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dc.description.abstractFor the purpose of effective bone regeneration, many studies using a guided tissue regeneration (GTR) technique have been attempted for decades. The barrier membrane system that is able to prevent connective tissue ingrowth and permeate the nutritive elements might be suitable for bone regeneration. For guided tissue regeneration, drug loaded poly (L-lactide) (PLLA) barrier membrane was fabricated using an in-air drying phase inversion technique. The three component of polymer solution (PLLA-methylene chloride-ethylacetate) was used to generate porous membrane during solvent evaporation. Tetracycline, PDGF-BB, and IGF-I were incorporated within the membrane as the osteogenic and onteoconductive drugs to improve bone regeneration efficacy in periodontal therapy. Additive such as sodium alginate or chondroitin sulfate was added with various ratios for the effect of controlling drug release kinetics and increasing malleability of the membrane. In addition, these additives were expected to enhance the water affinity and flexibility. PLLA was dissolved in a mixture of methylene chloride-ethylacetate, cast on glass plate using doctoring blade, and dried for 24 hours at room temperature. Then, membrane was further dried under vacuum for another 24 hours to remove possibly remaining organic solvents. Tricalcium phosphate (TCP) was added to increase supportability and regulate porosity of the PLLA membrane. Tetracycline was incorporated into PLLA membrane using with the ratio of 10% to PLLA by weight. For the morphological observation, both surface and sublayer of the membrane were observed by scanning electron microscope. For in vitro drug release investigation, fabricated membrane was immersed into glass vial which containing 10 mL of phosphate buffered saline (pH 7.4). Releasing media was withdrawn and replenished with fresh buffer in scheduled time intervals, Samples were analyzed by UV spectrophotometer at 276 nm. The release kinetic of tetracycline loaded PLLA membranes showed initial burst release at one day, and followed by the rate of 20㎍ per day. Leveling-off was merely reduced when sodium alginate or chondroitin sulfate was added. It is due to increased water affinity of the PLLA membrance although the ionic interaction between sodium alginate/chondroitin sulfate and tetracycline exists. For in vitro degradation test, the membranes were incubated under the same condition of the release test. The degradation profile of PLLA membrane shows drug loaded PLLA membranes decreased to 76 % after 8 weeks from the original weight. Withdrawn samples were weighed after vacuum drying to calculate the remaining portion of the original membrane. For the cellular activity test, isolated osteoblasts were seeded on the membranes with the density of 1×10^(5) cells/cm^(3), and were examined for attachment and proliferation. Cellular activity of the tetracycline loaded PLLA membrane was maintained about 80% against control. And cellular activity of tetracycline loaded membrane was higher than drug unloaded membrane, Cytotoxicity of the membrane was investigated by MTT test. Bone regenerative efficacy of the drug loaded membrane was examined with rabbits for 2weeks. The bone regeneration