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Novel biodegradable lamina for lamina repair and reconstruction
The Spine Journal 13 (2013) 1912–1920
Basic Science
Novel biodegradable lamina for lamina repair and reconstruction Chaoliang Lv, MDa,b, Zhongjie Zhou, MDa, Yueming Song, MDa, Limin Liu, MDa, Hao Liu, MDa, Quan Gong, MSa,*, Tao Li, MDa, Jiancheng Zeng, MDa, Chongqi Tu, MSa, Fuxing Pei, MSa a
Department of Orthopaedic Surgery, West China Hospital, Sichuan University, NO. 37 Guoxuexiang Rd, Wuhou District, Chengdu 610041, China b Jining NO. 1 People’s Hospital, NO. 6 Jiankang Rd, Central District, Jining City, Shandong Province 272002, China Received 13 April 2012; revised 18 March 2013; accepted 14 June 2013
Abstract
BACKGROUND CONTEXT: Posterior 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. PURPOSE: To evaluate the efficacy of a novel biodegradable multi-amino acid copolymer/nanohydroxyapatite composite artificial lamina. METHODS: A 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 (n512). In the control group, the incision was closed directly without implantation (n59). 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. RESULTS: No 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. CONCLUSIONS: Artificial lamina can prevent the epidural adhesions surrounding the defect and promote effectively bone tissue repair and new bone formation. Ó 2013 Elsevier Inc. All rights reserved.
Keywords:
Artificial lamina; Goats; Lamina reconstruction; Adhesions
Introduction Posterior laminectomy is an effective surgical procedure that is commonly used to treat spinal stenosis. The adhesion of postoperative scar tissue to surgically exposed dura and, occasionally, to nerve roots can cause failed back surgery syndrome [1,2]. Some patients require a second surgery,
FDA device/drug status: Not applicable. Author disclosures: CL: Nothing to disclose. ZZ: Nothing to disclose. YS: Nothing to disclose. LL: Nothing to disclose. HL: Nothing to disclose. QG: Nothing to disclose. TL: Nothing to disclose. JZ: Nothing to disclose. CT: Nothing to disclose. FP: Nothing to disclose. * Corresponding author. Jining NO. 1 People’s Hospital, NO. 6 Jiankang Rd, Central District, Jining City, Shandong Province 272002, China. Tel.: þ86-18980601396; fax: þ86-28-85423438. E-mail address: [email protected] (Q. Gong) 1529-9430/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spinee.2013.06.055
thereby increasing procedural difficulty and risk. Therefore, the prevention of epidural scar formation is important for successful surgical outcome. LaRocca and Macnab [1] proposed the laminectomy membrane theory that is widely accepted. They confirmed that fibroblasts from the rough surface of the injured sacral spine muscle infiltrate intraspinal hematomas, leading to the formation of epidural scar tissue, also known as the laminectomy membrane [3]. As a main component of the postoperative repair process, fibroblasts usually appear in the lamina defect area 2 to 3 days after an injury under the chemotactic stimulation of inflammatory mediators and growth factors. Fibroblast proliferation results in collagen synthesis and collagen fiber formation. Fibroblasts change to static fiber cells, and granulation tissue gradually converts into scar tissue with the proliferation and
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maturation of collagen fibers. A lamina membrane is formed that exerts pressure on the nerve root, blocking nutrition and nerve conduction in the back of the spinal cord. Therefore, scar tissue adhesion and oppression are significant causes of failed back surgery syndrome. The establishment of a barrier between scar tissue and the dura is an effective way of preventing scar adhesion. Biological and synthetic interposing materials have been employed as mechanical barriers between the dura and the scar tissue in an attempt to prevent or limit scar tissue formation [2,4]. Predominantly used biological materials are hyaluronic acid (HA) and chitosan. Kato et al. [5] have suggested that an HA sheet forms a solid interpositional membrane barrier that exhibits anti-inflammatory activity. Bin et al. [6] confirmed that chitosan promotes physical rehabilitation, inhibits scar tissue formation, enhances hemostatic effect, and acts as a barrier. However, many of these biodegradable materials exhibit poor mechanical properties [7]. Of the many nonbiodegradable materials used, gelatin sponge is currently a predominant treatment. However, Jacobs et al. [8] have found that the gelatin sponge does not effectively prevent epidural adhesions. Because it expands after absorbing blood, it can form a fixed hematoma that eventually converts into scar tissue while exerting pressure on nerve roots and the lamina dura. It has been suggested that a hard material can supply enough strength to prevent scar tissue adhesion and oppression [3]. The ideal biomedical material should have the following characteristics: be compatible and not cause local or systemic adverse reactions and immune rejection, be bioinert and should not induce scar tissue formation, have good biomechanical properties while preventing scar adhesion and oppression, and be biodegradable and can be absorbed according to a scheduled time. We developed a new biodegradable multi-amino acid copolymer/nanohydroxyapatite (MAACP/nHA) copolymer composite artificial lamina that satisfied the aforementioned properties. The efficacy of the material in preventing cervical vertebra scar formation was tested using a laminectomy model in goats. The novel material has significant advantages including biodegradability, compatibility, good biomechanical properties, and the ability to induce and guide bone regeneration. Thus, the artificial MAACP/nHA lamina can be potentially used to replace natural lamina in laminectomy patients. We hypothesize that the material prevents epidural adhesion surrounding the defect while promoting effectively bone tissue repair and new bone formation and bone reconstruction during degradation.
