대한화상학회지제 17 권제 2 호 73 Journal of Korean Burn Society Vol. 17, No. 2, 73-80, 2014 화상치료에서동종유래배양세포이식과젖산융합체합성창상치료제적용의비교 김대현ㆍ김경식ㆍ최준ㆍ김승홍 명지병원성형외과 Comparison of Cultured Keratinocyte Allograft versus Alloplastic Material in Management of Burn Injury Dae-Hyun Kim, M.D., Kyung-Sik Kim, M.D., Ph.D., Jun Choi, M.D., Ph.D. and Seung-Hong Kim, M.D., Ph.D. Department of Plastic & Reconstructive Surgery, Myong-Ji Hospital, Goyang, Korea Purpose: In the past days, the majority of 2nd degree burns were treated conservatively, and deep 2nd degree burns were usually covered by skin grafts. However, conservative treatment spends a long time in complete healing and accompanies severe pain and discomfort. Additionally, covering the wound with skin graft causes recipient site scarring and donor site morbidity. Since keratinocyte graft was introduced, nowadays it is widely used in burn wound. These treatment methods are proved to be clinically successful by many clinical and experimental studies. However, there are several disadvantages such as inconvenient using methods and limited usage in several cases. For that reason, at 2004, alloplastic material was first introduced to come over these problems of keratinocyte graft. There had been no precious reports comparing theses two methods, so we planned to focus on differences of two methods in our institute. Methods: From March 2013 to september 2014, among the 47 patients with burn wound (2nd degree - partial 3rd degree) underwent biologic dressing with cultured keratinocyte allograft (Kaloderm (Tegoscience, Korea)) alloplastic material (Suprathel (Polymedics Innovations GmbH, Germany). The outcomes were assessed using time for epithelization, TBSA (%), Vancouver Scar Scale and complication. Results: All burn wounds were completely epithelized without any complication. The average time for epithelization was 13.4/13.4 days. Conclusion: The result of this study suggests that Kaloderm and Suprathel did not show significant difference. Therefore, Suprathel may be considered as an alternative choice for 책임저자 : 김경식, 고양시덕양구화수로 14 번길 55 412-270, 명지병원성형외과 Tel: 031-810-6830, Fax: 031-810-6837 E-mail: kskimps@mjh.or.kr treating 2nd and 3rd degree burns in some clinical settings. (J Korean Burn Soc 2014;17:73-80) Key Words: Burn, Keratinocyte, Suprathel 서 화상환자의치료방법의결정에있어과거에는그깊이에따라 1도화상및표재성 2도화상에는주로보존적화상처치를선택하였으며심재성 2도화상이상의깊이에서는피부이식술및피판술을선택하였다. 하지만보존적화상처치의경우치유까지의기간이길고통증등으로인한환자들의치료순응도가떨어지는등의단점이있으며피부이식술및피판술의경우치료후의비후성반흔, 구축, 공여부합병증등의단점이있다. 따라서화상환자의치료방법의결정에있어환자들의치료과정순응도를높이고이를통하여치료후남을수있는비후성반흔, 구축, 색소침착, 공여부합병증등의최소화가중요한고려요소라고할수있겠다. 1975년동종유래배양피부이식 (cultured keratinocyte allograft) 이소개된이후 1) 환자본인또는보호자가수술적처치를원하지않는경우, 수술후협조가되지않을것으로판단되는심재성 2도화상및부분 3도화상환자에있어널리적용되어지고있다. 하지만안면부, 소아환자, 관절부의화상환자등의경우에동종유래배양피부이식 (cultured keratinocyte allograft (Kaloderm (Tegoscience, Korea)), 이하 Kaloderm) (Fig. 1) 의적용이부착및고정의문제그리고보관 ( 냉동보관및보유기간의제한 ) 상의이유로제한점이있다 9). 젖산융합체합성창상치료제 ((synthetic film made of Lacto-Capromer and Polylactic Acid, Suprathel (Polymedics Innovations GmbH, Germany), 이하 Suprathel) 8) (Fig. 2) 은 2004년소개된후화상창상에적용시생체에재흡수되는특성으로안면부, 소아, 관절부의화상환자등 Kaloderm의사용에제한이있는경우적용이용이하며실온에서 3년간보관이가능한것으로보고되고있다. 론
