Biomaterials Research (2013) 17(2) : 082-089 Biomaterials Research C The Korean Society for Biomaterials 자유형상제조기술을이용한조직재생용다공성생체세라믹스캐폴드제조기술 Solid Freeform Fabrication Techniques for Producing Porous Bioceramic Scaffolds for Tissue Regeneration 조인환 고영학 * In-Hwan Jo and Young-Hag Koh* 고려대학교일반대학원바이오융합공학과 Department of Bio-convergence Engineering, Korea University, Seoul, Korea (Received April 26, 2013/Acccepted May 8, 2013) The scaffolds with an open porous structure are one of the most important components for successful tissue regeneration, which can provide 3-dimensional space and biocompatible surfaces for favorable bone ingrowth. Fundamentally, the mechanical properties and biological functions of these porous scaffolds are strongly affected by their porous structure, such as porosity, pore size, interconnections between the pores. Thus, considerable effort has been made to develop new techniques for the production of porous scaffolds with a controlled porous structure, including sponge replication, freeze casting, direct foaming techniques, vacuum-assisted foaming of a ceramic suspension and solid freeform fabrications (SFFs). This paper reviews the operation principle and application of various state-of-the art SFFs, which can create porous scaffolds with an arbitrary geometry, as well as a tightly controlled porous structure. Key words: solid freeform fabrications (sffs), porous scaffolds, tissue regeneration, bioceramics 골 서론 및조직재생분야에서결손부위의회복을위해단순한구조의스캐폴드 (scaffold) 가생체재료에대한본격적인논의가시작되기전부터사용되어왔다. 초기스캐폴드의경우체내의주위조직과의반응을고려하지않았기때문에우수한생체적특성을기대하기어려웠다 1,2) 하지만, 최근조직공학및세포생물학적관점으로체내조직의회복및치료를목적으로식립되는재료에대한연구가활발히진행되고있다. 세포생물학적인접근즉식립부위의기능과형태를모두고려하여기계적특성 ( 강도 ) 과생물학적특성을만족하는다공성 3차원스캐폴드를제작하는연구가진행되었으며, 이를위한많은공정들이개발되었다. 3-7) 이러한노력을통해이상적인형태와기능을가지고체내에임시적 / 영구적으로식립되어조직의형태를지지하고기능을유지및수행할수있는적절한기계적특성, 나아가세포특성을포함하는우수한생물학적특성, 넓은표면적과혈액및조직에양분을공급하는체액 / 혈액의원활한순환을가능하게하는 3차원적으로연결된기공구조가있는다공성 3차원스캐폴드의제조및개발에대한훌륭한결과들이발표되고있다. 8,9) 따라서본논문에서는 3차원적으로연결된기공구조를갖는다 * 책임연락저자 : kohyh@korea.ac.kr 공성 3 차원스캐폴드에대한기계적, 화학적, 생물학적요구사항들을정리하고, 이를효과적으로제작하기위한컴퓨터기반의자유형상제조기술 (solid freeform fabrications; SFFs) 에대하여구체적으로기술할것이다. 또한, 저자의연구팀에서달성한최근의연구성과들을기반으로, 바이오세라믹 (bioceramics) 페이스트를이용한쾌속적층기술 (rapid direct deposition; RDD) 에대해부연설명하고자한다. 