An experimental study on prevention of postlaminectomy scar formation by the use of new materials

An experimental study was performed to investigate the prevention of scar formation after lumbar laminectomy, using Elastase and the new polylactic acid (PLA) membrane containing Elastase. The experimental animals consisted of four groups: control group, E group (using intravenous administration of Elastase), P group (covering the laminectomy defect with PLA membrane), and P-E group (covering the laminectomy defect with "PLA" + Elastase" membrane). The animals were killed at varying intervals (2-12 weeks) and changes in the lumbar spines were evaluated histologically. Scar formation was suppressed most significantly in the P-E group, followed in order by the E group, the P group, and the controls.     

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。     

椎板切除术后预防硬膜外瘢痕粘连的实验研究

为了寻找预防椎板切除后硬膜粘连的材料，选用家兔３０只，随机分为三组，每组１０只。每只作Ｌ３、Ｌ５椎板切除，形成两个大小１ｃｍ×０．５ｃｍ的缺损，一个缺损无任何覆盖，作空白对照；另一个缺损分别在硬膜外覆盖几丁糖、聚乳酸（ＰＬＡ）膜及明胶海绵，即为几丁糖组、ＰＬＡ膜组及明胶海绵组。术后２，４，６，８及１０周处死动物，通过肉眼、光镜及透射电镜，观察瘢痕生长及硬膜外粘连情况。结果表明，几丁糖组和ＰＬＡ膜组硬膜外均光滑、无增厚，硬膜外腔隙未见纤维组织增生或粘连；几丁糖具有明显抑制成纤维细胞生长和促进表皮细胞生长的作用，切口愈合快。而各组空白对照和明胶海绵组硬膜外纤维组织增生或粘连明显，硬膜外腔隙基本消失。认为，可生物降解吸收的几丁糖、ＰＬＡ膜能有效地预防椎板切除术后瘢痕粘连。     

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。     

Epidural scar tissue formation after spinal surgery: an experimental study

Summary Extensive epidural scar formation is a wellknown complication after spine surgery. Fibrous adhesions around nerve roots are a major reason for recurrent neurological symptoms following lumbar discectomy. A large variety of materials, implanted onto the dura, have been used to prevent or reduce laminectomy membrane, with conflicting results. We therefore carried out an experimental study in dogs to compare those materials that seemed to be most suitable. In each of 30 adult beagles, three lumbar laminectomies were performed. Each level was covered with a different material — free autologous fat graft, cellulose mesh, Gelfoam or triamcinolone suspension. In a control group nothing was implanted. After 7 days or 1, 3 or 6 months the animals were killed. The lumbar vertebral columns were harvested and prepared for further histological examination. To compare the results, we designed a new classification scheme (scar index). The data were obtained without knowledge of implanted material or time since operation. We found that free autologous fat grafts are able to reduce epidural scar formation in a high proportion of cases, especially after 3 and 6 months; cellulose mesh showed the worst results. We conclude that free autologous fat grafts are superior to other materials because of simple operative handling, good compatibility and effective prevention of laminectomy membrane.     

聚乳酸薄膜预防腰椎间盘突出症术后硬膜外粘连的临床研究

目的观察聚乳酸薄膜预防硬膜外粘连的临床效果. 方法将1998年7月～2000年4月入院的62例腰椎间盘突出症患者,随机分成实验组32例,对照组30例,行椎板间开窗或椎板切除、腰椎间盘切除术.实验组在椎板间缺损区域置入0.1 mm厚度的聚乳酸薄膜,对照组缺损区域未置入聚乳酸薄膜.术后2周对局部及全身不良反应进行观察,6个月对患者随访并作手术节段CT复查. 结果术后2周,实验组与对照组无局部及全身不良反应;体温在正常范围内,伤口均Ⅰ期愈合;复查血常规及肝肾功能均在正常值范围.术后6个月实验组27例痊愈,4例显效,1例有效;对照组24例痊愈,4例显效,1例有效,1例无效.两组间差异无统计学意义(P＞0.05).CT复查显示:实验组无硬膜外瘢痕粘连;对照组有不同程度的硬膜外瘢痕粘连. 结论聚乳酸薄膜组织相容性好,无毒,能有效预防硬膜外瘢痕粘连,具有临床应用价值.     

