Treatment of Osteomyelitis with Hydrogel Nanoparticles & Identification of biomakers in loosened total hip arthroplasty

• Main Authors: Kuo Ti Peng, 彭國狄
• Other Authors: P. J. Chang
• Format: Others
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/66655008471811897591

博士 === 長庚大學 === 臨床醫學研究所 === 98 === Part I : Treatment of osteomyelitis with teicoplanin-encapsulated biodegradable thermosensitive hydrogel nanoparticles Osteomyelitis characterized by an inflammatory response often leads to bone loss and the spread of bacterial infection to surrounding soft tissues. To overcome the side effects induced by the systemic antibiotic treatment for osteomyelitis, recent investigations have explored the use of antibiotic-loaded undegradable or biodegradable delivery implants at the infected bone. Here, we show a novel biodegradable thermosensitive implant composed of poly(ethylene glycol) monomethyl ether (mPEG) and poly(lactic-co-glycolic acid) (PLGA) copolymer as a sol-gel drug delivery system for treating bone infection. The physical properties of a series of mPEG-PLGA nanocomposites, including the critical micelle concentration (CMC), particle size, polyindex (PI), sol-gel transition, viscosity and degradation rate, have been characterized in vitro. This sol-to-gel drug delivery system could provide several advantages in treating osteomyelitis, including easy preparation, 100 % encapsulated rate, near-linear sustained release of drugs, injectable design and in situ gelling at the target tissue. Similar to the undegradable teicoplanin-impregnated polymethylmethacylate (PMMA) bone cements, we showed that implantation of the mPEG-PLGA hydrogel containing teicoplanin was effective for treating osteomyelitis in rabbits as detected by the histological staining and immunoblotting analyses. The use of the mPEG-PLGA-based biodegradable hydrogels may hold great promise as a therapeutic strategy for other infected diseases. Part II : Identification of ROS-associated Makers in Aseptic Loosened Total Hip Arthroplasty Aseptic loosening remains the major complication after total hip arthroplasty (THA). Several theories on the cause of aseptic loosening have been proposed. Wear-generated particles are commonly accepted that the initiating cause with an inflammatory response to phagocytosis and resulting in increased proliferation and differentiation of osteoclast precursors into mature osteoclasts. Progressive osteolysis caused by active-osteoclasts can result in prosthesis failure, eventually requiring revision surgery. More recently, it has been established that wear also inhibits the protective actions of antiosteoclastogenic cytokines such as interferon gamma, thus promoting differentiation of macrophages to bone-resorbing osteoclasts. At a molecular level, wear particles activate MAP kinase cascades, NFκB and other transcription factors, and induce expression of suppressors of cytokine signaling. Besides particles, stress shielding, high fluid pressure, genetic variations, and endotoxin were also considered the possible etiologies for loosening. Recently, the role of reactive oxygen species (ROS) (hydrogen peroxide [H2O2], hydroxyl radicals radical [OH*] and superoxide anion [O2-*]) as products of metal corrosion, mostly of titanium, is more often discussed with respect to the overall process of aseptic loosening [8]. In addition, a number of groups studied the influence of H2O2 and ROS from macrophages in process of inflammatory after implantation of prosthesis. However, aseptic loosening of joint implants is still a major problem and need to identify the possible makers. In present study, a proteomic approach was applied to discover novel loosened THA-specific proteins by comparing the expression profiles of synovial fluid from patients with loosened or non-loosened implant in-vivo. Two ROS-associated proteins, including transthyretin (TTR) and peroxiredoxin 2 (PRDX 2), were identified and verified. We also evaluated the role of ROS-associated enzymes (catalase, SOD 1, SOD 2 and SOD 3) in joint synovial fluid and capsule of loosened THA. Compare to non-loosened THA and primary groups, TTR and SOD 3 in synovial fluid of hip joint shows high expression in loosened THA group (p<0.05). PDRX 2 and SOD 2 in hip capsule demonstrate high expression in loosened THA group than non-loosened and primary THA groups To our knowledge, these special biomakers were firstly identified in loosen or non-loosened THA in present study. We believe increased knowledge of the biomakers in joint fluid or hip capsule of THA may prove useful for understanding the causes of THA failure.