조직재생을위한 3 차원다공성스캐폴드의요구조건 현재의조직공학및치료를위한 3 차원다공성스캐폴드는체내에식립되어조직의형태를유지하고본연의기능을임시적 / 영구적으로대체하며, 해당조직이회복되는것을돕고재건을촉진하는복합적인기능이요구된다. 즉, 외력에의하여손상되거나파괴없이조직을지지하는기계적특성과식립부위주위조직에대한비 - 독성, 세포친화성, 면역반응없이조직과융합되는능력, 주위조직을괴사 / 변이시키지않는특성및세포나조직의회복을촉진하는생체친화성등의생물학적특성이필요하다. 10-12) 이러한생물학적특성을결정하는가장중요한요소는다공성 3 차원스캐폴드를이루는기반재료 ( 재료가갖는재료본연의특성및물성 ) 에큰영향을받는다. 더불어다 82
자유형상제조기술을이용한조직재생용다공성생체세라믹스캐폴드제조기술 83 공성 3 차원스캐폴드의기공구조및표면특성에도매우큰영향을받는다. 바람직한기공구조는체액 / 혈액의순환을위한통로가되며 ( 주로매크로 / 마이크로크기의기공 ) 작은크기의기공은 ( 마이크로 ~ 나노크기의기공 ) 세포의부착, 증식및분화를유도하는신호가된다. 13-18) 나아가다양한결손부를갖는각각의환자에대한맞춤형다공성 3 차원스캐폴드의제작에대한필요성이주목받고있다. 기계적 ( 물리학적 ) 요구사항다공성 3 차원스캐폴드는조직이회복되는기간동안체내에식립되어있다가회복후적출되거나, 생분해성이있는다공성 3 차원스캐폴드의경우조직의회복과함께분해되어흡수되게된다. 즉, 스캐폴드는조직이회복되기까지충분한물성을가지고체내에서존재하며회복과정중기계적자극이나충격에변형되지않고, 세포가성장해들어오는구조적기반이되어야한다. 만약적출등의 2 차수술을적용하지않기위하여생분해성다공성 3 차원스캐폴드를사용한다면생분해속도를조절하여원래조직이외력을충분히견딜수있는정도로회복되기까지다공성 3 차원스캐폴드가충분한물리적강도를유지하도록해야한다는연구결과가발표되었다. 19,20) Goulet, R. W. 그룹의발표에따르면 21) 자연경조직의경우 10-1500 Mpa 의강도를, 자연연조직의경우 0.4-350 MPa 의강도를갖고있으며, 22) 해면골의경우 13-42 MPa 의강도를갖는다. 23) 다공성및기공연결도다공성 3차원스캐폴드에존재하는다양한형태와크기의기공은형태나크기에따라각기다른반응을유도한다는연구결과들이발표되었다. Dorozhkin 그룹의발표에따르면, 1 µm 이하의기공은체내단백질단위에서반응하여생체친화성을보이며 1-20 µm 정도의기공구조는세포가인식하는이상적인표면상태로세포의이동이나세포의표면인식을촉진해세포의부착및분화에긍정적인결과를준다고하였다. 또한 100-1000 µm 크기의기공들은세포의성장및증식, 골질의회복을촉진하는기공의크기이며다공성 3차원스캐폴드의강도를결정하는주된요인으로발표하고있다. 24) 또한 3차원적으로연결된기공구조는혈액과세포의성장및조직의회복을위한양분을운반하는체액의원활한순환을위해필요한요소이다. 이에대하여연결된기공을통해혈관및신경들이자라바람직한조직의회복을이룰수있다는연구결과들이발표되었다. 19,25) 생물학적요구사항생물학적요구사항은다공성 3 차원스캐폴드와주위조직간의친화도및예후를결정하는지표이다. 조직의회복과치료를촉진시킬수있는스캐폴드의바람직한화학적특성 ( 골조직의경우칼슘과인의구성비혹은인산칼슘의침착을유도할수있는화학적인조성 ) 과세포의부착을유도하고보다활발한증식및분화를위한표면측성등이이에해당한다. 19,26) 즉다공성 3 차원스캐폴드의식립시, 제작단계에서사용되는유기용매나기타잔류독성물질이용출되거나, 스캐폴드자체가주위조직및체액과반응하여생성하는 2 차반응물질이독성을갖는경우바람직한생물학적특성을기대하기어렵다. 이에대하여 Healy 그룹은스캐폴드의제작단계에서부터처치과정, 체내식립후의반응까지고려하여다공성 3 차원스캐폴드를만들어야한다고발표하였다. 27) 환자 ( 결손부 ) 맞춤형다공성 3 차원스캐폴드디자인의필요성환자 ( 결손부 ) 맞춤형디자인의다공성 3 차원스캐폴드의제작은조직공학적스캐폴드의최종목적이다 (Figure 1). 이는조직결손이사례나환자마다형태, 정도, 상황등이모두다르며환자의전신상태도모두다르기때문이다. 28) 하지만전통적인스캐폴드제작방식의경우정형화된형태의틀을사용하는경우가많아제작할수있는형상이제한적이다. 그렇기때문에다양하고복잡한형상의다공성 3 차원스캐폴드의자유로운제작이어렵다는한계점이있다. 이러한한계점을극복하기위해많은연구팀들의연구와발표들이있어왔고나아가컴퓨터기반의자유형상제조기술 (SFFs) 방법이소개되었다. SFF 법에대해서는이후구체적으로서술하고있다. 다공성 3 차원스캐폴드제작을위한전통적방식 Table 1 은지금까지개발되고발표된전통적제작방법들과그장단점이다. 29) 다공성 3 차원스캐폴드제작을위한최신기술동향 골및조직재생분야에사용되는다공성 3 차원스캐폴드의최종목적인환자 ( 결손부 ) 맞춤형스캐폴드제작을위해복잡하고 Figure 1. Defect (patient) specific 3D porous scaffold. Vol. 17, No. 2
