腹壁修补材料的研究及应用进展

巨大腹壁缺损的修补是外科医生经常面临的难题,寻找理想的修补材料以修复缺损至关重要。用于修复腹壁缺损的材料一般分为生物性和非生物性两种。前者的力学性能较好,而后者的生物相容性更佳。目前公认尚没找到一种完全理想的腹壁替代材料.作者对常用生物材料和非生物材料的特性、应用、优缺点等做一综述。     

胶原蛋白作为医用生物材料的应用

胶原蛋白是一类具有活跃生物功能的细胞外间质成分,占人体总蛋白质总量的1/3。胶原蛋白是组织的支持物和填充物,也主动参与了细胞迁移、分化及增殖,并与创伤修复及胚胎发育有关。以胶原蛋白为原料制备的生物替代物(如人造皮肤等)必然大大优于非生物材料的同类产品。目前,大量不同性能及用途的胶原蛋白医用材料不断涌现,有些已结束实验室及动物实验阶段,大批量投入临床应用。     

肿瘤细胞三维培养支架、血管及细胞间的相互作用

背景：肿瘤组织工程通过构建综合的培养模型,充分模拟肿瘤在体内生长的微环境,可以较好地研究肿瘤发生发展的动力学及相关治疗策略。 目的：综述肿瘤工程技术中的肿瘤细胞三维培养。 方法：以“tumor engineering; 3D culture; biological materials; dynamic”为关键词,检索PubMed数据库1992年1月至2013年3月相关文献,纳入有关肿瘤工程、肿瘤细胞三维培养、生物支架材料及肿瘤微环境的相关文章。 结果与结论：三维培养因其可再现组织细胞的体内生长情况,已成为研究肿瘤耐药性、侵袭性和肿瘤微环境的重要平台,在许多领域表现出逐步取代平面培养技术的趋势,为肿瘤研究提供了一个非常接近于体内真实情况的研究平台。近年来,随着肿瘤工程学的发展,多种新型高分子聚合材料被应用于肿瘤细胞的三维立体培养,三维培养技术逐渐成为肿瘤生物学领域研究的热点,其利用各种方法及材料使细胞呈空间立体方式生长,形成类似体内生长环境的生物支撑或基质,建立细胞间及细胞与胞外基质间的相互联系,并形成特定的类似组织样的三维空间结构。生物材料就是种子细胞生长的土壤,在肿瘤工程中起着替代细胞外基质或组织、器官的基质的作用。而随着三维细胞培养技术在肿瘤研究中的广泛应用,其已成为肿瘤耐药、血管形成、细胞间相互作用、信号转导、干细胞等方面研究不可或缺的有力工具。     

硫酸钙人工骨复合培养骨髓间充质干细胞对骨诱导脊柱融合的影响

BACKGROUND: Biodegrable calcium sulfate artificial bone has a good biocompatibility, so it is used as a bone graft substitute in the treatment of spinal fusion. OBJECTIVE: To investigate the osteoinductive effects of the tissue-engineered bone made of bone marrow mesenchymal stem cells and calcium sulfate artificial bone in spinal fusion. METHODS: Bone marrow mesenchymal stem cells were cultured in vitro, and then combined with the calcium sulfate artificial bone. The composite material was observed under electron microscope. Totally 67 patients undergoing spinal fusion were enrolled, who were divided into control group (n=35) and observation group (n=32), receiving autologous iliac bone graft and autologous bone marrow mesenchymal stem cells combined with calcium sulfate transplantation, respectively. Subsequently, spinal fusion Lenke classification and low back outcome score were conducted. RESULTS AND CONCLUSION: Under electron microscope, the visible calcium sulfate artificial bone presented a good porous structure, on which bone marrow mesenchymal stem cells grew and adhered well. Slightly but insignificantly better outcomes in the spinal fusion through the use of the Lenke classification system were obtained in the observation group than the control group after surgery (P > 0.05). Besides, scores on low back outcomes in both two groups were significantly higher than baseline data (P < 0.05). These results suggest that the tissue-engineered bone made of calcium sulfate artificial bone as the scaffold and bone marrow mesenchymal stem cells as seed cells can exert a good osteoinduction in spinal fusion, and obtain ideal effects.     

