新型蜂巢样聚己内酯-硅酸钙复合晶体材料修复颅骨极限缺损
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摘要
背景:聚己内酯作为高分子材料的生物相容性较差,需将其与其他天然生物材料复合增加生物相容性,促进机体组织再生。目的:观察新型蜂巢样聚己内酯-硅酸钙复合晶体材料在SD大鼠颅骨缺损中的成骨修复作用。方法:取18只SD大鼠,制作颅骨极限缺损模型,随机分3组干预,空白组不植入任何材料,对照组植入普通聚己内酯-硅酸钙复合晶体材料,实验组植入新型蜂巢样聚己内酯-硅酸钙复合晶体材料。植入6周后,进行骨缺损处X射线扫描、Micro-CT三维重建及组织学分析。结果与结论:(1)X射线扫描:3组大鼠颅骨缺损变小,骨折线模糊,边缘骨密度增高,实验组、对照组新生骨面积百分比明显大于空白组,且实验组新生骨面积百分比大于对照组;(2)Micro-CT三维重建:空白组新生骨主要分布在缺损两侧,对照组、实验组新生骨分布于整个颅骨骨缺损处;与空白组比较,实验组、对照组均表现出更强的再生骨能力(P<0.05),且以实验组成骨能力最强(P<0.05);(3)组织学分析:3组均可见骨缺损处有不同程度新生骨长入,实验组新生骨组织及新生血管密度明显高于对照组、空白组(P<0.05);(4)结果表明:新型蜂巢样聚己内酯-硅酸钙复合晶体材料在颅骨缺损生物环境中具有明显的促成骨作用。
BACKGROUND: Polycaprolactone as a polymer material has poor biocompatibility, and needs to be combined with other natural biological materials to increase biocompatibility, thereby promoting tissue regeneration. OBJECTIVE: To develop a novel honeycomb-like polycaprolactone-calcium silicate crystal compound scaffold, and observe its osteogenic effects in Sprague-Dawley rats with skull defects.METHODS: Eighteen Sprague-Dawley rats were used to make skull defect models and randomized into three groups: blank control group with no implantation, control group with implantation of normal polycaprolactone-calcium silicate crystal compound scaffold, and experimental group with implantation of the novel honeycomb-like polycaprolactonecalcium silicate crystal compound scaffold. Six weeks after implantation, bone regeneration effect in the defect region measured via X-ray scanning, Micro-CT three-dimensional reconstruction, and histological analysis. RESULTS AND CONCLUSION:(1) X-ray scan: in all the rats, the size of bone defect was reduced, the fracture line became vague, and the marginal bone density was increased. The percentage of new bone area was highest in the experimental group, successively followed by the control group and blank control group.(2) Micro-CT three-dimensional reconstruction: new bones in the blank control group were mainly distributed on the both sides of the defect, but those in the control and experimental groups distributed in the defect region. The bone regeneration capacity was ranked as follows: experimental group > control group > blank control group(P < 0.05).(3) Histological analysis: new bone ingrowth was visible in all the three groups to different extents. Compared with the other two groups, new bone formation and microvessel density were significantly higher in the experimental group(P < 0.05). To conclude, this novel honeycomb-like polycaprolactone-calcium silicate crystal compound scaffold can obviously promote bone formation in the skull defect region.
BACKGROUND: Polycaprolactone as a polymer material has poor biocompatibility, and needs to be combined with other natural biological materials to increase biocompatibility, thereby promoting tissue regeneration. OBJECTIVE: To develop a novel honeycomb-like polycaprolactone-calcium silicate crystal compound scaffold, and observe its osteogenic effects in Sprague-Dawley rats with skull defects.METHODS: Eighteen Sprague-Dawley rats were used to make skull defect models and randomized into three groups: blank control group with no implantation, control group with implantation of normal polycaprolactone-calcium silicate crystal compound scaffold, and experimental group with implantation of the novel honeycomb-like polycaprolactonecalcium silicate crystal compound scaffold. Six weeks after implantation, bone regeneration effect in the defect region measured via X-ray scanning, Micro-CT three-dimensional reconstruction, and histological analysis. RESULTS AND CONCLUSION:(1) X-ray scan: in all the rats, the size of bone defect was reduced, the fracture line became vague, and the marginal bone density was increased. The percentage of new bone area was highest in the experimental group, successively followed by the control group and blank control group.(2) Micro-CT three-dimensional reconstruction: new bones in the blank control group were mainly distributed on the both sides of the defect, but those in the control and experimental groups distributed in the defect region. The bone regeneration capacity was ranked as follows: experimental group > control group > blank control group(P < 0.05).(3) Histological analysis: new bone ingrowth was visible in all the three groups to different extents. Compared with the other two groups, new bone formation and microvessel density were significantly higher in the experimental group(P < 0.05). To conclude, this novel honeycomb-like polycaprolactone-calcium silicate crystal compound scaffold can obviously promote bone formation in the skull defect region.
