支架材料层叠的有限元计算分析论证
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摘要
背景:组织工程软骨修复结果的不确定性与修复区的力学行为有关,缺损修复的形状、层深及载荷特性均会不同程度地改变修复区的力学环境,因此可通过对上述参数的研究探索人工软骨合适的力学性能指标。目的:采用有限元方法分析支架材料修复形状及堆叠方式对修复区力学行为的影响。方法:采用MRI-3D打印丝素蛋白/胶原蛋白复合支架,将支架分别裁剪为圆形与矩形,每种形状分别以垂直堆叠与倾斜堆叠形成三维实体,利用ANSYS12.0、Solid95单元进行建模、网格划分,对材料顶部施加10 kPa的均匀载荷(Z=10 mm),分析材料的位移、应力与应变分布。结果与结论:①圆形和矩形材料的垂直堆叠具有整体规则形状,X轴和Y轴具有严格的对称性;倾斜堆叠的圆形和矩形材料呈不规则形状,只能满足X轴对称性,Y和Z具有阶梯特性;②在相同荷载条件下与垂直堆叠相比,倾斜堆叠材料的轴向位移更明显,不利于骨组织生长修复;③圆形和矩形材料垂直堆叠时,模型内部的应变分布比较均匀,具有严格的轴对称性,且只有底部边缘或角点有小面积的由应力集中导致的大应变(应力)区域;圆形和矩形材料倾斜堆叠时,由于形状和载荷的不对称性导致局部应变呈不均匀、阶梯状分布,且存在较大面积的大应变(应力)区域;④结果说明,圆形材料垂直堆叠更有利于骨组织的修复。
BACKGROUND: The uncertainty of repairing results of tissue-engineered cartilage is related to the mechanical behavior of repairing area. The shape, depth and load characteristics of repairing defects will change the mechanical environment of repairing area in varying degrees. Therefore, the appropriate mechanical properties of artificial cartilage can be explored by studying the above parameters.OBJECTIVE: To analyze the effect of the shape and stacking method of the scaffold material on the mechanical behavior of the repairing area by finite element method.METHODS: MRI-3D printed silk fibroin/collagen composite scaffolds were used. These scaffolds were cut into circular and rectangular products. Each shape of products were stacked vertically and obliquely to form a three-dimensional entity. ANSYS12.0 and Solid95 units were used for modeling and mesh generation. 10 kPa load(Z=10 mm) was uniformly added to the top of the material. The displacement, stress,and strain distribution of the material were analyzed.RESULTS AND CONCLUSION: Vertical stacking of circular and rectangular products had regular shapes, with strict symmetry of X and Y axis. Oblique stacking of circular and rectangular products had irregular shapes, which can only meet the symmetry of the X axis, and Y and Z axes had characteristics of ladder. Compared with the vertical stacking, the axial displacement of obliquely stacked products was more obvious, which did not facilitate bone tissue ingrowth. Vertical stacking of circular and rectangular products led to uniform stress distribution,with strict axial symmetry. There was a small area of large strain(stress) region caused by stress concentration in the bottom edge or corner.When circular and rectangular products were obliquely stacked, asymmetries in shape and loads led to nonuniform and ladder-shaped local stress, and there was a large area of strain(stress) region. These results suggest that circular product is preferable over rectangular product,and vertical stacking is conductive to repairing bone tissue compared with oblique stacking.
BACKGROUND: The uncertainty of repairing results of tissue-engineered cartilage is related to the mechanical behavior of repairing area. The shape, depth and load characteristics of repairing defects will change the mechanical environment of repairing area in varying degrees. Therefore, the appropriate mechanical properties of artificial cartilage can be explored by studying the above parameters.OBJECTIVE: To analyze the effect of the shape and stacking method of the scaffold material on the mechanical behavior of the repairing area by finite element method.METHODS: MRI-3D printed silk fibroin/collagen composite scaffolds were used. These scaffolds were cut into circular and rectangular products. Each shape of products were stacked vertically and obliquely to form a three-dimensional entity. ANSYS12.0 and Solid95 units were used for modeling and mesh generation. 10 kPa load(Z=10 mm) was uniformly added to the top of the material. The displacement, stress,and strain distribution of the material were analyzed.RESULTS AND CONCLUSION: Vertical stacking of circular and rectangular products had regular shapes, with strict symmetry of X and Y axis. Oblique stacking of circular and rectangular products had irregular shapes, which can only meet the symmetry of the X axis, and Y and Z axes had characteristics of ladder. Compared with the vertical stacking, the axial displacement of obliquely stacked products was more obvious, which did not facilitate bone tissue ingrowth. Vertical stacking of circular and rectangular products led to uniform stress distribution,with strict axial symmetry. There was a small area of large strain(stress) region caused by stress concentration in the bottom edge or corner.When circular and rectangular products were obliquely stacked, asymmetries in shape and loads led to nonuniform and ladder-shaped local stress, and there was a large area of strain(stress) region. These results suggest that circular product is preferable over rectangular product,and vertical stacking is conductive to repairing bone tissue compared with oblique stacking.
