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Less invasive anterior column reconstruction in thoracolumbar fractures
Oner, F. C., W. J. Dhert, et al. (2005), Injury 36 Suppl 2: B82-9.
Abstract: Posterior short-segment pedicle screw constructs are commonly used for reduction and fixation of traumatic thoracolumbar spine fractures. Although this technique is usually simple and effective, complications such as loss of fixation or recurrence of deformity are common because of the insufficiency of the damaged anterior column. Anterior approaches to address this deficiency are associated with high morbidity and complications. We have developed a technique to reduce and support the fractured anterior column through a transpedicular approach. Balloon-assisted-endplate-reduction (BAER) followed by vertebroplasty (VTP) with calcium phosphate cement in combination with short segment pedicle screw construct seem to be a safe and effective technique to reconstruct the anterior column in a less invasive manner. In this article, the rationale behind this technique, experimental studies, and the first clinical results are discussed.

Leukocyte chemosensory migration on vascular prosthetic biomaterial is mediated by an integrin beta2 receptor chain
Chang, C. C., R. S. Rosenson-Schloss, et al. (2000), Biomaterials 21(22): 2305-13.
Abstract: The ability of adherent activated leukocytes to migrate on implanted prosthetic biomaterial surfaces may be an early rate-limiting step in eliminating periprosthetic infection. The goal of this study was to explore the molecular mechanism governing leukocyte migration on the implantable cardiovascular prosthetic biomaterial, expanded polytetrafluoroethylene (ePTFE), in response to stimulation by the soluble chemokine, N-formyl-methionyl-leucyl-phenylalanine (fMLP). We used a population level migration assay to study the migration of polymorphonuclear leukocytes (PMN) on ePTFE, overlaid by a gelatin/agar composite. A theoretical random walk model was applied to describe fMLP-induced PMN migration on ePTFE in terms of an objective random cell migration coefficient, mu. Our results show that following stimulation with 0-10(-7) M fMLP, the value of mu ranged from 5.43 x 10(-9) to 1.08 x 10(-7) cm2/s, with a maximum value obtained at 10(-8) M fMLP. We probed the expression levels of various beta2 integrin receptor subunits and their contribution to the migratory function of ePTFE-adherent PMN over a wide range of fMLP concentration. We found that the expression of the integrin beta-chain, CD18, was also maximized at 10(-8) M fMLP, along with only slight changes in the expression of integrin alpha-chains (CD11a,b,c). We report that treatment with antibodies against either beta or combined alpha chains, but not individual alpha chains, inhibited PMN attachment to ePTFE at 10(-8) M fMLP, suggesting the likely role of combined beta2 receptor subunits in early adhesion events following stimulation. However, treatment with only anti-CD18 significantly lowered PMN migration on ePTFE (mu = 5.98 x 10(-9) cm2/s), and this degree of inhibition was much greater than that elicited by the combined treatment with antibodies recognizing all possible alpha-chains. Overall, we conclude that migratory behavior of chemokinetically stimulated PMN on ePTFE is mediated by the integrin beta chain pool, and is only weakly regulated by the integrin alpha chain.