Materials and methods Composite materials The MAACP/nHA artificial lamina was developed at Sichuan University. It is a polyamide copolymer with nHA, strength of 257.53 MPa, yield strength of 42.77 MPa, and
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a modulus of 0.35 GPa. The HA content in the composite is 30%, and the calcium:phosphate molar ratio is 1.5 to 1.7. The nHA component is responsible for maintaining the original morphologic structure, and it is distributed uniformly throughout the composite. The material has biological properties similar to that of the human cortical bone and can form strong bone bonding with natural bone. The composite material forms a smooth rectangular plate (28164 mm) with a processus spinosus similar to that of natural laminae. There is a flat panel on the copolymer surface with two small circular holes 3.5 mm in diameter. The distance from the center of the hole to the edge of the plate is 17 mm. The composites can be sterilized using ethylene oxide. Animals The animal experiments were approved by the Ethics Committee at Sichuan University. Twenty-four 2-year-old male goats weighing 3062 kg were obtained from the Sichuan University Animal Center. The goats were randomly divided into three groups: a test group that underwent cervical 4 laminectomies followed by MAACP/nHA composite artificial lamina implantations (n512), a control group of nine goats whose cervical 4 vertebra plates were removed, and a normal group of three goats that did not undergo any surgical procedures or treatments. At 4, 12, and 24 weeks postsurgery, 2, 2, and 3 goats, respectively, from the test and control groups underwent X-ray, computed tomography (CT), and magnetic resonance imaging analysis. They were subsequently sacrificed for histologic examinations and scanning electronic microscope (SEM) analysis. At Week 24, the level of scar tissue adhesion was assessed according to the Rydell degree of adhesion criteria [9]. Three goats in the test group, three in the control group, and three in the normal group were sacrificed at Week 24 for biomechanical measurements. Surgical procedures The goats received anesthesia via an intramuscular injection of Aetna (0.1 mL/kg). In addition, tracheal intubation and balloon-assisted breathing were used. The goats’ limbs were fixed in a prone position, and skin disinfectant was applied. A sterile neck incision was made, and subcutaneous tissue was separated. Cervicals 3 to 5 were exposed before cervical 4 was removed using laminectomy. A vertebral defect of 279 mm was made without damaging the small facet joints. The lamina dura was kept intact during the surgery. In the test group, biodegradable MAACP/ nHA composite artificial laminas were used to cover the dura and were fixed on the pedicle cervical 4 via two screws. The incision was washed with saline solution before the surrounding skin and soft tissue were sutured. In the control group, the incision was closed directly without a polymer artificial lamina implantation (Figs. 1 and 2).
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Fig. 1. Cervical 4 removal by laminectomy.
The goats received penicillin shots via intramuscular injection for 5 days postoperation to prevent infection. Fig. 2. Insertion of the artificial lamina.
Histologic analysis
Scanning electronic microscope
The cervical vertebra 4 specimens were removed en bloc. A portion of these were cut and fixed in 10% buffered formalin followed by running water overnight and then infiltrated and embedded in methyl methacrylate. Methyl methacrylate was also carefully injected into the spinal canal to ensure full embedding of the tissue. Each of the surgical sites was identified, and three 2-mm–thick sections were obtained, one from the center and one from each of the boundaries of the site. The sections were stained with Masson-Goldner trichrome and hematoxylin and eosin.
At 24 weeks postoperation, SEM was used to observe the microstructure of the interface between the artificial material and the natural bone and the interface gap.
Imaging analysis X-ray and CT were used to evaluate artificial laminar location, shape, spinal canal morphology, and bone bonding between the artificial material and natural bone. Computed tomography scans were used to measure the spinal canal area of cervical vertebrae 3 to 5 and the sagittal diameter of the spinal canal in cervical 4. Magnetic resonance imaging was used to assess adhesion and repression of scar tissue on the dura and the nerve root.
Biomechanical measurements The cervical spine (C2–C6) was dissected and freshly frozen at 20 C. Before testing, the specimens were thawed, and all musculature were carefully removed so that the ligamentous and bony structures were not damaged. Specimens were analyzed using flexion-extension, lateral bending, and axial rotation tests (Instron 8874, High Wycombe, United Kingdom). The range of motion was measured for each test as the angular deflection at the maximum moment in both the positive and the negative directions. The specimens were subjected to three cycles, and the data were recorded on the final cycle. Statistical analysis Data are presented as means and standard deviations. Statistical analysis was performed using a one-way analysis of variance, followed by the Bonferroni t test for
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comparison with the control group. Statistical significance was determined at p value less than .05.
Results Gross observation Four weeks after the procedure, incision wounds in the test group goats had healed well. Soft-tissue membranes had formed on the surface of artificial laminas, and they were easily separated from the materials. There were no broken or shifted artificial laminae in any of the test animals. Moreover, no dural adhesions were observed. In the control group, granulation tissue had formed, and it had entered into the spinal canal and dura. After 12 weeks, the test group’s laminae were surrounded by fibrous tissue and were difficult to separate. In addition, the dura in the control group were pressed inward by fibrous scars. After 24 weeks, the artificial laminae in the test group goats were still integrated. New bone had formed around the junction between the artificial lamina and autologous bone. In the control group, scar tissue adhesion to the dura was apparent, and the dura were pressed by fibrous tissue. After 24 weeks, no paralysis was observed and gait was normal in all the experimental and control goats. Imaging After 4 weeks, the artificial lamina shape was still maintained in the test group animals and no shifting was observed. A longitudinal translucent shadow was observed at the cervical lamina 4 defect, and the spinous process was absent in the control group (Fig. 3, Top, Middle, and Bottom). Computed tomography showed that the artificial lamina had made close contact with the surrounding natural bone, and no stenosis of the spinal canal was found in the test group. In the control group, the CT scan revealed lamina defects, a soft-tissue shadow in the spinal canal, and the pressure exerted on the dura (Fig. 3, Top, Middle, and Bottom). After 12 weeks, the artificial lamina had still maintained its form without any displacement or shift, and the edge of the artificial lamina was slightly blurred in the test group. There was no change in the control group goats at this time. Computed tomography showed callus around the junction between the artificial lamina and the autologous bone, and no spinal canal stenosis was found in the test group. In the control group, CT scans revealed that the density of the lamina had increased, and soft tissue had invaded the spinal canal. At 24 weeks, no artificial laminar location shift was seen in the test group, and longitudinal calluses along the edge of the artificial lamina were observed. There was no change in the control group. Computed tomography showed new bone formation around the artificial lamina and the new lamina reconstruction in the defect in the test group. However, the dura had almost completely adhered to scar tissues in the control group (Fig. 4, Top, Middle, and Bottom). Spinal area measurements of
Fig. 3. X-ray and computed tomography (CT) scan images of goat cervicals from the control group after 24 weeks. (Top) A longitudinal translucent shadow was observed at the cervical lamina 4 defect. (Middle) The C4 spinous process is absent. (Bottom) CT scan revealed lamina defects, the soft-tissue shadow in the spinal canal, and the pressure exerted on the dura.