84 조인환 고영학 Table 1. Traditional technologies for fabricating 3D porous scaffolds Technology Benefits Drawbacks Fiber bonding 30,31) Phase separation 32,33) Solvent casting and particulate leaching 34-37) Membrane lamination 38) Melt moulding 39) Polymer/ceramic fiber composite-foam 40,41) High-pressure processing 42,43) High-pressure processing and particulate leaching 44) Freeze drying 45,46) Hydrocarbon templating 47) - Simple and easy method - Large surface area - Bioactive agentsincorporation - Porosity control (high) - Crystallinity control - Morphology control (Macro) - Morphology control (Macro) - Proper mechanical properoty - Toxic solvent free - Bioactive agentsincorporation - Toxic solvent free - High porosity - High porosity - Good pore interconnection - Various filament thickness - High temperature required - Limit of polymers selection - Poor mechanical property - Difficult of over micro-scale architecture fabrication - Difficult of over micro-scale architecture fabrication - Difficult of pore sizes control - Limited membrane thickness - Poor mechanical property - Poor mechanical property - Timeconsuming - Poorpore interconnection - High temperature required - Relatively dense surface - Poorpore interconnection - Poorpore interconnection - Poor mechanical property - Small pore sizes - Small pore sizes 다양한조직결손부위의형태를구현하고우수한생체활성도및조직회복능력을갖는스캐폴드를제작해야한다. 또한스캐폴드의구조 ( 기공도, 기공연결, 기공의형태등 ) 에대한정밀한제어가필요하다. 이를위하여종전의전통적공정의한계점을극복하고재현성, 정밀도및작업속도와경제성등의제작공정상의요구사항을만족하는컴퓨터제어기반방식의기술들이개발되고여러연구진들에의해제시되고있다. 이에본논문에서는다공성 3 차원스캐폴드제작을위한최신기술동향으로컴퓨터기반의자유형상제조기술을소개하고, 여러가지방식의기술들을제시하며각각의목적과원리에따라공정들을분류하였다. 또한저자의연구진의연구성과인바이오세라믹을기반으로한쾌속적층기술 (RDD) 을통해 3 차원적으로연결된기공구조를갖는이상적인다공성 3 차원스캐폴드를제시할것이다. 컴퓨터기반의자유형상제조기술 (Solid Freeform Fabrications; SFFs) 에대한소개컴퓨터기반의자유형상제조기술은복잡하고다양한 3 차원 적구조를구현하는기술로, 산업분야에서 CAD기술과함께먼저도입되었다. 48,49) Hutmacher 그룹을비롯하여많은연구팀들은조직공학분야, 결손조직의처치및치료를위한다공성 3차원스캐폴드제작에컴퓨터기반의자유형상제조기술을도입하여우수한스캐폴드를제작하고, 이를평가한결과를발표하였다. 50-53) 이러한연구결과들은복잡한형상에대한정밀하고우수한재현성을갖는 3차원형상구현능력과컴퓨터기반의디자인및양산성을위한자동화기술을포함하는컴퓨터제어기반공정을통해다양한변수들을손쉽게조작하여요구되는물성및다양한특성들을스캐폴드에반영할수있다는결론을도출한다. 아래에서소개할다양한공정및결손조직의처치및치료를위한다공성 3차원스캐폴드의제작을위한자유형상제조기반의기술들은층간적층방식을기본으로하고있으며, 금속분말이나세라믹, 고분자등을적층하여복잡하고다양하며형상이고도로제어되는다공성 3차원스캐폴드를제작하는데유연하게적용되고있다. 54,55) 이러한공정상의유연성은한가 Biomaterials Research 2013