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.     

自体真皮移植预防硬膜外纤维化及粘连的实验研究

目的 探讨自体真皮移植预防硬膜外纤维化及粘连的效果,为临床应用提供实验依据.方法 选取5头西藏小型猪,手术切除L2、L4全椎板造成缺损,去除硬膜后方硬膜外脂肪暴露硬脊膜,切取自体真皮移植于L2椎板缺损处覆盖硬脊膜(实验组),L4椎板缺损处硬脊膜外不用任何移植物覆盖(自身空白对照组).于术后2、4、6、8、10周全麻下股动脉放血法各处死1头动物,大体观察移植真皮存活情况及是否存在毛发生长、皮脂腺和汗腺分泌物.采用改良Robertson记分法评定硬膜外瘢痕量及粘连程度,SPSS 13.0统计学软件进行统计分析.组织学观察移植真皮内皮肤附属器变化情况.结果 移植真皮全部成活,与体表真皮比较明显增厚(P<0.05).实验组未见移植真皮毛发生长、皮脂腺囊肿和汗液囊肿形成;真皮与硬脊膜之间存在潜在的易分离平面,只有极少量瘢痕组织,粘连疏松,硬膜表面和移植真皮表皮面光滑.对照组大量的瘢痕形成,竖脊肌前方瘢痕组织严重且广泛长人硬膜外腔,与硬脊膜粘连紧密,硬脊膜从瘢痕组织上分离困难.改良Robertson记分法评分,实验组硬膜外瘢痕量及粘连程度明显低于对照组(P<0.05).组织学观察见毛囊萎缩、毛根坏死、皮脂腺及汗腺消失.结论 自体真皮是一种具有良好的抑制瘢痕形成和物理隔离屏障作用的生物材料.自体真皮移植能有效地预防硬膜外纤维化及粘连,具有临床应用价值.     

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.     

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。     

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。     

Experimental rabbit hemilaminotomy model in the evaluation of peridural fibrosis: a minimally invasive peridural fibrosis model.

The neuronal adhesions of newly synthesized scar tissue to dura mater after spinal peridural operations represent an unsolved problem in neurosurgical practice. This experimental study was planned to compare the success of a rabbit hemilaminotomy procedure with the total laminectomy model in the evaluation of peridural fibrosis in terms of proposing a lesser invasive peridural adhesion model. Fourteen New Zealand white rabbits were used in this experiment. Laminectomy was performed in one level, and hemilaminotomy was done in another level. Four weeks after operation the rabbits were sacrificed by perfusion with 10 % neutral buffered formalin solution. The lumbar spines were removed and immersed in 10 % neutral buffered formalin for approximately 24 hours. Then each specimen was decalcified in 5 % formic acid for approximately 3 weeks. Specimens were cut coronally for gross inspection. Two blocks of tissue were taken from each laminectomy site to be processed and embedded in paraffin. In seven (50 %) of the laminectomy sites of the rabbits, fibrous tissue penetrated the spinal canal through the laminectomy defect and produced neural compression (Grade III). Eight (57 %) hemilaminotomy sites were in Grade III fibrosis. There was no difference between laminectomy and hemilaminotomy in regard to the dural adhesions. In this experimental study, we modified the rabbit total laminectomy model by using a hemilaminotomy procedure in the study of peridural scar formation. The authors conclude that this procedure is more simple, reliable, and lesser invasive than the total laminectomy model.     

防止椎板切除术后硬脊膜外瘢痕粘连的实验研究

作者在４个平面间隔切除１１只山羊的椎板，分别用硅胶膜、自体游离脂肪片、带蒂肌肉瓣覆盖硬脊膜，一处平面作空白对照。术后４个月组织学检查，结果显示，硅胶膜后方有少许瘢痕组织增生，间质中有炎细胞灶状浸润，硅胶膜与硬膜囊无瘢痕形成，新形成的椎管后壁光滑，硬膜囊无受压；脂肪片被纤维组织取代，周围纤维组织增生轻微，形成菲薄之纤维膜，与硬脊膜容易分离；带蒂肌肉瓣周围形成较多瘢痕与硬脊膜粘连重，肌肉瓣已完全纤维化，空白组形成瘢痕最多，与硬脊膜粘连最重。术后硬膜囊矢状径以硅胶膜组最大，脂肪片组次之，带蒂肌肉瓣组再次之，空白组最小。作者认为，硅胶膜与脂肪片能明显防止椎板切除术后纤维瘢痕粘连对硬膜囊的压迫，在支架诱导作用方面，硅胶膜优于脂肪片，在生物相容性方面脂肪片优于硅胶膜。带蒂肌肉瓣优于对照组，但不及前两者。     

