7.0T micro-MRI评价局部应用丝裂霉素C和消旋聚乳酸膜抑制大鼠硬膜外粘连及瘢痕形成

目的应用7.0Tmicro-MR比较单独应用丝裂霉素C（MMC）、消旋聚乳酸（DL-PLA）膜以及二者联合应用（MMC＋DL-PLA膜）时抑制大鼠椎板切除术后硬膜外粘连的效果。方法将16只SD大鼠随机分为4组,每组4只,椎板切除术后于硬膜外给予不同局部处理：单纯MMC组局部应用MMC 0.67mg/ml;单纯DL-PLA膜组给予生理盐水和0.05mm厚DL-PLA膜;MMC＋DL-PLA膜组给予MMC 0.67mg/ml和0.05mm厚DL-PLA膜;对照组单纯应用生理盐水。术后4周处死大鼠,分别行7.0Tmicro-MR扫描及瘢痕组织面积测定,并于镜下观察硬脊膜与后方瘢痕组织粘连情况。结果单纯MMC组和单纯DL-PLA膜组硬膜外瘢痕组织较疏松,瘢痕面积小,与硬脊膜部分粘连。MMC＋DL-PLA膜组硬膜外瘢痕组织较疏松,瘢痕面积更小,与硬脊膜未形成明显粘连。对照组标本硬膜外瘢痕组织致密,瘢痕面积大,与硬脊膜形成紧密粘连。结论局部单独应用浓度为0.67mg/ml的MMC或0.05mm厚的DL-PLA膜均能减少硬膜外瘢痕组织增生,二者联合应用时效果更显著。     

Effect of polylactic acid glue in preventing epidural scar mdhesion after laminectomy in rabbits

Objective： To determine the efficacy of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits. Methods： Twenty-four Japanese white rabbits underwent laminectomy （including the attached ligaments） at Lz and Ls. After laminectomy at Ls, polylactic acid glue was sprayed on the dura and nerve roots and this segment was taken as the experimental group. After laminectomy at Lz, nothing was used and this segment was enrolled as the self control group. Four rabbits were killed every two weeks postoperatively till the end of the experiment at 12 weeks. Then the operated spine was observed grossly, histologically and ultrastructurally to check the degree of scar formation, the status of epidural scar adhesion, the absorption of the glue, and the intraceHular structure of fibroblasts. Results： The glue coagulated immediately after spraying and showed excellent hemostatic effect. The glue membrane was easy to be taken away from the dura mater of the samples for 2 weeks and there were no cells in the epidural space in the experimental group. But the dura mater was covered by hematoma in the control group,which formed mild adhesion, with fibroblasts proliferating actively. In the 4th week, some glue shivers remained in the epidural space with fibroblasts increasing a little, and the dura mater was smooth in the experimental group. However, in the control group, the formed scar was fragile and conglutinated with the dura mater diffusely and fibroblasts were much more than those in the experimental group. In the 6th-12th weeks, there was a potential interspace between the scar and the dura mater, and the polylactic acid glue was absorbed completely in the experimental group. Much tough scar was found in the control group, which was very difficult to dissect from the dura mater and the surrounding tissues. From the ultrastructural observation of the fibroblasts, the nucleus became much bigger and the rough endoplasmic reticulum was much more plentiful in the control group than that in the experimental group. Conclusions： Polylactic acid glue can effectively reduce epidural cicatrization and adhesion.     

Effect of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits

Objective: To determine the efficacy of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits. Methods: Twenty-four Japanese white rabbits underwent laminectomy (including the attached ligaments) at L2 and L5. After laminectomy at L5, polylactic acid glue was sprayed on the dura and nerve roots and this segment was taken as the experimental group. After laminectomy at L2, nothing was used and this segment was enrolled as the self control group. Four rabbits were killed every two weeks postoperatively till the end of the experiment at 12 weeks. Then the operated spine was observed grossly, histologically and ultrastructurally to check the degree of scar formation, the status of epidural scar adhesion, the absorption of the glue, and the intracellular structure of fibroblasts. Results: The glue coagulated immediately after spraying and showed excellent hemostatic effect. The glue membrane was easy to be taken away from the dura mater of the samples for 2 weeks and there were no cells in the epidural space in the experimental group. But the dura mater was covered by hematoma in the control group, which formed mild adhesion, with fibroblasts proliferating actively. In the 4th week, some glue shivers remained in the epidural space with fibroblasts increasing a little, and the dura mater was smooth in the experimental group. However, in the control group, the formed scar was fragile and conglutinated with the dura mater diffusely and fibroblasts were much more than those in the experimental group. In the 6th-12th weeks, there was a potential interspace between the scar and the dura mater, and the polylactic acid glue was absorbed completely in the experimental group. Much tough scar was found in the control group, which was very difficult to dissect from the dura mater and the surrounding tissues. From the ultrastructural observation of the fibroblasts, the nucleus became much bigger and the rough endoplasmic reticulum was much more plentiful in the control group than that in the experimental group. Conclusions: Polylactic acid glue can effectively reduce epidural cicatrization and adhesion.     