引文
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[2]孙凯,年争好,徐成,等.丝素蛋白复合胶原蛋白支架的制备及性能研究[J].中国修复重建外科杂志, 2014,28(7):903-908.
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[8] Fenn SL, Oldinski RA.Visible light crosslinking of methacrylated hyaluronan hydrogels for injectable tissue repair.J Biomed Mater Res B Appl Biomater. 2016;104(6):1229-1236.
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[12] Reyes R, Delgado A, Solis R,et al.Cartilage repair by local delivery of transforming growth factor-β1 or bone morphogenetic protein-2 from a novel, segmented polyurethane/polylacticco-glycolic bilayered scaffold.J Biomed Mater Res A.2014;102(4):1110-1120.
[13] Paul A,Manoharan V,Krafft D,et al.Nanoengineered biomimetic hydrogels for guiding human stem cell osteogenesis in three dimensional microenvironments.J Mater Chem B. 2016;4(20):3544-3554.
[14] Kotecha M,Klatt D,Magin RL.Monitoring cartilage tissue engineering using magnetic resonance spectroscopy, imaging,and elastography.Tissue Eng Part B Rev.2013(19):470-484.
[15] Aroni MAT,Spolidório LC,Andersen OZ,et al.Loading deproteinized bovine bone with strontium enhances bone regeneration in rat calvarial critical size defects.Clin Oral Investig.2018. doi:10.1007/s00784-018-2588-6.[Epub ahead of print]
[16] Zheng G,Qiu G,Ge M,et al.Human adipose-derived mesenchymal stem cells alleviate obliterative bronchiolitis in a murine model via IDO.Respir Res.2017;18(1):119.
[17] Trohatou O,Roubelakis MG. Mesenchymal stem/stromal cells in regenerative medicine:past,present,and future.Cell Reprogram.2017;19(4):217-224.
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[19] Holt BD,Wright ZM,Arnold AM,et al. Graphene oxide as a scaffold for bone regeneration.Wiley Interdiscip Rev Nanomed Nanobiotechnol.2017;9(3):e1437.
[20] Wang K,Xu J,Cai J,et al. Serum levels of resistin and interleukin-17 are associated with increased cartilage defects and bone marrow lesions in patients with knee osteoarthritis.Mod Rheumatol. 2017;27(2):339-344.
[21] Li F,Yao J,Tian H,et al.Correlations between traditional chinese medicine syndromes and IL-1,MMP and TIMP-1 in knee osteoarthritis.Int J Clin Exp Med. 2017;10(10):14660-14666.
[22] Duro-Castano A,Lim NH,Tranchant I,et al.In vivo imaging of MMP-13 activity using a specific polymer-FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy.Adv Funct Mater.2018:1802738.
[23]李乐,寇久社.三种质量浓度医用臭氧局部注射对兔膝OA行为学及滑膜匀浆中IL-1?TNF-α水平的影响[J].解放军预防医学杂志,2018,36(1):77-79.
[24] Yamasaki K,Nakasa T,Miyaki S,et al.Expression of micro RNA-146a in osteoarthritis cartilage. Arthritis Rheum.2009;60(4):1035-1041.
[25] Jones KJ,Sheppard WL,Arshi A,et al. Articular cartilage lesion characteristic reporting is highly variable in clinical outcomes studies of the knee. Cartilage. 2018:1947603518756464.doi:10.1177/1947603518756464.[Epub ahead of print].
[26] Zhang X,Wu S,Naccarato T,et al. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.PLo S One.2017;12(6):e0180138.
