Jin Ik Lim

Lotus-leaf-like structured heparin-conjugated poly(L-lactide-co-ɛ-caprolactone) as a blood compatible material

A heparin-conjugated biodegradable polymer was synthesized by direct coupling of heparin to poly(L-lactide-co-ɛ-caprolactone) (PLCL) and was manufactured into lotus-leaf-like structured films. We evaluated whether lotus-leaf-like structured heparin-conjugated PLCL (LH-PLCL) could be applied to blood vessel tissue engineering. Differences in the surface structures of the films with respect to hydrophobicity and the lotus effect as well as the antithrombotic efficiency in human whole blood were examined using scanning electron microscopy (SEM) and a contact angle meter. Recovery testing was conducted using a tensile strength testing machine, and quantitative analysis of conjugated heparin was performed using the toluidine blue colorimetric method. The concentration of conjugated heparin was 0.14 μg/mg H-PLCL, and the contact angle with the lotus-leaf-like surface was approximately 120°. Furthermore, the LH-PLCL film yielded a lower platelet adhesion rate (around less than 1.4%) in whole blood than that yielded by an untreated PLCL film. These results indicate a unique property of bound heparin and the lotus-leaf-like structure. This novel LH-PLCL polymer could be applied as a blood/tissue compatible biodegradable material for implantable medical devices and tissue engineering.

Preparation of lotus-leaf-like structured blood compatible poly(ɛ-caprolactone)-block-poly(l-lactic acid) copolymer film surfaces

Lotus-leaf-like structured poly(ε-caprolactone)-block-poly(L-lactic acid) copolymer (PCL-b-PLLA) films cast using the solvent-nonsolvent casting method. PCL-b-PLLA was synthesized by the well-known copolymerization process, and was confirmed by (1)H NMR analysis. The molecular weight of the synthesized PCL-b-PLLA was measured by gel permeation chromatography (GPC). The number-average (Mn), weight-average (Mw) molecular weights and polydispersity (Mw/Mn) were 3.9×10(4), 5.1×10(4), and 1.3, respectively. PCL-b-PLLA films were cast in vacuum conditions with various nonsolvent ratios. Tetrahydrofuran (THF) was used as solvent and ethanol was used as nonsolvent. Surface hydrophobicity was confirmed by the water contact angle. The water contact angle was increased from 90.9°±4.2° to 130.2°±3.6°. Water contact angle was found to be influenced by surface topography. The prepared film surfaces were characterized by scanning electron microscopy (SEM). Changes in crystalline property were characterized by X-ray diffraction (XRD). Platelet adhesion tests of the modified PCL-b-PLLA film surfaces were evaluated by platelet-rich plasma (PRP) and whole blood. Cell adhesive behavior on the modified film surfaces was evaluated by fibroblast cell culture. The prepared lotus-leaf-like structured film surfaces exhibited reduced platelet adhesion and an increased fibroblast cell proliferation ratio.

Preparation of topographically modified poly(L-lactic acid)-b-Poly(ɛ-caprolactone)-b-poly(L-lactic acid) tri-block copolymer film surfaces and its blood compatibility

Hindering early platelet adhesion and enhancing human vascular endothelial cell proliferation on surfaces of the foreign materials play a key role in the prevention of coagulation. In order to develop topographically suitable surface for artificial grafts, topographically modified poly(L-lactic acid)-b-poly(ɛ-caprolactone)-b-poly(L-lactic acid) tri-block copolymer (PLLA-PCL-PLLA) film surfaces were cast using a simple solvent-nonsolvent method. PLLA-PCL-PLLA copolymer was synthesized, and was confirmed by 1H nuclear magnetic resonance (NMR) analysis. The molecular weight of the copolymer was measured using gel permeation chromatography (GPC). PLLAPCL-PLLA films were cast with various ratios of non-solvent in the solvent mixture. Tetrahydrofuran (THF) and ethyl alcohol (EtOH) were used as solvent and nonsolvent respectively. The hydrophobic characteristic of the surfaces was confirmed by the water contact angle (WCA). The prepared film surfaces were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray diffraction (XRD). Anti-platelet adhesion characteristic was evaluated using Lactate Dehydrogenase (LDH) assay and SEM images. Proliferation behavior of human vascular endothelial cell was investigated by water-soluble tatrazolium salt (WST) assay after 3 h, 1 day, 2 days and 4 days of cell culture on the film surface. Fabricated morphologically unique surface, which consists of submicron size width and nano size height rough structure, shows anti platelet adhesive ability and relatively higher human vascular endothelial cell proliferation behavior.

