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.

생체용 바이오세라믹스 관련특허 통계분석 및 전망

김종헌,김상우,성용길,길상철 한국생체재료학회 2012 생체재료학회지 Vol.16 No.2

During the past several years there has been a major advance in the development of biomedical materials and this has been progressed in the innovation of ceramic materials for skeletal repair and reconstruction. The materials within this class of medical implant are often referred to as “Bioceramics” and the expansion in their range of biomedical applications has been characterized by a significant increase in the number of patents and publications in the field and an ever increasing number of major international conferences and symposia. The present paper is giving the global trends of technology and markets for bioceramics, through analyzing the patents released during past 10 years. The perspective of bioceramics for the future will be also proposed on the development of biomaterials for biomedical application.

Cobalt-containing calcium phosphate induces resorption of biomineralized collagen by human osteoclasts

Daniel de Melo Pereira,Matthias Schumacher,Pamela Habibovic 한국생체재료학회 2021 생체재료학회지 Vol.25 No.2

Background: Biomineralized collagen, consisting of fibrillar type-I collagen with embedded hydroxyapatite mineral, is a bone-mimicking material with potential application as a bone graft substitute. Despite the chemical and structural similarity with bone extracellular matrix, no evidence exists so far that biomineralized collagen can be resorbed by osteoclasts. The aim of the current study was to induce resorption of biomineralized collagen by osteoclasts by a two-fold modification: increasing the calcium phosphate content and introducing cobalt ions (Co2+), which have been previously shown to stimulate resorptive activity of osteoclasts. Methods: To this end, we produced biomineralized collagen membranes and coated them with a cobaltcontaining calcium phosphate (CoCaP). Human osteoclasts, derived from CD14+ monocytes from peripheral blood, were differentiated directly on the membranes. Upon fluorescent staining of nuclei, F-actin and tartrate-resistant alkaline phosphatase, the cells were analyzed by laser confocal microscopy. Their resorption capacity was assessed by scanning electron microscopy (SEM), as well as indirectly quantified by measuring the release of calcium ions into cell culture medium. Results: The CoCaP coating increased the mineral content of the membranes by 4 wt.% and their elastic modulus from 1 to 10 MPa. The coated membranes showed a sustained Co2+ release in water of about 7 nM per 2 days. In contrast to uncoated membranes, on CoCaP-coated biomineralized collagen membranes, osteoclasts sporadically formed actin rings, and induced formation of resorption lacunae, as observed by SEM and confirmed by increase in Ca2+ concentration in cell culture medium. The effect of the CoCaP layer on osteoclast function is thought to be mainly caused by the increase of membrane stiffness, although the effect of Co2+, which was released in very low amounts, cannot be fully excluded. Conclusions: This work shows the potential of this relatively simple approach to induce osteoclast resorption of biomineralized collagen, although the extent of osteoclast resorption was limited, and the method needs further optimization. Moreover, the coating method is suitable for incorporating bioactive ions of interest into biomineralized collagen, which is typically not possible using the common biomineralization methods, such as polymer-induced liquid precursor method.

Impact of simultaneous placement of implant and block bone graft substitute: an in vivo peri-implant defect model

Minh Khai Le Thieu,Amin Homayouni,Lena Ringsby Hæren,Hanna Tiainen,Anders Verket,Jan Eirik Ellingsen,Hans Jacob Rønold,Johan Caspar Wohlfahrt,Antonio Gonzalez Cantalapiedra,Fernando Maria Guzon Muñoz 한국생체재료학회 2021 생체재료학회지 Vol.25 No.4

Background: Insufficient bone volume around an implant is a common obstacle when dental implant treatment is considered. Limited vertical or horizontal bone dimensions may lead to exposed implant threads following placement or a gap between the bone and implant. This is often addressed by bone augmentation procedures prior to or at the time of implant placement. This study evaluated bone healing when a synthetic TiO2 block scaffold was placed in circumferential peri-implant defects with buccal fenestrations. Methods: The mandibular premolars were extracted and the alveolar bone left to heal for 4 weeks prior to implant placement in six minipigs. Two cylindrical defects were created in each hemi-mandible and were subsequent to implant placement allocated to treatment with either TiO2 scaffold or sham in a split mouth design. After 12 weeks of healing time, the samples were harvested. Microcomputed tomography (MicroCT) was used to investigate defect fill and integrity of the block scaffold. Distances from implant to bone in vertical and horizontal directions, percentage of bone to implant contact and defect fill were analysed by histology. Results: MicroCT analysis demonstrated no differences between the groups for defect fill. Three of twelve scaffolds were partly fractured. At the buccal sites, histomorphometric analysis demonstrated higher bone fraction, higher percentage bone to implant contact and shorter distance from implant top to bone 0.5 mm lateral to implant surface in sham group as compared to the TiO2 group. Conclusions: This study demonstrated less bone formation with the use of TiO2 scaffold block in combination with implant placement in cylindrical defects with buccal bone fenestrations, as compared to sham sites.

Design and clinical developments of aptamer-drug conjugates for targeted cancer therapy

Do-Hun Kim,Jin-Myung Seo,신경주,양수근 한국생체재료학회 2021 생체재료학회지 Vol.25 No.4

Background: Aptamer has been called “chemical antibody” which displays the specific affinity to target molecules compared to that of antibodies and possesses several therapeutic advantages over antibodies in terms of size, accessibility to synthesis, and modification. Based on the attractive properties, aptamers have been interested in many directions and now are emerged as new target-designed cancer drug. Main body: Currently, new types of aptamers have been reported and attracted many scientists’ interesting. Due to simplicity of chemical modification and ready-made molecular engineering, scientists have developed newly designed aptamers conjugated with a wide range of therapeutics, aptamer-drug conjugates; ApDCs, from chemotherapy to phototherapy, gene therapy, and vaccines. ApDCs display synergistic therapeutic effects in cancer treatment. Conclusion: In this paper, we reviewed various kinds of ApDCs, i.e., ApDC nucleotide analogs, ApDC by drug intercalation, and ApDC by using chemical linker. Current data prove these ApDCs have sufficient potential to complete clinical development soon. Advanced technology of cancer drug delivery and combination treatment of cancers enables aptamer and conjugated drug (ApDCs) efficient means for targeted cancer treatment that reduces potential toxicity and increases therapeutic efficacy.