[27] Sasaki T,Akagi R,Akatsu Y,et al.The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism:G-CSF for cartilage repair.Bone Joint Res.2017;6(3):123-131.
[28] Chang YH,Liu HW,Wu KC,et al.Mesenchymal stem cells and their clinical applications in osteoarthritis.Cell Transplant.2016;25:937-950.
[29] Yoshimura H,Muneta T,Nimura A,et al.Comparison of rat mesenchymal stem cells derived from bone marrow,synovium,periosteum,adipose tissue,and muscle.Cell Tissue Res.2007;327(3):449-462.
[30] Tao SC,Yuan T,Zhang YL,et al.Exosomes derived from mi R-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics. 2017;7(1):180-195.
[31] Zhang S,Chuah SJ,Lai RC,et al.MSC exosomes mediate cartilage repair by enhancing proliferation,attenuating apoptosis and modulating immune reactivity. Biomaterials.2017;156:16-27.
[32] Toh WS,Lai RC,Hui JHP,et al.MSC exosome as a cell-free MSC therapy for cartilage regeneration:implications for osteoarthritis treatment.Semin Cell Dev Biol.2017;67:56-64.
[33] Yubo M,Yanyan L,Li L,et al.Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment:A meta-analysis.PLo S One.2017;12(4):e0175449.
[34] Paek HJ,Kim C,Tuan RS. Stem cell-based repair and regeneration of articular cartilage. J Stem Cell Res Ther.2017;2(6):177-182.
[2]孙凯,年争好,徐成,等.丝素蛋白复合胶原蛋白支架的制备及性能研究[J].中国修复重建外科杂志, 2014,28(7):903-908.
[3] Curl WW,Krome J,Gordon ES,et al.Cartilage injuries:A review of 31, 516 knee arthroscopies. Arthroscopy. 1997;13(4):456-460.
[4] Sun K,Li R,Jiang W,et al.Comparison of three-dimensional printing and vacuum freeze-dried techniques for fabricating composite scaffolds.Biochem Biophys Res Commun. 2016;477(4):1085-1091.
[5] Sun K,Li R,Li H,et al.Comparison of three-dimensional printing for fabricating silk fibroin-blended scaffolds.Int J Polym Mater Polym Biomater.2018;8(67):480-486.
[6] Chen YN,Peng L,Liu T,et al.Poly(vinyl alcohol)-Tannic Acid Hydrogels with Excellent Mechanical Properties and Shape Memory Behaviors.ACS Appl Mater Interfaces. 2016;8(40):27199-27206.
[7] Sheu SY,Chen WS,Sun JS,et al.Biological characterization of oxidized hyaluronic acid/resveratrol hydrogel for cartilage tissue engineering.J Biomed Mater Res A. 2013;101(12):3457-3466.
[8] Fenn SL, Oldinski RA.Visible light crosslinking of methacrylated hyaluronan hydrogels for injectable tissue repair.J Biomed Mater Res B Appl Biomater. 2016;104(6):1229-1236.
[9] Zhou Y,Liang K,Zhao S,et al.Photopolymerized maleilated chitosan/methacrylated silk fibroin micro/nanocomposite hydrogels as potential scaffolds for cartilage tissue engineering.Int J Biol Macromol. 2018;108:383-390.
[10]年争好,李晖,李瑞欣,等.纳米羟基磷灰石/胶原蛋白/丝素蛋白复合骨组织工程支架材料的生物相容性[J].中国组织工程研究,2015,19(8):1149-1154.
[11]年争好,孙凯,徐成,等.大鼠BMSCs成骨诱导及复合支架材料构建组织工程骨组织的研究[J].生物骨科材料与临床研究, 2015,12(1):1-5.
[12] Reyes R, Delgado A, Solis R,et al.Cartilage repair by local delivery of transforming growth factor-β1 or bone morphogenetic protein-2 from a novel, segmented polyurethane/polylacticco-glycolic bilayered scaffold.J Biomed Mater Res A.2014;102(4):1110-1120.
[13] Paul A,Manoharan V,Krafft D,et al.Nanoengineered biomimetic hydrogels for guiding human stem cell osteogenesis in three dimensional microenvironments.J Mater Chem B. 2016;4(20):3544-3554.
[14] Kotecha M,Klatt D,Magin RL.Monitoring cartilage tissue engineering using magnetic resonance spectroscopy, imaging,and elastography.Tissue Eng Part B Rev.2013(19):470-484.