引文
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[25]Ni S,Chang J,Chou L.A novel bioactive porous Ca Si O3scaffold for bone tissue engineering.J Biomed Mater Res A.2006;76(1):196-205.
[26]Bohner M,Gbureck U,Barralet JE.Technological issues for the development of more efficient calcium phosphate bone cements:A critical assessment.Biomaterials.2005;26(33):6423-6429.
[27]Chow LC.Next generation calcium phosphate-based biomaterials.Dent Mater J.2009;28(1):1-10.
[28]Ginebra MP,Espanol M,Montufar EB,et al.New processing approaches in calcium phosphate cements and their applications in regenerative medicine.Acta Biomaterialia.2010;6(8):2863-2873.
[29]Dash TK,Konkimalla VB.Poly-?-caprolactone based formulations for drug delivery and tissue engineering:A review.J Control Release.2012;158(1):15-33.
[30]Labet M,Thielemans W.Synthesis of polycaprolactone:a review.Chem Soc Revi.2009;38(12):3484.
[31]Kim J,Mc Bride S,Donovan A,et al.Tyrosine-derived polycarbonate scaffolds for bone regeneration in a rabbit radius critical-size defect model.Biomed Mater.2015;10(3):035001.
[32]Sears NA,Seshadri DR,Dhavalikar PS,et al.A Review of Three-Dimensional Printing in Tissue Engineering.Tissue Eng Part B Rev.2016;22(4):298-310.
[33]Black CM,Goriainov V,Gibbs D,et al.Bone Tissue Engineering.Curr Mol Biol Rep.2015;1(3):132-140.
[34]Amini AR,Laurencin CT,Nukavarapu SP.Bone tissue engineering:recent advances and challenges.Crit Rev Biomed Eng.2012;40(5):363-408.
[35]Zhao L,Burguera EF,Xu HH,et al.Fatigue and human umbilical cord stem cell seeding characteristics of calcium phosphate–chitosan–biodegradable fiber scaffolds.Biomaterials.2010;31(5):840-847.
[36]Khan AF,Saleem M,Afzal A,et al.Bioactive behavior of silicon substituted calcium phosphate based bioceramics for bone regeneration.Mater Sci Eng C Mater Biol Appl.2014;35:245-252.
[37]Vila M,García A,Girotti A,et al.3D silicon doped hydroxyapatite scaffolds decorated with Elastin-like Recombinamers for bone regenerative medicine.Acta Biomater.2016;45:349-356.
[38]Avolio E,Alvino VV,Ghorbel MT,et al.Perivascular cells and tissue engineering:Current applications and untapped potential.Pharmacol Ther.2017;171:83-92.
[2]Dorozhkin SV.Bioceramics of calcium orthophosphates.Biomaterials.2010;31(7):1465-1485.
[3]DoblaréM,Garc?a JM,Gómez MJ.Modelling bone tissue fracture and healing:a review.Eng Fract Mech.2004;71(13-14):1809-1840.
[4]Tatara AM,Mikos AG.Tissue Engineering in Orthopaedics.J Bone Joint Surg.2016;98(13):1132-1139.
[5]Jeon OH,Elisseeff J.Orthopedic tissue regeneration:cells,scaffolds,and small molecules.Drug Deliv Transl Res.2016;6(2):105-120.
[6]Bastami F,Nazeman P,Moslemi H,et al.Induced pluripotent stem cells as a new getaway for bone tissue engineering:A systematic review.Cell Prolif.2017;50(2).doi:10.1111/cpr.12321.Epub 2016 Dec 1.
[7]Kimelman N,Pelled G,Helm GA,et al.Review:Gene-and Stem Cell–Based Therapeutics for Bone Regeneration and Repair.Tissue Eng.2007;13(6):1135-1150.
[8]Discher DE,Mooney DJ,Zandstra PW.Growth factors,matrices,and forces combine and control stem cells.Science.2009;324(5935):1673-1677.
[9]Burg KJ,Porter S,Kellam JF.Biomaterial developments for bone tissue engineering.Biomaterials.2000;21(23):2347-2359.
[10]Bose S,Roy M,Bandyopadhyay A.Recent advances in bone tissue engineering scaffolds.Trends Biotechnol.2012;30(10):546-554.
[11]Ma PX.Biomimetic materials for tissue engineering.Adv Drug Deliv Rev.2008;60(2):184-198.
[12]Fernandez-Yague MA,Abbah SA,Mc Namara L,et al.Biomimetic approaches in bone tissue engineering:Integrating biological and physicomechanical strategies.Adv Drug Deliv Rev.2015;84:1-29.
[13]Henstock JR,Canham LT,Anderson SI.Silicon:The evolution of its use in biomaterials.Acta Biomaterialia.2015;11:17-26.
[14]Liu W,Zhang J,Rethore G,et al.A novel injectable,cohesive and toughened Si-HPMC(silanized-hydroxypropyl methylcellulose)composite calcium phosphate cement for bone substitution.Acta Biomaterialia.2014;10(7):3335-3345.
