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1 Bimaterials Research (2007) 11(4) : <Review> Bimaterials Research 7 The Krean Sciety fr Bimaterials œw w w š ³ Sterilizatin f Bidegradable Plymer Scafflds fr Tissue Engineering ½x 1,2 Á 3 Á 1,2 * Hye-Lee Kim 1,2, Seung Jin Lee 3, and Jng-Chul Park 1,2 * 1 BK 21 fš, 2 Š fš fšš, 3 fœfš ŠŠ 1 Brain Krea 21 Prject fr Medical Science, Ynsei University Cllege f Medicine, Seul , Krea 2 Department f Medical Engineering, Ynsei University Cllege f Medicine, Seul , Krea 3 Cllege f Pharmacy, Ewha Wmans University, Seul , Krea (Received Nvember 9, 2007/Accepted Nvember 20, 2007) It is necessary t sterilize all medical implants after fabricatin and prir t their surgical placement t reduce the risk f infectins and assciated cmplicatin. Bidegradable plymers are susceptible f misture and heat. Als, the sterilizatin techniques by EO gas, gamma irradiatin r plasma treatment can significantly affect the mechanical and physical prperties f the scafflds made f plyglyclide acid(pga), plylactide acid(pla) r plylactide-c-glyclide acid(plga). Sterilizatin techniques especially change the bidegradatin rate f the scafflds. The changes f the mechanical and physical prperties f the scafflds cause them t fail in viv. Therefre, it is necessary t develp new sterilizatin standards, which d nt change the special character f bidegradable scafflds. Kye wrds: Sterilizatin, bidegraded plymer, Ethylene xide, Gamma irradiatin, Plasma treatment Œjf f dœ Œf lš fš ff f g f lš. hf tilf eš f Š f l. t ilf eš eš ~ff g fš tg fil g fdš e e Š f f. gf lf hš f Š f f Œff lš f ~ff g fš f d vi~ 1). fil g fdš tilf eš f Š lhf fl f fil gf d lš hf. fh e f d Š fœšf fdš e eš llt (scaffld) e Š. Š fœš llt e g Š t r llt hvš Šd. Š, Š fœšf l } Œf hff Š, ŒŠhh lf d d *sfhf: parkjc@yuhs.ac ihš f ghf f 2). g f Š fœšf g heef lhf lš f f ff 3), f d f eš f f f. Š fœš j plyglyclide acid(pga), plylactide acid(pla)f t h f if, ff Š e ŒŠŠ plylactidec-glyclide acid(plga)f ef ihšjf t Š ihš f. ff fdš 2,4,5) 2,6,7), Œ 2,8,9) f tš eš lš f. t h tg hiš lltf Š Š. fd fhf,, f fdš Š 10), ff fdš f ghf Table 1 ~. g fhf d f l(steam sterilizatin)f l fdš ˆf Š Š. f f ˆ f fš hš ff, f l f tlz f f g hf f 10). f fdš Š x fœšf PLA, PGA, PLGA hiš llt lf sš, lltf Œ dš ~ 13,14)., (dry heat sterilizatin)f 160~180 C fdš Š fœšf df fi Š ff fœ 151

김혜리 이승진 박종철 152 Standard sterilizatin techniques and applicatin Sterilizatin technique(temperature) Advantages Simplicity Steam sterilizatin (100-135 C) N txic residues Nn-aqueus system Dry heat