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C. Lv et al. / The Spine Journal 13 (2013) 1912–1920 Table 1 Cervical spinal canal area of the test, control, and normal groups (mean6standard deviation) (mm2) Cervical spinal canal area (mm2) Groups
Samples
C3
C4
C5
Test* Control Normal
5 2 2
114.569.6 110.969.2y 113.6610.4
139.7611.7 92.867.6z 138.4610.7
148.3613.9 151.9612.8y 135.4610.5
Note: In the control group, the four cervical spinal canal areas were significantly smaller than the experimental and normal groups. * The control group compared with the normal group in the cervical spinal area of cervicals 3, 4, and 5 (pO.05). y The control group compared with the normal group in the cervical spinal area of cervicals 3 and 5 (pO.05). z The control group compared with the normal group in the cervical spinal area of cervical 4 (p!.05).
cervicals 3 to 5 for both the test and control groups are shown in Table 1. Significant differences could be seen in cervical 4, whereas no significant differences were observed in cervicals 3 and 5 (p!.05). Computed tomography scanning also showed a significant difference in the sagittal diameter of cervical 4 between the test and the control groups (p!.05, Table 2). Magnetic resonance imaging showed that the cerebrospinal fluid signal of the test group was unobstructed, and no soft tissue had grown into the spinal canal. As for the control group, the dura was compressed by soft tissue (Fig. 5, Top and Bottom).
Histologic analysis After 4 weeks, the artificial lamina in the test group was wrapped by fibrous tissue. Connective tissue had formed and had separated the fibers from the copolymer material. In addition, small amounts of osteoblast bone cells and osteoid formation were seen (Fig. 6, Top). There was no scar tissue in the spinal canal. In contrast, soft tissue grew in the lamina defects of goats in the control group, and interorganizational vascular proliferation was not obvious. Also, there was a small osteoid bone stump and osteoblasts on the bone side (Fig. 6, Bottom). After 12 weeks, the trabecular bone in goats in the test group could be observed around the junction between the artificial lamina and the autologous bone. There was no adhesion or pressure on the dura. The defect in the control group was filled with dense connective tissue. Furthermore, striated muscle and
Fig. 4. X-ray and computed tomography scan images of goat cervicals from the test group after 24 weeks. (Top) A defect was covered by C4 artificial lamina 24 weeks postoperation, and no artificial laminar location shift was seen in the test group. (Middle) A longitudinal callus along the edge of the artificial lamina was observed, and the C4 spinous process is absent. (Bottom) Computed tomography scanning revealed new bone formation around the artificial lamina and the new lamina reconstruction in the defect.
Table 2 Sagittal diameters of spinal canal of cervical 3 to 5 (mean6standard deviation) (mm2) Cervical spinal canal area (mm) Groups
Samples
C3
C4
C5
Test* Control Normal
5 2 2
12.662.6 12.562.4 12.761.3
13.961.2 11.362.1 14.162.2
14.962.3 14.962.5 13.961.2
* Compared with the control and normal groups (pO.05).
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Fig. 5. Magnetic resonance images of goat cervicals from the control and test groups. (Top) The dura was pressed by soft tissue. (Bottom) No compression of the dural sac was observed in the test group.
fibrous tissue had broken into the spinal canal, and pressure exerted by the scar tissue on the dura was apparent. After 24 weeks, abundant natural trabecular and lamellar bone had formed around the interface between the artificial lamina and the autologous bone in goats in the test group, and no degraded polymer fragments were observed. Again, no dural adhesion or pressure was found (Fig. 7, Top). In the control group, fibrous scar tissue filled the defect and scar tissue continued to exert pressure on the dura (Fig. 7, Bottom). According to the Rydell degree of adhesion criteria, the experimental group was significantly better than the control group (p!.01, Table 3). Scanning electronic microscope At 24 weeks, fibrous tissue attached to the artificial lamina surface was arranged in order in goats in the test group. No obvious degradation or absorption of the artificial lamina had occurred, and no significant gap had appeared between the artificial lamina and the autologous bone (Fig. 8, Top). In the control group, the lamina defect was filled with disordered fibers (Fig. 8, Bottom). Biomechanical tests Results indicate that the test group had smaller motion ranges in the flexion than the control group (p!.01). There
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Fig. 6. Histologic images of goat cervicals from the test group (Top) and the control group (Bottom). (Top) Appearance of osteoblasts and osteoid formation after 4 weeks (hematoxylin and eosin [HE] 40). (Bottom) Both osteoblasts and scar tissue can be seen after 4 weeks (HE 40).
was no significant difference in motion ranges for all directions between the test and the normal groups (pO.05, Table 4).
Discussion It is well known that bone structure comprised hydroxyapatite crystals reinforced by collagen [10]. Multi-amino acid copolymer/nanohydroxyapatite is a novel, bioactive, and bone-like composite that can be used for bone repair. It consists of a polyamide copolymer and nHA. The nHA in this composite is a nanograde HA crystal, similar to bone apatite in morphology, composition, crystal structure, and crystallinity [11]. Bioactivity of the composite is dependent on nHA content. However, pure HA ceramic is brittle; its use is restricted in load-bearing sites for bone repair or bone substitutions [12,13]. To enhance its strength, the polyamide copolymer was added. Amino acids are the main components of human protein, are nontoxic, and are easily metabolized and excreted. Polyamide is compatible with the human body [14,15]. It is an excellent medical polymer and commonly used as a biomedical material (eg, surgical sutures) [16]. Therefore, the MAACP/nHA composite material developed for this study will not increase the chance
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Fig. 7. (Top) After 24 weeks, an abundant natural trabecular and lamellar bone formation around the interface between the artificial lamina and autologous bone was revealed. No compression on the subdural was observed. (Bottom) After 24 weeks, defects were filled with fibers and scar tissue exerted pressure on the dura mater.
of severe inflammatory reactions or scar tissue formation. In our experiment, inflammatory cell infiltration was not observed. During the recovery period, there was no observed toxicity, rejection, material exposure, or tissue necrosis. Test results on the material’s biomechanics revealed that the physical properties are similar to that of human cortical bone in bending strength and compressive elastic modulus. Thus, the MAACP/nHA composite is an ideal material for lamina repair. After 24 weeks, magnetic resonance imaging and histology showed no epidural adhesions or oppression. The lamina was intact and had not been displaced in goats in the test group. In the control group, the scar tissue had grown into the spinal canal and had exerted pressure on the dura. The test group was significantly better than the control group according to the Rydell degree of adhesion criteria. Table 3 Adhesion levels of surgical parts in the test and control groups Grade Groups (n)
0
1
2
3
Test* (9) Control (6)
7 0
2 0
0 1
0 5
* Compared with the control group (p!.01).
