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 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.
【摘要】 目的 探讨纳米羟基磷灰石/聚酰胺66（nano-hydroxyapatite polyamide66，n-HA/PA66）颈椎融合器在颈椎间盘突出症前路手术重建中的临床疗效。 方法 2008年12月-2010年6月，对14例颈椎间盘突出症患者行前路椎间盘切除、椎管减压，以n-HA/PA66椎间融合器支撑植骨、钢板螺钉内固定治疗。随访时间3～12个月，平均6.3个月；随访时以日本矫形外科学会（Japan Orthopaedic Assoctiation， JOA）评分改善率评价患者神经功能恢复情况，复查X线片评估椎间融合器植骨融合情况，包括椎间高度及椎间融合器下沉情况。 结果 14例患者均成功完成颈椎前路减压手术以及椎间融合器的安放固定。所有患者术前症状均得到不同程度的改善，术后3、6、12个月的JOA改善率分别为87.0%、94.0%、97.0%。影像学检查显示所有患者植骨融合，椎间高度及椎间融合器的位置维持良好，无下沉、移位。 结论 n-HA/PA66颈椎间融合器具有早期支撑稳定功能，可有效维持颈椎椎间高度；术后植骨融合率高且便于X线片观察，是颈椎间盘突出症患者前路手术植骨的理想支撑材料，但长期效果需进一步随访观察。【Abstract】 Objective To evaluate the clinical effect of artificial cervical vertebra fusion apparatus of n-HA/PA66 in anterior reconstruction of cervical intervertebral disc herniation. Methods From December 2008 to June 2010, 14 patients with cervical intervertebral disc herniation underwent anterior cervical discectomy,spinal canal decompression,spinal canal decompression and reconstruction by n-HA/PA66 composite artificial vertebral body combined with plate instrumentation. The patients were followed up for 3 to 12 months with an average of 6.3 months. Neurological function was evaluated by improvement rate of JOA score and situations of the supporting body was observed by X-ray in 3,6,and 12 months after the surgery.The intervertebral height,the 1ocations, and the fusion rate of the supporting body were assessed in order to evaluate the stability of the cervical spine and alignment improvements. Results All the patients had undergone the operation successfully.The preoperative symptoms improved to varying degrees.JOA improvement rate were 87.0%, 94.0%, and 97.0% 3,6,and 12 months after the operation,respectively.Imaging studies showed that in all cases graft fusion were achieved,and cervical alignments,intervertebral height,cervical spine stability and the locations of the artificial vertebral body were well maintained.No displacement and subsidence of the artificial vertebral body occurred. Conclusion n-HA/PA66 artificial vertebral body can provide early cervical spine support and stability and cervical intervertebral height.It has a high rate of graft fusion and is convenient to observe by X-ray.Therefore,n-HA/PA66 can be taken as an ideal graft for anterior degenerative cervical spine operation,but further follow-up study is still needed to evaluate the long-term effects.
Objective To prepare collagen-chitosan /nano-hydroxyapatite-collagen-polylactic acid (Col-CS/ nHAC-PLA) biomimetic scaffold and to examine its biocompatibility so as to lay the foundation for its application on the treatment of osteochondral defect. Methods PLA was dissolved in dioxane for getting final concentration of 8%, and the nHAC power was added at a weight ratio of nHAC to PLA, 1 ∶ 1. The solution was poured into a mold and frozen. CS and Col were dissolved in 2% acetum for getting the final concentrations of 2% and 1% respectively, then compounded at a weight ratio of CS to Col, 20 ∶ 1. The solution was poured into the frozen mold containing nHAC-PLA, and then biomimetic osteochondral scaffold of Col-CS/nHAC-PLA was prepared by freeze-drying. Acute systemic toxicity test, intracutaneous stimulation test, pyrogen test, hemolysis test, cytotoxicity test, and bone implant test were performed to evaluate its biocompatibility. Results Col-CS/nHAC-PLA had no acute systemic toxicity. Primary irritation index was 0, indicating that Col-CS/nHAC-PLA had very slight skin irritation. In pyrogen test, the increasing temperature of each rabbit was less than 0.6℃, and the increasing temperature sum of 3 rabbits was less than 1.3℃, which was consistent with the evaluation criteria. Hemolytic rate of Col-CS/nHAC-PLA was 1.38% (far less than 5%). The toxicity grade of Col-CS/nHAC-PLA was classified as grade I. Bone implant test showed that Col-CS/nHAC-PLA had good biocompatibility with the surrounding tissue. Conclusion Col-CS/ nHAC-PLA scaffold has good biocompatibility, which can be used as an alternative osteochondral scaffold.
