulsion occurred in 4 cases (2 cases in single-level group, 2 cases in double-level group), 1 case of single-level group, and 1 case of double-level group, respectively. The intervertebral height of fusion segments after operation significantly improved compared with preoperative ones in both groups (P<0.05). At last follow-up, the intervertebral height in double-level group was superior to which in single-level group (P<0.05). The coronal Cobb angles after operation significantly improved compared with preoperative ones (P<0.05), and no significant difference was found between 2 groups at each time point (P>0.05). The disc insertion depth showed no significant difference between different time points after operation in 2 groups (P>0.05) and between 2 groups at each time point after operation (P>0.05). Bony fusion was obtained in all patients at last follow-up. The VAS score and modified ODI after operation in both groups were superior to those before operation (P<0.05). The VAS score in double-level group was higher than that in single-level group (P<0.05) at last follow-up, and no significant difference was found in VAS score and modified ODI between 2 groups at other time points (P>0.05). According to the MacNab criteria, the excellent and good rates at last follow-up were 94.4% and 84.0% in single-level group and double-level group, respectively.ConclusionThe n-HA/PA66 Cage can effectively restore and maintain the disc height of fusion segment, normal sequence, and biomechanical stability of the spine, and gain favorable effectivenss for degenerative lumbar scoliosis. And double-level fusion is superior to single-level fusion in maintaining disc height of fusion segment.
Objective To evaluate the security and effectiveness of nano-hydroxyapatite/polyamide 66 (n-HA/PA66) cage in reconstruction of spinal stabil ity after resection of spinal tumor. Methods Between January 2008 and December2009, 11 patients with spinal tumor underwent surgical resection and strut graft with n-HA/PA66 cage. There were 6 males and 5 females with an average age of 44.5 years (range, 16-61 years). The average disease duration was 6.8 months (range, 2-14 months). The locations of lesions included cervical spine (2 cases), thoracic spine (6 cases), and lumbar spine (3 cases). Among them, there were 5 metastatic carcinomas, 2 giant cell tumors, 1 osteoblastsarcoma, 1 chondrosarcoma, and 2 non-Hodgkin lymphoma. According to Frankel criteria for nerve function classification, there were 1 case of grade A, 3 cases of grade B, 2 cases of grade C, 2 cases of grade D, and 3 cases of grade E. Results Incisions healed by first intention in all patients, no operative or postoperative compl ication occurred. Four cases of metastatic carcinoma died of primary disease during 5-9 months after operation. Seven cases were followed up 14.4 months on average (range, 10-18 months). All patients gained significant improvement of the neurological function at 3 months after operation. All cases obtained bone fusion and good spinal stabil ity without displacement and subsidence of the n-HA/PA66 cage. The intervertebral height of the adjacent segments was (110.5 ± 16.1) mm at 3 months after operation and (109.4 ± 16.2 ) mm at the final follow-up, showing significant differenecs when compared with the preoperative height [(97.5 ± 15.4) mm, P lt; 0.05], but no significant difference between 3 months after operation and the final follow-up. In 2 patients undergoing surgery via anterior approach, bilateral pleural effusion on both sides occurred and were cured after closed thoracic drainage. During the follow-up, 2 cases (1 chondrosarcoma and 1 giant cell tumor) relapsed and underwent reoperations. Conclusion n-HA/PA66 cage can provide satisfactory bone fusion and ideal spinal stabil ity without increasing the risk of recurrence and compl ications during the surgical treatment of spinal tumors. It is an idealselection for reconstruction of spinal stability.
Objective To study the clinical effects of artificial vertebral laminae of the biomimetic nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composites in prevention of the scar formation in lumbar spinal canal and the reconstruction of posterior vertebral laminae structure. Methods From January 2003 to December 2005, 23 patients were treated with artificialvertebral laminae of the biomimetic n-HA/PA66 composites. There were 16 males and 7 females, aging from 48 to 76 years with an average of 59 years. Of 23 cases,11 cases had spinal stenosis, 7 cases had spinal stenosis with spondylolysis, 3 cases had lumbar disk herniation and 2 cases had spinal tumor. Twenty cases of vertebral laminae were reconstructed by 1 artificial vertebral laminae and 3 cases by 2.The affected locations were C5,6,L1 and L2 in 1 case respectively; L4,5 in 5 cases; L4-S1 in 9 cases; and L5, S1 in 6 cases. Results First intension was achieved in 22 cases and infection occured in 1 case.In the period of follow-up for all cases lasted from 5 to 24 months,the postoperative CT showed that the nHA/PA66 artificial vertebral laminae enlarged the spinal canal. MRI showed little scar formation and adhesion in the lumbar spinal canal. CT showed illdefined boundary between artificial vertebral laminae and recipient vertebral laminae. No neural symptoms occured in all cases except onebecause of stretch injury of nerve root in operation. Also no rejection reaction was observed. Conclusion The artificial vertebral laminae of the biomimetic nHA/PA66 composites can effectively prevent the compression to the nerve root and dural sac from the scar and restore the vertebral laminae.