聚乳酸凝胶预防硬膜外瘢痕粘连的实验研究

目的 探讨新型生物可吸收材料聚乳酸凝胶(polyactic acid glue，PLA-G)预防椎板切除术后硬膜外瘢痕粘连的作用。方法 切除24只成年日本大耳白兔的L2和L5椎板；在L5外露的硬膜及神经根表面喷涂液态PLA-G形成胶冻膜，为实验组；L2处只做椎板切除，为自身空白对照组。术后2、4、6、8、10及12周随机处死各4只兔，取标本行大体、组织学及超微结构的观察。结果 2周时实验组PLA-G未降解为机械屏障膜，硬膜与外侧瘢痕组织(scartissue，ST)间有明显间隙，光镜下显示间隙内无细胞；对照组为血肿覆盖较易分开，硬膜与ST间有血细胞团块，成纤维细胞(fibroblast，FB)增生活跃。4周时实验组PLA-G部分降解，机械屏障及间隙存在，光镜下ST中FB增多；对照组为较多质脆ST与硬膜广泛粘连，光镜下可见组织细胞浸润间隙，ST内FB明显多于实验组。6周时实验组PLA-G完全降解，少量ST与硬膜无粘连，光镜下FB已减少；对照组有大量质韧难以从硬膜分离的ST，FB继续增生活跃。8、10及12周时实验组ST与硬膜无粘连；对照组ST与硬膜粘连严重，光镜下见ST和硬膜粘连紧密伴毛细血管再造。超微结构观察：4周时实验组FB的粗面内质网较稀疏，分泌胶原纤维少；对照组FB的粗面内质网极丰富，胶原纤维多而成束。结论 PLA-G在实验兔腰椎板切除后的硬膜外能有效地减少瘢痕形成和粘连。     

Novel biodegradable lamina for lamina repair and reconstruction

Background contextPosterior laminectomy is an effective spinal surgical procedure. The adhesion of postoperative scar tissue to surgically exposed dura and, occasionally, to nerve roots can cause failed back surgery syndrome. The establishment of a barrier between scar tissue and dura that is made of hard material may prevent scar adhesions.PurposeTo evaluate the efficacy of a novel biodegradable multi-amino acid copolymer/nanohydroxyapatite composite artificial lamina.MethodsA cervical laminectomy animal model in goats was used, and the animals were randomly divided into three groups. In the test group, cervical 4 was removed by laminectomy and the artificial lamina was inserted (n=12). In the control group, the incision was closed directly without implantation (n=9). The goats in the normal group did not undergo any procedure or treatment. Copolymer efficiency was tested by using X-ray, computed tomography scanning, magnetic resonance imaging, scanning electronic microscope, and histologic and biomechanical measurements 4, 12, and 24 weeks postoperation.ResultsNo shifting of the artificial lamina or dural adhesion pressure was observed. New cervical natural bone formed in the defect and the bony spinal canal was rebuilt. In the control group, fibrous scar tissue filled the defect and exerted pressure on the dura. No paralysis was observed, and gait was normal in all test and control goats.ConclusionsArtificial lamina can prevent the epidural adhesions surrounding the defect and promote effectively bone tissue repair and new bone formation.     