不同植骨材料诱导兔腰椎横突间的融合

背景：生物玻璃作为骨修复植入体可以在材料界面与人体骨组织之间形成化学键合,可诱导骨的修复与再生,但是其抗弯强度不足,引起的应力屏蔽可造成骨修复失败。 目的：评价不同植骨材料对兔腰椎横突间融合的影响,探讨其替代自体骨用于腰椎横突间融合的可行性。 方法：将健康成年雄性新西兰大白兔28只随机均分4组,壳聚糖/硅酸钙组,硅酸钙组,壳聚糖组,自体髂骨组。分别行腰椎后外侧横突间脊柱融合术,将植入材料植入两侧的L4/5横突间。 结果与结论：术后12周,大体及手法检测发现壳聚糖/硅酸钙组7例均融合,硅酸钙组、壳聚糖组和自体髂骨组分别为4例,4例和5例;组织学观察显示壳聚糖/硅酸钙组材料对于降解、成骨有显著促进作用;生物力学检测结果表明,壳聚糖/硅酸钙组抗拉伸强度优于其他组(P < 0.05)。结果显示3种材料均能代替自体骨行脊柱横突间融合,壳聚糖/硅酸钙复合材料更能促进脊柱融合,并能提高脊柱融合的生物力学强度。     

不同融合方式对腰椎生物力学的影响

背景：腰椎融合已广泛应用于腰椎疾患,但腰椎融合后对邻近节段的影响尚存争议,不同融合方式的节段稳定性及对邻近节段的影响尚不清楚。 目的：利用动物模型研究腰椎融合节段生物力学稳定性及相邻上节段的生物力学特点。 方法：将新西兰大白兔随机分为前路椎体间融合组(切除L_5~6椎间盘,终板去皮质化,自体髂骨移植)、后外侧融合组(L_5~6双侧横突去皮质化后自体髂骨移植)、环状融合组(先行前路椎体间融合,1周后作后外侧融合)、对照组(不作手术)。术后12周处取标本作影像学检查、手触测试、生物力学测试。对融合标本分别施加屈伸,左右侧弯,左右旋转6个方向的纯力矩,比较不同融合方式融合节段的稳定性及邻近节段运动范围。 结果与结论：与对照组比较,前路椎体间融合组、环状融合组、后外侧融合组L_5~6节段屈曲活动度分别下降86.24%(P < 0.05),88.74%(P < 0.05),73.10%(P < 0.05),融合节段近上节段L4~5屈曲运动范围分别增加52.22%(P < 0.05),55.89%(P < 0.05),27.11%(P < 0.05)。说明3种融合方式均显著提高融合节段稳定性,环状融合提供的节段稳定性最高,后外侧融合提供的节段稳定性最低。3种融合方式均使融合节段邻近上节段运动范围显著增加。前路椎体间融合,360°融合使邻近上节段屈曲运动范围增加无统计学差异。后外侧融合使邻近上节段屈曲运动范围增加最少。     

后外侧腰椎融合应用成骨蛋白1与同种自体骨的Meta分析

背景：如何提高腰椎融合术后腰椎融合率、降低并发症是骨科的一个重要课题。 目的：通过检索和分析国内外相关文献,评价成骨蛋白1和同种自体骨在后外侧腰椎融合术中的有效性和安全性。 方法：计算机检索Pubmed和Embase等数据库并结合手工检索,按照既定的纳入和排除标准查找有关成骨蛋白1和同种自体骨应用于后外侧腰椎融合术方面的相关文献。比较两种不同材料在未融合率、手术时间、出血量、住院天数等方面的差异,对部分数据通过Meta分析方法进行处理,估计结局指标的比值比(OR)及95%可信区间(CI)。 结果与结论：纳入4篇文献,共4项随机对照试验,109例患者,使用成骨蛋白1 融合的61例,使用同种自体骨融合的48例。研究结果提示使用成骨蛋白1未融合率[OR=1.16,95%CI (0.44,3.07)]、手术时间、术中出血量、平均住院天数、再手术率、Oswestry功能障碍指数与使用同种自体骨比较,差异无显著性意义(P > 0.05),且纳入的研究均无内植物相关性不良事件的发生。说明成骨蛋白1作为一种安全的骨材料在后外侧腰椎融合术中可能是一种有效的融合物替代品,其主要优势在于避免了髂骨取骨相关并发症的发生,同时满足了融合术对骨量的要求。由于纳入研究较少,需要进一步多中心、大样本的随机对照试验去验证。     