Fabrication and medical applications of lotus-leaf-like structured superhydrophobic surfaces

다양한 생체재료들이 이식용 인공장기나 의료용 장비로 폭넓게 사용되고 있으나 혈액과 접촉하는 경우가 많아짐으로써 발생되는 혈전의 문제로 인해 이식재와 혈액간의 혈액 친화성의 향상이 연구자들에게 관심의 대상이 되고 있다. 연잎의 표면구조는 항 오염 특성이라는 측면에서 많은 연구가 진행되어 왔으며, 산업적인 용도로 적용하고자 하는 주된 시도들이 있어 왔다. 대부분 주형법이나 졸-젤 방법, 층 쌓기 방법 등을 포함한 다양한 기법으로 표면처리를 함으로써 인위적인 모사가 가능해 왔다. 최근에 들어 이러한 표면의 초소수성 성질이 의료용 재료의 표면처리 기법으로써 혈관 이식재에서부터 항 박테리아용 표면에까지 널리 적용하려는 시도가 진행되고 있다. 본 리뷰논문에서는 최근 많이 사용되는 연잎 구조로의 표면처리 기법들을 중심으로 요약하였으며, 이들을 이용한 의료분야로의 적용 시도들을 정리하고자 하였다. 【Various biomaterials have been widely used for biomedical applications, including bio-organs, medical devices, and clinical devices like vessel, blood pumps, artificial kidneys and hearts, even in contact with blood. The issue of blood compatibility has been studied intensively to prevent negative effects such as thrombosis due to the implanted devices. The use of lotus-leaf-like structured surfaces has been extended to an increasing number of applications such as contamination prevention and anticorrosion applications. Various methods such as template, sol-gel transition, layer-by-layer, and other methods, developed for the fabrication of lotus-leaf-like surfaces have been reported for major industrial applications. Recently, the non-wettable character of these surfaces has been shown to be useful for biomedical applications ranging from blood-vessel replacement to antibacterial surface treatment. In this review, we provide a summary of current and future research efforts and opportunities in the development and medical applications of lotus-leaf-like structure surfaces.】

Histological behavior of HDPE scaffolds fabricated by the "Press-and-Baking" method

High density polyethylene (HDPE) scaffolds were fabricated by a new “Press-and-Baking” method without using solvents. This method involved mixing HDPE and salt particles, then pressing and baking to produce porous scaffolds after the salt was leached out. The HDPE scaffolds from 80wt% salt had strength and flexibility comparable to commercial Medpor HDPE implants. The HDPE scaffolds provided larger and more pores than Medpor. The HDPE scaffolds were oxidized by ozone to investigate the effect of increased hydrophilicity on tissue healing. The HDPE scaffolds fabricated were implanted subcutaneously into rats for 28 days to evaluate the biocompatibility compared with Medpor. The HDPE scaffolds exhibited suitable tolerance with surrounding tissue. Although the tissue ingrowth in the HDPE scaffolds infiltrated the pores slower, denser tissue formation was organized in the scaffolds, while Medpor allowed tissue to infiltrate more readily into the interconnective pores. These results indicate that the difference in porous structural morphology affects tissue ingrowth. In contrast, the increased hydrophilicity by ozone oxidation had little effect on tissue ingrowth.