羟基喜树碱预防硬膜外粘连的有效性和安全性研究

目的探讨局部应用羟基喜树碱(HCPT)预防椎板切除术后硬膜外粘连的效果,并进行安全性评价。方法48只SD大鼠随机分为4组,行L1全椎板切除术后,实验组局部应用不同浓度的HCPT[0.1 g/L(A组),0.05 g/L(B组),0.01 g/L(C组)],对照组(D组)应用生理盐水,测定用药前后的体感诱发电位(SEP),并行后肢运动功能评分(BBB评分)。术后4周行肉眼观察、组织学观察、硬膜外瘢痕面积测定及成纤维细胞计数。结果A组无明显硬膜外粘连,瘢痕组织面积及成纤维细胞计数均低于D组(P<0.01),而D组出现致密的硬膜外粘连。所有实验动物无明显中毒症状,用药前后的SEP及BBB后肢运动功能评分差异无统计学意义(P>0.05)。结论局部短时应用浓度为0.1 g/L的HCPT可有效预防硬膜外粘连,且未见明显的毒副作用。     

聚己内酯/聚乳酸膜防止硬膜外瘢痕粘连的实验研究

目的 探讨将聚己内酯／聚乳酸(polycaprolactone／polylactic acid,PCL/PIA)膜置于硬膜外,以减少硬膜外瘢痕粘连的方法。方法 用大鼠96只,L1、L3全椎板切除,分为空白对照组、自体游离脂肪片组及PCI／PIA膜组3组。术后1、3、6、12周处死动物。对硬膜外瘢痕形成及粘连做大体及组织学观察,逆转录,聚合酶链式反应(RT-PCR)方法检测硬膜外瘢痕中转化生长因子β(TGF-β)的表达,并用免疫组化法及RT-PCR法检测相应脊髓中P物质、c-fos的表达。结果 与空白对照组相比,PCL/PIA膜组硬膜外瘢痕粘连减轻,术后3周及6周时硬膜外瘢痕组织中TGF-β表达量明显减少,脊髓中P物质、c-fos表达减少;脂肪片早期可减轻硬膜外瘢痕粘连,但后期粘连也有所加重,脊髓中P物质、c-fos表达也有相应改变。结论 聚己内酯／聚乳酸膜可减轻硬膜外的瘢痕形成及粘连,使脊髓中疼痛介质P物质、c-fos表达减少,有助于防止术后腰腿痛的复发。     

Reduction of epidural fibrosis and dural adhesions after lamina reconstruction by absorbable cement: an experimental study

Background contextPost-laminectomy epidural fibrosis complicates revision spine surgery and is implicated in cases of “failed back syndrome.” Several materials have been used to minimize epidural fibrosis with varying results.PurposeThe aim of this study was to examine the impact of reconstruction of laminectomy site with a type of absorbable cement (Jectos) to reduce epidural fibrosis.Study designThis investigation is an experimental controlled study, which is designed to evaluate the preventive effects of laminectomy site reconstruction in rat laminectomy model.MethodsTwenty wistar rats were included in this study and divided randomly to two equal groups, namely, subject and control. In both groups, laminectomy was performed in L2 and L4 levels. Control group received no additional treatment. In the subject group, L4 levels were reconstructed by Jectos and L2 levels were non-reconstructed as internal controls. Six months after surgery the rats were sacrificed and the dural adhesion and epidural fibrosis were evaluated macroscopically and microscopically. The study was financially supported by Brain and Spinal Cord Injuries Repair Center. None of the authors have any conflict of interest.ResultsNon-reconstructed levels in both groups showed dense epidural fibrosis with marked dural adherence. L4 reconstructed levels in subject group showed reduced epidural fibrosis macroscopically (p=.024) and microscopically (p=.041). No foreign body reaction or ossification occurred at reconstructed sites.ConclusionsIn the present study, lamina reconstruction with absorbable cement was a safe method that significantly reduced post-laminectomy epidural fibrosis and dural adhesions in rat laminectomy model.     