可塑性纳米羟基磷灰石/聚羟基丁酸酯-羟基戊酸酯共聚物-聚乙二醇释药系统治疗兔骨髓炎

背景：现有的局部药物缓释系统多为块状,不能任意塑形,难以与骨腔完全贴敷,易导致骨髓炎复发,且药物爆释作用明显、载药量不大、释放时间短、有一定抗原性。为此,课题组与华南理工大学合作研制一种新型的可塑性局部药物缓释系统,以期为骨髓炎的治疗提供更好方法。 目的：观察可塑性纳米羟基磷灰石/聚羟基丁酸酯-羟基戊酸酯共聚物-聚乙二醇[nanohydroxyapatite/poly (3-hydroxybutyrate- hydroxyvalerate)- polyethylene glycol, nano-HA/PHBV-PEG]载硫酸庆大霉素(gentamicin,GM)局部药物释放系统对骨髓炎的治疗作用。 方法：制备兔胫骨近端骨髓炎模型,于胫骨近端骨窗内注入金黄色葡萄球菌后2周,行病灶清除。Ⅰ组植入1 mL可塑性nano-HA/PHBV-PEG-GM局部药物释放系统;Ⅱ组植入可塑性nano-HA/PHBV-PEG 1 mL及23.2 mg硫酸庆大霉素粉;Ⅲ组植入1 mL可塑性nano-HA/PHBV-PEG并肌注硫酸庆大霉素5 d,共23.2 mg;Ⅳ组植入1 mL可塑性nano-HA/PHBV-PEG;Ⅴ组无任何植入。术后8周进行放射学、组织学、细菌学检查。 结果与结论：Ⅰ组细菌计数及改良X射线Norden 骨髓炎评分极低,明显小于其他各组(P < 0.01),其组织学观察无明显骨髓炎表现。Ⅱ、Ⅲ、Ⅳ组细菌计数逐渐增大,差异有显著性意义(P < 0.01)。但3组间改良X射线Norden 骨髓炎评分差异无显著性意义(P > 0.05),组织学观察骨髓炎表现也无本质差别。Ⅱ、Ⅲ、Ⅳ组细菌计数及改良X射线Norden 骨髓炎评分均较高,明显大于Ⅴ组(P < 0.01或0.05);其组织学显示出严重骨髓炎表现。结果提示：①在病灶清除后,一期将可塑性nano-HA/PHBV-PEG-DDS植入残留的感染性骨缺损,能快速有效地治疗骨髓炎。②传统的全身抗生素应用或单纯局部应用抗生素方法虽然较不用抗生素好,但不能确保一期植骨有效治疗慢性骨髓炎。③在不用药、传统全身用药或单纯局部用药条件下,一期植骨反而会加重骨髓炎。     

硫酸钙人工骨/骨髓间充质干细胞构建组织工程化骨诱导脊柱融合

背景：硫酸钙具有良好的组织相容性和可降解性,是一种安全有效的骨移植替代物。 目的：观察医用硫酸钙人工骨与兔骨髓间充质干细胞复合的成骨作用。 方法：取36只新西兰大白兔,行腰椎后路L4/5椎间盘摘除后,随机均分为3组,自体骨组在椎间隙植入自体髂骨,异种骨组在椎间隙植入异体脱钙小牛骨,组织工程骨组椎间隙植入医用硫酸钙人工骨与同种异体骨髓间充质干细胞复合物。植入后4,8,16周摄腰椎正侧位X射线片,观察椎体间植骨愈合及塑形情况;留取骨痂标本行组织学观察椎间植骨愈合程度;于16周对脊柱融合部位进行生物力学分析。 结果与结论：植入16周时,自体骨组椎间骨小梁连续,椎间融合基本完成,大量编织骨相互融合成片;异种骨组椎间隙形成不完全骨性融合,软骨组织大部分分化为骨组织,但中间仍为纤维组织;组织工程骨组椎间骨小梁连续,椎间融合基本完成,大量编织骨相互融合成片,人工骨基本吸收、骨化,仅有少部分残留;自体骨组、组织工程骨组失效强度和刚度均优于异种骨组(P < 0.05)。提示医用硫酸钙人工骨/骨髓间充质干细胞构建的组织工程骨具有具有良好的成骨和骨诱导作用,可以较好地促进脊柱椎体间融合。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

自体骨髓富集间质干细胞与羟基磷灰石磷酸三钙材料复合在脊柱融合中的应用

BACKGROUND: The use of bone graft materials can promote bone fusion and enhance the stability of the spine during the spinal fusion. OBJECTIVE: To investigate the effect of autologous bone marrow mesenchymal stem cells with hydroxyapatite/ tricalcium phosphate in the spinal fusion. METHODS: A retrospective analysis of clinical data of 64 patients with spinal fusion was carried out, and these patients were divided into two groups (n=32 per group): control group undergoing autogenous iliac bone grafting and observation group undergoing autologous bone marrow mesenchymal stem cells combined with hydroxyapatite/tricalcium phosphate. All patients were followed up for 12 months, and their recovery conditions about low back pain, spinal fusion and vertebral reset were assessed. RESULTS AND CONCLUSION: The low-back outcome scale scores and excellent rate, Lenke grading and Cobb angle had insignificant differences between the two groups after treatment (P > 0.05). No infection, inflammation and skin irritation occurred in the two groups. The coagulation function, renal function and inflammatory factor levels were at normal levels in all the patients, and there was no difference between the two groups (P > 0.05). These findings indicate that autologous bone marrow mesenchymal stem cells combined with hydroxyapatite/tricalcium phosphate can achieve clinical outcomes equivalent to the autologous iliac bone grafting.      