74 대한화상학회지 Vol. 17, No. 2, 2014 본연구는화상을주소로저자들의병원을내원한환자들중심재성 2도화상환자및부분 3도화상환자에서동일부위에환자및보호자의동의하에동종유래배양세포이식 (Kaloderm) 과젖산융합체합성창상치료제 (Suprathel) 를이용하여치료하였으며현재까지동종유래배양세포이식과젖산융합체합성창상치료제적용시효과에대한비교연구가진행되지않아그효용성의차이를비교, 평가하기위한목적으로진행되었다. 대상및방법 1. 연구설계본연구는심재성 2도화상환자및부분 3도화상환자에서동일부위에 Kaloderm과 Suprathel을적용하여그효용성의차이를비교, 평가하기위한비교연구이다. 2. 연구대상본연구의대상자는 2013년 3월 10일부터 2014년 9월 30 일까지저자들병원의성형외과에내원한 2도화상환자로 5일이내에입원한총 47명을대상으로하였으며, 환자및보호에게설명후동의를얻고 Kaloderm 및 Suprathel을적용하는연구에참여시켰다. 동일한깊이의심재성 2도화상및부분3도화상환자에서 100 cm 2 이상의화상면적을대상으로하였으며성별, 연령, 수상부위등을고려하여연구에참여시켰다. 단, 회음부, 점막부의화상환자및임산부, 수유부, 스테로이드제재, 항응고제및항암제복용의과거력이있거나현재복용중인환자는연구에서제외하였다. 3. 연구도구및방법 Fig. 1. Cultured keratinocyte allogaft (Kaloderm (Tegoscience, Korea) 3.5 3.5 cm sized). Fig. 2. Synthetic film made of Lacto-Capromer and Polylactic Acid, Suprathel (Polymedics Innovations GmbH, Germany 5 5 cm sized).
김대현등 : 화상치료에서동종유래배양세포이식과젖산융합체합성창상치료제적용의비교 75 Fig. 3. A 37-year-old woman had Deep 2 nd and partial 3 rd degree scalding burn. After radical debridement, Kaloderm and Suprathel were applied. 까지의기간을치료효과에대한평가및효용성의비교, 평가의기준으로설정하였다. 저자들은상피화의기간을화상상처에 Kaloderm 및 Suprathel을적용한시점부터화상상처가치료되어더이상의드레싱이필요없고상처를열어놓고연고나보습제를바르기시작한상태를상피화가완료된것으로정의하였다 (Fig. 4). 화상반흔의정도를판단하기위해치료가완료되어퇴원후외래방문시 Vancouver Scar Scale 10) 을이용하였고관찰기간은 3개월부터 13개월 ( 평균 6.3개월 ) 이었다. Fig. 4. Follow-up on postoperative 15 days. 심재성 2도및부분3도화상환부의삼출물이감소하면서괴사조직, 가피 (eschar) 및딱지 (scab) 이충분히제거되어진피층이노출되고, 세균배양검사에서균이동정되지않을때 Kaloderm과 Suprathel을적용하였으며적용부위는무작위로선정하였다. 환부에 Kaloderm 및 Suprathel을적용후메피렉스폼드레싱 (Mepilex, Molnlycke Health Care, Sweden) 을이용하여드레싱하였으며 3 5일후첫드레싱교체를하였으며이후 2일간격으로재상피화시까지메피렉스폼드레싱을시행하였다 (Fig. 3). Kaloderm은환부에적용하고 7일째제거하였으며 Suprathel은환부에서재흡수되어제거의필요성이없었다. 고정이필요한경우에는 Kaloderm 을나일론봉합및의료용스테플러를이용하여피부에고정하여주였고, Suprathel 은고정이필요하지않았다. 환부가사지인경우부목을대어 Kaloderm 및 Suprathel의움직임을최소화하였다. 상피화의기준은각각다를수있지만상피화의완료시 4. 자료분석수집된자료의통계적분석은 SPSS 17.1 for Windows (SPSS Inc., Chicago, IL, USA) 를사용하였다. Kaloderm과 Suprathel을적용한부위의상피화의기간에대한비교분석은평균과표준편차로기술하였고 Paired t-test를이용하였으며 P-value가 0.05이하일경우통계학적으로유의성이있는것으로판단하였다. 결과연구에참여한대상자는 47명으로남성이 26명 (55.3%), 여성이 21명 (44.7%) 이었으며평균연령은나이는 33세 (range, 2 81세 ) 였고평균화상범위 5.4% 였다. 평균추적관찰기간은 6.2개월 (3개월 13개월) 이었다. 화상의원인으로는열탕화상이 41예, 화염화상이 2예, 증기화상이 4예였다 (Table 1). 화상후환부에서괴사조직, 가피 (eschar) 및딱지 (scab) 를제거하고 Kaloderm 및 Suprathel을적용하기까지는평균 4.3일이적용후상피화가완료될때까지는 Kaloderm이평균 13.4일, Suprathel이평균 13.4일이소요되었다.
