Jimin Park

Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy

Significance In the past decade, countless studies have been performed to control the mechanical and corrosion property of magnesium-based alloy, which degrades in the physiological environment, to overcome the flaws of the inert implant materials and shift the paradigm of conventional bone fixation devices. Controlled degradation of Mg-5wt%Ca-1wt%Zn alloy results in the formation of biomimicking calcification matrix at the degrading interface to initiate the bone formation process. This process facilitates early bone healing and allows the complete replacement of biodegradable Mg implant by the new bone within 1 y of implantation, as demonstrated in 53 cases of successful long-term clinical study. There has been a tremendous amount of research in the past decade to optimize the mechanical properties and degradation behavior of the biodegradable Mg alloy for orthopedic implant. Despite the feasibility of degrading implant, the lack of fundamental understanding about biocompatibility and underlying bone formation mechanism is currently limiting the use in clinical applications. Herein, we report the result of long-term clinical study and systematic investigation of bone formation mechanism of the biodegradable Mg-5wt%Ca-1wt%Zn alloy implant through simultaneous observation of changes in element composition and crystallinity within degrading interface at hierarchical levels. Controlled degradation of Mg-5wt%Ca-1wt%Zn alloy results in the formation of biomimicking calcification matrix at the degrading interface to initiate the bone formation process. This process facilitates early bone healing and allows the complete replacement of biodegradable Mg implant by the new bone within 1 y of implantation, as demonstrated in 53 cases of successful long-term clinical study.

Apoptosis-inducing effect of diketopiperazine disulfides produced by Aspergillus sp. KMD 901 isolated from marine sediment on HCT116 colon cancer cell lines.

Aims:  Research is to identify the bioactive secondary metabolites produced by Aspergillus sp. KMD 901 isolated from marine sediment and to assess their apoptosis‐inducing effects.

Creating Hierarchical Topographies on Fibrous Platforms Using Femtosecond Laser Ablation for Directing Myoblasts Behavior.

Developing an artificial extracellular matrix that closely mimics the native tissue microenvironment is important for use as both a cell culture platform for controlling cell fate and an in vitro model system for investigating the role of the cellular microenvironment. Electrospinning, one of the methods for fabricating structures that mimic the native ECM, is a promising technique for creating fibrous platforms. It is well-known that align or randomly distributed electrospun fibers provide cellular contact guidance in a single pattern. However, native tissues have hierarchical structures, i.e., topographies on the micro- and nanoscales, rather than a single structure. Thus, we fabricated randomly distributed nanofibrous (720 ± 80 nm in diameter) platforms via a conventional electrospinning process, and then we generated microscale grooves using a femtosecond laser ablation process to develop engineered fibrous platforms with patterned hierarchical topographies. The engineered fibrous platforms can regulate cellular adhesive morphology, proliferation, and distinct distribution of focal adhesion proteins. Furthermore, confluent myoblasts cultured on the engineered fibrous platforms revealed that the direction of myotube assembly can be controlled. These results indicate that our engineered fibrous platforms may be useful tools in investigating the roles of nano- and microscale topographies in the communication between cells and ECM.

Approximating bone ECM: Crosslinking directs individual and coupled osteoblast/osteoclast behavior.

Osteoblast and osteoclast communication (i.e. osteocoupling) is an intricate process, in which the biophysical profile of bone ECM is an aggregate product of their activities. While the effect of microenvironmental cues on osteoblast and osteoclast maturation has been resolved into individual variables (e.g. stiffness or topography), a single cue can be limited with regards to reflecting the full biophysical scope of natural bone ECM. Additionally, the natural modulation of bone ECM, which involves collagenous fibril and elastin crosslinking via lysyl oxidase, has yet to be reflected in current synthetic platforms. Here, we move beyond traditional substrates and use cell-derived ECM to examine individual and coupled osteoblast and osteoclast behavior on a physiological platform. Specifically, preosteoblast-derived ECM is crosslinked with genipin, a biocompatible crosslinker, to emulate physiological lysyl oxidase-mediated ECM crosslinking. We demonstrate that different concentrations of genipin yield changes to ECM density, stiffness, and roughness while retaining biocompatibility. By approximating various bone ECM profiles, we examine how individual and coupled osteoblast and osteoclast behavior are affected. Ultimately, we demonstrate an increase in osteoblast and osteoclast differentiation on compact and loose ECM, respectively, and identify ECM crosslinking density as an underlying force in osteocoupling behavior.

