Biomedical subjects

Hsu-Wei Fang

Publications and source records attributed to Hsu-Wei Fang.

4 recordsLinked to original sources

PubMed2006

Preparation of UHMWPE particles and establishment of inverted macrophage cell model to investigate wear particles induced bioactivites.

Total joint replacement surgery has been widely applied to patients with severe osteoarthritis. Aseptic loosening induced by wear particles generated during joint movement is the major reason causing the failure of joint implants. Interaction of ultra-high molecular weight polyethylene (UHMWPE) wear particles with macrophages stimulates the release of inflammatory cytokines and leads to bone resorption and osteolysis. Effect of UHMWPE particle size and shape on the bioactivities remains unclear due to the lack of particles with controlled morphology as well as adequate in-vitro cell culture models for further investigations. We have developed a micro-cutting procedure to generate UHMWPE particles with desired sizes and shapes by rubbing UHMWPE with microfabricated surfaces. A narrow distribution and sterility of the generated particles was achieved. An inverted cell culturing apparatus and procedures were created and the contact between particles and macrophage cells was observed. No significant difference of the cell proliferations under normal and inverted positions further demonstrates the feasibility of the system. This newly developed platform can assist in the further understanding of the mechanism and therapy strategies of osteolysis induced by polyethylene particles.

Bone Resorption↗

PubMed2006

Structural analysis of human lysozyme using molecular dynamics simulations.

In this study, various molecular dynamics simulations were conducted to investigate the effects of ethanol and temperature on the conformational changes of human lysozyme, which may lead insights into amyloidosis. The analyses of some important structural characteristics, such as backbone root-mean-square deviation, secondary structural stability, radius of gyration, accessible surface area, and hydrophobic contact of the hydrophobic core all show that ethanol tends to destabilize human lysozyme at high temperatures. It can be attributed to that higher temperatures result in the destruction of the native structure of this protein, leading to the exposure of the interior hydrophobic core. At this stage, ethanol plays a role to destroy this region by forming hydrophobic interactions between protein and solvent due to its lower polarity comparing to water. Such newly formed intermolecular interactions accelerate the unfolding of this protein, starting from the core between the alpha- and beta-domains. Our results are in good agreement with the previous hypothesis suggesting that the distortion of the hydrophobic core at the alpha- and beta-interface putatively results in the formation of the initial "seed" for amyloid fibril. Although the present results cannot directly be linked to fibril formation, they still provide valuable insights into amyloidosis of human lysozyme.

Amyloid↗

PubMed2003

Generation of narrowly distributed ultra-high-molecular-weight polyethylene particles by surface texturing techniques.

Ultra-high-molecular-weight polyethylene (UHMWPE) wear particles have been recognized as the cause of aseptic loosening in total joint replacement. Macrophage phagocytosis of wear particles induces human biological/physiological responses which eventually lead to bone resorption and osteolysis. However, the dependence of these reactions on the size and shape of the particles has not been elucidated and is not understood. This article describes a procedure to generate narrowly distributed UHMWPE particles of controlled size and shape through surface texturing by microfabrication. The textured surface is then used to rub against the polymer pins to produce wear particles in water. The surface texture produces elongated particles or equiaxed particles by design. The distribution of the particles, due to the surface-texture control, is quite narrow as compared with randomly produced surfaces. With this technique, we are able to generate UHMWPE wear particles of different size and shape within phagocytosable and nonphagocytosable populations for biological response studies.

Biocompatible Materials↗

PubMed2003

Distinct gene expression of receptor activator of nuclear factor-kappaB and rank ligand in the inflammatory response to variant morphologies of UHMWPE particles.

Recent studies have examined the role of wear debris-induced bone resorption in the aseptic loosening of orthopedic prostheses. Research has shown that inflammation depends not only on the amount of particulate debris, but also the shape and size of the accumulated wear particles. Our previous studies have demonstrated that variant shapes of ultra-high molecular weight polyethylene (UHMWPE) particles induce diverse cellular and apoptotic responses in a murine inflammation model. Since enhanced osteoclastogenesis is recognized as a hallmark of bone loss in prosthetic loosening, we have now investigated the gene expression of receptor activator of nuclear factor-kappaB (RANK) and receptor activator of nuclear factor-kappaB ligand (RANKL) during the inflammatory response to different shapes of UHMWPE particles. Two shapes of UHMWPE particles (globular or elongated) were implanted in established air pouches on BALB/c mice, and pouches harvested 7 days after stimulation with UHMWPE particles. Gene levels of RANK, RANKL, TNFalpha, IL-1beta, and cathepsin K (CK) were quantified by real time RT-PCR, and TRAP staining of pouch membrane was used to evaluate osteoclastogenesis. We found that (i) elongated particles generated significantly higher RANK and RANKL gene expression than globular particles in pouch tissue; (ii) elongated particles provoked significantly higher IL-1beta and TNFalpha gene expression; (iii) a positive association was found between tissue inflammation status and the gene level of RANK/RANKL; and (iv) elongated particles stimulated significantly higher CK gene expression in comparison with globular particles. Histology revealed that clusters of TRAP+ cells were located in regions in contact with elongated particles. Overall, these data suggest that the morphology of wear debris may be a critical factor in the pathogenesis of prosthetic loosening.

Animals↗