Research in motion

Advances in Biomaterials and Medical Devices PanelOrthopaedic disorders of the major joints, specifically, osteoarthritis of the hip and knee joints have an enormous economic and functional impact on our society, affecting millions of patients every day. In the late 1960s and early 1970s, replacement of diseased joints with metal and plastic components was developed as a salvage technique for elderly, and relatively sedentary patients. Now, with an aging and active population that expects to maintain function and mobility, the demand for major joint reconstruction is increasing worldwide. Younger, heavier, and active patients place greater demands on biomaterials and implants. Our collaborative team is focused on developing new biomaterials that can meet the challenge of skeletal repair, and joint replacement, and on exploring tissue-engineered cartilage as a possible biological replacement of diseased and arthritic joints. An interdisciplinary team approach to these goals has resulted in peer-reviewed publications, graduate student education opportunities, and extramural funding. Going forward, a major goal is to leverage our resources to create products that can be positioned profitably in the commercially-attractive orthopaedic device market

Modulating Notochordal Differentiation of Human Induced Pluripotent Stem Cells using Natural Nucleus Pulposus Tissue Matrix

Human induced pluripotent stem cells (hiPSCs) can differentiate into notochordal cell (NC)-like cells when cultured in the presence of natural porcine nucleus pulposus (NP) tissue matrix. The method promises massive production of high-quality, functional cells to treat degenerative intervertebral discs (IVDs). Based on our previous work, we further examined the effect of cell-NP matrix contact and culture medium on the differentiation, and further assessed the functional differentiation ability of the generated NC-like. The study showed that direct contact between hiPSCs and NP matrix can promote the differentiation yield, whilst both the contact and non-contact cultures can generate functional NC-like cells. The generated NC-like cells are highly homogenous regarding the expression of notochordal marker genes. A culture medium containing a cocktail of growth factors (FGF, EGF, VEGF and IGF-1) also supported the notochordal differentiation in the presence of NP matrix. The NC-like cells showed excellent functional differentiation ability to generate NP-like tissue which was rich in aggrecan and collagen type II; and particularly, the proteoglycan to collagen content ratio was as high as 12.5-17.5 which represents a phenotype close to NP rather than hyaline cartilage. Collectively, the present study confirmed the effectiveness and flexibility of using natural NP tissue matrix to direct notochordal differentiation of hiPSCs, and the potential of using the generated NC-like cells for treating IVD degeneration

Method for Fabricating Biocompatible Porous Titanium

A method for fabricating porous metal constructs (such as porous Ti constructs) which may be used as implants in bone repair is disclosed. The method employs a new saltbath sintering process coupled with conventional powder metallurgy technology which is capable of fabricating porous metal constructs with controlled porosity and pore size having a lower production cost than conventional powder metallurgy methods

Overutilization of magnetic resonance imaging in the diagnosis and treatment of moderate to severe osteoarthritis

Advanced imaging is a major driver of health care expenditures. Magnetic resonance imaging provides advantages over radiography because of its ability to visualize soft tissues within the knee joint. The clinical relevance of these findings in osteoarthritis, however, is not well understood. For example, MRI can detect meniscal tears, but these are frequent findings in patients with osteoarthritis, with no difference in prevalence among those with and without symptoms. In addition to concerns about excessive cost, it is possible that patients may undergo unnecessary procedures due to MRI findings. A randomized placebo-controlled trial showed no benefit of arthroscopy for osteoarthritis. Our goal was to examine how prevalent this practice is at this institution, and to examine the characteristics of physicians who ordered these MRIs. Our hypothesis is that many providers order MRI for evaluation of osteoarthritis before referring to an orthopedic surgeon, and that providers with higher levels of training are less likely to order these unnecessary MRIs

Freeze Extrusion Fabrication of 13-93 Bioactive Glass Scaffolds for Bone Repair

There is an increasing demand for synthetic scaffolds with the requisite biocompatibility, internal architecture, and mechanical properties for the bone repair and regeneration. In this work, scaffolds of a silicate bioactive glass (13-93) were prepared by a freeze extrusion fabrication (FEF) method and evaluated in vitro for potential applications in bone repair and regeneration. The process parameters for FEF production of scaffolds with the requisite microstructural characteristics, as well as the mechanical and cell culture response of the scaffolds were evaluated. After binder burnout and sintering (60 min at 700°C), the scaffolds consisted of a dense glass network with interpenetrating pores (porosity ≈ 50%; pore width = 100-500 μm). These scaffolds had a compressive strength of 140 ± 70 MPa, which is comparable to the strength of human cortical bone and far higher than the strengths of bioactive glass and ceramic scaffolds prepared by more conventional methods. The scaffolds also supported the proliferation of osteogenic MLO-A5 cells, indicating their biocompatibility. Potential application of these scaffolds in the repair and regeneration of load-bearing bones, such as segmental defects in long bones, is discussed

In Vitro versus In Vivo Phase Instability of Zirconia-Toughened Alumina Femoral Heads: A Critical Comparative Assessment

A clear discrepancy between predicted in vitro and actual in vivo surface phase stability of BIOLOX (R) delta zirconia-toughened alumina (ZTA) femoral heads has been demonstrated by several independent research groups. Data from retrievals challenge the validity of the standard method currently utilized in evaluating surface stability and raise a series of important questions: (1) Why do in vitro hydrothermal aging treatments conspicuously fail to model actual results from the in vivo environment? (2) What is the preponderant microscopic phenomenon triggering the accelerated transformation in vivo? (3) Ultimately, what revisions of the current in vitro standard are needed in order to obtain consistent predictions of ZTA transformation kinetics in vivo? Reported in this paper is a new in toto method for visualizing the surface stability of femoral heads. It is based on CAD-assisted Raman spectroscopy to quantitatively assess the phase transformation observed in ZTA retrievals. Using a series of independent analytical probes, an evaluation of the microscopic mechanisms responsible for the polymorphic transformation is also provided. An outline is given of the possible ways in which the current hydrothermal simulation standard for artificial joints can be improved in an attempt to reduce the gap between in vitro simulation and reality

Bioactive silicon nitride: A new therapeutic material for osteoarthropathy

While the reciprocity between bioceramics and living cells is complex, it is principally governed by the implant's surface chemistry. Consequently, a deeper understanding of the chemical interactions of bioceramics with living tissue could ultimately lead to new therapeutic strategies. However, the physical and chemical principles that govern these interactions remain unclear. The intricacies of this biological synergy are explored within this paper by examining the peculiar surface chemistry of a relatively new bioceramic, silicon nitride (Si3N4). Building upon prior research, this paper aims at obtaining new insights into the biological interactions between Si3N4 and living cells, as a consequence of the off-stoichiometric chemical nature of its surface at the nanometer scale. We show here yet unveiled details of surface chemistry and, based on these new data, formulate a model on how, ultimately, Si3N4 influences cellular signal transduction functions and differentiation mechanisms. In other words, we interpret its reciprocity with living cells in chemical terms. These new findings suggest that Si3N4 might provide unique new medicinal therapies and effective remedies for various bone or joint maladies and diseases