Mitomycin C, 5-fluorouracil, and cyclosporin A prevent epidural fibrosis in an experimental laminectomy model

This study examined the preventive effects of the local application of mitomycin C (MMC), 5-fluorouracil (5-FU), and cyclosporine A (CsA) in minimizing spinal epidural fibrosis in a rat laminectomy model. Thirty-two 2-year-old male Wistar albino rats, each weighing 400 ± 50 g, were divided into four equal groups: sham, MMC, 5-FU, and CsA. Each rat underwent laminectomy at the L5–L6 lumbar level. Cotton pads (4 × 4 mm²) soaked with MMC (0.5 mg/ml), 5-FU (5 ml/mg), or CsA (5 mg/ml) were placed on the exposed dura for 5 min. Thirty days after surgery, the rats were killed and the epidural fibrosis, fibroblast density, inflammatory cell density, and arachnoid fibrosis were quantified. The epidural and arachnoid fibroses were reduced significantly in the treatment groups compared to the sham group. Fibroblast cell density and inflammatory cell density were decreased significantly in the MMC and 5-FU groups, but were similar in the sham and CsA groups. The decreased rate of epidural fibrosis was promising. Further studies in humans are needed to determine the short- and long-term complications of the agents used here. Presented as special poster in 2006 Annual Meeting of the Spine Society of Europe, October 25–28, İstanbul, Turkey.     

活血止痛汤对硬膜外瘢痕组织中羟脯氨酸含量及其超微结构的影响

目的:评价活血止痛汤预防实验性椎板切除术后硬膜外瘢痕形成与粘连的疗效。方法:雄性SD大鼠90只随机分成空白对照组、透明质酸钠组、活血止痛汤组,每组30只。手术切除L4-L5腰椎椎板,造成0.25cm×1cm硬脊膜裸露区,透明质酸钠组于硬膜囊外均匀地涂抹一层透明质酸钠约0.3ml,其余2组以等量生理盐水处理。术后2周内活血止痛汤组予活血止痛汤2.5ml/kg灌胃;空白对照组和透明质酸钠组予等量生理盐水。术后第2、4、8周末处死动物,测定其硬膜外瘢痕组织中羟脯氨酸含量,按Rydell法评定粘连程度,透射电镜观察其超微结构。结果:第2周时,透明质酸钠组羟脯氨酸含量明显低于空白对照组(P<0.05),而活血止痛汤组虽然也较低,但差异无统计学意义(P>0.05);第4周时,与空白对照组相比,透明质酸钠组和活血止痛汤组羟脯氨酸含量均较低(P<0.05),但透明质酸钠组和活血止痛汤组的差异缺乏显著性。第8周时,活血止痛汤组羟脯氨酸含量不仅低于空白对照组(P<0.01),而且其与透明质酸钠组亦有显著性差异(P<0.05)。大体观察也发现透明质酸钠组和活血止痛汤组粘连程度明显降低(P<0.05)。各时相透明质酸钠组和活血止痛汤组瘢痕中成纤维细胞以及细胞内的细胞器数量均减少,胶原纤维的合成受到抑制。结论:活血止痛汤能降低硬膜外瘢痕中羟脯氨酸的含量,抑制瘢痕组织中成纤维细胞和胶原的代谢,减少硬膜外瘢痕的形成和粘连。     

几丁糖膜预防椎板切除术后硬膜周围粘连的实验研究

目的：观察几丁糖膜对预防椎板切除术后硬膜周围粘连的作用。方法：２４只成年新西兰白兔Ｌ３、Ｌ５水平切除椎板１０×０５ｃｍ,Ｌ３硬膜外放置几丁糖膜（Ａ点）,Ｌ５作为空白对照（Ｂ点）。分别于术后３周、６周、１２周进行大体形态、组织学观察。结果：Ａ点硬膜与瘢痕无明显粘连,硬膜外有空隙,未见明显异物、炎症反应;Ｂ点硬膜与瘢痕紧密粘连,瘢痕侵入椎管内,对硬膜有压迫。结论：几丁糖膜具有明显的预防硬膜周围粘连的作用。     

