A5034557839- Orthopedic Infections and Treatments
- Osteoarthritis Treatment and Mechanisms
- Bone Metabolism and Diseases
- Bone Tissue Engineering Materials
- Orthopaedic implants and arthroplasty
- Cell Adhesion Molecules Research
- Catalytic C–H Functionalization Methods
- Synthesis and Catalytic Reactions
- Bacterial biofilms and quorum sensing
- Bone health and treatments
- Cancer-related molecular mechanisms research
- X-ray Diffraction in Crystallography
- NF-κB Signaling Pathways
- Crystallization and Solubility Studies
- Dental Implant Techniques and Outcomes
- Antimicrobial Peptides and Activities
- Aquatic Ecosystems and Phytoplankton Dynamics
- Cyclopropane Reaction Mechanisms
- Cell death mechanisms and regulation
- Synthetic Organic Chemistry Methods
- Aquatic Ecosystems and Biodiversity
- RNA Interference and Gene Delivery
- Polymer Surface Interaction Studies
- MicroRNA in disease regulation
- Crystallography and molecular interactions
Philadelphia College of Osteopathic Medicine
2010-2019
University of Wisconsin–Madison
2012-2016
Madison Group (United States)
2014
Thomas Jefferson University
2002-2010
Appalachian State University
2010
Jefferson College
2010
University of California, Irvine
2009
Irvine University
2009
University of Pennsylvania
2000-2008
Thomas Jefferson University Hospital
2004-2008
Antibiotic concentrations associated with antibiotic bone cements may cause skeletal cell toxicity and prevent fracture healing. We investigated effects of dose treatment time after exposure to three antibiotics commonly used in orthopaedic local drug delivery systems. hypothesized a threshold exists for osteoblasts chondrocytes ciprofloxacin, vancomycin, or tobramycin. To test this hypothesis, we first determined whether caused differences cellular morphology. Cells exposed ciprofloxacin...
Abstract Periprosthetic infection is a devastating consequence of implant insertion and can arise from hematogenous sources or surgical contamination. Microbes preferentially colonize the surface and, by forming biofilm, escape immune surveillance. We hypothesized that if an antibiotic be tethered to titanium alloy (Ti) surface, it will inhibit bacterial colonization, prevent biofilm formation, avert late‐stage infection. To test this hypothesis, Ti rod was covalently derivatized with...
As easy as 1, 2, 3: A palladium-catalyzed three-component coupling generates alpha,beta-unsaturated gamma-amino acids in a single step (see scheme). The reaction is believed to involve migration of vinyl substituent highly electrophilic palladium carbene. Unlike previous synthetic approaches, this synthesis provides access with non-natural side chains.
Previously, we noted that inorganic phosphate (Pi), a major component of bone extracellular matrix, induced osteoblast apoptosis (Meleti, Z., Shapiro, I. M., and Adams, C. S. (2000) Bone (NY) 27, 359–366). Since Ca2+ along with Pi is released from during the resorption process, advanced hypothesis modulates Pi-mediated apoptosis. To test this hypothesis, osteoblasts were incubated both ions, cell death was determined. We modest increase in medium concentrations ([Ca2+]e) 0.1–1 mm caused...
Background Apoptosis in vivo has been identified developing cartilage from embryonic chick sterna and avian murine growth plates. To date, no evidence exists that chondrocytes articular undergo apoptosis. Methods We examined the distribution of cells demonstrating fragmented DNA knee C57BL/6 mice (aged 11, 18, 24, 30 months) Wistar rats 6, 12, 24 using a end-labeling technique. Results Control experiments utilizing retinoic acid-induced apoptosis chondrocyte cell line, established correlated...
This article reports that surface modification of poly(dimethylsiloxane) (PDMS) influences fibronectin (Fn) adsorption and enhances cell attachment. Controlled Fn on chemically activated polymer substrates is known to influence cellular function. Thin films PDMS were spun cast silicon wafers obtain homogeneous molecularly smooth surfaces. The made hydrophilic by exposure ultraviolet ozone activation (PDMS*). then characterized contact angle goniometry, ellipsometry, atomic force microscopy...