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 compare the biomechanical differences between the kidney-shaped nano-hydroxyapatite/polyamide 66 (n-HA/PA66) Cage and the bullet-shaped n-HA/PA66 Cage. MethodsL2-L5 spinal specimens were selected from 10 adult male pigs. L2, L3 and L4, L5 served as a motor unit respectively, 20 motor units altogether. They were divided into 4 groups (n=5):no treatment was given as control group (group A); nucleus pulposus resection was performed (group B); bullet-shaped Cage (group C), and kidney-shaped Cage (group D) were used in transforaminal lumbar interbody fusion (TLIF) through left intervertebral foramen and supplemented by posterior pedicle screw fixation. The intervertebral height (IH) and the position of Cages were observed on the X-ray films. The range of motion (ROM) was measured. ResultsThere was no significant difference in the preoperative IH among 4 groups (F=0.166, P=0.917). No significant change was found in IH between at pre- and post-operation in group B (P>0.05); it increased after operation in groups C and D, but difference was not statistically significant (P>0.05). There was no significant difference in the postoperative IH among groups B, C, and D (P>0.05). The distance from Cage to the left margin was (3.06±0.51) mm in group C (close to the left) and (5.68±0.69) mm in group D (close to the middle), showing significant difference (t=6.787, P=0.000). The ROM in all directions were significantly lower in groups C and D than in groups A and B (P<0.05), and in group A than in group B (P<0.05). The right bending and compression ROM of group C were significantly higher than those of group D (P<0.05), but no statistically significant difference was found in the other direction ROM (P>0.05). ConclusionThe bullet-shaped and kidney-shaped Cages have similar results in restoring IH and maintaining the stability of the spine assisted by internal fixation. Kidney-shaped Cage is more stable than bullet-shaped Cage in the axial compression and the bending load opposite implant, it can be placed in the middle and back of the vertebral body more ideally.
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.
Objective To fabricate a nanohydroxyapatite-chitosan(nano-HA-CS) scaffold with high porosity by a simple and effective technique and to evaluate the physical and chemical properties and the cytocompatibility of the composite scaffold. Methods The threedimensional nano-HA-CS scaffolds with high porosity were prepared by the in situ hybridization-freeze-drying method. The microscopic morphology and components of the composite scaffolds were analyzed by the scanning electron microscopy (SEM), the transmission electron microscopy（TEM）, the X-ray diffraction（XRD）examination, and the Fourier transformed infrared spectroscopy（FTIR）. The calvarial osteoblasts were isolated from the neonatal Wistar rats. The serial subcultured cells (3rd passage) were respectively seeded onto the nanoHACS scaffold and the CS scaffold, and then were cocultured for 2, 4, 6 and 8 hours. At each time point,four specimens from each matrix were taken to determine the celladhesion rate. The cell morphology was observed by the histological staining and SEM. Results The macroporous nanoHACS scaffolds had a feature of high porosity with a pore diameter from 100 to 500 μm (mostly 400500 μm). The scaffolds had a high interval porosity; however, the interval porosity was obviously decreased and the scaffold density was increased with an increase in the contents of CS and HA. The SEM and TEM results showed that the nanosized HA was synthesized and was distributed on the pore walls homogeneously and continuously. The XRD and FTIR results showed that the HA crystals were carbonatesubstituded and not wellcrystallized. The cytocompatibility test showed that the seeded osteoblasts could adhere the scaffolds, proliferating and producing the extracellular matrix on the scaffolds. The adherence rate for the nanoHACS scaffolds was obviously higher than that for the pure CS scaffolds. Conclusion The nano-HA-CS scaffolds fabricated by the in situ hybridization-freeze-drying method have a good physical and chemical properties and a good cytocompatibility; therefore, this kind of scaffolds may be successfully used in the bone tissue engineering.