同种异体骨板覆盖预防硬膜外瘢痕粘连的实验研究

目的 探讨经冻干辐照处理后的同种异体骨板预防椎板切除术后硬膜外瘢痕粘连的作用。方法 12只成年雄性绵羊,随机分成A、B两组,每组6只。两组均作L3,4和L4,5椎板切除,A组的L4,5和B组的L3,4椎板缺损用“H”形同种冻干辐照骨板覆盖,为实验节段;A组的L3,4和B组的L4,5不覆盖骨板作为对照节段。于术后4、8、12、16、20和24周取材,行大体、X线平片和组织切片观察;并对4、24周取材行CT扫描。结果 术后4周,实验节段可见同种骨板形态、位置保持完好,椎管内无狭窄,硬膜囊无压迫,镜下椎板咬除缘有多量新生骨小梁生成,周边有大量软骨细胞及其分泌黏多糖和坏死后所留下的空腔,骨板内侧有增生纤维组织及少量炎性细胞浸润;对照节段可见大范围致密的纤维组织夹杂变性坏死肌肉嵌入椎板缺损处,硬膜广泛粘连,硬膜囊受压。术后24周,实验节段椎管重建基本完成,覆盖骨板吸收完全,并与再生椎板融合,椎管形态完好,硬膜外未见瘢痕组织;对照节段椎板再生未完成,瘢痕组织自椎管外嵌入椎管内,压迫硬膜囊及脊髓,硬膜外间隙几乎消失。统计学分析表明手术后期（16～24周）,实验节段与对照节段相比硬膜粘连程度明显减轻,椎管矢状径均较对照节段大,硬膜囊形状保持良好,无明显压迫。结论 同种异体冻干辐照骨板在实验羊椎板切除后的硬膜外能有效减少瘢痕形成和粘连。     

Vertebral plate regeneration induced by radiation-sterilized aliogeneic bone sheets in sheep

Objective: To evaluate the effects and mechanism of radiation-sterilized allogeneic bone sheets in inducing vertebral plate regeneration after laminectomy in sheep. Methods: Twelve adult male sheep (aged 1.5 years and weighing 27 kg on average) provided by China Institute for Radiation Protection underwent L3-4 and L4-5 laminectomy. Then they were randomly divided into two groups: Group A ( n = 6 ) and Group B ( n = 6 ). The operated sites of L4-5 in Group A and L3-4 in Group B were covered by " H-shaped" freeze-drying and radiation-sterilized allogeneic bone sheets ( the experimental segments), while the operated sites of L3-4 in Group A and L4-5 in Group B were uncovered as the self controls (the control segments ). The regeneration process of the vertebral plate and the adhesion degree of the dura were observed at 4,8,12,16,20 and 24 weeks after operation. X-ray and CT scan were performed in both segments of L3-4 and L4-5 at 4 and 24 weeks after operation. Results: In the experimental segments, the bone sheets were located in the anatomical site of vertebral plate, and no lumbar spinal stenosis or compression of the dura was observed. The bone sheets were absorbed gradually and fused well with the regenerated vertebral plate. While in the control segments, the regeneration of vertebral plate was not completed yet, the scar was inserted into the spinal canal, compressing the dura and the spinal cord, and the epidural area almost disappeared. Compared with the control segments, the dura adhesion degree in the experimental regenerated segments was much milder (P<0.01), the internal volume of the vertebral canal had no obvious change and the shape of the dura sack remained well without obvious compression. Conclusions: Freeze-drying and radiation-sterilized allogeneic bone sheets are ideal materials for extradural laminoplasty due to their good biocompatibility, biomechanical characteristics and osteogenic ability. They can effectively reduce formation of post-laminectomy scars, prevent recurrence of post-laminectomy spinal stenosis, and induce regeneration of vertebral plates.     

Influence of TachoComb in comparison to local hemostyptic agents on epidural fibrosis in a rat laminectomy model.

This animal experimental study was designed to examine the effects of TachoComb, a fixed combination of collagen with tissue adhesive, as an interposition membrane on the development of spinal epidural fibrosis in comparison to other hemostyptic materials. In 10 Wistar rats, four laminectomies were performed at lumbar and sacral vertebrae. Alternately, a piece of TachoComb, Spongostan, or Tabotamp was placed into each laminectomy site. One laminectomy site served as an empty control (n = 10). 8 weeks later, the animals were sacrificed, and the spinal column including surrounding muscle tissue was removed en bloc from each rat and fixed in formaldehyde. After decalcification and staining the specimens were graded by a neuropathologist in a blindfold test for severity of epidural fibrosis as "light-moderate" or "marked". Epidural scarring of variable density was seen in all laminectomy sites. Light epidural fibrosis, without any adhesion to dura, as only noted in cases after application of TachoComb (n = 4/10) and Spongostan (n = 1/10). All other slices showed marked epidural fibrosis with dura adherence regardless of the implanted material. Statistical analysis revealed significantly lower epidural fibrosis after application of TachoComb compared to all other groups (p < 0.05). In this series, TachoComb is more effective in reducing the epidural fibrosis than Spongostan, and Tabotamp. However, complete prevention of scar tissue formation was not achieved.     