potential of the membrane showed that the drug loaded membrane demonstrated significantly enhanced bone regenerative potential in the bone defect of rabbit. Tetracycline-loaded PLLA membranes appear to have a promising modality for periodontal regenerative therapy and might be a beneficial tool for improving the current GTR status, which uses non-drug-loaded membranes. Rapid release at the initial step and the maintenance of proper concentration in local sites would be favorable for antibiotic delivery.;효율적인 골재생을 위해 다양한 유도재생 기법이 활용되어 왔다. 그 중 차폐막을 도입한 골재생 기법은 차폐막이 결체조직의 침입을 막아냄과 동시에 골재생에 필수적인 기초 영양물질의 통과를 용이하게 하는 장점을 지님과 동시에 약제학적 접근으로써 골재생을 유도, 증진 시키는 약물을 함입시킬 수 있으므로 골재생연구에 적합하다고 사료된다. 유도재생을 위해서 약물이 함입된 폴리락트산을 소재로 한 다공성 차폐막을 이중 용매 휘발 기법을 이용하여 제조하였다. 이때 사용된 용매는 디클로로메탄과 에틸아세테이트 두 가지이며 이 용매의 비점 차에 따른 상전이 효과를 이용함으로써 폴리락트산 차폐막의 내, 외부에 미세공을 형성하여 차폐막의 친수성 및 유연성을 증가시켰다. 골재생을 증진시키는 약물로서 테트라사이클린과 혈소판 유도 조직 성장인자, 인슐린 유사 조직 성장인자 등이 도입되었으며, 차폐막의 물성 개선을 위하여 알긴산 나트륨과 황산 콘드로이틴이 사용되었다 또한 차폐막의 기계적 강도 증진 및 미세공의 균일한 형성을 위하여 트리 칼슘인산세라믹이 폴리락트산에 대하여 동량의 비율로 사용되었다 제조된 차폐막은 시차 주사 현미경을 이용하여 그 성상을 관찰하였고, 차폐막을 이용한 생체 외 용출 실험 및 분해 실험을 실시하였다 차폐막으로부터의 약물 용출은 초기 속방출 이후에 일정한 정도의 용출을 보이는 양상을 나타내었으며,용충실험과 동일한 조건하에서의 차폐막 분해실험 결과, 약 8 주가 지나면 차폐막 초기 중량의 20% 이상이 감소하는 것이 관찰되었다. 세포 접착성 실험을 위해 골아세포를 분리해 낸 뒤, 이를 차폐막 위에 접종 시킨 뒤 1 일, 7 일 후에 이를 떼어내어 접착된 세포의 수를 측정하였으며, 그 결과 약물을 함유한 차폐막의 경우 그 세포 접착 정도가 약물 비함유 차폐막에 비해 비교적 높았고 특히 혈소판 유래 조직 성장인자를 함유한 차폐막의 경우 가장 높은 세포 접착력을 보였다. 인공적으로 형성된 골 결손부에 대한 차폐막의 골재생력 측정 및 함유 약물에 따른 골재생 효과의 확인을 위해 반구 형태의 약물 함유 차폐막을 제조하여 이를 가토의 두개골 결손부에 적용하여 신생골이 측정되는 것을 확인하였으며, 혈소판 유래 조직 성장인자 및 인슐린 유사 조직 성장인자를 함께 적용한 결손부에서의 신생골 재생효과가 가장 뛰어났다. 이와 같은 실험을 통해 국소부위의 골결손부 재생에 있어 약물을 함유한 폴리락트산 차폐막을 이용함으로써 뛰어난 효과를 얻을 수 있음을 확인 하였고 나아가 치주 조직에서의 결손부 치료에 효과적인 유도 재생 능력을 지니며 동시에 효과적으로 약물을 전달할 수 있는 차폐막의 제조가 가능할 것으로 사료되었다.-
dc.description.tableofcontentsList of Figures = ⅲ Abstract = ⅵ 1. Introduction = 1 2. Experiments = 4 2.1. Materials = 4 2.2. Membrane fabrication = 4 2.3. Scanning electron microscopy (SEM) observation = 5 2.4. In vitro drug release test = 5 2.5. In vitro degradation of PLLA membranes = 6 2.6. Cell attachment test = 6 2.6.1 Cell isolation and culture = 6 2.6.2. Osteoblast cell attachment = 7 2.7. In vitro cellular growth and survival (MTT test) = 8 2.8. Guided bone regenerative potential of drug loaded PLLA membranes = 9 2.9. Histologic preparation = 10 3. Results and Discussion = 11 3.1. Pore generation of the PLLA membrane = 11 3.2. Morphology of drug loaded PLLA membranes = 11 3.3. Release of drugs from porous poly PLLA membranes = 12 3.4. In vitro degradation test of PLLA membranes = 13 3.5. Osteoblastic cell attachment test = 13 3.6. In vitro cellular growth and survival with PLLA membranes = 14 3.7. Guided bone regenerative potential of PLLA membranes = 15 4. Conclusion = 33 5. References = 34 6. Summary in Korean = 38-
dc.format.extent2044999 bytes-
dc.publisherThe Graduate School of Ewha Womans University-
dc.subjectmoldable porous poly-
dc.subjectbone regeneration-
dc.titleDrug loaded moldable porous poly(L-lactide) membrane for bone regeneration-
dc.typeMaster's Thesis-
dc.title.subtitle유도 골재생을 위한 조형기능성 약물함유 차폐막에 관한 연구-
dc.format.pageviii, 39 p. : ill. (some col.).-
dc.identifier.major대학원 약학과- 2-
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