Expanded polytetrafluoroethylene membrane for the prevention of peridural fibrosis after spinal surgery: a clinical study

Peridural fibrosis developing after laminectomy may cause pain that can necessitate reoperation. Many materials have been used as a barrier to invasion of fibrous tissue into the vertebral canal, but the ideal material has not been found. Various studies in animals have achieved favourable results with an expanded polytetrafluoroethylene (ePTFE) membrane. In a prospective, randomized study, we compared postoperative results in 33 patients who had an ePTFE membrane implanted to cover the defect caused by laminectomy during lumbar spine decompression with the results in 33 patients in whom no material was implanted. At operation, an ePTFE membrane was placed after the decompression procedure to cover the laminectomy defect completely. Systematic clinical and MRI follow-up evaluations of patients with and without the membrane were conducted 3, 6, 12, and 24 months postoperatively. The effect of ePTFE membrane implantation over laminectomy sites on postoperative peridural fibrosis, pain and neurological claudication was assessed. The ePTFE-membrane group had a significantly lower rate of epidural fibrosis on MRI (P < 0.0001) and of clinical manifestations of radiculalgia (P = 0.002) compared with the no-material group. Epidural fibrosis that occurred in the ePTFE group was generally less extensive than that in the no-material group. There was no significant difference in the rate of postoperative claudication in the two groups. Significantly more seromas occurred in the ePTFE group (P = 0.0002). There were no infections or other complications in either group. The results showed that placement of an ePTFE spinal membrane over the laminectomy defect produced by lumbar spine surgery provided a physical barrier to invasion of fibrous tissue into the vertebral canal, and patients with the membrane had less postoperative radicular pain. Received: 24 November 1997 Revised: 26 November 1998 Accepted: 2 December 1998     

聚乳酸薄板预防椎板切除术后硬脊膜外纤维瘢痕粘连的实验研究

以60只家兔全椎板（L3，L5）切除为实验模型，研究了自制的聚乳酸薄板、明胶海绵在预防硬膜外纤维瘢痕粘连中的作用。通过大体观察及组织学检查，结果显示，聚乳酸薄板生物相容性好，能降解，可吸收，局部存留时间长，能有效地防止椎板切除后硬膜外纤维瘢痕粘连；明胶海绵早期防止纤维瘢痕粘连有一定作用，晚期作用不明显。     

Evaluation of hyaluronic acid sheet for the prevention of postlaminectomy adhesions.

BACKGROUND CONTEXT: Various materials have been tested for their ability to maintain a barrier between muscles and epidural space in order to physically or chemically inhibit scar ingrowths. Hyaluronic acid (HA) solution and gel have been reported to be effective in preventing adhesions postlaminectomy; however, neither has been used clinically after spinal surgery. PURPOSE: To determine the efficacy of HA sheet for the prevention of postlaminectomy adhesions compared with that of HA gel or another sheet. STUDY DESIGN/SETTING: An animal model of lumbar laminectomy in rabbits was used to study postoperative scar tissue formation around the spinal cord. The histologic effects of HA sheet were compared with those of Gelfoam (GF) and further evaluated by an inflammation model using rhTNF-alpha. PATIENT SAMPLE: Rabbit. OUTCOME MEASURES: Histologic examination. METHODS: Five rabbits were killed at 2, 4, 8, and 24 weeks after laminectomy, respectively. Another 18 rabbits were examined in an environment of active inflammation experimentally induced by rhTNF-alpha to compare the effects of HA sheet with those of GF or HA gel. Histologic examination was performed to quantitatively assess invasive scar formation or inflammation postlaminectomy, and then, the histologic effects of HA sheet were compared with those of GF or HA gel. RESULTS: In the HA group, significantly, the area of subarachnoid space was larger, distance from the surface of dura to scar tissues was greater, the number of inflammatory cells in the scar tissues at the site of laminectomy was less, and enlargement of dura was suppressed. Using an inflammation model, we also demonstrated the efficacy of HA sheet treatment. CONCLUSIONS: In an experimental laminectomy model, HA sheet formed a solid interpositional membrane barrier and exhibited anti-inflammatory activity. Further investigations will be needed for HA sheet to be used clinically.     