生物骨材料混合自体髂骨修复寰枢椎可复性脱位：后路固定植骨融合

BACKGROUND: Studies have shown that biological bone and autogenous iliac bone exhibit equivalent lumbar fusion effects, but the former one significantly reduces the risk of secondary surgery and contributes to improving vertebral dysfunction. OBJECTIVE: To evaluate the effect of biological bone mixed with autologous bone in posterior screw rod internal fixation with bone graft fusion for reducible atlantoaxial dislocation. METHODS: Seventy-two patients with recoverable atlantoaxial dislocation, including 37 males and 35 females, aged 28-72 years old, were all subjected to posterior atlantoaxial screw rod fixation with bone graft fusion: the atlas was fixed with lateral mass screw or pedicle screw, and the axis fixed with the pedicle screw, lamina screws or lateral mass screw. These patients were assigned into experimental group (n=34) undergoing biological bone mixed with autologous iliac particle bone graft fusion, or control group (n=38) undergoing autologous iliac bone graft fusion. Twelve months later, fusion rate, pain relief, cervical function recovery, cervical activity and complications were compared between the two groups. RESULTS AND CONCLUSION: After postoperatively 12 months, all patients were satisfied with atlantoaxial dislocation reduction, with a good bone fusion rate up to 100%, and their neck incision healed well by primary intention. The pain, cervical function, cervical curvature and activity were improved significantly in the two groups after treatment (P < 0.05), but there was no significant difference between the two groups. Compared with the control group, the amount of bone mass taken from the patient and pain relief time were lower in the experimental group (P < 0.05). Taken together, the biological bone mixed with autogenous iliac bone for reducible atlantoaxial dislocation via posterior screw rod internal fixation and bone graft fusion can rapidly relieve pain, reduce the amount of bone mass taken from patients, and achieve good fusion effect and cervical functional recovery.     

Evaluation of DBM/AM composite as a graft substitute for posterolateral lumbar fusion

Demineralized bone matrix (DBM) has been investigated as a bone graft substitute for spinal fusion with less morbidity. Various carriers have been added to DBM to enhance its handling characteristics. This study investigates the spinal fusion induced by a composite of DBM and acellular dermal matrix (AM) in comparison with autologous bone in an athymic rat spinal fusion model. Single-level intertransverse process fusions were performed in 60 athymic nude rats grafted with 2 mL/kg of DBM/AM composite, AM alone, or autologous bone. Fusion was assessed at 6 weeks by radiography, manual palpation, and histology. At 6 weeks, 70% of the animals from the DBM/AM composite group exhibited complete spine fusion, whereas 35% from the autologous bone group and 20% from AM group showed bridging with some gaps. The DBM/AM composite induced a significantly higher fusion rate than both the autologous bone and AM groups (p < 0.001) in all measured parameters. The current study demonstrated that using DBM/AM composite can have more robust fusion than autologous bone at 6 weeks in an athymic rat spinal fusion model.     

自体骨、同种异体骨及骨形态发生蛋白重组骨治疗腰椎骨折

背景：骨形态发生蛋白重组骨是一种新型植骨材料,已逐步应用于临床,但在腰椎骨折植骨融合中效果仍少见报道。 目的：比较自体骨、同种异体骨及骨形态发生蛋白重组骨治疗腰椎骨折的疗效差异。 方法：选择2005年3月至2009年3月南阳医学高等专科学校附属第一医院收治的腰椎骨折患者78例,根据植骨材料不同随机分为3组,分别植入自体骨、同种异体骨、骨形态发生蛋白重组骨。 结果与结论：78例腰椎骨折患者均获24个月的随访。植骨后24个月JOA评分改善率骨形态发生蛋白植入组90%>自体骨植入组85%>同种异体骨植入组70%(P < 0.05);植骨后12,24个月,同种异体骨植入组Cobb角较其他2组和植骨后6个月增大(P < 0.05),较植骨前减小(P < 0.05);自体骨植入组与骨形态发生蛋白植入组相比,差异无统计学意义(P > 0.05);同种异体骨植入组植骨后各时间点骨融合率均低于其他2组(P < 0.05)。提示骨形态发生蛋白重组骨与自体骨应用于脊椎腰椎骨折近期疗效相似,均优于同种异体骨移植,骨形态发生蛋白重组骨在腰椎骨折脊柱融合快,效果更好,临床应用更有优势。