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The application of alveolar distraction osteogenesis following nonresorbable hydroxyapatite grafting in the anterior maxilla: a clinical report
Aragon, C. E. and R. N. Bohay (2005), J Prosthet Dent 93(6): 518-21.
Abstract: Distraction osteogenesis is a method of increasing bone length through the application of slow, controlled force on bone segments where periosteum and medullary blood supply are maintained. Recently, the procedure has been adapted to alveolar augmentation prior to prosthodontic rehabilitation. This report describes the use of alveolar distraction in the anterior maxilla and presents, to the authors' knowledge, the first reported successful application of the technique following nonresorbable hydroxyapatite grafting.

The application of Fourier-transform Raman spectroscopy to the analysis of pharmaceuticals and biomaterials
Tudor, A. M., C. D. Melia, et al. (1990), J Pharm Biomed Anal 8(8-12): 717-20.
Abstract: Near infrared Fourier-transform (FT) Raman spectroscopy is shown to be a useful spectroscopic tool for the molecular structural analysis of drugs and biomedical polymers. The technique has been applied to the non-invasive investigation of the hydrolytic degradation of a biodegradable polymer in water over a period of 15 days and to the analysis of a drug within a polymer vehicle over a wide drug concentration range. This work demonstrates the potential value of FT Raman spectroscopy in the field of pharmaceutical science.

The application of ion beam analysis to calcium phosphate-based biomaterials
Russell, S. W., T. L. Alford, et al. (1996), J Biomed Mater Res 30(2): 165-74.
Abstract: Ion beam technology may be applied in a straightforward fashion to the analysis and modification of biomaterials. For analytical purposes, characterization using megaelectron-volt He2+ ions provides a standardless, nondestructive means for accurately quantifying the composition of material surfaces and the thickness of thin films. In this study, three complementary ion backscattering techniques were utilized to characterize hydroxyapatite (HA) films: Rutherford backscattering spectrometry (RBS) can determine composition and amounts of elements heavier than He; forward recoil elastic spectrometry (FRES) can determine hydrogen content; resonance-enhanced RBS can quantify small amounts of light elements, e.g. carbon, by choosing a particular incident beam energy resulting in excitation of the light element nucleus. At this resonance energy, the scattering cross section greatly increases, improving elemental sensitivity. Sol-gel chemistry was used to synthesize HA films by spin coating and annealing in a rapid thermal processor. Using these techniques, the chemical composition of unfired films was Ca1.63O5.4H1.8C0.24P with a thickness of 3.01 x 10(18) atoms/cm2 and after firing at 800 degrees C as Ca1.66O4.0H0.26C0.09P with a thickness of 2.11 x 10(18) atoms/cm2. This compares favorably to stoichiometric HA, which has a composition of Ca1.67O4.33H0.33P.

The application of polyhydroxyalkanoates as tissue engineering materials
Chen, G. Q. and Q. Wu (2005), Biomaterials 26(33): 6565-78.
Abstract: Polyhydoxyalkanoates (PHA) are polyesters produced by microorganisms under unbalanced growth conditions. They are generally biodegradable and thermoprocessable, making them attractive as biomaterials for applications in both conventional medical devices and tissue engineering. Over the past years, PHA, particularly poly 3-hydroxybutyrate (PHB), copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV), poly 4-hydroxybutyrate (P4HB), copolymers of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) and poly 3-hydroxyoctanoate (PHO) and its composites have been used to develop devices including sutures, repair devices, repair patches, slings, cardiovascular patches, orthopedic pins, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, bone marrow scaffolds, and wound dressings. The changing PHA compositions also allow favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under specific physiological conditions. This paper reviews what have been achieved in the PHA tissue engineering area and concluded that the PHA prospective will look very bright in the near future.