The goal of our investigation was to explore the mechanism by which hypoxia regulates growth plate chondrocyte survival. At low O2 tension, chondrocytes were refractory a staurosporine (i.e., apoptosis-inducing) challenge. To determine whether hypoxic survival due expression HIF-1, we evaluated response HIF silenced cells staurosporine. Both, and control equally sensitive apoptogen learn if resistance mediated proteins autophagic pathway, examined Beclin 1 LC3. Both present in as well N1511...
Proper growth and development require the orderly synthesis deposition of individual components extracellular matrix (ECM) into well ordered networks. Once formed, ECM maintains tissue structure houses resident cells. One component, βig-h3, is a highly conserved transforming factor-β-inducible protein that has been hypothesized to function as bifunctional linker between To gain insights its physiological function, full-length βig-h3 was produced using baculovirus expression system purified...
Abstract Objective We have previously demonstrated that the transcription factor hypoxia‐inducible 1 (HIF‐1) promotes onset of autophagy in chondrocytes. The overall goal this study was to test hypothesis another HIF family factor, HIF‐2, modulates induction by Methods Expression HIF‐1, and light chain 3 (LC3) human murine articular cartilage visualized immunohistochemistry. Suppression HIF‐2 achieved using small interfering RNA technology. Assessments autophagic flux lysosomal activity, as...
Peri-prosthetic infection remains a serious complication of joint replacement surgery. Herein, we demonstrate that vancomycin-containing sol-gel film on Ti alloy rods can successfully treat bacterial infections in an animal model. The films exhibited predictable release kinetics, while significantly inhibiting S. aureus adhesion. When evaluated rat osteomyelitis model, microbiological analysis indicated the caused profound decrease number. Radiologically, control side showed extensive bone...
Nitrogen-containing stereotriads, compounds with three adjacent stereodefined carbons, are commonly found in biologically important molecules. However, the preparation of molecules bearing these motifs can be challenging. Herein, we describe a modular oxidation protocol which converts substituted allene to triply functionalized amine form C-X/C-N/C-Y. The key step employs Rh-catalyzed intramolecular conversion strained bicyclic methylene aziridine. This reactive intermediate is further...
A major challenge in treating periprosthetic infection is the predilection of certain bacteria to colonize implants, form biofilms, and resist treatment. We engineered an innovative self-protective implant with covalently bound antibiotics that prevents bacterial colonization remains stable for extended periods time. To test this surface vivo, we developed a rat model intramedullary S. aureus-infected femora. Using model, then evaluated effect vancomycin-modified titanium rods on clinical...
Despite improved strategies for treating periprosthetic infection, current antibiotic delivery approaches are imperfect and can result in bacterial resistance recalcitrant bio-films. To address the issues, we developed a covalently linked vancomycin-titanium implant interface that prevents possibly eliminates colonization. We determined amount of vancomycin immobilized on titanium surface assessed stability activity over time. When incubated with Staphylococcus aureus, showed an almost...
Abstract Cell adhesion to biomaterials is a prerequisite for tissue integration with the implant surface. Herein, we show that can generate model silica surface contains minimal‐length arginine‐glycine‐aspartic acid (RGD) peptide maintains its biological activity. In first part of this study, attachment MC3T3‐E1 osteoblast‐like cells was investigated on silicon oxide, amine terminated substrates [i.e., 3‐aminopropyl triethoxysilane (APTS)], grafted RGD, and physisorbed RGD control. The APTS...
We tested the hypothesis that RGDS peptides regulate osteoblast survival in culture. Osteoblast-like MC3T3-E1 cells were allowed to attach had been tethered a silicone surface utilizing previously described grafting technique. The RGDS-modified caused up-regulation of alpha(v)beta(3) integrin. noted there was an increase expression activated focal adhesion kinase and Akt. There no change level anti-apoptotic protein Bcl-2, pro-apoptotic Bad, or inactivated form pBad. Attachment RGDS-treated...