조직공학제품의 현황과 미래

이성미,노인섭 한국생체재료학회 2002 생체재료학회지 Vol.6 No.2

서구화와 문명화에 따라 발생되는 손상•손실된 장기들의 수가 급증하고 이들을 복원하기 위한 다양한 노력에도 불구하고 기증되는 장기부족과 이식술의 제한으로 인하여 이식을 필요로 하는 장기의 수는 심각할 정도로 부족하다. 이러한 장기부족 문제점을 해결하기 위한 방법으로, 조직공학기법을 이용하여 환자조직과 유사한 생화학적 및 생기계적 기능을 가진 조직공학 인공장기를 개발하고자 하는 연구노력이 활발히 이루어져, 조직공학 제품의 시장성은 매우 빠르게 증가하고 있다. 1960년 대 중반에 화상환자 치료를 위하여 합성섬유를 이식재료로 하는 인공피부 개발이 처음 시도된 이래로, Transcyte , IntegraTM, TerudermisTM, EpicelTM 등과 같은 조직공학제품이 출시되었다. 최근에는 궤양치료용 Apligraft 인공피부 상품과 Carticel㉯繭遮 연골치료용 세포의 상품화와 함께, 혈관, 방광, 뼈, 건, 간, 심장 등과 같은 기타 인공장기 개발연구로 상품화가 점진적으로 이루어지고 있다. 그러나 조직공학이라는 학문이 미래의 핵심산업으로 성장하기 위해서는 수많은 과제들을 극복해야 할 것이다. 구체적으로 조직공학의 핵심요소인 지지체 개발측면에서, 환자에게 필요한 특정조직의 구조와 표면생화학을 정확히 모방할 수 있는 보다 생체적합한 조직공학용 지지체의 개발이 필요하다. 이와 함께 조직공학의 또 다른 핵심요소인 세포측면에서, 미분화된 줄기세포와 특정세포들을 이용한 조직공학제품의 개발이 필요하다. 제품 출시와 함께 제품에 대한 품질관리와 추적검사를 함으로써, 개발되는 제품의 안전성 보장과 새로운 제품개발에 필요한 데이터베이스로 활용하려는 노력 또한 조직공학회사들을 중심으로 진행되고 있다. 조직공학제품의 개발에 필요한 지지체, 세포 및 제품의 안전성 문제와 함께, 조직공학제품 다양화•세분화로 산업의 확대도 시도되고 있다. 이러한 시장성과 사회적 필요성을 가진 조직공학제품의 현황과 미래의 핵심 바이오산업이 되기 위하여 조직공학 산업이 극복하여야 할 과제들을 본 고에서 고찰하고자 한다.

골이식용 생체재료로서 생체 활성 유리와 표면처리

한인호,이인섭,최재혁,백홍수 한국생체재료학회 2006 생체재료학회지 Vol.10 No.2

Since middle of 20 century, so many efforts have been conducted to make excellent biocompatible biomaterials especially for quick and firm osseointegration. SiO2-CaO-NaO-P2O5 system was proposed with the name of 멊ioglass? Bioglasses provide the convenient surface for hydroxyapatite formation when they are immersed in the body fluids. Bioglasses are the first artificial materials which can make direct bonding to the bone. Alkali treatment to metals and zeta-potential experiment are reviewed to investigate the essential component for the hydroxyapatite formation. It is uncovered that the essential component is not Si, Ca nor P but hydroxyl group.

Film-trigger applicator (FTA) for improved skin penetration of microneedle using punching force of carboxymethyl cellulose film acting as a microneedle applicator

