再生医学之组织工程耳廓软骨再生与功能重建
|
摘要
<正>对于人类来说,耳廓收集声波的功能意义远低于其外观价值,因此,耳廓外形或位置的任何异常都是难以接受的。耳廓组织缺损的常见原因包括四类:先天畸形、炎症、外伤或手术(医源性)。支撑耳廓外形的软骨属于弹力软骨,维持着耳廓独特的外形与功能,相对于软骨表面的皮肤组织,软骨再生能力弱,而且来源有限,因此耳廓缺损重建的重点在于如何恢复其弹性软骨支架。另外,与其他部位的软骨修复不同,耳廓软骨重建不仅要考虑其功能,而且对外观的要求更高。传统的耳廓重建方
Deformity of the auricle can result from congenital defects, oncologic resection, or traumatic injury. Current clinical strategy is to utilize autologous costal cartilage for reconstructing auricular scaffolds with long-term stability. However, this method is limited by donor-site morbidity, a complex surgical sculpting process, and differing mechanical properties compared to elastic auricular cartilage. Alternatively, alloplastic implants can offer precise shape and avoid donor-site surgery, but suffer from poor biocompatibility and high rates of infection and extrusion. A tissue engineering approach to auricular reconstructions would overcome the limitations of both autologous and alloplastic transplants. In this review we focus on tissue engineering auricular cartilage reconstruction, including auricular seed cells culture and their differentiated control strategy, scaffolds choices and design technique. Many studies found that auricular chondrocytes were the most suitable seed cells to fabricate elastic cartilage; progenitor cells from auricular cartilage could differentiate into elastic chondrocytes, and other types of chondrocytes had its limitation because of the final ossification. Many types of growth factors had the differing potential ability for accelerating chondrocytes growth, differentiation, or maintaining chondrocytes phenotype. Recent advances in tissue engineering auricular cartilage, including several clinic applications, implied that tissue engineering auricules would become a hopefully potential soulution for the future of auricular reconstruction.
Deformity of the auricle can result from congenital defects, oncologic resection, or traumatic injury. Current clinical strategy is to utilize autologous costal cartilage for reconstructing auricular scaffolds with long-term stability. However, this method is limited by donor-site morbidity, a complex surgical sculpting process, and differing mechanical properties compared to elastic auricular cartilage. Alternatively, alloplastic implants can offer precise shape and avoid donor-site surgery, but suffer from poor biocompatibility and high rates of infection and extrusion. A tissue engineering approach to auricular reconstructions would overcome the limitations of both autologous and alloplastic transplants. In this review we focus on tissue engineering auricular cartilage reconstruction, including auricular seed cells culture and their differentiated control strategy, scaffolds choices and design technique. Many studies found that auricular chondrocytes were the most suitable seed cells to fabricate elastic cartilage; progenitor cells from auricular cartilage could differentiate into elastic chondrocytes, and other types of chondrocytes had its limitation because of the final ossification. Many types of growth factors had the differing potential ability for accelerating chondrocytes growth, differentiation, or maintaining chondrocytes phenotype. Recent advances in tissue engineering auricular cartilage, including several clinic applications, implied that tissue engineering auricules would become a hopefully potential soulution for the future of auricular reconstruction.
引文
[1] CAO Y,VACANTI J P,PAIGE K T,et al.Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear[J].Plast Reconstr Surg,1997,100:297-302.
[2] REIFFEL A J,KAFKA C,HERNANDEZ K A,et al.High-fidelity tissue engineering of patient-specific auricles for reconstruction of pediatric microtia and other auricular deformities[J].PLoS One,2013,8:e56506.
[3] NIMESKERN L,VAN OSCH G J,MüLLER R,et al.Quantitative evaluation of mechanical properties in tissue-engineered auricular cartilage[J].Tissue Eng Part B Rev,2014,20:17-27.
