Orthopedic Nanotechnology Research Program
Anuj Bellare, Ph.D.
Director, Orthopedic Nanotechnology Laboratory
Assistant Professor of Orthopedic Surgery, Harvard Medical School
Research Interests
Our laboratory focuses on the following research areas : orthopedic biomaterials; nanostructured materials; x-ray and neutron scattering of orthopedic polymers; implant tribology; mechanics of materials
Members & Collaborators
1) Thomas S. Thornhill, MD, Dept of Orthopedic Surgery, Brigham & Women’s Hospital, Boston, MA, USA
2) Wolfgang Fitz, MD, Dept of Orthopedic Surgery, Brigham & Women’s Hospital, Boston, MA, USA
3) Robert E. Cohen, PhD, Professor, Dept of Chemical Engineering, Massachusetts Institute of Technol., Cambridge, MA, USA
4) Lisa A. Pruitt, PhD, Professor, Dept of Mechanical Engineering, University of California at Berkeley, Berkeley, CA, USA
5) Alessandro Bistolfi, MD, Centro Traumatologico Ortopedico, Università di Torino, Turin, Italy
6) Fabio D’Angelo, MD, Sant’Andrea Hospital, University of Rome La Sapienza, Rome, Italy
7) Michele Boffano, MD, Centro Traumatologico Ortopedico, Università di Torino, Turin, Italy
The goal of this research program is to apply Nanotechnology to formulate high-performance biomaterials for application in orthopaedic implants. Currently, we have targeted two biomaterials that have a long history of use in total joint replacement prostheses. The first is ultra-high molecular weight polyethylene, which is a tough, highly wear resistant nanostructured semicrystalline polymer. Recently, we have used high-pressure processing to alter the nanostructure of radiation crosslinked polyethylene to increase its mechanical properties, while maintaining its high resistance to wear. The second biomaterial is bone cement, which is used as a grouting agent to fill the space between joint replacement prostheses and peri-prosthetic bone. We have developed nanocomposite bone cement with higher fatigue strength, which has been the primary focus of our research program in recent months.
Nanocomposite Bone Cements
Currently, bone cement used to treat infections has antibiotics powders, such as tobramycin and gentamicin, added to it. These powders are micrometer in size and are hard particles, which decrease the fracture toughness of acrylic bone cement, which usually comprises polymethyl methacrylate, a hard, glassy polymer. We hypothesized that decreasing the particle size of the antibiotics to the nanometer scale would increase the mechanical strength of bone cement instead of decreasing it. This would occur with well-dispersed nanoparticles since they would act as craze initiators. Crazing, a precursor to microcrack formation, is desirable since it leads to dissipation of energy, which would otherwise be directed to microcrack formation. The microcracks would then coalesce into large cracks, ultimately leading to failure of the acrylic bone cement. Thus, the use of antibiotic nanoparticles, may slow down crack formation in cement, leading to longer in-vivo use. We recently acquired the Superparticle SAS200, which is is an innovative equipment to fabricate particles from solutions of antibiotics. The water-soluble antibiotics are injected thru a nozzle into supercritical carbondioxide (SCF-CO2). The size of the spray droplets can be manipulated by controlling the temperature and pressure applied to the SCF-CO2. When these temperatures and pressure are higher than the critical point for CO2, the CO2 attains properties intermediate between liquids and gases. When the antibiotic containing solution is injected into the SCF-CO2, it acts as a non-solvent, thereby precipitating the antibiotic into small particles. The use of water and CO2 ensures that biocompatible, environmentally benign processing method is used to create the micro and nanoparticles of antibiotics.
We have conducted preliminary experiments to test our hypothesis that the use of hard nanoparticles would increase the mechanical strength of acrylic bone cement. Like antibiotic particles, bone cements also contains 10 wt% of micrometer size particles of barium sulfate (BaSO4) for radiopacity. Incomplete dispersion of radiopacifiers has been implicated in the fatigue fracture of cements. In this preliminary study, nanometer size BaSO4 particles were added to form a nanocomposite bone cement. As with the antibiotics, we hypothesized that well dispersed barium sulfate particles of nanometer size can improve the fatigue life of bone cement compared to well dispersed micrometer size barium sulfate (see Figure 1).