김유성,Hye Su Min,Jiwoo Shin,남지혜,Geonwoo Kang,Jeeho Sim,양휘석,정형일 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Background: Dissolving microneedle (DMN) is a transdermal drug delivery system that creates pore in the skin and directly deliver drug through the pore channel. DMN is considered as one of the promising system alternatives to injection because it is minimally invasive and free from needle-related issues. However, traditional DMN patch system has limitations of incomplete insertion and need of complex external devices. Here, we designed film-trigger applicator (FTA) system that successfully delivered DMN inside the skin layers using fracture energy of carboxymethyl cellulose (CMC) film via micropillars. We highlighted advantages of FTA system in DMN delivery compared with DMN patch, including that the film itself can act as DMN applicator. Methods: FTA system consists of DMNs fabricated on the CMC film, DMN array holder having holes aligned to DMN array, and micropillars prepared using general purpose polystyrene. We analyzed punching force on the film by micropillars until the film puncture point at different CMC film concentrations and micropillar diameters. We also compared drug delivery efficiency using rhodamine B fluorescence diffusion and skin penetration using optical coherence tomography (OCT) of FTA with those of conventional DMN patch. In vivo experiments were conducted to evaluate DMN delivery efficiency using C57BL/6 mice and insulin as a model drug. Results: FTA system showed enhanced delivery efficiency compared with that of the existing DMN patch system. We concluded CMC film as a successful DMN applicator as it showed enhanced DMN penetration in OCT and rhodamine B diffusion studies. Further, we applied FTA on shaved mouse dorsal skin and observed successful skin penetration. The FTA group showed higher level of plasma insulin in vivo than that of the DMN patch group. Conclusions: FTA system consisting of simple polymer film and micropillars showed enhanced DMN delivery than that of the existing DMN patch system. Because FTA works with simple finger force without sticky patch and external devices, FTA is a novel and promising platform to overcome the limitations of conventional microneedle patch delivery system; we suggest FTA as a next generation applicator for microneedle application in the future.

국소 환부 적용을 위한 수용성 항생제 함유 플루로닉 겔 시스템의 제조 및 서방형 방출거동 분석

임성묵,오세행,조진생,박경유,이진호 한국생체재료학회 2009 생체재료학회지 Vol.13 No.3

Effective medical treatment of infection depends on achieving therapeutic concentrations of antibiotics within the body fluids and tissues. Local delivery offers several advantages over systemic administration of a medicine, including fewer side effects, higher local concentration, and the ability to use more of a given medicine that might be tolerated in a systemic route of administration. However, the burst release of commonly used antibiotics due to their water-soluble property has been considered as a practical limitation in local delivery. In this study, we prepared ion-complexed Teicoplanin/ Pluronic F127/F68 (7/3, 30 wt%) mixture to provide the sustained release of Teicoplanin, even though it is a water-soluble antibiotic. To this, the ion-complexed Teicoplanin was fabricated by simple mixing of Teicoplanin solution and CaCl2 solution (Ca2+ acts as an ion linker between Teicoplanin molecules). The ion-complexed Teicoplanin was mixed with Pluronic F127/F68 (7/3, 30 wt%) solution to apply as a local delivery system. The amount of ion-complexed Teicoplanin was increased with the increasing CaCl2 concentration, up to 0.5 wt%. The ion-complexed Teicoplanin showed much slower release behavior than Teicoplanin itself from the Pluronic F127/F68 (7/3, 30 wt%) gel, indicating the sustained release of Teicoplanin. This result suggests that the ion-complexed Teicoplanin/Pluronic F127/ F68 (7/3, 30 wt%) mixture system can be a good candidate as a local antibiotic sustained delivery system.

새로운 비대칭 미세다공성 뼈재생유도막의 제조 및 분석

김준호,오세행,이진호 한국생체재료학회 2006 생체재료학회지 Vol.10 No.2

Porous guided bone regeneration (GBR) membranes with selective permeability, hydrophilicity, and adhesiveness with bone were prepared using polydioxanone (PDO) and Pluronic F127 by an immersion precipitation method. The PDO/Pluronic F127 membranes were fabricated by immersing PDO/Pluronic F127 mixture solution [in N-Methyl-2-pyrrolidone (NMP)] in a mold into water. The PDO/Pluronic F127 mixture was precipitated in water by the diffusion of water into PDO/Pluronic F127 mixture solution. It was observed that the membrane has an asymmetric column-shape porous structure. The top surface of the membrane (water contact side) had nano-size pores (~100 nm) which can effectively prevent from fibrous connective tissue invasion but permeate nutrients, while the bottom surface (mold contact side) had micro-size pores (~70 mm) which can improve adhesiveness with bone. From the investigations of mechanical property, water absorbability, and model nutrient permeability of the membranes, the hydrophilized PDO/F127 (3 wt%) membrane seems to be a good candidate as a GBR membrane for the effective permeation of nutrients as well as the good mechanical strength to maintain a secluded space for the bone regeneration.