[15]Lin K,Liu Y,Huang H,et al.Degradation and silicon excretion of the calcium silicate bioactive ceramics during bone regeneration using rabbit femur defect model.J Mater Sci Mater Med.2015;26(6):197.
[16]Khan AF,Saleem M,Afzal A,et al.Bioactive behavior of silicon substituted calcium phosphate based bioceramics for bone regeneration.Mater Sci Eng C Mater Biol Appl.2014;35:245-252.
[17]Shadjou N,Hasanzadeh M.Silica-based mesoporous nanobiomaterials as promoter of bone regeneration process.J Biomed Mater Res A.2015;103(11):3703.
[18]Alfotawei R,Naudi KB,Lappin D,et al.The use of Tri Calcium Phosphate(TCP)and stem cells for the regeneration of osteoperiosteal critical-size mandibular bony defects,an in vitro and preclinical study.J Craniomaxillofac Surg.2014;42(6):863-869.
[19]Samavedi S,Whittington AR,Goldstein AS.Calcium phosphate ceramics in bone tissue engineering:A review of properties and their influence on cell behavior.Acta Biomaterialia.2013;9(9):8037-8045.
[20]Choo T,Marino V,Bartold PM.Effect of PDGF-BB and beta-tricalcium phosphate(β-TCP)on bone formation around dental implants:a pilot study in sheep.Clin Oral Implants Res.2013;24(2):158-166.
[21]Fujihara K,Kotaki M,Ramakrishna S.Guided bone regeneration membrane made of polycaprolactone/calcium carbonate composite nano-fibers.Biomaterials.2005;26(19):4139-4147.
[22]Causa F,Netti PA,Ambrosio L,et al.Poly-epsilon-caprolactone/hydroxyapatite composites for bone regeneration:in vitro characterization and human osteoblast response.J Biomed Mater Res A.2006;76(1):151-162.
[23]Yeo MG,Kim GH.Preparation and Characterization of 3D Composite Scaffolds Based on Rapid-Prototyped PCL/β-TCP Struts and Electrospun PCL Coated with Collagen and HA for Bone Regeneration.Chem Mater.2012;24(5):903-913.
[24]Wu C.Methods of improving mechanical and biomedical properties of Ca-Si-based ceramics and scaffolds.Expert Rev Med Devices.2009;6(3):237-241.
[25]Ni S,Chang J,Chou L.A novel bioactive porous Ca Si O3scaffold for bone tissue engineering.J Biomed Mater Res A.2006;76(1):196-205.
[26]Bohner M,Gbureck U,Barralet JE.Technological issues for the development of more efficient calcium phosphate bone cements:A critical assessment.Biomaterials.2005;26(33):6423-6429.
[27]Chow LC.Next generation calcium phosphate-based biomaterials.Dent Mater J.2009;28(1):1-10.
[28]Ginebra MP,Espanol M,Montufar EB,et al.New processing approaches in calcium phosphate cements and their applications in regenerative medicine.Acta Biomaterialia.2010;6(8):2863-2873.
[29]Dash TK,Konkimalla VB.Poly-?-caprolactone based formulations for drug delivery and tissue engineering:A review.J Control Release.2012;158(1):15-33.
[30]Labet M,Thielemans W.Synthesis of polycaprolactone:a review.Chem Soc Revi.2009;38(12):3484.
[31]Kim J,Mc Bride S,Donovan A,et al.Tyrosine-derived polycarbonate scaffolds for bone regeneration in a rabbit radius critical-size defect model.Biomed Mater.2015;10(3):035001.
[32]Sears NA,Seshadri DR,Dhavalikar PS,et al.A Review of Three-Dimensional Printing in Tissue Engineering.Tissue Eng Part B Rev.2016;22(4):298-310.
[33]Black CM,Goriainov V,Gibbs D,et al.Bone Tissue Engineering.Curr Mol Biol Rep.2015;1(3):132-140.
[34]Amini AR,Laurencin CT,Nukavarapu SP.Bone tissue engineering:recent advances and challenges.Crit Rev Biomed Eng.2012;40(5):363-408.
[35]Zhao L,Burguera EF,Xu HH,et al.Fatigue and human umbilical cord stem cell seeding characteristics of calcium phosphate–chitosan–biodegradable fiber scaffolds.Biomaterials.2010;31(5):840-847.
[36]Khan AF,Saleem M,Afzal A,et al.Bioactive behavior of silicon substituted calcium phosphate based bioceramics for bone regeneration.Mater Sci Eng C Mater Biol Appl.2014;35:245-252.
[37]Vila M,García A,Girotti A,et al.3D silicon doped hydroxyapatite scaffolds decorated with Elastin-like Recombinamers for bone regenerative medicine.Acta Biomater.2016;45:349-356.
[38]Avolio E,Alvino VV,Ghorbel MT,et al.Perivascular cells and tissue engineering:Current applications and untapped potential.Pharmacol Ther.2017;171:83-92.