76 대한화상학회지 Vol. 17, No. 2, 2014 Table 1. Etiology, Site, Body Surface Area and Re-epithelialization of Patients No. Age Sex Etiology Site TBSA (%) Duration of Epithelization (day) Kaloderm / Suprathel Time for application (PBD or PTD) Complication 1 33 M Scalding burn (2nd) Dorsum of foot and ankle 3 12/12 5 None 2 17 M Scalding burn (2nd) Lateral tibia 4 11/12 3 None 3 60 F Scalding burn (2nd and partial 3rd) Buttock and lower leg 11 14/15 6 None 4 42 F Steam burn (2nd) Abdomen and thigh 10 12/14 2 None 5 9 M Scalding burn (2nd) Tight 3 10/11 5 None 6 71 M Scalding burn (2nd and partial 3rd) Dorsum of foot 5 15/16 6 None 7 20 F Scalding burn (2nd) Tight 6 13/15 6 None 8 37 F Scalding burn (2nd and partial 3rd) Tight 6 17/18 4 None 9 51 M Scalding burn (2nd and partial 3rd) Dorsum of foot 3 15/17 3 None 10 33 M Scalding burn (2nd) Dorsum of foot 2 12/14 4 None 11 46 F Scalding burn (2nd) Tibia 3 15/15 5 None 12 42 F Scalding burn (2nd) Forearm 3 13/14 5 None 13 4 M Scalding burn (2nd and partial 3rd) Dorsum of hand 3 17/16 3 None 14 68 M Scalding burn (2nd) Thigh 5 12/12 4 None 15 21 F Flame burn (2nd) Hand 3 12/10 2 None 16 7 M Scalding burn (2nd) Tight 7 10/10 5 None 17 81 M Scalding burn (2nd and partial 3rd) Trunk and shoulder 12 15/15 5 None 18 17 F Scalding burn (2nd) Tight and knee 6 13/12 6 None 19 49 F Scalding burn (2nd and partial 3rd) Upper arm 4 17/16 4 None 20 48 M Scalding burn (2nd) Lateral tibia 3 11/11 3 None 21 60 F Flame burn (2nd and partial 3rd) Buttock and abdomen 11 14/14 6 None 22 16 F Steam burn (2nd) Hand and wrist 3 12/10 2 None 23 2 M Scalding burn (2nd) Chest and abdomen 12 10/8 5 None 24 55 M Scalding burn (2nd and partial 3rd) Dorsum of foot and ankle 5 15/14 4 None 25 35 M Scalding burn (2nd and partial 3rd) Thigh and pretibia 8 15/15 5 None 26 30 F Scalding burn (2nd) Tight 6 13/13 6 None 27 47 F Scalding burn (2nd and partial 3rd) Tight 5 17/19 4 None 28 26 M Scalding burn (2nd and partial 3rd) Dorsum of foot 3 17/17 3 None 29 39 M Scalding burn (2nd) Dorsum of foot 2 12/13 4 None 30 6 F Scalding burn (2nd) Chest and hand 13 15/13 5 None 31 3 M Scalding burn (2nd) Dorsum of