Fig. 8. Scanning electronic microscope images of the goat cervicals from the test group (Top) and the control group (Bottom). (Top) No obvious degradation and absorption of the artificial lamina occur, and no significant gap appeared between the artificial lamina and the natural bone. (Bottom) In the control group, the defect of the lamina was filled with disorder fibers (1,000).
These results suggest that the artificial lamina can effectively block epidural adhesion and oppression. We hypothesize that this is because the material’s physical properties are similar to that of human cortical bone in bending strength and compressive elastic modulus. In addition, we suggest that the implantation of a fixed artificial lamina can prevent scar penetration behind the spinal canal. Urist and McLean [17] presumed that the fibroblasts surrounding bone tissue proliferation grow into the bone defect faster than bone formation tissue and that bone formation and fiber formation competed against one another. After 24 weeks, the test group’s lamina defects were repaired, whereas the control group’s defects were filled with fibrous connective tissue and slight new bone formation. This shows that the MAACP/nHA composite material can be used as a mechanical barrier in preventing the fibroblast growth, guiding the slower osteoblast migration to the defect area and allowing for new bone formation. Osteoblasts appeared in the junction between the artificial laminae and autologous bone. No cracks were observed between these two when scrutinized with SEM under 1,000 magnification. Therefore, the material formed a strong bone bond with the autologous bone. These results suggest that HA crystals in the material can be adsorbed and activated
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Table 4 Motion range of the goat cervicals (mean6standard deviation) Groups
Flexion ( )
Extension ( )
Left lateral bending ( )
Right lateral bending ( )
Left axial rotation ( )
Right axial rotation ( )
Test Control Normal
5.3960.35 7.2160.41 5.3660.47
3.4160.25 4.4560.28 3.5460.34
3.6960.23 3.7160.24 3.7260.23
3.7060.26 3.6960.22 3.7460.25
3.2060.19 3.2460.21 3.2660.22
3.2160.22 3.2260.25 3.4960.28
osteoblasts can form bone apatite nuclei that support osteoconductivity and osteogenesis [18]. Computed tomography scanning after 24 weeks showed no significant difference in the sagittal diameter and spinal area of cervical 4 between the test group and the normal group with (pO.05). Therefore, the bony spinal canal had been successfully rebuilt. After 24 weeks, absorption and degradation of the material was not observed, allowing sufficient time for the lamina defect to undergo bone tissue repair and remodeling. Our results show that the final artificial material-autologous bone complexes form adequate lamina defects and that the mechanical properties of the lamina can be maintained for a long period of time. Therefore, the best functional and morphologic reconstruction was achieved. According to Miyamoto et al. [19], the cervical spinous process, the supraspinous ligament, and the interspinous ligament collectively form the posterior cervical ligamentous complex. Its main physiological function is to fight back stretch stress, also known as the ‘‘bow.’’ The complex also maintains cervical lordosis and cervical stability. Clinically, cervical back surgery tends to undermine the posterior cervical ligamentous complex that can lead to cervical kyphosis and instability and the appearance of neurologic symptoms [20]. The artificial lamina used in this study has good biocompatibility and might provide an attachment point for rear soft tissues that would help stabilize posterior column reconstruction. In this experiment, the artificial lamina may have helped the cervical ligamentous complex and contributed to cervical vertebrae stability within a certain motion range. Our results indicated that the control group had a greater motion range of flexion than the test or normal group (p!.01). In addition, the motion ranges in all directions were not significantly different between the test and the normal groups (pO.05, Table 4). This suggests that the cervical laminectomy destroyed flexion stability in the control group and that this stability was rescued by the artificial lamina. In the spinal research, the goat spine is frequently considered as a model for the human spine. One might presume that there are differences between an upright human spine and that of a quadruped, as their spines are supposedly subjected to loads that differ considerably from those in humans. However, neither experimental nor theoretical studies have found fundamental differences between the mechanical loading of quadruped and human spines. A previous analysis has demonstrated that considerable bending and torsion moments must be sustained by the horizontal trunk in a quadruped. Because of the low resistance of
the spine against such loads, these moments must be counterbalanced by tensile forces from muscles and/or ligaments and a compression force in the spine. Furthermore, the vertebral bone architecture analyzed showed that trabeculae run from end plate to end plate. This indicates that the main load in the quadruped spine is axial compression, which is similar to that of the human spine [21,22]. Kandziora et al. [23] biomechanically compared goat and human spines biomechanically by testing goat spines and comparing the data with previously published studies. Range of motion and stiffness data were comparable. The researchers concluded that if the goat model is used, motion segments C2–C3 and C3–C4 are the most suitable for biomechanical tests. Therefore, use of the goat model is suitable for the evaluation of implant systems and surgical procedures. The main purpose of our research was to evaluate the efficacy of a novel artificial lamina for the prevention of postlaminectomy adhesions during lamina reconstruction. Because there are no fundamental differences in adhesion formation between the cervical and the thoracic or lumbar spine, the lamina might also be effective in the thoracic or lumbar spine. Additionally, cervical back surgery tends to undermine the role of the posterior cervical ligamentous complex leading to cervical instability, and the artificial cervical lamina could provide attachment point for rear soft tissues and then help the stability of the posterior column reconstruction. Theoretically, the situation may be similar in the thoracic or lumbar spine. Further animal studies on the thoracic or lumbar spine are needed to confirm this hypothesis.
Conclusions The MAACP/nHA composite artificial lamina had excellent biomechanical properties that can effectively prevent epidural adhesions in goats. The artificial lamina also promoted effective bone tissue repair and new bone formation, and lamina reconstruction was successful in the test animals. Degradation of the composite material was slow, and biomechanical properties were maintained during this process.
