Polyethylene particle-induced osteolysis is the primary limitation in the long-term success of total joint replacement with conventional ultra high molecular weight polyethylene (UHMWPE). Highly cross-linked polyethylene (HXLPE) and vitamin E-doped cross-linked polyethylene (VE-HXLPE) have been developed to increase the wear resistance of joint surfaces. However, very few studies have reported on the incidence of particle-induced osteolysis for these novel materials. The aim of this study was to use a particle-induced osteolysis animal model to compare the in vivo biological response to different polymer particles. Three commercially available polymers (UHMWPE, HXLPE, and VE-HXLPE) were compared. Osseous properties including the bone volume relative to the tissue volume (BV/TV), trabecular thickness (Tb. Th), and bone mineral density (BMD) were examined using micro computed tomography. Histological analysis was used to observe tissue inflammation in each group. This study demonstrated that the osseous properties and noticeable inflammatory reactions were obviously decreased in the HXLPE group. When compared with the sham group, a decrease of 12.7% was found in BV/TV, 9.6% in BMD and 8.3% in Tb.Th for the HXLPE group. The heightened inflammatory response in the HXLPE group could be due to its smaller size and greater amount of implanted particles. Vitamin E diffused in vivo may not affect the inflammatory and osteolytic responses in this model. The morphological size and total cumulative amount of implanted particles could be critical factors in determining the biological response.

The project was initiated as a direct result of the NIST Orthopaedic Wear Consortium established by John Tesk and Stephen Hsu. One of the ongoing concerns of the biomedical community is how to test the bioactivity of wear particles generated by the artificial joints. Mr. Hsu-Wei Fang at University of Maryland chose this topic as his Ph.D. thesis and this report is a summary of his research in the past five years. Prof. Jan Sengers lent his support to this project by serving as co-advisor to Mr. Fang and helped guide the thesis research to a successful conclusion. In this report, you will find how wear particles induce bone loosening, how particles can be generated, the particle formation mechanisms, and theoretical models describing how to control the size and shape of particles using microfabricated surface textures. Bioactivity tests on particles were performed by the Federal Food and Drug Administration and the Wayne State University through collaborations. We sincerely thank them for their technical assistances. It is always a pleasure to work with someone like Dr. Hsu-Wei Fang who has persevered through the past five years to reach a successful goal. Cooperative research such as this furthers one's educational goals while serving the programmatic goals of NIST. This is a model that merits encouragement.

Protein misfolding and aggregation cause a large number of neurodegenerative diseases in humans due to (i) gain of function as observed in Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and Prion’s disease or (ii) loss of function as observed in cystic fibrosis and α1-antitrypsin deficiency. These misfolded proteins could either lead to the formation of harmful amyloids that become toxic for the cells or to be recognized and prematurely degraded by the protein quality control system. An increasing number of studies has indicated that some low-molecular-weight compounds named as chemical chaperones can reverse the mislocalization and/or aggregation of proteins associated with human conformational diseases. These small molecules are thought to non-selectively stabilize proteins and facilitate their folding. In this review, we summarize the probable mechanisms of protein conformational diseases in humans and the use of chemical chaperones and inhibitors as potential therapeutic agents against these diseases. Furthermore, recent advanced experimental and theoretical approaches underlying the detailed mechanisms of protein conformational changes and current structure-based drug designs towards protein conformational diseases are also discussed. It is believed that a better understanding of the mechanisms of conformational changes as well as the biological functions of these proteins will lead to the development and design of potential interfering compounds against amyloid formation associated with protein conformational diseases.

Chondrocytes have been demonstrated to be sensitive to mechanical stimuli, such as compression, tension, shear force, and hydrostatic pressure. The responses of chondrocytes to mechanical compression have been often studied in vitro with cartilage and chondrocyte/hydrogel systems. The aim of this study was to investigate the effects of dynamic compression on gene expression of rabbit chondrocytes which were seeded in elastic polyurethane scaffolds with or without collagen gel encapsulation. Dynamic compression of 20% or 30% strain with 0.1 Hz frequency was applied to the cell-seeded scaffolds for 4, 8, 12, or 24 h, and then the expression of the three genes related to chondrogenic phenotype, type I and II collagens and aggrecan, was analyzed by RT-PCR. We also investigated the gene expression of the compressed chondrocytes, which had experienced 12-h 30% strain dynamic loading, during the post-compression resting period. We found that the expression of type II collagen did not seem to respond to cyclic compression. On the other hand, aggrecan gene was stimulated by dynamic compression. The stimulatory effect disappeared gradually after the dynamic compression was ceased. Furthermore, the mechano-response of the chondrocytes to aggrecan expression was delayed by collagen gel encapsulation. The expression of type I collagen was enhanced by collagen gel. We found that collagen gel encapsulation prolonged the expression of aggrecan and type I collagen during post-compression resting period. We demonstrated that mechanical and biochemical stimuli modulate the gene expression of chondrocytes.

Demineralized bone matrix (DBM) is a decalcified allo/xenograft retaining collagen and noncollagenous proteins, which has been extensively used because of its osteoconductive and osteoinductive properties. Calcium sulfate (CaSO4, CS) is a synthetic bone substitute used in bone healing with biocompatible, nontoxic, bioabsorbable, osteoconductive, and good mechanical characteristics. This study aims to prepare a DBM/CS composite bone graft material in a moldable putty form without compromising the peculiar properties of DBM and CS. For this purpose, firstly, porcine femur was defatted using chloroform/methanol and extracted by acid for demineralization, then freeze-dried and milled/sieved to obtain DBM powder. Secondly, the α-form and β-form of calcium sulfate hemihydrate (CaSO4 •0.5H2O, CSH) were produced by heating gypsum (CaSO4 •2H2O). The morphology and particle sizes of α- and β-CSH were obtained by SEM, and their chemical properties were confirmed by EDS, FTIR and XRD. Furthermore, the DBM-based graft was mixed with α- or β-CSH at a ratio of 9:1, and glycerol/4% HPMC was added as a carrier to produce a putty. DBM/CSH putty possesses a low washout rate, good mechanical strength and biocompatibility. In conclusion, we believe that the moldable DBM/CSH composite putty developed in this study could be a promising substitute for the currently available bone grafts, and might have practical application in the orthopedics field as a potential bone void filler.