[15] Aroni MAT,Spolidório LC,Andersen OZ,et al.Loading deproteinized bovine bone with strontium enhances bone regeneration in rat calvarial critical size defects.Clin Oral Investig.2018. doi:10.1007/s00784-018-2588-6.[Epub ahead of print]
[16] Zheng G,Qiu G,Ge M,et al.Human adipose-derived mesenchymal stem cells alleviate obliterative bronchiolitis in a murine model via IDO.Respir Res.2017;18(1):119.
[17] Trohatou O,Roubelakis MG. Mesenchymal stem/stromal cells in regenerative medicine:past,present,and future.Cell Reprogram.2017;19(4):217-224.
[18] Shimomura K,Ando W,Moriguchi Y,et al. Next generation mesenchymal stem cell(MSC)-based cartilage repair using scaffold-free tissue engineered constructs generated with synovial mesenchymal stem cells.Cartilage.2015;6(2 Suppl):13-29.
[19] Holt BD,Wright ZM,Arnold AM,et al. Graphene oxide as a scaffold for bone regeneration.Wiley Interdiscip Rev Nanomed Nanobiotechnol.2017;9(3):e1437.
[20] Wang K,Xu J,Cai J,et al. Serum levels of resistin and interleukin-17 are associated with increased cartilage defects and bone marrow lesions in patients with knee osteoarthritis.Mod Rheumatol. 2017;27(2):339-344.
[21] Li F,Yao J,Tian H,et al.Correlations between traditional chinese medicine syndromes and IL-1,MMP and TIMP-1 in knee osteoarthritis.Int J Clin Exp Med. 2017;10(10):14660-14666.
[22] Duro-Castano A,Lim NH,Tranchant I,et al.In vivo imaging of MMP-13 activity using a specific polymer-FRET peptide conjugate detects early osteoarthritis and inhibitor efficacy.Adv Funct Mater.2018:1802738.
[23]李乐,寇久社.三种质量浓度医用臭氧局部注射对兔膝OA行为学及滑膜匀浆中IL-1?TNF-α水平的影响[J].解放军预防医学杂志,2018,36(1):77-79.
[24] Yamasaki K,Nakasa T,Miyaki S,et al.Expression of micro RNA-146a in osteoarthritis cartilage. Arthritis Rheum.2009;60(4):1035-1041.
[25] Jones KJ,Sheppard WL,Arshi A,et al. Articular cartilage lesion characteristic reporting is highly variable in clinical outcomes studies of the knee. Cartilage. 2018:1947603518756464.doi:10.1177/1947603518756464.[Epub ahead of print].
[26] Zhang X,Wu S,Naccarato T,et al. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.PLo S One.2017;12(6):e0180138.
[27] Sasaki T,Akagi R,Akatsu Y,et al.The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism:G-CSF for cartilage repair.Bone Joint Res.2017;6(3):123-131.
[28] Chang YH,Liu HW,Wu KC,et al.Mesenchymal stem cells and their clinical applications in osteoarthritis.Cell Transplant.2016;25:937-950.
[29] Yoshimura H,Muneta T,Nimura A,et al.Comparison of rat mesenchymal stem cells derived from bone marrow,synovium,periosteum,adipose tissue,and muscle.Cell Tissue Res.2007;327(3):449-462.
[30] Tao SC,Yuan T,Zhang YL,et al.Exosomes derived from mi R-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics. 2017;7(1):180-195.
[31] Zhang S,Chuah SJ,Lai RC,et al.MSC exosomes mediate cartilage repair by enhancing proliferation,attenuating apoptosis and modulating immune reactivity. Biomaterials.2017;156:16-27.
[32] Toh WS,Lai RC,Hui JHP,et al.MSC exosome as a cell-free MSC therapy for cartilage regeneration:implications for osteoarthritis treatment.Semin Cell Dev Biol.2017;67:56-64.
[33] Yubo M,Yanyan L,Li L,et al.Clinical efficacy and safety of mesenchymal stem cell transplantation for osteoarthritis treatment:A meta-analysis.PLo S One.2017;12(4):e0175449.
[34] Paek HJ,Kim C,Tuan RS. Stem cell-based repair and regeneration of articular cartilage. J Stem Cell Res Ther.2017;2(6):177-182.