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Basic Science
Novel biodegradable lamina for lamina repair and reconstruction Chaoliang Lv, MDa,b, Zhongjie Zhou, MDa, Yueming Song, MDa, Limin Liu, MDa, Hao Liu, MDa, Quan Gong, MSa,*, Tao Li, MDa, Jiancheng Zeng, MDa, Chongqi Tu, MSa, Fuxing Pei, MSa a
Department of Orthopaedic Surgery, West China Hospital, Sichuan University, NO. 37 Guoxuexiang Rd, Wuhou District, Chengdu 610041, China b Jining NO. 1 People’s Hospital, NO. 6 Jiankang Rd, Central District, Jining City, Shandong Province 272002, China Received 13 April 2012; revised 18 March 2013; accepted 14 June 2013
Abstract
BACKGROUND CONTEXT: Posterior 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. PURPOSE: To evaluate the efficacy of a novel biodegradable multi-amino acid copolymer/nanohydroxyapatite composite artificial lamina. METHODS: A 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 (n512). In the control group, the incision was closed directly without implantation (n59). 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. RESULTS: No 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. CONCLUSIONS: Artificial lamina can prevent the epidural adhesions surrounding the defect and promote effectively bone tissue repair and new bone formation. Ó 2013 Elsevier Inc. All rights reserved.
Keywords:
Artificial lamina; Goats; Lamina reconstruction; Adhesions
Introduction Posterior laminectomy is an effective surgical procedure that is commonly used to treat spinal stenosis. The adhesion of postoperative scar tissue to surgically exposed dura and, occasionally, to nerve roots can cause failed back surgery syndrome [1,2]. Some patients require a second surgery,
FDA device/drug status: Not applicable. Author disclosures: CL: Nothing to disclose. ZZ: Nothing to disclose. YS: Nothing to disclose. LL: Nothing to disclose. HL: Nothing to disclose. QG: Nothing to disclose. TL: Nothing to disclose. JZ: Nothing to disclose. CT: Nothing to disclose. FP: Nothing to disclose. * Corresponding author. Jining NO. 1 People’s Hospital, NO. 6 Jiankang Rd, Central District, Jining City, Shandong Province 272002, China. Tel.: þ86-18980601396; fax: þ86-28-85423438. E-mail address: [email protected] (Q. Gong) 1529-9430/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spinee.2013.06.055
thereby increasing procedural difficulty and risk. Therefore, the prevention of epidural scar formation is important for successful surgical outcome. LaRocca and Macnab [1] proposed the laminectomy membrane theory that is widely accepted. They confirmed that fibroblasts from the rough surface of the injured sacral spine muscle infiltrate intraspinal hematomas, leading to the formation of epidural scar tissue, also known as the laminectomy membrane [3]. As a main component of the postoperative repair process, fibroblasts usually appear in the lamina defect area 2 to 3 days after an injury under the chemotactic stimulation of inflammatory mediators and growth factors. Fibroblast proliferation results in collagen synthesis and collagen fiber formation. Fibroblasts change to static fiber cells, and granulation tissue gradually converts into scar tissue with the proliferation and
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maturation of collagen fibers. A lamina membrane is formed that exerts pressure on the nerve root, blocking nutrition and nerve conduction in the back of the spinal cord. Therefore, scar tissue adhesion and oppression are significant causes of failed back surgery syndrome. The establishment of a barrier between scar tissue and the dura is an effective way of preventing scar adhesion. Biological and synthetic interposing materials have been employed as mechanical barriers between the dura and the scar tissue in an attempt to prevent or limit scar tissue formation [2,4]. Predominantly used biological materials are hyaluronic acid (HA) and chitosan. Kato et al. [5] have suggested that an HA sheet forms a solid interpositional membrane barrier that exhibits anti-inflammatory activity. Bin et al. [6] confirmed that chitosan promotes physical rehabilitation, inhibits scar tissue formation, enhances hemostatic effect, and acts as a barrier. However, many of these biodegradable materials exhibit poor mechanical properties [7]. Of the many nonbiodegradable materials used, gelatin sponge is currently a predominant treatment. However, Jacobs et al. [8] have found that the gelatin sponge does not effectively prevent epidural adhesions. Because it expands after absorbing blood, it can form a fixed hematoma that eventually converts into scar tissue while exerting pressure on nerve roots and the lamina dura. It has been suggested that a hard material can supply enough strength to prevent scar tissue adhesion and oppression [3]. The ideal biomedical material should have the following characteristics: be compatible and not cause local or systemic adverse reactions and immune rejection, be bioinert and should not induce scar tissue formation, have good biomechanical properties while preventing scar adhesion and oppression, and be biodegradable and can be absorbed according to a scheduled time. We developed a new biodegradable multi-amino acid copolymer/nanohydroxyapatite (MAACP/nHA) copolymer composite artificial lamina that satisfied the aforementioned properties. The efficacy of the material in preventing cervical vertebra scar formation was tested using a laminectomy model in goats. The novel material has significant advantages including biodegradability, compatibility, good biomechanical properties, and the ability to induce and guide bone regeneration. Thus, the artificial MAACP/nHA lamina can be potentially used to replace natural lamina in laminectomy patients. We hypothesize that the material prevents epidural adhesion surrounding the defect while promoting effectively bone tissue repair and new bone formation and bone reconstruction during degradation.