[4] KAMIL S H,VACANTI M P,AMINUDDIN B S,et al.Tissue engineering of a human sized and shaped auricle using a mold[J].Laryngoscope,2004,114:867-870.
[5] 李雪盛,孙建军.组织工程学技术在耳科的研究进展[J].山东大学耳鼻喉眼学报,2009,23(3):30-33.
[6] NAYYER L,PATEL K H,ESMAEILI A,et al.Tissue engineering:revolution and challenge in auricular cartilage reconstruction[J].Plast Reconstr Surg,2012,129:1123-1137.
[7] INGBER D E.Mechanical control of tissue growth:function follows form[J].Proc Natl Acad Sci USA,2005,102:11571-11572.
[8] GUILLOTIN B,GUILLEMOT F.Cell patterning technologies for organotypic tissue fabrication[J].Trends Biotechnol,2011,29:183-190.
[9] 康宁,刘霞,曹谊林,等.猪耳廓及关节来源软骨细胞构建组织工程软骨的实验研究[J].中华整形外科杂志,2014,30(1):33-40.
[10] HE A,XIA H,XIAO K,et al.Cell yield,chondrogenic potential,and regenerated cartilage type of chondrocytes derived from ear,nasoseptal,and costal cartilage[J].J Tissue Eng Regen Med,2018,12:1123-1132.
[11] ISOGAI N,KUSUHARA H,IKADA Y,et al.Comparison of different chondrocytes for use in tissue engineering of cartilage model structures[J].Tissue Eng,2006,12:691-703.
[12] KUSUHARA H,ISOGAI N,ENJO M,et al.Tissue engineering a model for the human ear:assessment of size,shape,morphology,and gene expression following seeding of different chondrocytes[J].Wound Repair Regen,2009,17:136-146.
[13] BERNSTEIN J L,COHEN B P,LIN A,et al.Tissue Engineering Auricular Cartilage Using Late Passage Human Auricular Chondrocytes[J].Ann Plast Surg,2018,80:S168-S173.
[14] MELGAREJO-RAMíREZ Y,SáNCHEZ-SáNCHEZ R,GARCíA-LóPEZ J,et al.Characterization of pediatric microtia cartilage:a reservoir of chondrocytes for auricular reconstruction using tissue engineering strategies[J].Cell Tissue Bank,2016,17:481-489.
[15] ISHAK M F,SEE G B,HUI C K,et al.The formation of human auricular cartilage from microtic tissue:An in vivo study[J].Int J Pediatr Otorhinolaryngol,2015,79:1634-1639.
[16] HUSELSTEIN C,LI Y,HE X.Mesenchymal stem cells for cartilage engineering[J].Biomed Mater Eng,2012,22:69-80.
[17] TAN A R,HUNG C T.Concise Review:Mesenchymal Stem Cells for Functional Cartilage Tissue Engineering:Taking Cues from Chondrocyte-Based Constructs[J].Stem Cells Transl Med,2017,6:1295-1303.
[18] MORRISON K A,COHEN B P,ASANBE O,et al.Optimizing cell sourcing for clinical translation of tissue engineered ears[J].Biofabrication,2016,9:015004.
[19] ZHAO X,HWANG N S,BICHARA D A,et al.Chondrogenesis by bone marrow-derived mesenchymal stem cells grown in chondrocyte-conditioned medium for auricular reconstruction[J].J Tissue Eng Regen Med,2017,11:2763-2773.
[20] CAI Z,PAN B,JIANG H,et al.Chondrogenesis of Human Adipose-Derived Stem Cells by In Vivo Co-graft with Auricular Chondrocytes from Microtia[J].Aesthetic Plast Surg,2015,39:431-439.
[21] DOWTHWAITE G P,BISHOP J C,REDMAN S N,et al.The surface of articular cartilage contains a progenitor cell population[J].J Cell Sci,2004,117:889-897.
[22] OTTO I A,LEVATO R,WEBB W R,et al.Progenitor cells in auricular cartilage demonstrate cartilage-forming capacity in 3D hydrogel culture[J].Eur Cell Mater,2018,35:132-150.