Leukocyte spreading behavior on vascular biomaterial surfaces: consequences of chemoattractant stimulation
Chang, C. C., S. M. Lieberman, et al. (1999), Biomaterials 20(3): 273-81.
Abstract: Chemoattractant-induced phenomena of polarity and migration of polymorphonuclear leukocytes (PMN) are believed to play a key physiological role in controlling bacterial infections on implantable vascular biomaterials. Our study targeted the spreading behavior of human PMN adherent to expanded polytetrafluoroethylene (ePTFE), pretreated with various plasma proteins, in response to the chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (fMLP). To this end, a novel imaging configuration was developed to allow in situ reconstructive analysis of PMN 3-D morphology on opaque ePTFE surfaces, using optical sectioning confocal microscopy. Following fMLP stimulation, PMN morphological polarity was enhanced on all substrates studied except fibrinogen treated ePTFE. 3-D PMN morphometry revealed that in the absence of fMLP, overall cell spreading was minimized on albumin-treated ePTFE and maximized on fibrinogen and immunoglobulin-G-treated ePTFE. Following fMLP stimulation, overall PMN spreading increased markedly on untreated and albumin-coated ePTFE, while it stayed invariant on IgG and plasma treated ePTFE, and decreased on fibrinogen-treated ePTFE. Spatial analysis of PMN spreading following fMLP stimulation revealed enhanced PMN attachment on untreated and albumin treated ePTFE and diminished attachment on fibrinogen and plasma treated ePTFE. Thus, chemoattractant stimulation altered a wide range of PMN spreading attributes on ePTFE, including morphological polarity, substrate attachment, and 3-D membrane spreading, in a substrate dependent manner. These chemoattractant-induced spreading responses may also have important consequences for PMN phagocytosis. We report that fMLP stimulation led to enhanced unopsonized particulate phagocytosis on untreated and albumin treated ePTFE, but caused no discernible change in phagocytosis on other protein substrates. Thus, chemoattractant modulation of PMN spreading on ePTFE is highly substrate-regulated, and manifests in concerted effects on PMN phagocytosis.

Leukocyte-biomaterial interactions in the presence of Staphylococcus epidermidis: flow cytometric evaluation of leukocyte activation
Sapatnekar, S., W. J. Kao, et al. (1997), J Biomed Mater Res 35(4): 409-20.
Abstract: The adhesion of bacteria on a biomaterial surface is believed to be the first step in the development of biomaterial-related infection. The goal of this study was to investigate the mechanisms that permit adherent bacteria to persist on the surface of an implanted cardiovascular biomaterial. We hypothesized that circulating leukocytes are unable to adhere to the biomaterial surface under physiologic shear stress conditions, and this prevents them from interacting with adherent bacteria. To address this hypothesis, we investigated the adhesion profiles of Staphylococcus epidermidis and polymorphonuclear leukocytes (PMN), incubated under controlled shear stress conditions with the test biomaterial. We found that bacteria could adhere on the biomaterial surface, even when their concentration in the test medium was as low as 10(3) cfu/mL. At this concentration, the bacteria did not induce significant complement activation. PMN adhesion on the biomaterial surface was sensitive to shear stress and minimal at shear stress > 10 dynes/cm2. Low concentrations of bacteria could induce a significant increase in the expression of PMN adhesion molecules CD11b and CD11c. We conclude that the presence of bacteria induces PMN activation but does not increase PMN adhesion on biomaterial surfaces under physiologic shear stress conditions. This could be a major mechanism that protects adherent bacteria from PMN antibacterial activity.

LF-NMR and multivariate data analysis: compression of data to classify hydrogel contact lenses
Manetti, C., L. Casciani, et al. (2005), J Biomater Sci Polym Ed 16(4): 421-34.
Abstract: Hydrogel contact lenses swollen in viscoelastic artificial tears solution have been studied, measuring transversal relaxation times of water molecules using LF-NMR techniques. Data were processed by classical multiexponential fitting, by principal component analysis and by SLICING, a multi-way analysis method. The reason for using multivariate data analysis was not to obtain a better fitting, but rather more effective data description. The single-sample relaxation curves were projected in a space spanned by the loading curves, and in this space it was simpler to compare data. In particular, it contributed to the description of the variability of motion characteristics of the water molecule 'families' contained in the studied samples. Applying multivariate techniques, we were able to group lenses with different Equilibrium Water Content (EWC) and with the same water content but different compositions. Accordingly, we were able to point out that, if the lenses are swollen first in physiological solution and then in viscoelastic artificial tears solution, hydration characteristics remained unchanged in all the studied samples, except for 38% EWC lenses.