foot and ankle 3 12/11 5 None 32 8 M Scalding burn (2nd) Lateral tibia 4 11/11 3 None 33 51 F Scalding burn (2nd and partial 3rd) Buttock and back 11 14/14 6 None 34 15 F Steam burn (2nd) Forearm 3 12/11 2 None 35 18 M Scalding burn (2nd) Abdomen and tight 10 12/13 5 None 36 28 M Scalding burn (2nd and partial 3rd) Dorsum of foot and ankle 4 15/14 7 None 37 12 F Steam burn (2nd) Tight 6 13/14 6 None
김대현등 : 화상치료에서동종유래배양세포이식과젖산융합체합성창상치료제적용의비교 77 Table 1. Continued Complication Time for application (PBD or PTD) Duration of Epithelization (day) Kaloderm / Suprathel TBSA (%) No. Age Sex Etiology Site 38 38 F Scalding burn (2nd and partial 3rd) Tight 6 15/16 4 None 39 51 M Scalding burn (2nd and partial 3rd) Dorsum of foot 3 17/16 3 None 40 15 M Scalding burn (2nd) Forearm and elbow 5 12/11 4 None 41 49 F Scalding burn (2nd) Sholder and upper arm 6 15/13 5 None 42 22 F Scalding burn (2nd) Face and neck 3 10/9 6 None 43 56 F Scalding burn (2nd and partial 3rd) Tight 6 15/16 4 None 44 55 M Scalding burn (2nd and partial 3rd) Dorsum of foot 3 13/13 3 None 45 42 M Scalding burn (2nd) Dorsum of foot 2 11/10 4 None 46 5 M Scalding burn (2nd and partial 3rd) Tight 6 14/13 4 None 47 12 M Scalding burn (2nd and partial 3rd) Dorsum of foot 3 13/13 3 None Average 33 4.3 (2 7) 13.4/13.38 (10 17/8 19) 5.4 (2 13) (2 81) Table 2. Burn Wound Re-epithelialization Period Difference between The Kaloderm and Suprathel Application No. Kaloderm Suprathel Difference (δ) 1 12 12 0 2 11 12 1 3 14 15 1 4 12 14 2 5 10 11 1 6 15 16 1 7 13 15 2 8 17 18 1 9 15 17 2 10 12 14 2 11 15 15 0 12 13 14 1 13 17 16 +1 14 12 12 0 15 12 10 +2 16 10 10 0 17 15 15 0 18 13 12 +1 19 17 16 +1 20 11 11 0 21 14 14 0 22 12 10 +2 23 10 8 +2 24 15 14 +1 25 15 15 0 26 13 13 0 27 17 19 2 28 17 17 0 29 12 13 1 30 15 13 +2 31 12 11 +1 32 11 11 0 33 14 14 0 34 12 11 +1 35 12 13 1 36 15 14 +1 37 13 14 1 38 15 16 1 39 17 16 +1 40 12 11 +1 41 15 13 +2 42 10 9 +1 43 15 16 1 44 13 13 0 45 11 10 +1 46 14 13 +1 47 13 13 0 Mean±SD Min Max 13.4±2.1 10 17 13.4±2.4 8 19 0.02±1.2* 2 +2 Difference in Re-epithelialization period between The Kaloderm and Suprathel application. *P<0.0001.