The argument for lightweight polypropylene mesh in hernia repair
Cobb, W. S., K. W. Kercher, et al. (2005), Surg Innov 12(1): 63-9.
Abstract: The development of polypropylene prosthetics revolutionized surgery for the repair of abdominal wall hernias. A tension-free mesh technique has drastically reduced recurrence rates for all hernias compared to tissue repairs and has made it possible to reconstruct large ventral defects that were previously irreparable. The repair of abdominal wall defects is one of the most commonly performed general surgical procedures, with over 1 million polypropylene implants inserted each year. Surprisingly, little research has been performed to investigate the interaction of abdominal wall forces on a ventral hernia repair or the required amount or strength of the foreign-body material necessary for an adequate hernia repair. The long-term consequences of implantable polypropylene prosthetics are not without concern. The body generates an intense inflammatory response to the prosthetic that results in scar plate formation, increased stiffness of the abdominal wall, and shrinkage of the biomaterial. Reducing the density of polypropylene and creating a ''light weight'' mesh theoretically induces less foreign-body response, results in improved abdominal wall compliance, causes less contraction or shrinkage of the mesh, and allows for better tissue incorporation. A review of the laboratory data and short-term clinical follow-up is reviewed to provide a strong basis or argument for the use of ''light weight'' prosthetics in hernia surgery.

The assessment of hookworm calreticulin as a potential vaccine for necatoriasis
Winter, J. A., O. R. Davies, et al. (2005), Parasite Immunol 27(4): 139-46.
Abstract: A vaccine against the human hookworm Necator americanus is urgently required to reduce hookworm-induced morbidity in endemic areas. In the present study, recombinant hookworm calreticulin, a nominated vaccine candidate, has been tested in mice. Mice given calreticulin had 43-49% fewer worms in their lungs, compared to non-vaccinated controls, following challenge infection with infective hookworm larvae. These levels of protection were achieved in the absence of adjuvant following intraperitoneal administration of three doses of 15 microg antigen. Antigen was also encapsulated in PLG microparticles. Encapsulated calreticulin elicited higher levels of anti-calreticulin IgG1 than free antigen but failed to induce protective immunity. The protection induced by free calreticulin was associated with low levels of serum IgE and moderate lung eosinophilia whilst administration of calreticulin-loaded microparticles was associated with high levels of serum IgE and higher lung eosinophil activity, suggesting that the classical Th2 phenotype may not always be associated with protective immunity, albeit in experimental necatoriasis.

The behaviour of titanium as a biomaterial: microscopy study of plates and surrounding tissues in facial osteosynthesis
Acero, J., J. Calderon, et al. (1999), J Craniomaxillofac Surg 27(2): 117-23.
Abstract: Titanium has become the biomaterial of choice for facial osteosynthesis. Titanium is considered a highly biocompatible and corrosion resistant material, although the ultrastructural behaviour of titanium in human tissues after bone fixation is not well documented. A prospective scanning electron microscopy study was carried out on 37 commercially pure titanium miniplates which were removed from 23 patients who had undergone surgery for maxillofacial trauma or deformity. Twenty two cases were used as a control group. Implant-bone specimens were excised using tungsten burs and studied with a scanning electron microscope (Jeol JSM-T-300). Findings at the bone-titanium interface were analyzed, as well as the presence of contaminating bodies on the specimen surface. Biopsies were also obtained from the soft tissues adjacent to 20 miniplates, then sectioned and stained with Haematoxilin-Eosin for histological evaluation by light microscopy. The results showed good ultrastructural osseointegration of the osteosynthesis material in most cases (81.8%). Mobility was found upon removal in 80% of plates which showed clinical complications. A significant correlation was found between the degree of microscopical osseointegration and macroscopic fixation of the plate. Microscopical contamination was found in 100% of the nine plates with intraoral exposure, while only 36% of the 22 miniplates of the control group had contaminating elements (P < 0.001). Thirty-five point one percent of the plates showed hole-like substance loss images, whose size ranged from 10-25 mu. Light microscopy showed granular deposits in soft tissues surrounding the plates in 80% of the 20 specimens investigated. Our findings suggest a higher development of corrosion in titanium than previously reported. These findings are not correlated, however with the clinical complications.