Objective To evaluate the application of artificial lamina of multi-amino-acid copolymer (MAACP)/nano-hydroxyapatite (n-HA) in prevention of epidural adhesion and compression of scar tissue after posterior cervical laminectomy. Methods Fifteen 2-year-old male goats [weighing, (30 ± 2) kg] were randomly divided into experimental group (n=9) and control group (n=6). In the experimental group, C4 laminectomy was performed, followed by MAACP/n-HA artificial lamina implantations; in the control group, only C4 laminectomy was performed. At 4, 12, and 24 weeks after operation, 2, 2, and 5 goats in the experimental group and 2, 2, and 2 goats in the control group were selected for observation of wound infection, artificial laminar fragmentation and displacement, and its shape; Rydell’s degree of adhesion criteria was used to evaluate the adhesion degree between 2 groups. X-ray and CT images were observed; at 24 weeks after operation, CT scan was used to measure the spinal canal area and the sagittal diameter of C3, C4, and C5 vertebrea, 2 normal goats served as normal group; and MRI was used to assess adhesion and compression of scar tissue on the dura and the nerve root. Then goats were sacrificed and histological observation was carried out. Results After operation, the wound healed well; no toxicity or elimination reaction was observed. According to Rydell’s degree of adhesion criteria, adhesion in the experimental group was significantly slighter than that in the control group (Z= — 2.52, P=0.00). X-ray and CT scan showed that no dislocation of artificial lamina occurred, new cervical bone formed in the defect, and bony spinal canal was rebuilt in the experimental group. Defects of C4 vertebral plate and spinous process were observed in the control group. At 24 weeks, the spinal canal area and sagittal diameter of C4 in the experimental group and normal group were significantly larger than those in the control group (P lt; 0.05), but no significant difference was found between experimental group and normal group (P gt; 0.05). MRI showed cerebrospinal fluid signal was unobstructed and no soft tissue projected into the spinal canal in the experimental group; scar tissue projected into the spinal canal and the dura were compressed by scar tissue in the control group. HE staining and Masson trichrome staining showed that artificial lamina had no obvious degradation with high integrity, some new bone formed at interface between the artificial material and bone in the experimental group; fibrous tissue grew into defect in the control group. Conclusion The MAACP/n-HA artificial lamina could maintaine good biomechanical properties for a long time in vivo and could effectively prevent the epidural scar from growing in the lamina defect area.
ObjectiveTo evaluate the effect of poly-amino acid/nano-hydroxyapatite/calcium sulfate (PHC) Cage in lumbar interbody fusion of the goat. MethodsEighteen mature female goats (weighing 29-33 kg) were divided into 3 groups randomly: PHC Cage group (group A), titanium Cage group (group B), and ilium group (group C). A left extraperitoneal approach was used to establish the animal model of discectomy and interbody fusion with Cage or ilium. The general situation was observed for 24 weeks after operation. X-ray films were taken to measure disc space height (DSH) before operation and at 4, 12, and 24 weeks after operation. CT three dimensional reconstuction was performed at 24 weeks after operation to evaluate the interbody fusion according to modified Brantigan grading. The specimens of L3, 4 were harvested for mechanical test, histological, and scanning electron microscope (SEM) observation at 24 weeks after operation. ResultsAll goats survived to the end of experiment. DSH at 4 weeks after operation increased when compared with preoperative one in each group, and then decreased;DSH was significantly lower at 12 and 24 weeks after operation than preoperative one in group C (P<0.05). There was no significant difference in DSH among 3 groups at preoperation and 4 weeks after operation (P>0.05);at 12 and 24 weeks after operation, DSH of groups A and B was significantly higher than that of group C (P<0.05), but no significant difference was found between groups A and B (P>0.05). CT three dimensional reconstuction showed that bony fusion was obtained in all goats of groups A and C, and in 3 goats of group B;according to modified Brantigan grading, the scores of groups A and C were significantlly higher than that of group B (P<0.05), but no significant difference between groups A and C (P>0.05). The biomechanical test showed that there was no significant difference in range of motion between group A and group B (P>0.05), which were significantly lower than that of group C (P<0.05). Microscopy and SEM observations showed that the interface between the Cage and vertebral body in group A was compact without obvious gap, and most conjunctive region was filled with osseous tissue;the interface was filled with soft tissue, and the connection was slack with obvious gap in some region in group B;the interface connection was compact, most region was filled with osseous tissue in group C. ConclusionThe interbody fusion with PHC Cage is effective in goat lumbar interbody fusion model. The interface connection is compact between the Cage and the host bone followed by micro-degradation of PHC Cage, but the long-term degradation need further observation.
The present study is aimed to investigate the early clinical effects of nano-hydroxyapatite/polyamide 66 intervertebral fusion cage (n-HA/PA66 cage) for the treatment of lumbar degenerative diseases. We selected 27 patients with lumbar degenerative diseases who were managed by posterior decompression or reset operation combined with n-HA/PA66 cage intervertebral fusion and internal fixation from August 2010 to January 2012. The oswestry disability index (ODI), low back and leg pain visual analogue score (VAS), and intervertebral height (IH) were evaluated at preoperation, 1 week postoperation and the last follow-up period, respectively. Intervertebral bony fusion was evaluated at the last follow-up time. The patients were followed up for 12-24 months (averaged 19 months). The ODI, VAS and IH were significantly improved at 1 week postoperation and the last follow-up time compared with those at preoperative period (P<0.05). But there was no significant difference between 1 week postoperative and the last follow-up time (P<0.05). Brantigan's standard was used to evaluate fusion at the last follow-up time. There were 19 patients with grade 5 fusion, 8 with grade 4 fusion, with a fusion rate of 100%, and none with grade 1-3 fusions. There was no cage translocation and internal fixation breakage. These results suggested that n-HA/PA66 cage was an ideal biological material in the posterior lumbar interbody fusion and internal fixation operation for treatment of lumbar degenerative diseases. It can effectively maintain the intervertebral height and keep a high rate of bony fusion. The early clinical effect has been satisfactory.