Ligament cells stretch-adapted on a microgrooved substrate increase intercellular communication in response to a mechanical stimulus
Jones, B. F., M. E. Wall, et al. (2005), J Biomech 38(8): 1653-64.
Abstract: An in vitro model was used to investigate the effect of mechanical stimuli on adaptation to load and calcium signaling in aligned medial collateral ligament cells (MCL). This model used a patterned silicone membrane to align the cells parallel with the direction of the microgrooves. Alignment created an architecture that simulated a degree of cell orientation in native ligament tissue. It was hypothesized that aligned ligament cells would be more efficient at calcium wave propagation than cells that were randomly oriented. It was further hypothesized that calcium wave propagation would be greater among cells that were both aligned and subjected to mechanical stretch compared to cells that were aligned but not stretched. Rat MCL cells were loaded with Fura-2AM, a calcium-binding dye, and mechanically indented using a micropipette tip. A ratio-imaging fluorescence technique was used to quantitate the calcium (Ca2+) response. It was concluded that stretching ligament cells prior to stimulation increased their sensitivity to load and their ability to propagate a calcium wave. However, the ability of aligned cells to propagate this wave was not significantly different when compared to nonaligned cells. Treatment of cultures with inhibitors such as apyrase and suramin significantly reduced the number of cells recruited in the calcium response. Hence, it was concluded that ATP released from mechanically stimulated cells was a principal mediator responsible for the rise in intracellular calcium in ligament cells. Further, purinoceptor activation may amplify the signal to alert and recruit more cells in a response to mechanical stimulation.

Ligament tissue engineering: an evolutionary materials science approach
Laurencin, C. T. and J. W. Freeman (2005), Biomaterials 26(36): 7530-6.
Abstract: The anterior cruciate ligament (ACL) is important for knee stabilization. Unfortunately, it is also the most commonly injured intra-articular ligament. Due to poor vascularization, the ACL has inferior healing capability and is usually replaced after significant damage has occurred. Currently available replacements have a host of limitations, this has prompted the search for tissue-engineered solutions for ACL repair. Presently investigated scaffolds range from twisted fiber architectures composed of silk fibers to complex three-dimensional braided structures composed of poly (L-lactic acid) fibers. The purpose of these tissue-engineered constructs is to apply approaches such as the use of porous scaffolds, use of cells, and the application of growth factors to promote ligament tissue regeneration while providing mechanical properties similar to natural ligament.

Ligand density characterization of peptide-modified biomaterials
Barber, T. A., G. M. Harbers, et al. (2005), Biomaterials 26(34): 6897-905.
Abstract: A simple fluorescence based characterization method was developed to assess ligand density on peptide-modified biomaterials. The method exploits the exquisite sensitivity of proteolysis for the purpose of liberating a fluorescently labeled probe fragment from an immobilized peptide. The released fragment can then be detected in solution using high-throughput fluorometry. In silico screening tools identified the enzyme chymotrypsin as a promising candidate for releasing a detectable probe fragment from the fluorescently labeled peptide, Ac-CGGNGEPRGDTYRAYK(FITC)GG-NH(2). After chymotrypsin digestion of the peptide in solution was first characterized using mass spectrometry and HPLC, a basic enzyme mediated release protocol was developed and implemented to generate peptide-binding isotherms on various peptide-modified biomaterials. The new method is sensitive, has good signal-to-noise ratio (S/N), and is easily standardized. Furthermore, the technique can be applied independent of material chemistry and geometry, making it a suitable alternative to radiolabeling for a wide range of biomaterial applications.

Light microscopic and scanning electron microscopic retrieval analyses of implanted biomaterials retrieved from humans and experimental animals
Steflik, D. E., R. S. Corpe, et al. (2001), J Oral Implantol 27(1): 5-15.
Abstract: This paper reports analysis obtained from 200 implant cases retrieved from humans and submitted to the American Academy of Implant Dentistry Research Foundation, Medical College of Georgia implant retrieval center. The samples that were not decalcified were embedded in polymethylmethacrylate and examined with scanning electron microscopy and routine light, polarized, or Nomarski microscopy. Cases included both orthopedic and dental implants, as well as entire mandibles and portions of maxillae obtained at autopsy. A significant number of submitted implants had substantial amounts of adhered bone, which permitted evaluation of human bone remodeling to osseointegrated implants. These implants failed because of implant fracture. As was observed with animal studies, healthy bone supported these implants, with the bone containing an interdigitating canaliculi network that provided communication between interfacial osteocytes and osteocytes deeper within the remodeled osteonal and trabecular bone. Early dental implants containing a coating of beads showed a connective tissue interface, which corresponded to the bead surface of specific orthopedic implants that underwent some degree of micromovement. This is in contrast with the excellent response reported for successful contemporary beaded implants. Significant numbers of osseointegrated fractured hydroxyapatite (HA)-coated dental implants demonstrated the adequate serviceability of these implants before biomaterial fracture. In contrast, the HA coating was dissociated from retrieved orthopedic implants, leading to extensive cup loosening and case failure. This study, therefore, underscores the need for evaluation of failed human dental and orthopedic implants. Correlations can be drawn between human retrieval and experimental animal studies.