2 김혜리 이승진 박종철 152 Standard sterilizatin techniques and applicatin Sterilizatin technique(temperature) Advantages Simplicity Steam sterilizatin ( C) N txic residues Nn-aqueus system Dry heat sterilizatin ( C) N txic residues Lw temperature Ethylene xide gas (38-60 C) Cmpatibility with varius materials High penetratin Gamma irradiatin (-) Lw chemical reactivity 10-12) Table 1. Disadvantages Degradatin f plymer and sme ceramic Melting and sftening f plymer Txic residues React with sme funcinal grups 합물에 대한 멸균방법으로 적합하지 않다. 그러므로 최종 적으로 요구되는 형태와 분자구조를 갖는 지지체를 얻기 위해 서는 재료와 형상에 알맞은 멸균법을 선택하는 것이 중요하다. 본고에서는 고열을 사용하지 않는 ethylene xide(eo) gas 멸 균법과 감마선(gamma irradiatin) 멸균법이 PLA, PGA, PLGA로 제조한 지지체에 미치는 영향에 대하여 상세히 기술 하고자 한다. 또한, 새로운 멸균법 중 열과 화학약품을 사용하 지 않는 플라스마(plasma) 멸균법 이 지지체에 미치는 영향 에 대해서도 기술하고자 한다. 10,15) 16,17) EO gas 멸균법 EO gas 멸균법은 고열과 물을 사용하지 않기 때문에 고압증 기멸균법만큼 광범위하게 사용된다. 피멸균품에 있는 미생물의 물과 유기산, 아미노산, 아민 등이 EO gas와 반응하여 사멸하 여 멸균하는 방법으로 광범위한 미생물을 사멸시킬 수 있다. EO gas의 효율을 높이기 위하여 멸균기 내부의 습도는 25~ 50%로 유지한다. EO gas 침투력에 의해 멸균력이 정해지므로 피멸균품의 형상에 따라서 멸균의 효율이 변하며, 세균포자에 대해서는 침투력이 떨어져서 살균력이 약하다. 또한, 피멸균품 의 표면에 침투한 EO gas가 흡착이 되면 멸균 후 제품에서 세포독성을 보이기도 한다. EO gas로 멸균 후 PLA와 PGA, PLGA 지지체의 분자량 (mlecular weight)과 총 부피가 감소한다는 보고가 있다. PLA와 PGA의 화학구조는 Figure 1에서 보이는 바와 같이 카 르복시기를 갖고 있는데, 카르복시기가 EO gas와 화학반응 을 하여 변형되어서 지지체의 분자량과 총 부피가 감소하는 것 으로 판단된다. 이러한 분자량과 분자구조의 변화는 고분 10,18) Crss-linking/breakage f plymer chains 자화합물의 생체내 분해도에 영향을 미치지만, EO gas 멸균 한 지지체의 생체내 분해도는 멸균전과 큰 차이를 보이지 않 았다. EO gas 멸균을 하는 동안 PLA의 결정성이 향상되어 PLA 지지체의 탄성계수는 EO gas 멸균 전 600 kn/m에서 멸균 후 613 kn/m으로 증가하였고, PLGA 지지체에서도 유사한 경향을 보일 것으로 예상된다. Micrparticle PLGA를 EO gas 멸균하면 Figure 2와 같이 particles의 형상이 무너지 고 서로 뭉치는 형상을 보이는데, 이러한 현상은 멸균하는 온도에 의한 영향이 아니라 위에서 언급한 화학반응에 의한 영 향으로 판단된다. 따라서 나노섬유나 다공성으로 이뤄진 PLA 와 PGA, PLGA지지체를 EO gas로 멸균하면 나노섬유나 기공 의 형태가 없어지고 서로 뭉쳐져서 원하는 형상을 얻을 수 없 을 것으로 예상된다. 그러므로 EO gas로 멸균하면 PLA와 PGA, PLGA지지체의 생체내 분해도는 유지할 수 있지만 원하 는 형태의 지지체를 얻기는 어려운 것으로 판단된다. 22) 21) 23) 21) 24) 감마선(Gamma Irradiatin) 멸균법 최근 감마선 멸균법은 열과 화학약품을 사용하지 않고 멸균 할 수 있어서 점차적으로 사용도가 증가하고 있다. 감마선 멸 균법은 주로 C 방사성 동위원소에서 나오는 감마선을 피멸 60 19) 20) 19,21) Figure 1. Structural frmulae f plylactic acid and plygluclic acid. Bimaterials Research 2007 Surface mrphlgy f PLGA micrparticles (a), (c) nn-sterilized and (b), (d) EO treated. Figure 2. 25)

3 ilšf eš Š f lltf 153 Figure 3. Prpsed mechanism f gamma radilysis f plylactide-cglyclid acid. ˆ f ~f ~ f. f f dš v Švl h ~ ff, ˆf Œ~ g } f l fš Š f. f ~ g } Š f x f d f fœšf f f l fš ŒŠŠf h f 10,25,26). f PLA PGA, PLGA hiš lltf ff Š 19,27,28), lltf f Šl 19). PLGA llt ff 54% Š EO gas Š llt ff 4.5 } Šl, EO gas Š llt 50% Š Š Š llt h jl f. Šl lltf ff } Š lltf t Š Š lš 21). fš PLA PGA, PLGAf ŒŠŠf Figure 3 eš hf Š lltf ff Š f 29). llt Œf Œ f Š 27), Š f fdš Š Œ f Œf hš f. f PLA PGA, PLGA llt Š lltf Œ~ el Š fl, ŒŠŠf ff Š t Š ihš hhf Š f. v(plasma) ³ f hf Figure 4 ~. t, h Šj Œ fš, vš Œ h Š UV irradiatin fš f. v Œ phtdesrptin fš llt, f llt f f f f f 16,29-31). lf f x t f UV irradiatinf Š f f f Figure 4. Schematic illustratin f the three-phase survival curve characterizing plasma sterilizatin, shwing the mechanisms predminantly acting during each phase. l 16,32). f f Šl lf Š ff, f x f 0.01~0.1 mmf d lltf háœšh ƒf Œ ~l. Š, f Š f gš hš ff, lltf Œf ~ hf f ff ~ f 29,32-35). f Š Š vš fll f hœœ f. f l Š ˆ Š vš f fll f ff f l f f f Š f ˆf Œ~ f. Š, x f ~f ŠdŠ ~f Š v f 32). f fdš PLA, PGA, PLGA llt Š f všl. d Œf PLA llt f sšf, lltf f h, h ƒf f Šl lltf f fš 36). eœ~f PLGA llt f sš lltf ff h Šl EO gas } Š. PLGAlltf t Š f Šl 21). PLAf llt Œf PLGA llt e f Šf v lltf hf rf ff f. h v Œf llt e Œ ll t ff Œ h f. Š, h t f i rf f l lt Š f rf fš f f. Vl. 11, N. 4

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( )-103.fm Jurnal f the Krean Ceramic Sciety Vl. 46, N. 6, pp. 643~647, 2009. DOI:10.4191/KCERS.2009.46.6.643 Densificatin Behavir f C/C Cmpsite Derived frm Cal Tar Pitch with Small Amunt f Idine Additin Kwang Yun