원심분리법을 이용한 다양한 형태의 조직공학용 다공성 알지네이트 지지체의 제조 및 분석

오세행,이진호,석경록,박일규 한국생체재료학회 2003 생체재료학회지 Vol.7 No.1

In recent years, several techniques have been used to fabricate porous polymeric scaffolds having 3-dimensional pore structure. However, it is not easy to fabricate the porous scaffolds with complicated shapes by conventional methods and thus the prepared scaffolds usually have simple shapes, such as sheet, disc, cylinder and tube. In this study, we developed a new porous scaffold fabrication method (centrifugation method) to prepare scaffolds with uniform surface and interior pore structures as well as various shapes. The porosity and pore size of the scaffolds could be controlled by adjusting centrifugation speeds. The pore sizes of the prepared alginate scaffolds decreased with the increasing centrifugation speed: as the centrifugation speed increased from 1,000 rpm to 3,000 rpm, the pore size of the scaffolds decreased from 250 m to 130 m. The alginate scaffolds were impregnated into chitosan solution with the different concentration (0~1.0 wt%) to improve mechanical strengths as well as cell adhesiveness. The maximum load and modulus analog of the scaffolds gradually increased by the chitosan impregnation. This study demonstrate that the centrifugation method is an effective method for preparing porous 3-dimensional scaffolds with complicated shapes for tissue engineering applications.

히알루론산 유도체의 생체재료 응용

노인섭 한국생체재료학회 2008 생체재료학회지 Vol.12 No.3

Hyaluronic acid has been studied for tens of years in biomedical society due to its excellent biocompatibility and specific biological activities. To improve its mechanical, chemical and biological properties in its specific biomedical applications, numerous methods of the chemical derivatizations of hyaluronic acid have been reported. We have reviewed its diverse applications in biomedical materials by analyzing mainly derivative chemistries of hyaluronic acid via its functrional groups such as carboxylic acid, alcohol and others.

바이오 플라스틱의 산업동향과 전망

박노형,김동현,김창목,정의섭,이준우 한국생체재료학회 2013 생체재료학회지 Vol.17 No.2

Recently, the research paradigm for plastics has been moved from petrochemical polymers to either biodegradable plastics, bioplastics, produced from plant-derived raw materials or both. Bioplastics are highlighted as materials to solve the environmental regulations from petrochemical dependence and applied to many fields such as vehicles, electronics, architectures and commodities etc. Although bioplastics have begun to achieve some degrees of commercial success, the industry is still in an embryonic stage. For bioplastics, the market will continue to evolve as products become more widely available and their performances are improved closely to those of the conventional polymers such as PE, PP, PET and PS. According to Frost & Sullivan Report (Global Bio-based Plastics Market), it is expected that bioplastic market and CAGR at 2014 be approximately $ 2.1 billion and 21.2%, respectively. For bioplastics industry, market success will depend mostly on lowering production costs and performances to compete with those of conventional polymers.

인공 혈관용 나노 섬유 지지체에 관한 연구 : 세포 부착 및 조직 형성

신정욱,신호준,이용재,김인애,이창훈,조은희,김은정 한국생체재료학회 2004 생체재료학회지 Vol.8 No.2

The purpose of this study is to examine the potential of the nanofiber scaffold as a substrate for forming an artificial vascular graft. Aligned and randomly aligned polylatic-co-glycolic acid (PLGA) and polyurethane(PU) nanofiber scaffolds fabricated by electrospinning were used as square sheets. Fibroblasts harvested from human foreskin were seeded and cultured over 1 week period on a nanofiber scaffold, followed by seeding of endothelial cells harvested from human vessel. Thereafter the new tissue was analyzed for DNA, collagen and stained for immunohistochemistry with von Willebrand factor. DNA and collagen analysis of the seeded scaffold demonstrated that the human fibroblasts and endothelial cells attached to the polymeric fibers had begun to spread out (day 7) and extracellular matrix was saturated after 2 week. The immunohistochemistry examination demonstrated the seeded endothelial cells formed a monolayer on the fibroblasts and no endothelial cell invasion or new formation of capillaries could be detected. Indeed, there's no significant difference between aligned and randomly aligned nanofiber scaffold in all analyses. These results demonstrated that nanofiber scaffold used in this study might be a promising base material for tissue-engineered blood vessels.

Recent Advances of Biodegradable Polymers for Medical Applications

성정석,성용결 한국생체재료학회 2006 생체재료학회지 Vol.10 No.3

The recent advances of biodegradable polymers for medical applications have been reviewed on the basis of biodegradability, functionality, and biocompatibility. These include the functional biodegradable polymers synthesized in our research laboratory and some injectable biodegradable polymers developed for biomedical applications. The biodegradable polymers synthesized from Krebs cycle acid derivatives, injectable biodegradable block copolymers, biodegradable polymers for RNA interference and DNA matrix-based biopolymeric systems for tissue engineering have been also discussed briefly.