Light scattering experiments on aqueous solutions of selected cellulose ethers: contribution to the study of polymer-mineral interactions in a new injectable biomaterial
Bohic, S., P. Weiss, et al. (2001), J Mater Sci Mater Med 12(3): 201-5.
Abstract: Hydroxypropylmethylcellulose (HPMC) is used as a ligand for a bioactive calcium phosphate ceramic (the filler) in a ready-to-use injectable sterilized biomaterial for bone and dental surgery. Light scattering experiments were usually used to study high water-soluble polymers and to determine the basic macromolecular parameters. In order to gain a deeper understanding of polymer/mineral interactions in this type of material, we have investigated the effect of divalent and trivalent ions (Ca(2+), PO(4)(3-)) and steam sterilization on dilute solutions of HPMC and hydroxyethylcellulose (HEC). The sterilization process may cause some degradation of HEC taking into account its high molecular weight and some rigidity of the polymer chain. Moreover, in the case of HPMC, the changes in the conformations rather than degradation process are supposed. These effects of degradation and flocculation are strengthened in alkaline medium. Experimental data suggested the formation of chelate complexes between Ca(2+) and HPMC which improve its affinity to the mineral blend and consolidate the injectable biomaterial even in the case of its hydration by biological fluid.

Linker-based bio-compatible microemulsions
Acosta, E. J., T. Nguyen, et al. (2005), Environ Sci Technol 39(5): 1275-82.
Abstract: In this work we have studied the formulation of biocompatible microemulsions using lecithin as the main surfactant and bio-compatible linker molecules (hexyl polyglucoside asthe hydrophilic linker and sorbitan monoleate as the lipophilic linker). These bio-compatible systems are discussed as potential substitutes for chlorinated solvents in dry-cleaning applications and as solvent delivery systems for pharmaceutical applications. Formulation parameters and conditions were evaluated using isopropyl myristate (IPM) as the model oil. It was found that the proposed linker-based formulations were able to form alcohol-free microemulsions while achieving higher solubilization capacity than similar systems reported in the literature. In addition, these lecithin/linker formulations were able to form microemulsions with a wide range of oils, from polar chlorinated hydrocarbons to hydrophobic oils such as squalene. These microemulsions were achieved under isotonic conditions (0.9% NaCl) by only varying the relative proportions of the linkers. The "solvency" power of these bio-compatible formulations was tested for the removal of hexadecane (used as model oil) from cotton fabrics and compared to the solvency power of a typical dry cleaning solvent tetrachloroethylene (PCE). While PCE and the linker-based lecithin formulation removed the same amount of hexadecane at low loading ratios (less than 1% oil volume fraction), at higher loading ratios the linker-based lecithin formulation retained its oil removal capacity while the efficiency of the PCE system declined rapidly. These initial results thus demonstrate the remarkable oil solubilization capacity of these bio-compatible linker-based lecithin formulations and illustrate their potential as environmentally friendly replacements for organic solvents.