78 대한화상학회지 Vol. 17, No. 2, 2014 Table 3. Vancouver Scar Scale Score Pigmentation Pliability Height Vascularity 0 Normal Normal Flat Normal 1 Hypopigmented Supple <2 mm Pink (minimal resistance) 2 Mixed Yielding (moderate resistance) 2 5 mm Red 3 Hyperpigmented Firm >5 mm Purple 4 Ropes 5 Contracture Kaloderm 및 Suprathel 적용부위의상피화에따른기간에차이는통계학적으로유의한차이를보이지않았다 (Table 2). 하지만통계학적으로는유의한차이를보이지않는다하더라도대부분의수부, 관절및소아화상환자의경우에서는 Suprathel 적용부위가 Kaloderm 적용부위보다 1 2일빠른상피화를보였고그외의화상환자에서는 Kaloderm 적용부위의상피화가 1 2일빠른상피화를보였다고임상적으로판단할수있다 (Table 1, 2). Vancouver Scar Scale을이용하여반흔의상태를평가하였으며, 환자전체의평균총점수는 Kaloderm 및 Suprathel 이동일하게 1.8점이었고, 항목별로도 pigmentation 평균 0.5점, Vascularity 평균 0.5점, Pliability 평균 0.5, Height 평균 0.3점으로판단되었다. 상피화에대한평가및반흔의상태평가는 3명의성형외과전문의가하였다 (Table 3, 4). 고 화상으로의하여손상을받았을때화상의깊이와범위에따라서적절한치료가이루어져야화상으로인한후유증을최소화할수있다. 이에화상의깊이에따라보존적화상처치및피부이식술, 피판술이선택되고있으나수술적처치를원하지않거나수술적처치에제한이있는경우에적용될수있는다양한방법들이개발되고있다. 1975년에 Rheiwald와 Green이인간피부각질세포 (human keratinocyte) 를배양하는조건을확립하고발표한 이후 1) 자가유래배양피부가연구, 개발되어사용되면서 1980년대말부터는동종유래배양피부가개발되고발전되어왔다 2-7). 국내에서는여러연구를통해동종유래배양피부를이용하여치료한부분층 2도화상치료에있어서상처치유촉진효과및환부의상피화정도, 환자의만족도, 통증의감소정도가우수한것으로보고되었다 9). 국내에서제품화되어사용하고있는동종유래배양피부 찰 인칼로덤 (Kaloderm, Tegoscience, Korea) 은면역세포를포함하지않아거부반응이나타나지않고냉동상태로보관되어실온에서 5 10분정도해동후사용할수있다. 동종유래배양피부의상처치유효과의기전은 TGF-α, IL-1 α, IL-1β, IL-6, IL-8, GM-CSF, keratinocyte derived T-cell growth factor등과같이동종유래배양피부에서생성, 분비되는 cytokine에의하여화상상처내와상처주변의피부세포의증식과이동을일으키고치유를촉진하는것으로알려져있다 11-14). 또한동종배양피부는 Epidermal Cell-derived Factor (EDF) 을분비하는것으로밝혀졌는데이는섬유모세포의수축을억제하여반흔형성과구축을줄인다고보고되었다 7,15). 이러한작용을통하여동종유래배양피부는피부의재상피화를촉진하고비후성반흔이나구축을최소화할수있다. 젖산융합체합성창상치료제인수프라셀 ((synthetic film made of Lacto-Capromer and Polylactic Acid, Suprathel (Polymedics Innovations GmbH, Germany) 은 2004년독일에서제품화되어사용중으로창상에적용시생체에재흡수되는특성으로관절부및안면부특히소아환자들에적용이용이하며재흡수시의산물로인해상처주변의산도가증가되어 Protease의작용저해및 Collangen 합성, Fibroblast의이동, Vascular Endothelial Growth Factor (VEGF) 의활성화를촉진시키는것으로보고되었다 8). 본연구의결과에서 Kaloderm 및 Suprathel 적용시상피화의기간의차이는통계학적으로유의한차이를보이지않았다. 하지만수부, 관절, 소아환자의경우 Suprathel의적용시상피화에서더적은기간이소요된것을확인할수있다. 이는 Kaloderm이환부에잘부착되도록유지되지못하여상피화가더뎠을것으로생각된다. Kaloderm 및 Suprathel을적용시환부에적용한후상피화까지약 13.4일걸렸고 3개월에서부터 13개월까지외래경과관찰시비후성반흔, 구축및색소침착의발생은거의관찰되지않았다. 47명의연구대상환자에서이상반응으로판단할수있는증상은보이지않았으며이는 3명의성형외과전문의가평가하였다. Kaloderm의적용에대한연구는매우활발히진행되었으며그효과및치료범위에대해서도널리알려져있으나 Suprathel의경우, 국내에서화상환자들에게적용된보고및연구가많지않으며화상치료에서널리사용되는 Kaloderm과의효과에대한비교연구가존재하지않아연구계획단계에서부터이를비교하는것이중요한점이었다. 단, 본연구의제한점으로는첫째, 대조군의설정에있어