Materials and methods Composite materials The MAACP/nHA artificial lamina was developed at Sichuan University. It is a polyamide copolymer with nHA, strength of 257.53 MPa, yield strength of 42.77 MPa, and
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a modulus of 0.35 GPa. The HA content in the composite is 30%, and the calcium:phosphate molar ratio is 1.5 to 1.7. The nHA component is responsible for maintaining the original morphologic structure, and it is distributed uniformly throughout the composite. The material has biological properties similar to that of the human cortical bone and can form strong bone bonding with natural bone. The composite material forms a smooth rectangular plate (28164 mm) with a processus spinosus similar to that of natural laminae. There is a flat panel on the copolymer surface with two small circular holes 3.5 mm in diameter. The distance from the center of the hole to the edge of the plate is 17 mm. The composites can be sterilized using ethylene oxide. Animals The animal experiments were approved by the Ethics Committee at Sichuan University. Twenty-four 2-year-old male goats weighing 3062 kg were obtained from the Sichuan University Animal Center. The goats were randomly divided into three groups: a test group that underwent cervical 4 laminectomies followed by MAACP/nHA composite artificial lamina implantations (n512), a control group of nine goats whose cervical 4 vertebra plates were removed, and a normal group of three goats that did not undergo any surgical procedures or treatments. At 4, 12, and 24 weeks postsurgery, 2, 2, and 3 goats, respectively, from the test and control groups underwent X-ray, computed tomography (CT), and magnetic resonance imaging analysis. They were subsequently sacrificed for histologic examinations and scanning electronic microscope (SEM) analysis. At Week 24, the level of scar tissue adhesion was assessed according to the Rydell degree of adhesion criteria [9]. Three goats in the test group, three in the control group, and three in the normal group were sacrificed at Week 24 for biomechanical measurements. Surgical procedures The goats received anesthesia via an intramuscular injection of Aetna (0.1 mL/kg). In addition, tracheal intubation and balloon-assisted breathing were used. The goats’ limbs were fixed in a prone position, and skin disinfectant was applied. A sterile neck incision was made, and subcutaneous tissue was separated. Cervicals 3 to 5 were exposed before cervical 4 was removed using laminectomy. A vertebral defect of 279 mm was made without damaging the small facet joints. The lamina dura was kept intact during the surgery. In the test group, biodegradable MAACP/ nHA composite artificial laminas were used to cover the dura and were fixed on the pedicle cervical 4 via two screws. The incision was washed with saline solution before the surrounding skin and soft tissue were sutured. In the control group, the incision was closed directly without a polymer artificial lamina implantation (Figs. 1 and 2).
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Fig. 1. Cervical 4 removal by laminectomy.
The goats received penicillin shots via intramuscular injection for 5 days postoperation to prevent infection. Fig. 2. Insertion of the artificial lamina.
Histologic analysis
Scanning electronic microscope
The cervical vertebra 4 specimens were removed en bloc. A portion of these were cut and fixed in 10% buffered formalin followed by running water overnight and then infiltrated and embedded in methyl methacrylate. Methyl methacrylate was also carefully injected into the spinal canal to ensure full embedding of the tissue. Each of the surgical sites was identified, and three 2-mm–thick sections were obtained, one from the center and one from each of the boundaries of the site. The sections were stained with Masson-Goldner trichrome and hematoxylin and eosin.
At 24 weeks postoperation, SEM was used to observe the microstructure of the interface between the artificial material and the natural bone and the interface gap.
Imaging analysis X-ray and CT were used to evaluate artificial laminar location, shape, spinal canal morphology, and bone bonding between the artificial material and natural bone. Computed tomography scans were used to measure the spinal canal area of cervical vertebrae 3 to 5 and the sagittal diameter of the spinal canal in cervical 4. Magnetic resonance imaging was used to assess adhesion and repression of scar tissue on the dura and the nerve root.
Biomechanical measurements The cervical spine (C2–C6) was dissected and freshly frozen at 20 C. Before testing, the specimens were thawed, and all musculature were carefully removed so that the ligamentous and bony structures were not damaged. Specimens were analyzed using flexion-extension, lateral bending, and axial rotation tests (Instron 8874, High Wycombe, United Kingdom). The range of motion was measured for each test as the angular deflection at the maximum moment in both the positive and the negative directions. The specimens were subjected to three cycles, and the data were recorded on the final cycle. Statistical analysis Data are presented as means and standard deviations. Statistical analysis was performed using a one-way analysis of variance, followed by the Bonferroni t test for
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comparison with the control group. Statistical significance was determined at p value less than .05.
Results Gross observation Four weeks after the procedure, incision wounds in the test group goats had healed well. Soft-tissue membranes had formed on the surface of artificial laminas, and they were easily separated from the materials. There were no broken or shifted artificial laminae in any of the test animals. Moreover, no dural adhesions were observed. In the control group, granulation tissue had formed, and it had entered into the spinal canal and dura. After 12 weeks, the test group’s laminae were surrounded by fibrous tissue and were difficult to separate. In addition, the dura in the control group were pressed inward by fibrous scars. After 24 weeks, the artificial laminae in the test group goats were still integrated. New bone had formed around the junction between the artificial lamina and autologous bone. In the control group, scar tissue adhesion to the dura was apparent, and the dura were pressed by fibrous tissue. After 24 weeks, no paralysis was observed and gait was normal in all the experimental and control goats. Imaging After 4 weeks, the artificial lamina shape was still maintained in the test group animals and no shifting was observed. A longitudinal translucent shadow was observed at the cervical lamina 4 defect, and the spinous process was absent in the control group (Fig. 3, Top, Middle, and Bottom). Computed tomography showed that the artificial lamina had made close contact with the surrounding natural bone, and no stenosis of the spinal canal was found in the test group. In the control group, the CT scan revealed lamina defects, a soft-tissue shadow in the spinal canal, and the pressure exerted on the dura (Fig. 3, Top, Middle, and Bottom). After 12 weeks, the artificial lamina had still maintained its form without any displacement or shift, and the edge of the artificial lamina was slightly blurred in the test group. There was no change in the control group goats at this time. Computed tomography showed callus around the junction between the artificial lamina and the autologous bone, and no spinal canal stenosis was found in the test group. In the control group, CT scans revealed that the density of the lamina had increased, and soft tissue had invaded the spinal canal. At 24 weeks, no artificial laminar location shift was seen in the test group, and longitudinal calluses along the edge of the artificial lamina were observed. There was no change in the control group. Computed tomography showed new bone formation around the artificial lamina and the new lamina reconstruction in the defect in the test group. However, the dura had almost completely adhered to scar tissues in the control group (Fig. 4, Top, Middle, and Bottom). Spinal area measurements of
Fig. 3. X-ray and computed tomography (CT) scan images of goat cervicals from the control group after 24 weeks. (Top) A longitudinal translucent shadow was observed at the cervical lamina 4 defect. (Middle) The C4 spinous process is absent. (Bottom) CT scan revealed lamina defects, the soft-tissue shadow in the spinal canal, and the pressure exerted on the dura.