자유형상제조기술을이용한조직재생용다공성생체세라믹스캐폴드제조기술 85 지기술뿐아니라복수의공정을융합하여이상적인 3 차원스캐폴드의제작을가능하게하는컴퓨터기반의자유형상제조기술의강점이다. 앞서언급한컴퓨터기반의자유형상제조기술의공정상의장점들과작업의유연성을기반으로제어된디자인을갖는다공성 3 차원스캐폴드는인체의뼈및장기등의연조직을포함하는조직의재생및처치에광범위하게적용되고있다. 56,57) 대표적인자유형상제조기술 Hollister 그룹과 Leong 그룹은그들의발표를통해대표적컴퓨터제어자유형상제조기술들을제시하고있다 (Stereolithography, 58-60) Selective laser sintering, 61,62) 3D printing, 63,64) Wax printing, 65) Bio-plotter, 66-68) Fused deposition modeling 69-72) 이에본논문에서는이와같은다양한 SFF 공정들을그들의구동원리 (driving principle) 를레이저를기반으로하는 laser base (L), 열을이용해재료를연화시킨후적층하는 Heat base (H), 화학물질이나화학적원리를이용하여형상을구현하는 chemical binder base (C), 특수한파장을조사하거나조건을형성하여고분자를중합하는 photo-polymerization base (P) 공정및노즐팁을사용하여압출하는 nozzle extrude base (N) 로분류하였다. 구체적으로, 레이저를기반으로하는공정의경우 (L), 레이저를조사하여대상이되는재료인금속이나세라믹을부분적으로녹여선택적부분소결방식으로 3차원형상을구현하는방식이다. 이의경우 3차원스캐폴드의최종특성은조사하는레이저의밀도, 강도및조사되는지점의크기등에강한영향을받는다. 열을이용해재료를연화시킨후적층하는 heat base (H) 공정의경우, 주로고분자물질이나왁스와같이열가소성이있는물질을연화시켜노즐이나압출등의공정과융합하여 3차원형상을구현하는방식이다. 이의경우적용되는온도와융합되는다른공정상의변수에의해 3차원스캐폴드의최종성질이결정된다. 또한, 화학적원리를이용하여형상을구현하는 chemical binder base (C) 공정은 3 차원형상 ( 형태 ) 유지를위하여고분자의중합이나석출등을화학적으로유도하여 3차원스캐폴드를제작하는기술로고분자를기반으로한물질에생체활성물질이나약물및세포등을포함시켜 3차원스캐폴드를제작하는용도로응용되고있다. 특수한광원이나파장등을이용해고분자를중합시키는원리를이용하는 photo-polymerization base (P) 공정은자외선 (UV light) 과같이고분자를중합시킬수있는파장을갖는광원을액상의고분자에조사해선택적으로중합시켜 3차원형상을구현하는원리이다. Nozzle extrude base (N) 의경우독립적으로사용되기보다는형상을구형하는과정에서열원에의해연화된열가소성고분자를압출하여성형하거나노즐을통해적층하여 3차원스캐폴드를제작하는공정이다. 이와같이컴퓨터기반의자유형상제조기술공정의경우복수의공정및원리들을유연하게결합하고응용하여원하는형상및성질을갖는 3차원스캐폴드를제작할수있다. 또한, 이를다시공정시스템인직접자유형상제조법 73,74) Figure 2. Computer controlled- based Solid Freeform Fabrications for fabricating 3D porous scaffolds. Table 2. Computer controlled- based Solid Freeform Fabrications for fabricating 3D porous scaffolds Technology Driving Principle System Materials Stereolithography L, P both (IS, DS) Polymer Selective laser sintering L DS Metal, Ceramic 3D printing C both (IS, DS) Polymer Wax printing H IS Wax Bio-plotter H, C DS Fused deposition modelling Rapid direct deposition* Materials with biofactors H both (IS, DS) Polymer H, C DS Metal, Ceramic, Polymer (Direct SFF- 자유형상제조공정을통해제작된다공성 3차원스캐폴드를별도의 2차공정없이소결하거나멸균하여스캐폴드로사용하는것 ) 과간접자유형상제조법 65,75) (Indirect SFF- 자유형상제조공정을통해제작된다공성 3차원스캐폴드를다시형틀로사용하여최종다공성 3차원스캐폴드를이루는원재료를주조성형하는등의 2차공정을거처최종적인 3차원형상을구현하는것 ) 으로항목화하여정리하였다 (Figure 2, Table 2). 