The biocompatibility and osteoconductive activity of a novel hydroxyapatite/collagen composite biomaterial, and its function as a carrier of rhBMP-2
Itoh, S., M. Kikuchi, et al. (2001), J Biomed Mater Res 54(3): 445-53.
Abstract: A hydroxyapatite/type I collagen (HAp/Col) composite, in which the hydroxyapatite nanocrystals align along the collagen molecules, has been prepared. The biocompatibility, osteoconductive activity, and efficacy as a carrier of recombinant human bone morphogenetic proteins (rhBMPs) of this novel biomaterial were examined. The composite material was implanted in the backs of Wistar rats, and specimens were collected for histological observations until week 24. In a second experiment, other samples of the composite material (5 x 5 x 10 mm3) were drilled and immersed in a solution of rhBMP-2 (0, 200, 400 microg/mL), and subsequently grafted in radii and ulnae in beagle dogs. As a control, three unfilled holes were left in one radius and ulna. X-ray images were prepared, and specimens collected for histological observation at weeks 8 and 12. Histological findings of the composites grafted in rats showed that the surface of the material was eroded as a result of macrophage infiltration. X-ray images and histological findings for the composites implanted in dogs support the idea that HAp/ Col has a high osteoconductive activity and is able to induce bone-remodeling units. In cases where the implants are grafted at weight bearing sites, treatment with rhBMP-2 at a dose of 400 microg/mL may be useful to shorten the time needed until bone union has occurred.

The biocompatibility of dibutyryl chitin in the context of wound dressings
Muzzarelli, R. A., M. Guerrieri, et al. (2005), Biomaterials 26(29): 5844-54.
Abstract: Dibutyryl chitin (DBC) is a modified chitin carrying butyryl groups at 3 and 6 positions; its peculiarity is that it dissolves promptly in common solvents, while being insoluble in aqueous systems. The high biocompatibility of dibutyryl chitin in the form of films and non-wovens has been demonstrated for human, chick and mouse fibroblasts by the Viability/Cytotoxicity assay, In situ Cell Proliferation assay, Neutral Red Retention assay, Lactate Dehydrogenase Release assay, MTS cytotoxicity assay, and scanning electron microscopy. DBC was hardly degradable by lysozyme, amylase, collagenase, pectinase and cellulase over the observation period of 48 days at room temperature, during which no more than 1.33% by weight of the DBC filaments (0.3 mm diameter) was released to the aqueous medium. DBC non-wovens were incorporated into 5-methylpyrrolidinone chitosan solution and submitted to freeze-drying to produce a reinforced wound dressing material. The latter was tested in vivo in full thickness wounds in rats. The insertion of 4x4 mm pieces did not promote any adverse effect on the healing process, as shown histologically. DBC is therefore suitable for contacting intact and wounded human tissues.

The biocompatibility of silk fibroin films containing sulfonated silk fibroin
Ma, X., C. Cao, et al. (2005), J Biomed Mater Res B Appl Biomater
Abstract: Sulfonation reaction may be an effective method for preparation of heparin-like materials. However, no sulfonated polymer based on protein backbone was used for improving the blood compatibility of biomaterials. In this study, the biocompatibility of new kind of composite materials films obtained by blending silk fibroin (SF) with sulfonated silk fibroin (SSF) was evaluated. The anticoagulant activity was characterized with prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), which all increased remarkably, the clot times exceeded the measurement limit of clot detection instrument. Its platelet adhesion was also investigated as another parameter of blood compatibility. The cell compatibility of composite films was evaluated through cell morphologies on the films and cell viability by methyl thiazolyl tetrazolium (MTT) assay. Tensile strength and elongation at break of the composite films reached to 44.6 MPa and 50.3%, respectively. All these results indicated that SF/SSF composite film was a potential material for blood-contact materials and tissue engineering matrix. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006.