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C. Lv et al. / The Spine Journal 13 (2013) 1912–1920 Table 1 Cervical spinal canal area of the test, control, and normal groups (mean6standard deviation) (mm2) Cervical spinal canal area (mm2) Groups
Samples
C3
C4
C5
Test* Control Normal
5 2 2
114.569.6 110.969.2y 113.6610.4
139.7611.7 92.867.6z 138.4610.7
148.3613.9 151.9612.8y 135.4610.5
Note: In the control group, the four cervical spinal canal areas were significantly smaller than the experimental and normal groups. * The control group compared with the normal group in the cervical spinal area of cervicals 3, 4, and 5 (pO.05). y The control group compared with the normal group in the cervical spinal area of cervicals 3 and 5 (pO.05). z The control group compared with the normal group in the cervical spinal area of cervical 4 (p!.05).
cervicals 3 to 5 for both the test and control groups are shown in Table 1. Significant differences could be seen in cervical 4, whereas no significant differences were observed in cervicals 3 and 5 (p!.05). Computed tomography scanning also showed a significant difference in the sagittal diameter of cervical 4 between the test and the control groups (p!.05, Table 2). Magnetic resonance imaging showed that the cerebrospinal fluid signal of the test group was unobstructed, and no soft tissue had grown into the spinal canal. As for the control group, the dura was compressed by soft tissue (Fig. 5, Top and Bottom).
Histologic analysis After 4 weeks, the artificial lamina in the test group was wrapped by fibrous tissue. Connective tissue had formed and had separated the fibers from the copolymer material. In addition, small amounts of osteoblast bone cells and osteoid formation were seen (Fig. 6, Top). There was no scar tissue in the spinal canal. In contrast, soft tissue grew in the lamina defects of goats in the control group, and interorganizational vascular proliferation was not obvious. Also, there was a small osteoid bone stump and osteoblasts on the bone side (Fig. 6, Bottom). After 12 weeks, the trabecular bone in goats in the test group could be observed around the junction between the artificial lamina and the autologous bone. There was no adhesion or pressure on the dura. The defect in the control group was filled with dense connective tissue. Furthermore, striated muscle and
Fig. 4. X-ray and computed tomography scan images of goat cervicals from the test group after 24 weeks. (Top) A defect was covered by C4 artificial lamina 24 weeks postoperation, and no artificial laminar location shift was seen in the test group. (Middle) A longitudinal callus along the edge of the artificial lamina was observed, and the C4 spinous process is absent. (Bottom) Computed tomography scanning revealed new bone formation around the artificial lamina and the new lamina reconstruction in the defect.
Table 2 Sagittal diameters of spinal canal of cervical 3 to 5 (mean6standard deviation) (mm2) Cervical spinal canal area (mm) Groups
Samples
C3
C4
C5
Test* Control Normal
5 2 2
12.662.6 12.562.4 12.761.3
13.961.2 11.362.1 14.162.2
14.962.3 14.962.5 13.961.2
* Compared with the control and normal groups (pO.05).
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Fig. 5. Magnetic resonance images of goat cervicals from the control and test groups. (Top) The dura was pressed by soft tissue. (Bottom) No compression of the dural sac was observed in the test group.
fibrous tissue had broken into the spinal canal, and pressure exerted by the scar tissue on the dura was apparent. After 24 weeks, abundant natural trabecular and lamellar bone had formed around the interface between the artificial lamina and the autologous bone in goats in the test group, and no degraded polymer fragments were observed. Again, no dural adhesion or pressure was found (Fig. 7, Top). In the control group, fibrous scar tissue filled the defect and scar tissue continued to exert pressure on the dura (Fig. 7, Bottom). According to the Rydell degree of adhesion criteria, the experimental group was significantly better than the control group (p!.01, Table 3). Scanning electronic microscope At 24 weeks, fibrous tissue attached to the artificial lamina surface was arranged in order in goats in the test group. No obvious degradation or absorption of the artificial lamina had occurred, and no significant gap had appeared between the artificial lamina and the autologous bone (Fig. 8, Top). In the control group, the lamina defect was filled with disordered fibers (Fig. 8, Bottom). Biomechanical tests Results indicate that the test group had smaller motion ranges in the flexion than the control group (p!.01). There
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Fig. 6. Histologic images of goat cervicals from the test group (Top) and the control group (Bottom). (Top) Appearance of osteoblasts and osteoid formation after 4 weeks (hematoxylin and eosin [HE] 40). (Bottom) Both osteoblasts and scar tissue can be seen after 4 weeks (HE 40).
was no significant difference in motion ranges for all directions between the test and the normal groups (pO.05, Table 4).
Discussion It is well known that bone structure comprised hydroxyapatite crystals reinforced by collagen [10]. Multi-amino acid copolymer/nanohydroxyapatite is a novel, bioactive, and bone-like composite that can be used for bone repair. It consists of a polyamide copolymer and nHA. The nHA in this composite is a nanograde HA crystal, similar to bone apatite in morphology, composition, crystal structure, and crystallinity [11]. Bioactivity of the composite is dependent on nHA content. However, pure HA ceramic is brittle; its use is restricted in load-bearing sites for bone repair or bone substitutions [12,13]. To enhance its strength, the polyamide copolymer was added. Amino acids are the main components of human protein, are nontoxic, and are easily metabolized and excreted. Polyamide is compatible with the human body [14,15]. It is an excellent medical polymer and commonly used as a biomedical material (eg, surgical sutures) [16]. Therefore, the MAACP/nHA composite material developed for this study will not increase the chance
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Fig. 7. (Top) After 24 weeks, an abundant natural trabecular and lamellar bone formation around the interface between the artificial lamina and autologous bone was revealed. No compression on the subdural was observed. (Bottom) After 24 weeks, defects were filled with fibers and scar tissue exerted pressure on the dura mater.
of severe inflammatory reactions or scar tissue formation. In our experiment, inflammatory cell infiltration was not observed. During the recovery period, there was no observed toxicity, rejection, material exposure, or tissue necrosis. Test results on the material’s biomechanics revealed that the physical properties are similar to that of human cortical bone in bending strength and compressive elastic modulus. Thus, the MAACP/nHA composite is an ideal material for lamina repair. After 24 weeks, magnetic resonance imaging and histology showed no epidural adhesions or oppression. The lamina was intact and had not been displaced in goats in the test group. In the control group, the scar tissue had grown into the spinal canal and had exerted pressure on the dura. The test group was significantly better than the control group according to the Rydell degree of adhesion criteria. Table 3 Adhesion levels of surgical parts in the test and control groups Grade Groups (n)
0
1
2
3
Test* (9) Control (6)
7 0
2 0
0 1
0 5
* Compared with the control group (p!.01).