이와더불어저자의연구진은쾌속적층기술 (RDD) 과화학적인원리를융합하여이용한공정을다공성 3차원스캐폴드제작공정으로제시하고있다. 공정의유연한융합이가능한컴퓨터기반의자유형상제조기술저자의연구팀의연구결과를포함하여 Kruth 그룹과 Chua 그룹등과같이컴퓨터기반의자유형상제조기술을응용하여 3 차원스캐폴드를제작하는연구결과들이발표되고있다. 54,55) 이러한연구결과및최신연구동향을살펴보면, 본논문에서앞서기술한컴퓨터기반의자유형상제조기술이갖는원리및공 Vol. 17, No. 2
86 조인환 고영학 정간의유연한융합을제시하고있다. 대표적인자유형상제조기술 에서구체적으로기술한 3 차원형상구현을위한공정들과원리들을목적에맞는성질을갖는 3 차원스캐폴드제작에유연하게융합하여적용할수있으며, 열에의해연화된열가소성고분자를노즐기반의압출을통해압출하여층간적층방식으로 3 차원형상을효과적으로구현할수있다. 바이오세라믹을기반으로한쾌속적층기술 (Rapid Direct Deposition: RDD) 앞서언급한것과같이컴퓨터기반의자유형상제조기술을적용하여제작한조직결손부위의처치나회복을위한목적으로사용되는다공성 3 차원스캐폴드는바람직한구조적인측면 ( 물성및기공구조 ) 와뛰어난생물학적특성을갖도록컴퓨터기반으로설계할수있으며여러가지공정을유연하게복합화하여복잡하고다양한형상을구현해낼수있다는장점을가지고있다. 더욱이이러한기술들의유연한융합은기존의전통적방식의공정또한포함한다. 나아가컴퓨터제어기반의자유형상제조기술을이용하여제작하는다공성 3 차원스캐폴드는이미기술한바와같이빠르고정확하며경제적이라는공정상의이점도충분히가지고있다. 이에본연구팀은경조직재건를위한다공성 3 차원스캐폴드의대표적인요구조건인기계적특성, 화학적조성에대한골질과의유사성, 우수한생체적특성과더불어환자 ( 결손부위 ) 맞춤형처지를위한다공성 3 차원스캐폴드디자인의유용성이라는목표를달성하고자바이오세라믹, 특히인산칼슘계세라믹을기반으로한쾌속적층기술 ( 노즐기반의 3 차원직접적층기술 ) 기술을개발하고컴퓨터제어기반기술을이용한다공성 3 차원스캐폴드제작에성공하였다. 인산칼슘계세라믹의적용세라믹분말을이용한직접적층기술은 Evans 그룹을비롯한연구진들에의해서연구되고있지만, 76) 세라믹분말을기반으로다공성 3차원스캐폴드를제작하는것에대하여공정및압출용페이스트제작의기술적한계로인해생체세라믹이갖는여러이점들에도불구하고다른공정들에비해활발한연구가진행되지못하고있다. Bose 그룹의발표에따르면, 인산칼슘계세라믹은우수한생체적특성과세라믹특유의우수한강도 ( 압축강도 ) 덕분에약물의전달을위한미세구형입자나골형성을돕는골충전용재료및다른스캐폴드의표면생체특성을증진시키기위한표면코팅등에적용되고있다. 77-82) 이러한적용예시들중에서본논문의주된논의대상인다공성 3차원스캐폴드로의적용에대한연구가많이진행되었다 ( 주로전통적방식으로의제작 ). 그이유는인산칼슘계세라믹이생체분해성 (bio-degradability) 을가지고있기때문이다. 나아가 Dorozhkin 그룹의인산칼슘계세라믹의칼슘과인성분의비율에따른생체세라믹의생체분해성및특성을정리하였다. 83) 이에저자의연구팀은 여러가지생체세라믹중선행된연구들을기반으로약 60 wt% 의수산화인회석 (hydroxyapatite; HA) 과 40 wt% 제삼인산칼슘 (tricalcium phosphate; TCP) 의혼합비율을갖는베타 - 제삼인산칼슘 (β-tricalcium phosphate) 를사용하여컴퓨터제어기반의쾌속적층기술에사용할수있는노즐기반의압출용페이스트를제작하는데성공하였다. 이로인해본연구팀에서제작된생체세라믹기반의스캐폴드는생체세라믹이갖는재료적장점 ( 생체적특성및골조직과의화학적유사성, 생체분해성및적합한기계적강도등 ) 을갖고, 앞서기술한컴퓨터제어기반의쾌속적층기술의공정상의이점들과구조적강점들을가지고있다. 쾌속적층기술의소개쾌속적층기술 (rapid direct deposition: RDD) 은기존의노즐방식에압출방식을융합한기술로층간적층을통해 3 차원적구조물을구현하는공정이다. 다양한노즐을통해다양한지름을갖는필라멘트를적층하여, 기본 90 도격자구조는물론컴퓨터제어를통해다양한각도편차를갖는격자구조를만들어낼수있으며 3 차원적으로연결된기공구조를갖는다는강력한장점을가지고있다. 