A comparison of the effectiveness of mitomycin C and 5-fluorouracil in the prevention of peridural adhesion after laminectomy

OBJECT: The effectiveness of the topical application of mitomycin C (MMC) or 5-fluorouracil (5FU) in preventing peridural adhesion after laminectomy was compared in this study. METHODS: Laminectomies were performed at L-1 in 30 rats. Cotton pads soaked with 0.1 mg/ml MMC, 25 mg/ml 5FU, or 9 mg/ml saline (control) were applied to the operative sites. To evaluate neurological deficits pre- and postoperatively, somatosensory evoked potentials were monitored and the Basso-Beattie-Bresnahan locomotion test was performed. Four weeks postlaminectomy the rats were killed, and peridural scar adhesion was evaluated histologically. The level of hydroxyproline, the area of peridural scar tissue, and the number of fibroblasts were determined. The degree of peridural adhesion was classified according to the Rydell standard. RESULTS: No obvious adhesion formed in the rats in the MMC group, but severe peridural adhesions were found in those in the 5FU and control groups. The content of hydroxyproline, the area of peridural scar tissue, and the number of fibroblasts in the MMC group were significantly lower than those in the 5FU and control groups. CONCLUSIONS: The topical application of MMC rather than 5FU may be a successful method of preventing postlaminectomy peridural adhesions.     

壳多糖膜预防椎板切除术后硬膜周围粘连的实验研究

目的　观察壳多糖膜预防椎板切除术后硬膜周围粘连的作用。方法　２４ 只成年新西兰白兔 Ｌ３ 、 Ｌ５ 水平切除椎板１ ．０ ｃｍ ×０ ．５ ｃｍ , Ｌ３ 硬膜外放置壳多糖膜（ Ａ 点） , Ｌ５ 作为空白对照（ Ｂ 点） 。分别于术后３ 、６ 、１２ 周进行大体形态、光镜观察。结果　 Ａ 点硬膜外粘连程度明显低于 Ｂ 点;光镜观察 Ａ 点粘连范围明显低于 Ｂ 点, Ａ 点硬膜外有空隙,未见明显异物、炎症反应, Ｂ 点硬膜外与瘢痕紧密粘连,瘢痕侵入椎管内,对硬膜有压迫。结论　壳多糖膜具有明显的预防硬膜周围粘连的作用。     

预防椎板切除术后硬膜外粘连的实验研究

目的通过动物实验探索预防椎板切除术后硬膜外粘连的方法及其效果。方法64只新西兰兔随机分为A、B、C、D组,每组16只。手术切除L5椎板造成12 mm×6 mm硬脊膜裸露区,探查神经根。A组注入生理盐水1m l,B组充填高分子量透明质酸钠凝胶1 m l,C组用自体L6棘突重建L5椎板,D组用高分子量透明质酸钠凝胶1 m l充填后再进行L5椎板重建。术后2、4、6、8周行大体观察及组织学观察,于6周时行硬膜外瘢痕面积和致密度定量分析。结果①大体观察:A组术区明显粘连,B、C组轻度粘连,D组无明显粘连;②瘢痕面积百分比:C、D组分别为15.89%±1.88%、13.94%±1.89%,显著小于A、B组(22.66%±2.89%、20.70%±2.82%,P<0.05);③瘢痕密度:B、D组分别为42.03%±7.36%、36.50%±9.08%,显著小于A、C组(63.73%±6.06%、52.11%±4.10%,P<0.05)。结论高分子量透明质酸钠凝胶充填和椎板重建术对预防椎板切除术后硬膜外粘连具有协同作用,效果显著。     

Vertebral plate regeneration induced by radiation-sterilized allogeneic bone sheets in sheep