Objective To evaluate the short-term effectiveness of nano-hydroxyapatite/polyamide-66 (n-HA/PA66) intervertebral cage for lumbar interbody fusion in the patients with lower lumbar degenerative diseases. Methods Between January and October 2011, 20 patients with lower lumbar degenerative diseases underwent transforaminal lumbar interbody fusion with n-HA/PA66 intervertebral cage. There were 8 males and 12 females, aged 22-80 years (mean, 51 years). The disease duration was 1 to 24 months (mean, 4 months). L4, 5 fusion was performed in 8 cases, L5, S1 fusion in 9 cases, and L4-S1 fusion in 3 cases. Among 20 cases, 3 were diagnosed as having recurrent lumbar disc protrusion, 5 as having lumbar degenerative spondylolisthesis, 9 as having lumbar isthmic spondylolisthesis, and 3 as having lumbar spinal stenosis. The intervertebral height and lordosis were measured on X-ray film to assess the surgical correction and postoperative sustain while osseous fusion was observed on 3-dimensional CT. The Oswestry disability index (ODI) and short-form 36 health survey scale (SF-36) scores were obtained to assess the status of clinical recovery. Results All patients had incision healing by first intention. The pain and numb were relieved in varying degrees after operation. No cerebrospinal leakage, nerve root injury, or wound infection was occurred. All patients were followed up 6-9 months (mean, 7 months). No cage displacement or collapse was found. The intervertebral height and lordosis of single fusion segment were significantly improved at 3 days and 3, 6 months after operation when compared with those at preoperation (P lt; 0.01); there was no significant difference among each time point after operation (P gt; 0.05). The fusion rate was 74% at 3 months after operation and 96% at 6 months after operation, with an average of 4 months (range, 3-9 months) for interbody fusion. The ODI and SF-36 scores were significantly improved at 3 days and 6 months after operation when compared with the scores at preoperation (P lt; 0.01); there was no significant difference among each time point after operation (P gt; 0.05). Conclusion The interbody fusion with n-HA/PA intervertebral cage is effective and safe to treat the lower lumbar degenerative diseases. The n-HA/PA66 intervertebral cage is an ideal device of interbody fusion with high fusion rate, low subsidence rate, and high transmission X-ray, but the long-term effectiveness need further observation.
Objective To study the clinical effects of the artificial vertebral body of the biomimetic nanohydroxyapatite/polyamide 66 (nHA/PA66) compositefor the structural reconstruction and the height restoring of the vertebral body in the thoracolumbar fractures by the anterior surgical procedures. Methods From December 2003 to January 2006, 42 patients with thoracolumbar fractures received the anterior surgical procedures to decompress and reconstruct the spinal vertebral structure with the artificial vertebral body of the nHA/PA66 composite. Among the patients, there were 28 males and 14 females, aged 1767 years, averaged 43.6 years. The thoracolumbar fractures developed at T12 in 5 patients, at L1 in 17, at L2 in 14, and at L3 in 6. The height of the anterior border of thevertebral body amounted to 29%-47% of the vertebral body height, averaged 40.6%.The Cobb angle on the sagittal plane was 2138° averaged 27.6°. According tothe Frankel grading scale, the injuries to the nerves were as the following: Grade A in 7 patients, Grade B in 19, Grade C in 8, Grade D in 6, and Grade E in 2. Results All the 42 patients were followed up for 625 months. Among the patients, 36 were reconstructed almost based on the normal anatomic structure, and 6 were well reconstructed. The mean height of the anterior border of the vertebralbody was 40.6% of the vertebral body height before operation but 91.7% after operation. And the reconstructed height of the vertebra was maintained. The mean Cobb angle on the sagittal plane was 27.6°before operation but 13.4° after operation. All the patients had a recovery of the neurological function that had a 1grade or 2grade improvement except 7 patients who were still in Grade A and 2 patients who were in Grade D. The implant was fused 35 months after operation. No infection, nail break, bar/plate break or loosening of the internal fixation occurred. Conclusion The artificial vertebral body of the biomimetic nHA/PA66 composite can effectively restore the height and the structure of the vertebra, can be fused with the vertebral body to reconstruct the spinal structural stability effectively, and can be extensively used in the clinical practice.