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Figure 1. LVSEM image of 1000nm BaSO4 cement (left), and 100nm BaSO4 cement (right) scale bar = 1 micron |
Both uncoated and sodium citrate coated particles were examined since coating may further reduce nanoparticle agglomeration. Fatigue tests on notched specimens showed that the nanocomposite cements had a substantially higher total life than cements containing micrometer size radiopacifiers (see Figure 2). Low voltage scanning electron microscopy (LVSEM) revealed the mechanism of toughening associated with radiopacifier nanoparticles.
 | Figure 2. Total Fatigue Life of various cement groups (mean +/- standard deviation), such as Endurance (DePuy Orthopedics) and Simplex (Stryker, Inc.) cements, along with Endurance cements containing 1000 or 100nm size barium sulfate powders ("c" refers to sodium citrate coating while "u" refers to uncoated powder). |
Ultra-high Molecular Weight Polyethylene
Ultra-high molecular weight polyethylene (PE) is a tough, highly wear resistant nanostructured semicrystalline polymer used in total joint replacement prostheses. It is well known that the lifetime of total joint replacement prostheses is limited by wear of PE components. In recent years, laboratory wear tests that simulate wear in total hip replacement prostheses have shown that radiation crosslinked PE (XPE) have a very high resistance to wear, and they are currently in clinical use. However, reports that have shown that XPEs have lower mechanical properties such as ultimate tensile stress and strain, J-integral fracture toughness and, more importantly, resistance to fatigue crack propagation compared to uncrosslinked PE. In this research, we are investigating several processing routes to increase the mechanical properties of XPE while maintaining its high resistance to particulate wear.
In a recent study exemplifying our research in this area, we hypothesized that an increase in crystallinity of PE and XPE would increase their mechanical properties without substantially affecting wear resistance. We performed high-pressure crystallization on PE and XPE, and measured their morphological, tensile and wear properties. Ram-extruded rod stock of GUR 1050 PE (Hoechst-Ticona, Bayport, TX) was purchased from PolyHi Solidur (Fort Wayne, IN) and served as a control. The rod stock was crosslinked using gamma-irradiation to a dose of 50 kGy, melt annealed at 170°C for four hours, annealed at 125°C for 48 hours and cooled to ambient temperature. Cylindrical bars of 40mm length and 12.5mm diameter were machined from PE and XPE stock to snugly fit into a high-pressure mold. The PE bar was heated to 180°C, subjected to a pressure of 300 MPa for one hour, and slow cooled to room temperature under pressure. The XPE was subjected to a similar type of process except that it was raised to 240°C and the applied pressure was 500 MPa. These processes were chosen to induce a similar degree of crystallinity in the high-pressure PE (HP-PE) and high- pressure crosslinked PE (HP-XPE).
We are currently engaged in several ongoing studies, such as the effect of crystallographic orientation, effect of Vitamin E antioxidant and polymer blends on the morphology, mechanical and tribological properties of medical grade PE.
Selected References
Gomoll A, Wanich T, Bellare A. J-Integral Fracture Toughness and Tearing Modulus Measurement of Radiation Cross-Linked UHMWPE, Journal of Orthopaedic Research, 2002, 20(6): 1152-1156
Baker DA, Bellare A, Pruitt L. The Effects of Degree of Crosslinking on the Fatigue Crack Initiation and Propagation Resistance of Orthopedic Grade Polyethylene J. Biomed. Mat. Res.2003, 66A(1): 146-154.
Turell M, Wang A, Bellare A. Quantification of the effect of cross-path motion on the wear rate of ultra-high molecular weight polyethylene. Wear 2003, 255(17-22):1034-1039
Bellare A, Gomoll AH, Fitz W, Scott RD, Thornhill TS Improving the Fatigue Properties of Poly (Methyl Methacrylate) Orthopaedic Cement Containing Radiopacifier Nanoparticles. Materials Science Forum 2003 Vol 426-432: 3133-3139
Pavoor PV, Gearing BP, Gorga RE, Bellare A, Cohen RE. Engineering the friction-and-wear behavior of polyelectrolyte multilayer nanoassemblies through block copolymer surface capping, metallic nanoparticles, and multiwall carbon nanotubes. J. Appl Polym Sci, 2004, 92 (1): 439-448
Pavoor PV, Gearing BP, Bellare A, Cohen RE. Tribological characteristics of polyelectrolyte multilayers. Wear, 2004, 256(11-12): 1196-1207
Turell MB, Bellare A. A study of the nanostructure and tensile properties of ultra-high molecular weight polyethylene. Biomaterials 2004, 25(17):3389-3398
Turell ME, Friedlaender, GE, Wang A, Thornhill, TS, Bellare A. The effect of counterface roughness on the wear of UHMWPE for rectangular wear paths. Wear 2005, 259:984-91
Simis KS, Bistolfi A, Bellare A, Pruitt LA. The combined effects of crosslinking and high crystallinity on the microstructural and mechanical properties of ultra-high molecular weight polyethylene. Biomaterials 2006, 27(9): 1688-1694
Pavoor PV, Gearing BP, Muratoglu O, Cohen RE, Bellare A. Wear reduction of orthopaedic bearing surfaces using polyelectrolyte multilayer nanocoatings. Biomaterials 2006, 27(8): 1527-1533