Objective： To evaluate the effects and mechanism of radiation-sterilized allogeneic bone sheets in inducing vertebral plate regeneration after laminectomy in sheep. Methods ： Twelve adult male sheep （ aged 1.5 years and weighing 27 kg on average ） provided by China Institute for Radiation Protection underwent L3-4 and L4-5 laminectomy. Then they were randomly divided into two groups： Group A （n =6） and Group B （n =6）. The operated sites of L4-5 in Group A and L3-4 in Group B were covered by ＂ H-shaped＂ freeze-drying and radiationsterilized allogeneic bone sheets （ the experimental segments）, while the operated sites of L3-4 in Group A and L4-5 in Group B were uncovered as the self controls （ the control segments ）. The regeneration process of the vertebral plate and the adhesion degree of the dura were observed at 4,8,12,16,20 and 24 weeks after operation. X- ray and CT scan were performed in both segments of 1.34 and L4-5 at 4 and 24 weeks after operation. Results： In the experimental segments, the bone sheets were located in the anatomical site of vertebral plate, and no lumbar spinal stenosis or compression of the dura was observed. The bone sheets were absorbed gradually and fused well with the regenerated vertebral plate. While in the control segments, the regeneration of vertebral plate was not completed yet, the scar was inserted into the spinal canal, compressing the dura and the spinal cord, and the epidural area almost disappeared. Compared with the control segments, the dura adhesion degree in the experimental regenerated segments was much milder （ P 〈 0. 01 ）, the internal volume of the vertebral canal had no obvious change and the shape of the dura sack remained well without obvious compression. Conclusions： Freeze-drying and radiation-sterlilized allogeneic bone sheets are ideal materials for extradural laminoplasty due to their good biocompatibility, biomechanical characteristics and osteogenic ability. They can effectively reduce formation of post-laminectomy scars, prevent recurrence of post-lamlnectomy spinal stenosis, and induce regeneration of vertebral plates.     

Implantation of amniotic membrane to reduce postlaminectomy epidural adhesions

Postlaminectomy epidural adhesion is implicated as a main cause of “failed back surgery syndrome” and associated with increased risk of complications during revision surgery. Various materials acting as mechanical barriers to reduce fibroblasts infiltration into epidural space have met with limited success. In present research, amniotic membrane (AM) was studied to investigate its effects on reducing epidural scar adhesion after laminectomy in a canine model. Laminectomy sites were created at L-1, L-3, L-5, and L-7 levels in 24 adult mongrel dogs. Freeze dried AM (FAM), cross-linked AM (CAM), and autologous free fat (AFF) were implanted, respectively, at a randomly assigned site in each dog with the remaining untreated site serving as internal control. The animals were sacrificed at 1, 6, and 12 weeks postoperatively. Then, gross pathologic observation including scar amount and adhesion tenacity, qualitative histology evaluation, and quantitative histology analysis were compared. Gross observation demonstrated that scar amount and adhesion tenacity of CAM group were significantly lower in comparison with those of FAM and non-treatment groups. A white, slightly vascularized CAM layer covered the dura mater without tenacious scar adhesion. The histology analysis also indicated reduced fibroblasts infiltration and consequent epidural fibrosis, which were similar to the results of AFF group. In conclusion, the CAM is effective in reducing epidural fibrosis and scar adhesion after laminectomy in canine model. It is a promising biomaterial for future clinical applications.     

Topical high-molecular-weight hyaluronan and a roofing barrier sheet equally inhibit postlaminectomy fibrosis.