김대현등 : 화상치료에서동종유래배양세포이식과젖산융합체합성창상치료제적용의비교 79 Table 4. Vancouver Scar Scale Difference between The Kaloderm and Suprathel application (Kaloderm /Suprathel ) No. Pigmentation Pliability Height Vascularity 1 0/0 0/0 0/0 0/0 2 0/0 0/0 0/0 0/0 3 1/2 2/1 0/1 1/2 4 0/0 0/0 0/0 0/0 5 0/0 0/0 0/0 0/0 6 1/1 1/1 0/0 0/1 7 0/0 0/0 0/0 0/0 8 1/2 1/1 1/1 1/2 9 2/1 1/2 1/1 2/1 10 0/0 0/0 0/0 0/0 11 1/1 0/1 1/0 1/1 12 0/0 0/0 0/0 0/0 13 1/1 0/1 0/1 1/1 14 0/0 0/0 0/0 0/0 15 0/0 0/0 0/0 0/0 16 0/0 0/0 0/0 0/0 17 1/1 1/2 0/1 0/1 18 0/0 0/0 0/0 0/0 19 1/1 1/0 0/0 1/1 20 0/0 0/0 0/0 0/0 21 0/0 1/1 1/0 1/0 22 0/0 0/0 0/0 0/0 23 0/0 0/0 0/0 0/0 24 1/1 0/1 0/0 1/1 25 3/2 2/2 2/1 2/2 26 0/0 1/0 0/0 0/0 27 1/1 1/1 1/0 1/0 28 1/1 1/0 1/0 1/1 29 0/0 0/0 0/0 0/0 30 1/1 1/2 1/1 1/1 31 0/0 0/0 0/0 0/0 32 0/0 0/0 0/0 0/0 33 0/0 1/1 0/0 0/0 34 0/0 0/0 0/0 0/0 35 0/0 0/0 0/0 0/0 36 1/1 0/1 0/1 1/1 37 0/0 0/0 0/0 0/0 38 1/2 1/1 0/1 1/2 39 1/1 1/2 1/2 1/2 40 0/0 0/0 0/0 0/0 41 2/1 1/1 1/1 2/1 42 0/0 0/0 0/0 0/0 43 1/1 2/1 1/1 2/1 44 0/0 1/0 0/0 0/0 45 0/0 0/0 0/0 0/0 46 3/2 2/2 2/1 3/3 47 0/0 0/0 0/0 0/0 Mean±SD Min Max 0.5±0.7/0.5±0.7 0 3/0 2 0.5±0.6/0.5±0.7 0 2/0 2 0.3±0.5/0.3±0.5 0 2/0 2 0.5±0.7/0.5±0.8 0 3/0 3
80 대한화상학회지 Vol. 17, No. 2, 2014 메피렉스폼드레싱만을시행하는심재성 2도화상및부분 3도화상을연구에서제외하였다는것이다. 연구계획단계에서폼드레싱만을시행하는화상상처를함께디자인하였지만연구진행시피부이식술이필요한경우가발생하여폼드레싱만을시행하는대조군은연구에서제외하였다. 둘째, 대부분화상이열탕화상으로다른종류의화상환자에서의연구결과가부족하다는것과셋째, 단일기관에서의환자만을대상으로하였다는점이다. 소아환자및고령환자의경우, 수술적치료를원하지않는경우가있으며수술을시행한경우에도수술부위의유지및협조가어려운것이사실이다. 또한안면부의경우수술적처치로인한반흔의가능성으로수술의결정이쉽지않다. 이런경우 Kaloderm 혹은 Suprathel을이용한화상치료를선택할수있으며 Kaloderm의경우국민건강보험의혜택이적용되어환자의부담을덜어줄수있고, Suprathel 은 Kaloderm의적용에제한이있는안면부, 수부, 관절면, 소아및고령환자에게서적용을고려할수있다. 결 Kaloderm 및 Suprathel은수술적처치가어려운경우및원하지않는경우의심재성 2도및부분 3도화상치료에서고려가능한방법이다. Kaloderm의효능및효과에대한많은연구가진행되고실제임상에서많이적용되고있으나보관상의문제 ( 냉동보관및유효기간의존재 ) 와적용의제한점이있는환자및신체부위등이있어 Suprathel의적용을고려해볼수있으며본연구의결과화상치료효과는통계학적으로유의한차이를보이지않음을확인할수있다. 따라서 Kaloderm 및 Suprathel을이용한치료가모든심재성 2도이상의화상환자에게적용가능하다고할수는없지만적절한적응증을선별하여사용한다면수술적처치가아닌보조적치료방법으로선택가능하다는것을보고하는바이다. 론 REFERENCES 1) Rheinwald JG, Green H. Seria cultivation of strains of human epidemal keratinocytes: the formation keratinizin colonies from single cells. Cell. 1975;6:331-343. 2) O'Connora NE, Mullikena J, Susan BS, Kehindeb O, Green H. Gragting of burns with cultured epithelium prepared from autologous epidermal cellas. Lancet. 1981;1:75-78. 3) Gallico GG III, O'Connor NE, Compton CC, Kehinde O, Green H. Permanent coverage of large burn wounds with autologous cultured human epithelium. N Engl J Med. 1984; 311:448-451. 4) Siedler S, Sanja SP. Wound healing enhancement in leg ulcer: A case report. Cell and Tissue Banking. 