또한압출방식에대해서공기의압력을통한압출이나물리적인힘을통한압출하는등의공정이있으며공기의압력을통한공압출법이대표적이다. 또한격자구조로 3 차원형상을구현하는과정에서의압출노즐의이동속도및이동양상 ( 다공성 3 차원스캐폴드의외형디자인구현을위한움직임 - 환자및결부맞춤형디자인가능 ) 은컴퓨터를통해제어되며빠른공정속도로정확하고정밀한작업이가능하다. 76,84) 쾌속적층기술을이용하여다공성 3 차원스캐폴드를제작하는공정의주요변수와그결과들은 Table 3 에정리하였다. 이와같이컴퓨터제어기반의쾌속적층기술은공정변수를제어하는간단한과정을통해복잡하고다양한형상과구조를갖는 3 차원스캐폴드를제작할수있다. 쾌속적층기술의경우앞서기술한바와같이층간적층방식을이용하므로적층시노즐의상승거리나속도등을제어하고압출의대상이되는물질의성질및조성, 적층시의온도나화학적인반응을유도할수있는기타환경등에대한제어가필요하다. 이를위하여저자의연구팀에서는컴퓨터기반의쾌속적층기술과노즐을통한압출을융합하고, 이를화학적인원리를이용하여압출하는과정에서 3 차원스캐폴드의구조가안정적으로유지되도록하였다. Table 3. Processing parameters for RDD technique for fabricating 3D porous scaffolds Parameters Dependent Variables Nozzle diameter Filament diameter Ari pressure Filament diameter Moving speed Working time, Filament diameter Starting materials Final property (Mechanical, chemical, biological) Paste composition Final property, Filament diameter Scaffold design Scaffold morphology Biomaterials Research 2013
자유형상제조기술을이용한조직재생용다공성생체세라믹스캐폴드제조기술 87 Table 4. Various 3-D porous scaffolds produced by RDD Scaffold Type Image 쾌속적층기술로제작된바이오세라믹 3 차원다공성스캐폴드본연구팀에서개발한생체세라믹기반의컴퓨터제어쾌속적층기술을통해제작할수있는다양한종류의다공성 3 차원스캐폴드를 Table 4 에제시하였다. 필라멘트지름을제어하여제작한다양한판형 (sheet) 스캐폴드, 3 차원적으로연결된기공구조를갖는육면체형상의다공성 3 차원스캐폴드및보다복잡한구조로구현된플러그형태의스캐폴드등의제작이모두가능하다. 또한앞서기술한바와같이필요에따라서다양한세라믹섬유의지름을선택적으로적용하고형태및구조까지컴퓨터기반의제어기술로 3 차원형상을구현할수있다. 또한본연구진에서확인한바에따르면 ( 이논문에서는제시하고있지않음 ) 생체세라믹이갖는본연의특성에의해, 제작된모든다공성 3 차원스캐폴드는유사체액 (SBF solution) 침적실험에서우수한인산칼슘석출능력을보이며, in vitro 세포부착실험결과를통해다공성 3 차원스캐폴드의우수한세포친화성및생체적합성을확인하였다. 결론 Filament ø (µm) Simple sheet (thin) > 200 Simple sheet (thick) > 500 Scaffold (cube) > 500 Scaffold (Plug) > 250 오래전부터조직공학및결손부위조직재생을위한스캐폴드에연구가진행되었고, 많은제작공정이제시되었고, 최근조직공학적으로더욱바람직한특성을부여하고이를개선, 발전시키려는시도가계속되고있다. 더욱이환자 ( 결손부위 ) 맞춤형치료를표두로하여 결손부위맞춤형의료용스캐폴드 의필요성이강조되어다양한상황에서다양한형태를갖는결손부위의기능과형태의회복까지모두고려하고조직재생을촉진시키는능력까지의료용스캐폴드의요구사항에포함되고있다. 바람직한구조적, 물리적, 생물학적, 화학적성질이요구가 그것이며, 스캐폴드생산을위한공정상의정밀성과편이성또한생체공학적스캐폴드제작에서중요한요구사항이되었다. 이러한요구사항을만족하는스캐폴드를제작하는다양한공정중가장진보된기술중하나인컴퓨터기반의자유형상제조기술은 3 차원적으로연결된기공구조를갖는다공성 3 차원스캐폴드를제작하는방법으로주목받고있으며생체용다공성 3 차원스캐폴드의여러가지요구사항과더불어공정상의이점까지갖추고있어정형화되어있는전통적방식의한계점들을극복하고있다. 또한계속되는연구로현재의한계점 ( 비용및경제적측면 ) 을극복한다면조직공학및치료의최종목표인 결손부위맞춤형의료용스캐폴드 의제작을보다완벽하고손쉽게이루어내고, 의료및의료기기시장의성장에이르기까지기대할수있을것으로예상된다. 