BACKGROUND CONTEXT: The relevance of epidural fibrosis to failed back surgical outcomes remains controversial. Previous studies on the correlation between epidural fibrosis and clinical outcome after laminectomy are inconclusive, and clinical approaches applied to reduce postlaminectomy spinal canal scarring have produced mixed outcomes. PURPOSE: Improved preclinical models are required to address the fundamental question of the relationship between postlaminectomy fibrosis and chronic pain. This study is directed at establishing small animal postlaminectomy models characterized by significantly reduced scar within the spinal canal postoperatively. Such preclinical models are offered as a platform for future studies to explore the potential relationship between postlaminectomy epidural fibrosis and persistent neuropathy with its potential for altered spinal mechanisms for pain processing, so-called spinal facilitation. Such experiments could be constructed in these models for comparison of pain behavior and its underlying neurochemistry both in the presence and absence of extensive postlaminectomy epidural scar. STUDY DESIGN/SETTING: A modified rat laminectomy model was employed to assess epidural fibrosis using a quantitative biochemical collagen assessment approach along with correlative histology. This group served as the control for comparison with groups in which antifibrotic measures were employed. We compared antifibrotic efficacy of a bioabsorbable roofing barrier sheet placed over the laminectomy defect with topical high-molecular-weight hyaluronan (HMW HA) gel, each applied postoperatively to prevent proliferative epidural scarring. Routine biomechanical tensile strength testing was employed to assess wound-healing strength. METHODS: A bilateral laminectomy (L5 and L6) with associated unilateral disc injury (L5-L6) was performed in 98 male Harlan Sprague-Dawley rats. The laminectomy models described incorporated a unilateral disc injury at L5-L6 because herniated disc material has been shown to contribute proinflammatory cytokines in the postoperative wound. Five groups were employed for the study: 1) normal controls without surgery; 2) a laminectomy-disc injury group without treatment; 3) a laminectomy-disc injury group treated with topical HMW HA gel; 4) a laminectomy-disc injury group treated with 0.2-mm thick bioabsorbable roofing barrier sheet in which a protected space was maintained between overlying paraspinous muscles and the dura and 5) a 0.02-mm thin barrier sheet treatment group in which the sheet was placed directly on the dura. The animals were sacrificed at 3- and 8-week postoperative intervals for analysis. The dissected specimens were studied biochemically for hydroxyproline content to estimate total collagen within the canal and on the dura between L4 and L7. Additional specimens were prepared histologically and stained with Masson-Goldner Trichrome stain to confirm presence of proliferative collagen and to describe the presence or absence of wound-healing scar adherence to the dura. The surgical incisions were studied biomechanically by uniaxial tensile testing to determine ultimate force, strain and prefailure stiffness. Statistics were performed using analysis of variance. RESULTS: Gross appearance and histology studies showed that the untreated laminectomy group demonstrated postoperative scar formation that is adherent between the wound and the dorsum of the dura mater in both 3- and 8-week groups. Proliferative scar was substantially increased grossly between the 3- and 8-week intervals. By gross observation there was adherence of the L5 spinal nerve to the underlying disc and adjacent pedicle on the disc injury side. Gross observation of treatment groups, in contrast, disclosed that both the 0.2-mm thick roofing barrier sheet and topical HMW HA gel each prevented scar attachment to the dural sleeve at both the 3- and 8-week postoperative intervals. Furthermore, both the HMW HA gel and 0.2-mm thick roofing barrier sheet treatment groups had significant reduction of total collagen content in the laminectomy specimens measured biochemically at the two time periods compared with the untreated controls. Histologically, the HMW HA gel and the 0.2-mm thick barrier sheet findings were consistent with the gross observations concerning lack of adherence between scar of the overlying wound and the dura. Notably, both the 0.2- and the 0.02-mm barrier sheets became enveloped by a fibrotic envelope consistent with a foreign body reaction. In the group in which the 0.02-mm thin sheet was placed within the canal on top of the dura, there was an increase of fibrosis around the sheet within the canal leading to a space-occupying mass within the canal. Although the 0.2-mm thick roofing barrier placed external to the canal became enveloped by scar, it appeared to attract proliferative scar away from the epidural space, leaving the dura relatively free of scarring or adherence to overlying tissues. The mechanical properties of the incisional wound increased significantly between 3 and 8 weeks. The ultimate strength, stress, strain and stiffness of the several groups were similar at each time point. CONCLUSION: These results provide two preclinical rat laminectomy models of potential usefulness for the future study of the relevance of epidural fibrosis to behaviorally defined pain states, and for the study of the potential of an altered neurochemical signature in postlaminectomy pain conditions. Such preclinical models have become standard in studies of pain behavior and its neurochemistry in preclinical sciatic nerve and spinal nerve injury models, and should be of utility in the studies of postlaminectomy fibrosis. There was progressive scar proliferation and maturation in the untreated postlaminectomy group in the postoperative interval between 3 and 8 weeks. HMW HA gel applied topically and a 0.2-mm thick bioabsorbable Macropore sheet used as a roofing barrier each significantly reduced postlaminectomy proliferative scar without affecting the integrity of incisional wound healing. However, if the 0.02-mm thin barrier sheet used in this study is placed within the canal in contact with the dura and adjacent to the pedicles, the process of reabsorption results in a fibrotic mass within the canal. The preferred barrier sheet placement for this model is clearly in a roofing position bridging over the open epidural space. It must be placed in a manner to block off the paraspinous muscle healing response and still leave a gap between the sheet and the dura.