Hyaluronate/black phosphorus complexes as a copper chelating agent for Wilson disease treatment

김성종,한혜현,한세광 한국생체재료학회 2021 생체재료학회지 Vol.25 No.3

Background: Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD. Methods: We developed hyaluronate-diaminohexane/black phosphorus (HA-DAH/BP) complexes for capturing copper ions accumulated in the liver for the treatment of WD. Results: HA-DAH/BP complexes showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-DAH/BP complexes to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-DAH/BP complexes. Conclusion: HA-DAH/BP complexes would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.

Construction of magnetic nanochains to achieve magnetic energy coupling in scaffold

Cijun Shuai,Xuan Chen,Chongxian He,Guowen Qian,Yang Shuai,SHUPING PENG,Youwen Deng,Wenjing Yang 한국생체재료학회 2022 생체재료학회지 Vol.26 No.3

Background: Fe3O4 nanoparticles are highly desired for constructing endogenous magnetic microenvironment in scaffold to accelerate bone regeneration due to their superior magnetism. However, their random arrangement easily leads to mutual consumption of magnetic poles, thereby weakening the magnetic stimulation effect. Methods: In this study, magnetic nanochains are synthesized by magnetic-field-guided interface co-assembly of Fe3O4 nanoparticles. In detail, multiple Fe3O4 nanoparticles are aligned along the direction of magnetic force lines and are connected in series to form nanochain structures under an external magnetic field. Subsequently, the nanochain structures are covered and fixed by depositing a thin layer of silica (SiO2), and consequently forming linear magnetic nanochains (Fe3O4@SiO2). The Fe3O4@SiO2 nanochains are then incorporated into poly l-lactic acid (PLLA) scaffold prepared by selective laser sintering technology. Results: The results show that the Fe3O4@SiO2 nanochains with unique core–shell structure are successfully constructed. Meanwhile, the orderly assembly of nanoparticles in the Fe3O4@SiO2 nanochains enable to form magnetic energy coupling and obtain a highly magnetic micro-field. The in vitro tests indicate that the PLLA/Fe3O4@SiO2 scaffolds exhibit superior capacity in enhancing cell activity, improving osteogenesis-related gene expressions, and inducing cell mineralization compared with PLLA and PLLA/Fe3O4 scaffolds. Conclusion: In short, the Fe3O4@SiO2 nanochains endow scaffolds with good magnetism and cytocompatibility, which have great potential in accelerating bone repair

Overcome the barriers of the skin: exosome therapy

Gi Hoon Yang,Yoon Bum Lee,강동구,Eunjeong Choi,Yoonju Nam,Kyoung Ho Lee,Hi Jin You,Hyo Jin Kang,안상현,전호준 한국생체재료학회 2021 생체재료학회지 Vol.25 No.3

Exosomes are nano-sized cargos with a lipid bilayer structure carrying diverse biomolecules including lipids, proteins, and nucleic acids. These small vesicles are secreted by most types of cells to communicate with each other. Since exosomes circulate through bodily fluids, they can transfer information not only to local cells but also to remote cells. Therefore, exosomes are considered potential biomarkers for various treatments. Recently, studies have shown the efficacy of exosomes in skin defects such as aging, atopic dermatitis, and wounds. Also, exosomes are being studied to be used as ingredients in commercialized skin treatment products. In this review, we discussed the need for exosomes in skin therapy together with the current challenges. Moreover, the functional roles of exosomes in terms of skin treatment and regeneration are overviewed. Finally, we highlighted the major limitations and the future perspective in exosome engineering.

Application of Bonelike® as synthetic bone graft in orthopaedic and oral surgery in veterinary clinical cases.

José Miguel Campos,Ana Catarina Sousa,Pedro Olivério Pinto,Jorge Ribeiro,Miguel Lacueva França,Ana Rita Caseiro,Mariana Vieira Branquinho,Sílvia Santos Pedrosa,Carla Mendonça,Ana Brandão,José Domingos 한국생체재료학회 2019 생체재료학회지 Vol.23 No.1

Autologous bone remains the gold standard grafting substrate for bone fusions used for small gaps and critical defects. However, significant morbidity is associated with the harvesting of autologous bone grafts and, for that reason, alternative bone graft substitutes have been developed. In the present case series, a glass-reinforced hydroxyapatite synthetic bone substitute, with osteoinductive and osteoconductive proprieties, was applied. This synthetic bone substitute comprises the incorporation of P2O5-CaO glass-based system within a hydroxyapatite matrix, moulded into spherical pellets with 250-500 μm of diameter. A total of 14 veterinary clinical cases of appendicular bone defects and maxillary / mandibular bone defects are described. In all clinical cases, the synthetic bone substitute was used to fill bone defects, enhancing bone regeneration and complementing the recommended surgical techniques. Results demonstrated that it is an appropriate synthetic bone graft available to be used in veterinary patients. It functioned as a space filler in association with standard orthopaedic and odontological procedures of stabilization, promoting a faster bone fusion without any local or systemic adverse reactions. This procedure improves the animals’ quality of life, decreasing pain and post-operative recovery period, as well as increasing bone stability improving positive clinical outcomes.