Magnesium Corrosion Triggered Spontaneous Generation of H2O2 on Oxidized Titanium for Promoting Angiogenesis

Although the use of reactive oxygen species (ROS) has been extensively studied, current systems employ external stimuli such as light or electrical energy to produce ROS, which limits their practical usage. In this report, biocompatible metals were used to construct a novel electrochemical system that can spontaneously generate H2O2 without any external light or voltage. The corrosion of Mg transfers electrons to Au-decorated oxidized Ti in an energetically favorable process, and the spontaneous generation of H2O2 in an oxygen reduction reaction was revealed to occur at titanium by combined spectroscopic and electrochemical analyses. The controlled release of H2O2 noticeably enhanced in vitro angiogenesis even in the absence of growth factors. Finally, a new titanium implant prototype was developed by Mg incorporation, and its potential for promoting angiogenesis was demonstrated.

Direct and accurate measurement of size dependent wetting behaviors for sessile water droplets

The size-dependent wettability of sessile water droplets is an important matter in wetting science. Although extensive studies have explored this problem, it has been difficult to obtain empirical data for microscale sessile droplets at a wide range of diameters because of the flaws resulting from evaporation and insufficient imaging resolution. Herein, we present the size-dependent quantitative change of wettability by directly visualizing the three phase interfaces of droplets using a cryogenic-focused ion beam milling and SEM-imaging technique. With the fundamental understanding of the formation pathway, evaporation, freezing, and contact angle hysteresis for sessile droplets, microdroplets with diameters spanning more than three orders of magnitude on various metal substrates were examined. Wetting nature can gradually change from hydrophobic at the hundreds-of-microns scale to super-hydrophobic at the sub-μm scale, and a nonlinear relationship between the cosine of the contact angle and contact line curvature in microscale water droplets was demonstrated. We also showed that the wettability could be further tuned in a size-dependent manner by introducing regular heterogeneities to the substrate.

Elasticity Modulation of Fibroblast-Derived Matrix for Endothelial Cell Vascular Morphogenesis and Mesenchymal Stem Cell Differentiation.

Biophysical properties of the microenvironment, including matrix elasticity and topography, are known to affect various cell behaviors; however, the specific role of each factor is unclear. In this study, fibroblast-derived matrix (FDM) was used as cell culture substrate and physically modified to investigate the influence of its biophysical property changes on human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) behavior in vitro. These FDMs were physically modified by simply storing them at different temperatures: the one stored at 4°C, maintained its original properties, was considered natural FDM, whereas the ones stored at -20°C or -80°C, exhibited a distinct surface morphology, were considered physically modified FDM. Physical modification induced matrix fiber rearrangement in FDM, forming different microstructures on the surface as characterized by focused ion beam (FIB)-cryoSEM. A significant increase of matrix elasticity was found with physically modified FDMs as determined by atomic force microscopy. HUVEC and hMSC behaviors on these natural and physically modified FDMs were observed and compared with each other and with gelatin-coated coverslips. HUVECs showed a similar adhesion level on these substrates at 3 h, but exhibited different proliferation rates and morphologies at 24 h; HUVECs on natural FDM proliferated relatively slower and assembled to capillary-like structures (CLSs). It is observed that HUVECs assembled to CLSs on natural FDMs are independent on the exogenous growth factors and yet dependent on nonmuscle myosin II activity. This result indicates the important role of matrix mechanical properties in regulating HUVECs vascular morphogenesis. As for hMSCs multilineage differentiation, adipogenesis is improved on natural FDM that with lower matrix elasticity, while osteogenesis is accelerated on physically modified FDMs that with higher matrix elasticity, these results further confirm the crucial role of matrix elasticity on cell fate determination.

Ultrathin Metal Films with Defined Topographical Structures as In Vitro Cell Culture Platforms for Unveiling Vascular Cell Behaviors.

Implanted material surfaces make direct contact with body tissues to work on its own purpose. Therefore, studies of the surface properties of implantable materials that determine cell fate are very important for successful implantation. Although numerous studies have addressed the relationship between cells and material surfaces, nonmetallic surfaces and metallic surfaces likely produce different cellular responses because of their intrinsic differences in surface energy, roughness, and chemical composition. Moreover, given the nontransparent property of metal materials, which hampers the real-time imaging of cellular behavior, a detailed cellular-level analysis at the metal-tissue interface has not been performed. In this study, metal-based cell culture platforms (MCPs) with defined microscale topographical patterns are developed using a combination of photolithography and direct current magnetron sputtering techniques. The MCPs allow to observe vascular cells on metals in real time and identify the selective regulation of human aortic smooth muscle cells and Human umbilical vein endothelial cells (HUVECs) by metallic surface topography. Additionally, atomic force microscopy, contact angles, and energy-dispersive X-ray spectroscopy analyses show that the MCPs exhibit nearly identical chemical properties with their bulk counterparts, demonstrating that MCPs can be utilized as an in vitro cell culture platform system for understanding the cellular behavior on metal substrates.