[23] XUE K,ZHANG X,QI L,et al.Isolation,identification,and comparison of cartilage stem progenitor/cells from auricular cartilage and perichondrium[J].Am J Transl Res,2016,8:732-741.
[24] DERKS M,STURM T,HAVERICH A,et al.Isolation and chondrogenic differentiation of porcine perichondrial progenitor cells for the purpose of cartilage tissue engineering[J].Cells Tissues Organs,2013,198:179-189.
[25] ROSA R G,JOAZEIRO P P,BIANCO J,et al.Growth factor stimulation improves the structure and properites of scaffold-free engineered aruicular cartilage constructs[J].PLoS One,2014,9:e105170.
[26] LIU X,LIU J,KANG N,et al.Role of insulin-transferrin-selenium in auricular chondrocyte proliferation and engineered cartilage formation in vitro[J].Int J Mol Sci,2014,15:1525-1537.
[27] YANAGA H,IMAI K,YANAGA K.Cell-engineered human elastic chondrocytes regenerate natural scaffold in vitro and neocartilage with neoperichondrium in the human body post-transplantation[J].Tissue Eng Part A,2012,18:2020-2029.
[28] SHASTI M,JACQUET R,MCCLELLAN P,et al.Effects of FGF-2 and OP-1 in vitro on donor source cartilage for auricular reconstruction tissue engineering[J].Int J Pediatr Otorhinolaryngol,2014,78:416-422.
[29] NASRABADI D,REZAEIANI S,ESLAMINEJAD M B,et al.Improved protocol for chondrogenic differentiation of bone marrow derived mesenchymal stem cells-effect of PTHrP and FGF-2 on TGFβ1/BMP2-induced chondrocytes hypertrophy[J].Stem Cell Rev,2018,14:755-766.
[30] COHEN B P,HOOPER R C,PUETZER J L,et al.Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered,Patient-Specific Auricles In Vivo[J].Tissue Eng Part A,2016,22:461-468.
[31] VISSCHER D O,GLEADALL A,BUSKERMOLEN J K,et al.Design and fabrication of a hybrid alginate hydrogel/poly(ε-caprolactone)mold for auricular cartilage reconstruction[J].J Biomed Mater Res B Appl Biomater,2018,[Epub ahead of print]
[32] POMERANTSEVA I,BICHARA D A,TSENG A,et al.Ear-Shaped Stable Auricular Cartilage Engineered from Extensively Expanded Chondrocytes in an Immunocompetent Experimental Animal Model[J].Tissue Eng Part A,2016,22:197-207.
[33] HAISCH A.Ear reconstruction through tissue engineering[J].Adv Otorhinolaryngol,2010,68:108-119.
[34] ZHOU G,JIANG H,YIN Z,et al.In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction[J].EbioMedicine,2018,28:287-302.
[35] ZOPF D A,FLANAGAN C L,MITSAK A G,et al.Pore architecture effects on chondrogenic potential of patient-specific 3-dimensionally printed porous tissue bioscaffolds for auricular tissue engineering[J].Int J Pediatr Otorhinolaryngol,2018,114:170-174.
[36] PARK J Y,CHOI Y J,SHIM J H,et al.Development of a 3D cell printed structure as an alternative to autologs cartilage for auricular reconstruction[J].J Biomed Mater Res B Appl Biomater,2017,105:1016-1028.
[37] YANAGA H,IMAI K,FUJIMOTO T,et al.Generating ears from cultured autologous auricular chondrocytes by using two-stage implantation in treatment of microtia[J].Plast Reconstr Surg,2009,124:817-825.
[2] REIFFEL A J,KAFKA C,HERNANDEZ K A,et al.High-fidelity tissue engineering of patient-specific auricles for reconstruction of pediatric microtia and other auricular deformities[J].PLoS One,2013,8:e56506.