Lipopolysaccharide affinity for titanium implant biomaterials
Nelson, S. K., K. L. Knoernschild, et al. (1997), J Prosthet Dent 77(1): 76-82.
Abstract: STATEMENT OF PROBLEM: Lipopolysaccharide (LPS) affinity for titanium implant biomaterials could affect crevicular LPS concentrations and thereby influence periimplant inflammation. PURPOSE OF STUDY: The purpose of this study was to evaluate Porphyromonas gingivalis and Escherichia coli LPS affinity for titanium biomaterials groups that differed in surface oxide composition and surface roughness. MATERIAL AND METHOD: Polished and abraded grade 1 commercially pure titanium and grade 5 alloyed extra low interstitial titanium specimens were treated with 10 EU/mm2 and radiolabeled LPS. RESULTS: The resultant mean +/- SD LPS adherence values ranged from 4.17 +/- 0.29 to 4.79 +/- 0.40 EU/ mm2. No difference in adherence and elution was indicated on the basis of LPS type, surface oxide composition, or surface roughness. Moreover, P. gingivalis and F. coli LPS desorption was below detection. CONCLUSION: Clinically, the high affinity of both LPS types for titanium biomaterials may adversely influence the periimplant tissue response.

Liquid filled nanoparticles as a drug delivery tool for protein therapeutics
Venkatesan, N., J. Yoshimitsu, et al. (2005), Biomaterials 26(34): 7154-63.
Abstract: In the present study, an attempt was made to study the feasibility of nanoparticulate adsorbents in the presence of an absorption enhancer, as a drug delivery tool for the administration of erythropoietin (EPO) to the small intestine. Liquid filled nano- and micro-particles (LFNPS/LFMPS) were prepared using solid adsorbents such as porous silicon dioxide (Sylysia 550), carbon nanotubes (CNTs), carbon nanohorns, fullerene, charcoal and bamboo charcoal. Surfactants such as a saturated polyglycolysed C8-C18 glyceride (Gelucire 44/14), PEG-8 capryl/caprylic acid glycerides (Labrasol) and polyoxyethylene hydrogenated castor oil derivative (HCO-60) were used as an absorption enhancer at 50mg/kg along with casein/lactoferrin as enzyme inhibitors. The absorption of EPO was studied by measuring serum EPO levels by an ELISA method after small intestinal administration of EPO-LFNPS preparation to rats at the EPO dose level of 100 IU/kg. Among the adsorbents studied, CNTs showed the highest serum EPO level of 62.7 +/- 11.6 mIU/ml. In addition, with the use of casein, EPO absorption was improved, C(max) 143.1 +/- 15.2 mIU/ml. Labrasol showed the highest absorption enhancing effect after intra-jejunum administration than Gelucire 44/14 and HCO-60, 25.6 +/- 3.2 and 22.2 +/- 3.6 mIU/ml, respectively. Jejunum was found to be the best absorption site for the absorption of EPO from LFNPS. The use of CNTs as LFNPS, improved the bioavailability of EPO to 11.5% following intra-small intestinal administration.

Living patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells
Schmidt, D., A. Mol, et al. (2005), Eur J Cardiothorac Surg 27(5): 795-800.
Abstract: OBJECTIVE: A major shortcoming in contemporary congenital heart surgery is the lack of viable replacement materials with the capacity of growth and regeneration. Here we focused on living autologous patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells (EPCs) as a ready-to-use cell source for paediatric cardiovascular tissue engineering. METHODS: EPCs were isolated from 20 ml fresh umbilical cord blood by density gradient centrifugation and myofibroblasts were harvested from umbilical cord tissue. Cells were differentiated and expanded in vitro using nutrient media containing growth factors. Before seeding, cell-phenotypes were assessed by immuno-histochemistry. Biodegradable patches fabricated from synthetic polymers (PGA/P4HB) were seeded with myofibroblasts followed by endothelialization with EPCs. All patches were cultured in a perfusion bioreactor. A subgroup of patches was additionally stimulated by cyclic strain. Analysis of the neo-tissues comprised histology, immuno-histochemistry, extracellular matrix (ECM) analysis and biomechanical testing. RESULTS: Endothelial phenotypes of EPCs before seeding were confirmed by Ac-Dil-LDL, CD 31, von-Willebrand-Factor and eNOS staining. Histology of the seeded patches demonstrated layered viable tissue formation in all samples. The cells in the newly formed tissues expressed myofibroblast markers, such as desmin and alpha-SMA. The EPCs derived neo-endothelia showed constant endothelial phenotypes (CD 31, vWF). major constituents of ECM such as collagen and proteoglycans were biochemically detected. Stress-strain properties of the patches showed features of native-analogous tissues. CONCLUSIONS: Living tissue engineered patches can be successfully generated from human umbilical cord derived myofibroblasts and EPCs. This new cell source may enable the tissue engineering of versatile, living, autologous replacement materials for congenital cardiac interventions.