Prophylaxis of the laminectomy membrane. An experimental study in dogs.

Sixty laminectomies were performed in dogs to investigate the prevention of the laminectomy membrane and its side effects. These operations were distributed in six groups of 10, one was a control group, and in the others the bone defect was protected with different materials (Oxicel, Silastic, Dacron, methyl methacrylate, and Kiel bone graft). After a survival of 2 months, suboccipital myelography was performed, immediately after which the animals were sacrificed and the operated spinal slice obtained. The different radiographic densities of the tissues of each slice were calculated and the diverse histological nature identified by hematoxylin and eosin, periodic acid Schiff, Masson's trichrome, and Gomori's reticulin strains. Only the acrylic plastic and the Kiel bone graft prevented expansion of the scar tissue inside the spinal canal and adhesions between the dura and the cicatrical overlying muscles. Therefore, the authors suggest that a solid barrier is necessary to effectively prevent the so-called "laminectomy membrane."     

生物膜防止周围神经粘连的对比研究

目的：研究生物膜防止神经粘连的作用及与其它方法进行对比，探索促进神经再生的方法。方法：将兔的胫神经切断后作端端缝合，缝合口分别用生物膜、静脉包裹；己丁糖、强的松龙涂抹及不作任何处理。于术后2，4，10，16周行肉眼观察及光镜检查。术后第16周行电镜、电生理、轴突图像分析等检查。结果：生物膜在瘢痕闲上的使用可有效地防止瘢痕对修复段神经的压迫、粘连和固定。己丁糖和强的松龙也有防止神经粘连的作用，三者优于静脉包裹和单纯缝合组。经统计学处理，结果有显著性差异（P＜0．01）。结论：术中使用生物膜、己丁糖、强的松龙处理神经缝合口，能有效地防止周围神经粘连，促进周围神经再生。     

Reduction of adhesion formation and promotion of wound healing after laminectomy by pharmacological inhibition of pro-inflammatory cytokines: an experimental study in the rat

In a previous experiment using TNF inhibition in the rat it was accidentally found that adhesion and scar formation was reduced compared to previous experience. Wound and bone healing also seemed enhanced. The present study was conducted to assess if this observation could be verified in a controlled setting using a standardized laminectomy in the rat. Five rats received doxycycline and five other rats received saline and served as control. Macroscopic blinded evaluation 1 week after the laminectomy revealed that adhesion and scar formation was less in doxycycline-treated animals than in control animals. Wound and bone healing was found to be better in doxycycline-treated animals. The mechanisms for the observed effects cannot be fully understood but the data indicate that further research may lead to opportunities to design pharmacological modalities to reduce adhesion and scar formation, maybe in combination with suitable barriers.     

聚乳酸复合脱氧土霉素在骨缺损修复中的应用

目的：探讨聚乳酸复合脱氧土霉素构成的可吸收性膜的诱导成骨能力及可行性。方法：用聚乳酸材料制膜，实验膜中含有脱氧土霉素，空白膜不含药物成分。用SD大鼠桡骨3mm长骨缺损作为骨折模型。随机分为实验膜组，空白膜组，空白对照组3组。术后l、2、4、6、8、12周分别处死各组大鼠数只，分别行X线观察和组织学观察。结果：实验膜组的各项检测指标均表明其成骨效能优于其他各组。结论：实验膜组成骨效果优良的原因是由于PLA膜复合了脱氧土霉素，同时具有骨诱导和骨引导的两种成骨作用，而空白膜的骨引导作用虽然优于空白对照组，但比实验膜组效果差。