[3] NIMESKERN L,VAN OSCH G J,MüLLER R,et al.Quantitative evaluation of mechanical properties in tissue-engineered auricular cartilage[J].Tissue Eng Part B Rev,2014,20:17-27.
[4] KAMIL S H,VACANTI M P,AMINUDDIN B S,et al.Tissue engineering of a human sized and shaped auricle using a mold[J].Laryngoscope,2004,114:867-870.
[5] 李雪盛,孙建军.组织工程学技术在耳科的研究进展[J].山东大学耳鼻喉眼学报,2009,23(3):30-33.
[6] NAYYER L,PATEL K H,ESMAEILI A,et al.Tissue engineering:revolution and challenge in auricular cartilage reconstruction[J].Plast Reconstr Surg,2012,129:1123-1137.
[7] INGBER D E.Mechanical control of tissue growth:function follows form[J].Proc Natl Acad Sci USA,2005,102:11571-11572.
[8] GUILLOTIN B,GUILLEMOT F.Cell patterning technologies for organotypic tissue fabrication[J].Trends Biotechnol,2011,29:183-190.
[9] 康宁,刘霞,曹谊林,等.猪耳廓及关节来源软骨细胞构建组织工程软骨的实验研究[J].中华整形外科杂志,2014,30(1):33-40.
[10] HE A,XIA H,XIAO K,et al.Cell yield,chondrogenic potential,and regenerated cartilage type of chondrocytes derived from ear,nasoseptal,and costal cartilage[J].J Tissue Eng Regen Med,2018,12:1123-1132.
[11] ISOGAI N,KUSUHARA H,IKADA Y,et al.Comparison of different chondrocytes for use in tissue engineering of cartilage model structures[J].Tissue Eng,2006,12:691-703.
[12] KUSUHARA H,ISOGAI N,ENJO M,et al.Tissue engineering a model for the human ear:assessment of size,shape,morphology,and gene expression following seeding of different chondrocytes[J].Wound Repair Regen,2009,17:136-146.
[13] BERNSTEIN J L,COHEN B P,LIN A,et al.Tissue Engineering Auricular Cartilage Using Late Passage Human Auricular Chondrocytes[J].Ann Plast Surg,2018,80:S168-S173.
[14] MELGAREJO-RAMíREZ Y,SáNCHEZ-SáNCHEZ R,GARCíA-LóPEZ J,et al.Characterization of pediatric microtia cartilage:a reservoir of chondrocytes for auricular reconstruction using tissue engineering strategies[J].Cell Tissue Bank,2016,17:481-489.
[15] ISHAK M F,SEE G B,HUI C K,et al.The formation of human auricular cartilage from microtic tissue:An in vivo study[J].Int J Pediatr Otorhinolaryngol,2015,79:1634-1639.
[16] HUSELSTEIN C,LI Y,HE X.Mesenchymal stem cells for cartilage engineering[J].Biomed Mater Eng,2012,22:69-80.
[17] TAN A R,HUNG C T.Concise Review:Mesenchymal Stem Cells for Functional Cartilage Tissue Engineering:Taking Cues from Chondrocyte-Based Constructs[J].Stem Cells Transl Med,2017,6:1295-1303.
[18] MORRISON K A,COHEN B P,ASANBE O,et al.Optimizing cell sourcing for clinical translation of tissue engineered ears[J].Biofabrication,2016,9:015004.
[19] ZHAO X,HWANG N S,BICHARA D A,et al.Chondrogenesis by bone marrow-derived mesenchymal stem cells grown in chondrocyte-conditioned medium for auricular reconstruction[J].J Tissue Eng Regen Med,2017,11:2763-2773.
[20] CAI Z,PAN B,JIANG H,et al.Chondrogenesis of Human Adipose-Derived Stem Cells by In Vivo Co-graft with Auricular Chondrocytes from Microtia[J].Aesthetic Plast Surg,2015,39:431-439.
