Archive of Medical Research

Correlation of dynamic cartilage contact stress aberrations with severity of instability in ankle incongruity.

Joint instability is presumed to cause abnormality in cartilage contact mechanics, which accumulatively damages the articular surface, leading to osteoarthritis. The purpose of this study was to clarify the effect of instability on dynamic cartilage contact mechanics. Using human ankle cadaver specimens, potentially unstable ankles were modeled by introducing a coronally directed step-off incongruity of the anterior tibial surface and/or by transecting the anterior talofibular ligament. Specimens were subjected to a duty cycle with quasi-physiologic stance-phase motion and loading. AP tibial forces were modulated, causing a controlled, quantifiable ankle subluxation during the duty cycle. Instantaneous changes in local articular contact stresses were continuously measured using a thin, flexible pressure transducer. Tests were repeated while varying the tibial surface condition (anatomic, 1-mm step-off, and 2-mm step-off), both before and after transection of the anterior talofibular ligament, with various AP force magnitudes, so that situations of various degrees of instability were created for each specimen. Instability events occurred when the step-off incongruity was introduced, with the abnormality in joint kinematics being greater after ligament transection. Contact stress data revealed that these instability events involved distinctly abrupt increases/decreases in local articular contact stresses, and that the degree of abruptness was correlated nearly linearly with the abnormality in kinematics. The severity of contact stress aberration appeared to be correlated with the degree of instability. Given this linear relationship, even small instability events presumably involve appreciable abnormality in dynamic joint contact mechanics. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Tochigi Y, Rudert MJ, McKinley TO, Pedersen DR, Brown TD.

Department of Orthopedics and Rehabilitation, University of Iowa, 2181 Westlawn, Iowa City, IA 52242‐1100.

Collagen orientation in periosteum and perichondrium is aligned with preferential directions of tissue growth.

A feedback mechanism between different tissues in a growing bone is thought to determine the bone\’s morphogenesis. Cartilage growth strains the surrounding tissues, eliciting alterations of its matrix, which in turn, creates anisotropic stresses, guiding directionality of cartilage growth. The purpose of this study was to evaluate this hypothesis by determining whether collagen fiber directions in the perichondrium and periosteum align with the preferential directions of long bone growth. Tibiotarsi from chicken embryos across developmental stages were scanned using optical projection tomography (OPT) to assess preferential directions of growth at characteristic sites in perichondrium and periosteum. Quantified morphometric data were compared with two-photon laser-scanning microscopy images of the three-dimensional collagen network in these fibrous tissues. The diaphyseal periosteum contained longitudinally oriented collagen fibers that aligned with the preferential growth direction. Longitudinal growth at both metaphyses was twice the circumferential growth. This concurred with well-developed circumferential fibers, which covered and were partly interwoven with a dominant network of longitudinally oriented fibers in the outer layer of the perichondrium/periosteum at the metaphysis. Toward both articulations, the collagen network of the epiphyseal surface was randomly oriented, and growth was approximately biaxial. These findings support the hypothesis that the anisotropic architecture of the collagen network, detected in periosteum and perichondrium, concurs with the assessed growth directions. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Foolen J, van Donkelaar C, Nowlan N, Murphy P, Huiskes R, Ito K.

Biomedical Engineering, Eindhoven University of Technology, WH 4.118, P.O. Box 513, Eindhoven 5600 MB, The Netherlands.

The influence of wear paths produced by hip replacement patients during normal walking on wear rates.

Variation in wear paths is known to greatly affect wear rates in vitro, with multidirectional paths producing much greater wear than unidirectional paths. This study investigated the relationship between multidirectional motion at the hip joint, as measured by aspect ratio, sliding distance, and wear rate for 164 hip replacements. Kinematic input from three-dimensional gait analysis was used to determine the wear paths. Activity cycles were determined for a subgroup of 100 patients using a pedometer study, and the relationship between annual sliding distance and wear rate was analyzed. Poor correlations were found between both aspect ratio and sliding distance and wear rate for the larger group and between annual sliding distance and wear rate for the subgroup. However, patients who experienced a wear rate <0.08 mm/year showed a strong positive correlation between the combination of sliding distance, activity levels, and aspect ratio and wear rate (adjusted r(2) = 55.4%). This group may represent those patients who experience conditions that most closely match those that prevail in simulator and laboratory tests. Although the shape of wear paths, their sliding distance, and the number of articulation cycles at the hip joint affect wear rates in simulator studies, this relationship was not seen in this clinical study. Other factors such as lubrication, loading conditions and roughness of the femoral head may influence the wear rate. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Bennett D, Humphreys L, O\’Brien S, Kelly C, Orr J, Beverland DE.

Outcome Assessment Unit, Musgrave Park Hospital, Belfast, Northern Ireland.

Gene expression profiles of human chondrocytes during passaged monolayer cultivation.