Fig. 8. Scanning electronic microscope images of the goat cervicals from the test group (Top) and the control group (Bottom). (Top) No obvious degradation and absorption of the artificial lamina occur, and no significant gap appeared between the artificial lamina and the natural bone. (Bottom) In the control group, the defect of the lamina was filled with disorder fibers (1,000).
These results suggest that the artificial lamina can effectively block epidural adhesion and oppression. We hypothesize that this is because the material’s physical properties are similar to that of human cortical bone in bending strength and compressive elastic modulus. In addition, we suggest that the implantation of a fixed artificial lamina can prevent scar penetration behind the spinal canal. Urist and McLean [17] presumed that the fibroblasts surrounding bone tissue proliferation grow into the bone defect faster than bone formation tissue and that bone formation and fiber formation competed against one another. After 24 weeks, the test group’s lamina defects were repaired, whereas the control group’s defects were filled with fibrous connective tissue and slight new bone formation. This shows that the MAACP/nHA composite material can be used as a mechanical barrier in preventing the fibroblast growth, guiding the slower osteoblast migration to the defect area and allowing for new bone formation. Osteoblasts appeared in the junction between the artificial laminae and autologous bone. No cracks were observed between these two when scrutinized with SEM under 1,000 magnification. Therefore, the material formed a strong bone bond with the autologous bone. These results suggest that HA crystals in the material can be adsorbed and activated
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Table 4 Motion range of the goat cervicals (mean6standard deviation) Groups
Flexion ( )
Extension ( )
Left lateral bending ( )
Right lateral bending ( )
Left axial rotation ( )
Right axial rotation ( )
Test Control Normal
5.3960.35 7.2160.41 5.3660.47
3.4160.25 4.4560.28 3.5460.34
3.6960.23 3.7160.24 3.7260.23
3.7060.26 3.6960.22 3.7460.25
3.2060.19 3.2460.21 3.2660.22
3.2160.22 3.2260.25 3.4960.28
osteoblasts can form bone apatite nuclei that support osteoconductivity and osteogenesis [18]. Computed tomography scanning after 24 weeks showed no significant difference in the sagittal diameter and spinal area of cervical 4 between the test group and the normal group with (pO.05). Therefore, the bony spinal canal had been successfully rebuilt. After 24 weeks, absorption and degradation of the material was not observed, allowing sufficient time for the lamina defect to undergo bone tissue repair and remodeling. Our results show that the final artificial material-autologous bone complexes form adequate lamina defects and that the mechanical properties of the lamina can be maintained for a long period of time. Therefore, the best functional and morphologic reconstruction was achieved. According to Miyamoto et al. [19], the cervical spinous process, the supraspinous ligament, and the interspinous ligament collectively form the posterior cervical ligamentous complex. Its main physiological function is to fight back stretch stress, also known as the ‘‘bow.’’ The complex also maintains cervical lordosis and cervical stability. Clinically, cervical back surgery tends to undermine the posterior cervical ligamentous complex that can lead to cervical kyphosis and instability and the appearance of neurologic symptoms [20]. The artificial lamina used in this study has good biocompatibility and might provide an attachment point for rear soft tissues that would help stabilize posterior column reconstruction. In this experiment, the artificial lamina may have helped the cervical ligamentous complex and contributed to cervical vertebrae stability within a certain motion range. Our results indicated that the control group had a greater motion range of flexion than the test or normal group (p!.01). In addition, the motion ranges in all directions were not significantly different between the test and the normal groups (pO.05, Table 4). This suggests that the cervical laminectomy destroyed flexion stability in the control group and that this stability was rescued by the artificial lamina. In the spinal research, the goat spine is frequently considered as a model for the human spine. One might presume that there are differences between an upright human spine and that of a quadruped, as their spines are supposedly subjected to loads that differ considerably from those in humans. However, neither experimental nor theoretical studies have found fundamental differences between the mechanical loading of quadruped and human spines. A previous analysis has demonstrated that considerable bending and torsion moments must be sustained by the horizontal trunk in a quadruped. Because of the low resistance of
the spine against such loads, these moments must be counterbalanced by tensile forces from muscles and/or ligaments and a compression force in the spine. Furthermore, the vertebral bone architecture analyzed showed that trabeculae run from end plate to end plate. This indicates that the main load in the quadruped spine is axial compression, which is similar to that of the human spine [21,22]. Kandziora et al. [23] biomechanically compared goat and human spines biomechanically by testing goat spines and comparing the data with previously published studies. Range of motion and stiffness data were comparable. The researchers concluded that if the goat model is used, motion segments C2–C3 and C3–C4 are the most suitable for biomechanical tests. Therefore, use of the goat model is suitable for the evaluation of implant systems and surgical procedures. The main purpose of our research was to evaluate the efficacy of a novel artificial lamina for the prevention of postlaminectomy adhesions during lamina reconstruction. Because there are no fundamental differences in adhesion formation between the cervical and the thoracic or lumbar spine, the lamina might also be effective in the thoracic or lumbar spine. Additionally, cervical back surgery tends to undermine the role of the posterior cervical ligamentous complex leading to cervical instability, and the artificial cervical lamina could provide attachment point for rear soft tissues and then help the stability of the posterior column reconstruction. Theoretically, the situation may be similar in the thoracic or lumbar spine. Further animal studies on the thoracic or lumbar spine are needed to confirm this hypothesis.
Conclusions The MAACP/nHA composite artificial lamina had excellent biomechanical properties that can effectively prevent epidural adhesions in goats. The artificial lamina also promoted effective bone tissue repair and new bone formation, and lamina reconstruction was successful in the test animals. Degradation of the composite material was slow, and biomechanical properties were maintained during this process.
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