The biodegradation mechanism of calcium phosphate biomaterials in bone
Lu, J., M. Descamps, et al. (2002), J Biomed Mater Res 63(4): 408-12.
Abstract: This study was undertaken to understand the biodegradation mechanisms of calcium phosphate (Ca-P) biomaterials with different crystallization. Two types of sintered Ca-P porous ceramic (HA and beta-TCP) and a Ca-P bone cement (CPC) were implanted into cavities drilled in rabbit femoral and tibiae condyles. The results have shown that a material biodegradation was rapid in the beta-TCP and the CPC, but very weak in the HA. This biodegradation presented a decrease of material volume from the periphery to the center as well as a particle formation causing phagocytosis by numerous macrophages and multinucleated giant cells in the CPC. In the beta-TCP, there was a peripheral and central decrease of material volume as well as an absence of particle formation or visible phagocytosis. The process of biodegradation is considered to be directly influenced by the type of material crystallization. The sintered bioceramics processed at a high temperature exhibit good crystallization and are primarily degraded by a process dependent on interstitial liquids. However, the bone cement is formed by physicochemical crystallization and is degraded through a dissolution process associated with a cellular process.

The biologic tissue responses to uncoated and coated implanted biomaterials
Steflik, D. E., R. S. Corpe, et al. (1999), Adv Dent Res 13: 27-33.
Abstract: Ultrastructural examination of the morphology and morphometry of the bone supporting uncoated titanium and ceramic implants was assessed in an experimental animal model involving 120 implants placed into the mandibles of 30 adult mongrel dogs. Further, preliminary morphologic and morphometric observations of the bone supporting uncoated and hydroxylapatite-coated endosteal titanium implants was evaluated in a second investigation involving 72 implants placed into the mandibles and maxillae of 6 additional dogs. A densely mineralized collagen fiber matrix was observed directly interfacing with uncoated implants. The only material interposed between the implant and bone matrix was a 20- to 50-nm electron-dense material suggestive of a proteoglycan. Also seen in these same osseointegrated implants were narrow unmineralized zones interposed between the implant and bone matrix. In these zones of remodeling bone, numerous osteoblasts were observed interacting with the collagen fiber matrix. It was shown that a normal homeostasis of anabolic osteoblastic activity and catabolic osteoclastic activity resulted in bone remodeling and the resultant osseointegration of the implants. Hydroxylapatite-coated implants intimately interfaced with healthy bone. The mineralized matrix extended into the microporosity of the HA coating. This matrix contained viable osteocytes.

The Biomaterials Access Assurance Act of 1998
Walter, C. F. and E. P. Richards, 3rd (1999), IEEE Eng Med Biol Mag 18(2): 125-7.

The biomaterial-tissue interface: a morphological study utilizing conventional and alternative ultrastructural modalities
Steflik, D. E., R. V. McKinney, Jr., et al. (1984), Scan Electron Microsc(Pt 2): 547-55.
Abstract: The interface between oral tissues and ceramic endosteal dental implants was investigated in 36 experimental cases in dog jaws. Conventional electron microscopic modalities showed those tissues adjacent to the implants to be viable with no adverse cellular response to the biomaterial. A procedure to retrieve additional ultrastructural data from previously processed biological material was developed to expand upon these data. This included surface-etching with oxygen plasma of routinely processed electron microscopy specimens and formalin fixed histological specimens for scanning electron microscopy (SEM) study; and, cryofracturing of similar histological specimens for additional transmission electron microscopic (TEM) analysis. Results from these alternative protocols supported our observations from conventional studies of the direct association of bone and epithelia to the implant. In addition, they demonstrated a unique portrayal of the epithelial maturation patterns. Further, this alternative TEM method showed excellent retention of cellular integrity and demonstrated a hemidesmosomal-external basal lamina attachment apparatus at the junctional epithelial-implant interface. This latter composite attachment structure was not retained in our previous conventional microdissection procedures. Thus, the interface between oral tissues and the single crystal sapphire endosteal dental implant could be elucidated by these protocols.