[21] DOWTHWAITE G P,BISHOP J C,REDMAN S N,et al.The surface of articular cartilage contains a progenitor cell population[J].J Cell Sci,2004,117:889-897.
[22] OTTO I A,LEVATO R,WEBB W R,et al.Progenitor cells in auricular cartilage demonstrate cartilage-forming capacity in 3D hydrogel culture[J].Eur Cell Mater,2018,35:132-150.
[23] XUE K,ZHANG X,QI L,et al.Isolation,identification,and comparison of cartilage stem progenitor/cells from auricular cartilage and perichondrium[J].Am J Transl Res,2016,8:732-741.
[24] DERKS M,STURM T,HAVERICH A,et al.Isolation and chondrogenic differentiation of porcine perichondrial progenitor cells for the purpose of cartilage tissue engineering[J].Cells Tissues Organs,2013,198:179-189.
[25] ROSA R G,JOAZEIRO P P,BIANCO J,et al.Growth factor stimulation improves the structure and properites of scaffold-free engineered aruicular cartilage constructs[J].PLoS One,2014,9:e105170.
[26] LIU X,LIU J,KANG N,et al.Role of insulin-transferrin-selenium in auricular chondrocyte proliferation and engineered cartilage formation in vitro[J].Int J Mol Sci,2014,15:1525-1537.
[27] YANAGA H,IMAI K,YANAGA K.Cell-engineered human elastic chondrocytes regenerate natural scaffold in vitro and neocartilage with neoperichondrium in the human body post-transplantation[J].Tissue Eng Part A,2012,18:2020-2029.
[28] SHASTI M,JACQUET R,MCCLELLAN P,et al.Effects of FGF-2 and OP-1 in vitro on donor source cartilage for auricular reconstruction tissue engineering[J].Int J Pediatr Otorhinolaryngol,2014,78:416-422.
[29] NASRABADI D,REZAEIANI S,ESLAMINEJAD M B,et al.Improved protocol for chondrogenic differentiation of bone marrow derived mesenchymal stem cells-effect of PTHrP and FGF-2 on TGFβ1/BMP2-induced chondrocytes hypertrophy[J].Stem Cell Rev,2018,14:755-766.
[30] COHEN B P,HOOPER R C,PUETZER J L,et al.Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered,Patient-Specific Auricles In Vivo[J].Tissue Eng Part A,2016,22:461-468.
[31] VISSCHER D O,GLEADALL A,BUSKERMOLEN J K,et al.Design and fabrication of a hybrid alginate hydrogel/poly(ε-caprolactone)mold for auricular cartilage reconstruction[J].J Biomed Mater Res B Appl Biomater,2018,[Epub ahead of print]
[32] POMERANTSEVA I,BICHARA D A,TSENG A,et al.Ear-Shaped Stable Auricular Cartilage Engineered from Extensively Expanded Chondrocytes in an Immunocompetent Experimental Animal Model[J].Tissue Eng Part A,2016,22:197-207.
[33] HAISCH A.Ear reconstruction through tissue engineering[J].Adv Otorhinolaryngol,2010,68:108-119.
[34] ZHOU G,JIANG H,YIN Z,et al.In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction[J].EbioMedicine,2018,28:287-302.
[35] ZOPF D A,FLANAGAN C L,MITSAK A G,et al.Pore architecture effects on chondrogenic potential of patient-specific 3-dimensionally printed porous tissue bioscaffolds for auricular tissue engineering[J].Int J Pediatr Otorhinolaryngol,2018,114:170-174.
[36] PARK J Y,CHOI Y J,SHIM J H,et al.Development of a 3D cell printed structure as an alternative to autologs cartilage for auricular reconstruction[J].J Biomed Mater Res B Appl Biomater,2017,105:1016-1028.
[37] YANAGA H,IMAI K,FUJIMOTO T,et al.Generating ears from cultured autologous auricular chondrocytes by using two-stage implantation in treatment of microtia[J].Plast Reconstr Surg,2009,124:817-825.