Chondrocyte phenotype has been shown to dedifferentiate during passaged monolayer cultivation. Hence, we have investigated the expression profile of 27 chondrocyte-associated genes from both osteoarthritic cartilage tissue and healthy passaged human articular chondrocytes by quantitative real-time PCR. Our results indicate that the gene expression levels of matrix proteins and proteases in chondrocytes from monolayer culture decrease compared with those from cartilage tissue, while monolayer cultured chondrocytes from normal and osteoarthritic cartilage exhibit similar gene expression patterns. However, chondrocytic gene expression profiles were differentially altered at various stages of passage. The expression of the matrix proteins aggrecan, type II collagen, and fibromodulin inversely correlated with increasing passage number, while fibronectin and link protein exhibited a marked increase with passage. The expression of matrix proteinases MMP-3/9/13 and ADAMTS-4/5 decreased with passage, whereas proteinase inhibitors TIMP-2/3 were elevated. The cytokine IL-1 also showed increased expression with monolayer chondrocyte culture, while IGF-1 expression levels were diminished. No significant changes in TGF-beta, or the chondrogenic transcription factors Sox-9, c-fos, or c-jun were observed. Our data indicates that cultured chondrocytes undergo dedifferentiation during monolayer culture, although the gene expression level of transcription factors necessary for chondrogenesis remains unchanged. This data may prove important for the future development of more specific and efficacious cultivation techniques for human articular chondrocyte-based therapies. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Lin Z, Fitzgerald JB, Xu J, Willers C, Wood D, Grodzinsky AJ, Zheng MH.

Centre of Orthopaedic Surgery, University of Western Australia, M Block, QEII Medical Centre, Monash Avenue, Nedlands, Western Australia 6009, Australia.

Intervertebral disc degeneration in a naturally occurring primate model: Radiographic and biomechanical evidence.

Classic degenerative disc disease is a serious health problem worldwide, whose etiological basis-mechanical stimulus, biochemical changes, or natural aging-is poorly understood. Animal models are critical to the study of degenerative disc disease initiation and progression and for attempts to regulate, ameliorate, or eliminate it. The macaque represents a primate model with natural disc degeneration that might serve to advance the field; we aimed to provide radiographic (morphologic) and biomechanical evidence of natural disc degeneration in this model. A factorial study design was used to examine the relationship between the radiographic appearance of disc degeneration and its biomechanical consequences. Eighteen macaques of advanced age (22.3 +/- 0.9 years) had radiographs taken to assess the degree of thoracolumbar intervertebral disc degeneration using a standard atlas method. Each spine was harvested and dynamic biomechanical tests were performed. Advancing disc degeneration (degree of disc space narrowing and osteophytosis) was associated with increased stiffness, decreased energy absorption, and increased natural frequency of the intervertebral disc. These associations linking the dynamics of the intervertebral disc and its degree of degeneration are similar to those found in humans. Our results indicate the macaque model with morphologic and biomechanical efficacy could aid in understanding the progression of disc degeneration and in developing therapeutic strategies to prevent or inhibit its course. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Nuckley DJ, Kramer PA, Del Rosario A, Fabro N, Baran S, Ching RP.

Department of Mechanical Engineering, University of Washington, Box 352600, Seattle, Washington 98195.

PATHs approach to product introduction in developing countries.

Health interventions developed for wealthy nations are difficult to introduce in developing countries due to a lack of sufficient technological, financial, political, or infrastructural resources. Increasingly, however, product developers are creating new technologies that meet the needs of low-resource settings. Experience has shown that many activities must be undertaken to prepare health systems to accept and embrace new, improved, or under-utilized health technologies. This article describes three health technologies-a diagnostic test for vitamin A deficiency, new cervical cancer vaccines, and the vaccine vial monitor-that PATH, a global health organization, has helped advance for developing-country markets. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.

Harner-Jay C, Sherris J.

PATH, Technology Solutions, Program Officer, 1455 NW Leary Way, Seattle, Washington 98107.

Recombinant human bone morphogenetic protein-2/atelocollagen composite as a new material for ossicular reconstruction.

Ossicular reconstruction is the rebuilding of the damaged middle ear. There are many different prosthesis and techniques used to reconstruct the middle ear ossicles. However, precision in the surgical procedures and prostheses used for ossiculoplasty are still imperfect. The objective of this study was to evaluate the potential of recombinant human bone morphogenetic protein-2 (rhBMP-2)/ atelocollagen composite for ossicular reconstruction implanted in the tympanic cavity of rat. The ossicles were extirpated by perforating the tympanic membranes of rats. rhBMP-2/atelocollagen composite was implanted as substitute of ossicles in intimate contact with the tympanic membrane. Composites were subjected to histological, immunohistochemical, and radiological examination. To evaluate the auditory function, auditory brainstem response (ABR) was measured. rhBMP-2/atelocollagen composites showed good stability and durability without any inflammatory reaction within the tympanic cavity. The process of new bone formation was similar to intramembranous ossification. They also demonstrated that the hearing ability was re-established by ABR threshold shifts. rhBMP-2/atelocollagen composite exhibited excellent potential for ossicular reconstruction, maintaining their vibratory function. This ossicular tissue engineering may be considered as a future therapeutic strategy for ossiculoplasty. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

Takeuchi A, Tsujigiwa H, Murakami J, Kawasaki A, Takeda Y, Fukushima K, Rodriguez AP, Nagatsuka H, Yamada M, Nishizaki K.