이를위하여저자의연구팀에서는대표적생체재료인인산칼슘계열의세라믹분말을이용한페이스트의조성을개발하고이를기반으로하여컴퓨터제어쾌속적층기술을적용하여다양하고복잡한형태의다공성 3 차원스캐폴드제작에성공하였고, 계속해서연구를진행하고있다. 참고문헌 1. A. Sanan, and S. J. Haines, Repairing holes in the head: a history of cranioplasty, J.Neurosurg., 40, 588-603 (1997). 2. Langer, R. &Vacanti, and J. P. Tissue engineering, Science, 260, 920-926 (1993). 3. K. R. Cutroneo, Gene therapy for tissue regeneration, J. Cell Biochem., 88, 418-425 (2003). 4. J. Audet, Stem cell bioengineering for regenerative medicine, Expert Opin. Biol.Ther., 4, 631-644 (2004). 5. D. E. Ingber, Mechanical, chemical determinants of tissue development, Principles of tissue engineering, 2nd ed. San Diego: Academic Press, 101-110 (2000). 6. S. E. Haynesworth, D. Reuben, and A. I. Caplan, Cell-based tissue engineering therapies: the influence of whole body physiology, Adv. Drug Deliv. Rev., 33, 3-14 (1998). 7. J. Bonadio, Tissue engineering via local gene delivery, J. Mol. Med., 78, 303-311 (2000). 8. M. Martins-Green Dynamics of cell-ecm interactions, Principles of tissue engineering, 2nd ed. San Diego: Academic Press, 2000, pp. 33-56. 9. E. Bell, Tissue engineering in perspective, Principles of tissue engineering, 2nd ed. San Diego: Academic Press, (2000). 10. J. J. Klawitter, and S. F. Hulbert, Application of porous ceramics for theattachment of load bearing internal orthopedic applications, J Biomed Mater Res, 2, 161-168 (1971). 11. L. G. Cima, J. P. Vacanti, C. Vacanti, D. E Ingber, D. Mooney, and R. Langer, Tissue engineering by cell transplantation using degradablepolymer substrates, J Biomech Eng; 113, 143-51 (1991). 12. M. C. Wake, C. W. Patrick Jr, and A. G. Mikos, Pore morphology effectson the fibrovascular tissue growth in porous polymer substrates, Cell Transplant, 3, 339-343 (1994). 13. D. J. Mooney, L. G. Cima, R. Langer, L. Johnson, L. K. Hansen, D. E. Ingber, and J. P. Vacanti, Principles of tissue engineering and reconstructionusing polymer-cell constructs. Mater Res SocSympProc, 252-345 (1992). 14. C. S. Chen, M. Mrksich, S. Huang, G. M. Whitesides, and D. E. Ingber, Geometric control of cell life and death, Science, 276, Vol. 17, No. 2
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