2002;3:25-28. 5) Harvima IK, Virnes S, Kauppinen L, Huttunen M, Kivinen P, Niskanen L, et al. Cultured allogeneic skin cells are effective in the treatment of chronic diabetic leg and foot ulcers. Acta Derm Venereol. 1999;79:217-220. 6) Fratianne R, Papay F, Housini I, Lang C, Schafer IA. Keratinocyte allografts accelerate healing of split-thickness donor sites: applications for improved treatment of burns. The Journal of Burn Care & Rehabilitation. 1993;14:148-154. 7) Yanaga H, Udoh Y, Yamauchi T, Yamamoto M, Kiyokawa K, Inoue Y, et al. Cryopreserved cultured pidermal allografts achieved early closure of wounds and reduced scar formation in deep partial-thickness burn wounds (DDB) and splitthickness skin donor sites of pediatric patients. Burns. 2001;27:689-698. 8) Uhlig C, Rapp M, Hartmann B, Hierlemann H, Planck H, Dittel K.K. Suprathel - an innovative, resorbable skin substitute for the treatment of burn injury victims. Burns 2007;33: 221-229 9) Choi WY, Kim GB, Yang JY. The Usefulness of Cultured Allogenic Keratinocyte(Kaloderm ) for 2nd Degree Burn Patient Treatment. Journal of Korean Burn Society. 2011;14:111-117. 10) Shin JC, Seo CH, Jang KU. Scar Quality and Hand Function after Moist Exposed Burn Ointment and Skin Graft Treatment in Full Thickness Hand Burn J Korean Acad Rehab Med 2007;31:582-589 11) Robert JC Jr, Derynck R, Wilcox JN, Bringman ST, Goustin AS, Moses HL, et al. Production and auto-induction of transforming growth factor in human keratinocytes. Nature. 1987;328:817-820. 12) Kupper TS, Ballard DW, Chua AO, McGuire JS, Flood PM, Horowitz MC, et al. Human keratinocytes contain mrna indistinguishable from monocyte interleukin-1 alpha and beta mrna. Keratinocyte epidermal cell-derived thymocyte-activating factor is identical to interleukin 1. JEM. 1986;164:2095-2100. 13) Larsen CG, Anderson AO, Oppenheim JJ, Atsushima KM. Production of interleukin-8 by human dermal fibroblasts and keratinocytes in response to interleukin-1 or tumor necrosis factor. Immunology. 1989;68:31-36. 14) Kupper ST, Lee F, David C, Jeffrey C, Patrick F, Mark H. Keratinocyte derived T-cell growth factor(ktgf) is identical to granulocyte marcophage colony stimulating factor(gm- CSF). J Invest Dermatol. 1988;91:185-188. 15) Eisinger M, Sadan S, Silvers IA, Flick RB. Growth regulation of skin cells by epidermal cell-derived factors: Implications for wound healing(re-epithelization/keratinocytes/fibroblast inhibition). Proc Natl Acad Sci USA. 1988;86:1937-1941.