Department of Otolaryngology‐Head and Neck Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

Proteomic analysis of Staphylococcus aureus biofilms grown in vitro on mechanical heart valve leaflets.

The in vitro colonization of three commercial heart valve leaflets by Staphylococcus aureus was investigated. The leaflets, made of pyrolytic carbon alloyed with or without silicon, displayed similar surface properties (wettability, roughness) and were readily colonized by S. aureus that formed patchy biofilms on the three supports. A proteomic approach was used to assess the physiological status of biofilm populations by comparing their protein maps to those of bacteria cultured as free cells in the presence or absence of biofilm substratum. Principal component analysis (PCA) revealed, for each tested leaflet, statistical relationships between the protein maps of the biofilm and free-floating microbial populations. A spot-by-spot comparison of protein levels on two-dimensional electropherograms showed that many proteins were accumulated or underproduced by microbial populations grown in the presence of a leaflet compared with protein levels in control free populations. The number of accumulated proteins was noticeably higher than that of underproduced polypeptides. This protein overproduction was emphasized in biofilm populations. Several proteins, some of which were identified, were differentially produced by both surface-associated planktonic and biofilm-grown cell populations compared with control free-cell ones cultured in the absence of leaflet, whatever the leaflet tested. The potential of this proteomic approach for fighting against microbial adhesion and biofilm formation is discussed. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

Bénard L, Litzler PY, Cosette P, Lemeland JF, Jouenne T, Junter GA.

Research Group on Antimicrobials and Microorganisms, EA 2656, Charles Nicolle University Hospital, Rouen, France.

An in vitro comparison of possibly bioactive titanium implant surfaces.

The aim of the study was to compare Ca and P formation (CaP) and subsequent bone cell response of a blasted and four different possibly bioactive commercially pure (cp) titanium surfaces; 1. Fluoride etched (Fluoride), 2. Alkali-heat treated (AH), 3. Magnesium ion incorporated anodized (TiMgO), and 4. Nano HA coated and heat treated (nano HA) in vitro. Furthermore, to evaluate the significance of the SBF formed CaP coat on bone cell response. The surfaces were characterized by Optical Interferometry, Scanning Electron Microscopy (SEM) and X-ray Photoelectron Spectroscopy (XPS). CaP formation was evaluated after 12, 24 and 72 h in simulated body fluid (SBF). Primary human mandibular osteoblast-like cells were cultured on the various surfaces subjected to SBF for 72 h. Cellular attachment, differentiation (osteocalcin) and protein production (TGF-beta(1)) was evaluated after 3 h and 10 days respectively. Despite different morphological appearances, the roughness of the differently modified surfaces was similar. The possibly bioactive surfaces gave rise to an earlier CaP formation than the blasted surface, however, after 72 h the blasted surface demonstrated increased CaP formation compared to the possibly bioactive surfaces. Subsequent bone cell attachment was correlated to neither surface roughness nor the amount of formed CaP after SBF treatment. In contrast, osteocalcin and TGF-beta(1) production were largely correlated to the amount of CaP formed on the surfaces. However, bone response (cell attachment, osteocalcin and TGF-F production) on the blasted controls were similar or increased compared to the SBF treated fluoridated, AH and TiMgO surface. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

Göransson A, Arvidsson A, Currie F, Franke-Stenport V, Kjellin P, Mustafa K, Sul YT, Wennerberg A.

Department of Biomaterials, Institute of Surgical Science, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.

Supramolecular hydrogels based on self-assembly between PEO-PPO-PEO triblock copolymers and alpha-cyclodextrin.

This article reports a detailed study on the hydrogel formation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers with alpha-cyclodextrin (alpha-CD) in aqueous solutions. The gelation kinetics and the gel rheological properties were studied using viscometry. The sol-gel phase transitions were studied using phase diagrams, while the gelation mechanism was studied using differential scanning calorimetric analysis. It was concluded that the gelation was induced by the complex formation between the PEO segments of the PEO-PPO-PEO triblock copolymer and alpha-CD, and the further self-assembly of the partially formed inclusion complexes. The addition of alpha-CD largely reduced the concentration of the copolymer needed for gel formation. The gels were thixotropic and reversible, and potentially suitable for use as an injectable drug-delivery system. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

Ni X, Cheng A, Li J.

Institute of Materials Research and Engineering, National University of Singapore, 3 Research Link, Singapore 117602, Singapore.