Local and systemic activity of the polysaccharide chitosan at lymphoid tissues after oral administration
Porporatto, C., I. D. Bianco, et al. (2005), J Leukoc Biol 78(1): 62-9.
Abstract: Chitosan is a cationic polysaccharide derived from the partial deacetylation of chitin, which exhibits particular properties: interacts with negatively charged sites on the cell surface; changes the permeability of intestinal epithelium, enhancing the uptake of peptides and proteins; and activates leukocytes. Antigens coadministered or encapsulated with the polysaccharide show improved mucosal and systemic humoral immune responses, although the mechanism is poorly understood. Herein, we characterized in Peyer's patches mesenteric lymph nodes and spleen molecular events triggered after oral administration of chitosan in the absence of protein antigen. Sixteen hours after feeding, we studied the uptake and distribution of the polysaccharide, the phenotype of recruited antigen-presenting cells (APC), the induction of cytokines such as tumor necrosis factor alpha, interleukin (IL)-12, IL-4, IL-10, and transforming growth factor-beta (TGF-beta), and the activation of T lymphocytes. We show here that the uptake of chitosan at inductive mucosal sites involves CD11b/c+ APC and that chitosan feeding increases the percentage of OX62+ dendritic cells, which up-regulate the major histocompatibility complex class II antigens without changing the expression of costimulatory CD80 or CD86 molecules. The polysaccharide elicits the release of IL-10 as well as the expression of IL-4 and TGF-beta in mucosa, and in spleen, the activation of CD3+ T cells occurs. Our results demonstrate that chitosan acts by enhancing the T helper cell type 2 (Th2)/Th3 microenvironment in the mucosa. A single dose of this polysaccharide exhibits local and systemic effects, and its activity could be relevant in the maintenance of the intestinal homeostasis.

Local and systemic levels of tobramycin delivered from calcium sulfate bone graft substitute pellets
Turner, T. M., R. M. Urban, et al. (2005), Clin Orthop Relat Res(437): 97-104.
Abstract: We asked if tobramycin-loaded calcium sulfate pellets could be used to maintain high local site antibiotic concentrations for an extended period with minimal systemic levels and without adverse effects on vital organs. Calcium sulfate pellets loaded with 10% tobramycin were implanted in contained medullary defects in the proximal humeri of canines. The number of pellets implanted was calculated to yield an equivalent human maximum prescribed dose, and 1.8-fold this dose. These doses converted to approximately 20 mg/kg, and 36 mg/kg, respectively, for the canine. Local and systemic tobramycin levels, pellet resorption, bone response, clinical pathology parameters, and histopathologic responses of potential target organs were analyzed to determine if there was any adverse response for a 28-day period. Serum tobramycin was elevated for less than one day while local levels remained elevated for at least 14 days, and in some animals, 28 days. Tobramycin delivered locally from calcium sulfate pellets had no apparent adverse effect on clinical pathology parameters or on any of the organs that were analyzed. In addition, bone formation and pellet resorption followed patterns typically seen with calcium sulfate materials.

Local antibiotic delivery vehicles in the treatment of musculoskeletal infection
Hanssen, A. D. (2005), Clin Orthop Relat Res(437): 91-6.
Abstract: The primary benefit achieved with local antibiotic delivery vehicles is the ability to obtain extremely high levels of local antibiotics without increasing systemic toxicity. Antibiotic-loaded bone cement represents the current standard as an antibiotic delivery vehicle in orthopaedic surgery. Biodegradable alternatives to antibiotic-loaded bone cement also are being used clinically and there are many new products in the active stages of development. These alternatives can be categorized as bone graft, bone graft substitutes or extenders, natural polymers (protein-based products), and synthetic polymers. Composite biomaterials that simultaneously provide the functions of variable antibiotic delivery patterns and also contribute to the process of bone regeneration represent the most ideal class of local antibiotic delivery vehicles. High concentrations of certain antibiotics have been shown to affect the process of normal bone regeneration adversely in a dose dependent response. Considerable investigation still is required to determine the proper use of locally administered antibiotics to negotiate the balance between eradicating infection without excessively inhibiting the processes of bone regeneration.

Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(epsilon-caprolactone) stent cuff
Pires, N. M., B. L. van der Hoeven, et al. (2005), Biomaterials 26(26): 5386-94.
Abstract: The introduction of drug-eluting stents (DES) to prevent in-stent restenosis is one of the major advances in interventional cardiology. Currently many types of DES are under evaluation for effectiveness and safety, a time-consuming and difficult procedure in humans. An animal model that allows rapid evaluation of the present and upcoming therapeutic approaches to prevent in-stent restenosis is most valuable and still lacking. Here, a perivascular cuff to induce restenosis was constructed of a poly(epsilon-caprolactone) (PCL) formulation suitable for the controlled delivery of drugs. Placing the PCL cuff around the femoral artery, in vivo, resulted in reproducible restenosis-like lesions containing predominantly smooth muscle-actin positive cells. Loading the cuff with the anti-restenotic compounds paclitaxel and rapamycin resulted, in vitro, in a sustained and dose-dependent release for at least 3 weeks. Paclitaxel- and rapamycin-eluting PCL cuffs placed around the femoral artery of mice in vivo significantly reduced intimal thickening by 76 +/- 2% and 75 +/- 6%, respectively, at 21 days. Perivascular sustained release of both anti-restenotic agents is restricted to the cuffed vessel segment with no systemic adverse effects or effect on cuffed contralateral femoral arteries. Drug-eluting PCL cuffs provide an easy and rapid tool to evaluate anti-restenotic agents to be used in combination with the DES strategies.

Local response to biomaterials: bone loss in cementless femoral stems
Jacobs, J. J., J. O. Galante, et al. (1992), Instr Course Lect 41: 119-25.
Abstract: While cementless, porous-coated prosthetic components have shown a high percentage of satisfactory clinical results in short and intermediate term follow-up, there are biologic problems associated with implantation of cementless devices that may predispose to clinical failure at longer term follow-up. Central to the issue of long-term performance is the problem of bone loss secondary either to adaptive bone remodeling processes or to the phenomenon of focal osteolysis. The stiffness of the femoral stem and the relative biologic inertness of the materials used are two properties of critical importance. In the future, continuing developments in the areas of prosthetic design, enhancement of fixation, biocompatibility, and biomaterials research will seek to address and resolve these problems.

Local structure of channel ions in carbonate apatite
Fleet, M. E. and X. Liu (2005), Biomaterials 26(36): 7548-54.
Abstract: Refinement of the single-crystal X-ray diffraction structure of a type A carbonate apatite [CAp; Ca10(PO4)6-y(CO3)x+(3/2)y(OH)2-2x, x=0.75, y=0.0; space group P3] has been continued with independent positional and isotropic displacement parameters for the carbonate oxygen atoms, reducing the residual indices significantly (R=0.024, Rw=0.020) and confirming the earlier structure assignment. The carbonate ion is located in the apatite channel at z approximately 0.5, and oriented with two oxygen atoms close to the c-axis. Rigid body refinement, giving a preferred structure, used a novel procedure for defining the ideal equilateral triangular geometry of the channel carbonate ion. Resolution of the channel carbonate ions in type A-B CAp (x=0.69, y=0.57; P63/m) is also improved. Channel carbonate ions in CAp are canted, rotated and displaced to optimize Ca2-O bond distances. The rotation of the A1 carbonate in type A-B CAp is opposite to that of the channel carbonate in type A CAp, due mainly to the accommodation of a second channel carbonate ion (A2). These structures simulate the local structure of type A carbonate in hydroxyapatite of bone and dental enamel.

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Last Modified: 8 February 2006