The biomimetics of enamel: a paradigm for organized biomaterials synthesis
Mann, S. (1997), Ciba Found Symp 205: 261-9; discussion 269-74.
Abstract: The formation of enamel takes place through a sequence of processes that can be mimicked in inorganic materials chemistry. This chapter describes the generic features of enamel biomineralization in terms of a house-building analogy. Four stages are identified: supramolecular preorganization and spatial patterning; interfacial molecular recognition in inorganic nucleation; vectorial crystallization; and pattern evolution and hierarchy. Each of these concepts can be translated into synthetic approaches to the formation of inorganic materials with organized architectures. An example of applying this biomimetic paradigm is described. Supersaturated water-in-oil microemulsions have been used to synthesize microskeletal calcium phosphates by controlled nucleation and vectorial growth in constrained reaction environments. The results of these preliminary studies suggest that biomimetic concepts could be useful in the fabrication of biomaterial implants with controlled porosity and microstructure.

The bone formation in vitro and mandibular defect repair using PLGA porous scaffolds
Ren, T., J. Ren, et al. (2005), J Biomed Mater Res A 74(4): 562-9.
Abstract: Highly porous scaffolds of poly(lactide-co-glycolide) (PLGA) were prepared by solution-casting/salt-leaching method. The in vitro degradation behavior of PLGA scaffold was investigated by measuring the change of normalized weight, water absorption, pH, and molecular weight during degradation period. Mesenchymal stem cells (MSCs) were seeded and cultured in three-dimensional PLGA scaffolds to fabricate in vitro tissue engineering bone, which was investigated by cell morphology, cell number and deposition of mineralized matrix. The proliferation of seeded MSCs and their differentiated function were demonstrated by experimental results. To compare the reconstructive functions of different groups, mandibular defect repair of rabbit was made with PLGA/MSCs tissue engineering bone, control PLGA scaffold, and blank group without scaffold. Histopathologic methods were used to estimate the reconstructive functions. The result suggests that it is feasible to regenerate bone tissue in vitro using PLGA foams with pore size ranging from 100-250 microm as scaffolding for the transplantation of MSCs, and the PLGA/MSCs tissue engineering bone can greatly promote cell growth and have better healing functions for mandibular defect repair. The defect can be completely recuperated after 3 months with PLGA/MSCs tissue engineering bone, and the contrastive experiments show that the defects could not be repaired with blank PLGA scaffold. PLGA/MSCs tissue engineering bone has great potential as appropriate replacement for successful repair of bone defect.

The bone response of oxidized bioactive and non-bioactive titanium implants
Sul, Y. T., C. Johansson, et al. (2005), Biomaterials 26(33): 6720-30.
Abstract: A number of experimental and clinical data on so-called oxidized implants have reported promising outcomes. However, little is investigated on the role of the surface oxide properties and osseointegration mechanism of the oxidized implant. Sul [On the Bone Response to Oxidized Titanium Implants: The role of microporous structure and chemical composition of the surface oxide in enhanced osseointegration (thesis). Goteborg: Department of Biomaterials/Handicap Research, University of Goteborg, Sweden; 2002; Biomaterials 2003; 24: 3893-3907] recently proposed two action mechanisms of osseointegration of oxidized implants, i.e. mechanical interlocking through bone growth in pores/other surface irregularities (1) and biochemical bonding (2). The aim of the present study is two-fold: (i) investigating the role of the implant surface chemistry on bone responses; (ii) investigating the validity of the biochemical bonding theory of the oxidized, bioactive bone implants with specific implant surface chemistry. Two groups of oxidized implants were prepared using micro arc oxidation process and were then inserted in rabbit bone. One group consisted of magnesium ion incorporated implants (MgTiO implant), the other consisted of TiO2 stoichiometry implants (TiO implant). Surface oxide properties of the implants were characterized with various surface analytic techniques. After 6 weeks of follow up, the mean peak values of removal torque of Mg implants dominated significantly over TiO implants (p < or = 0.0001). Bonding failure generally occurred in the bone away from the bone to implant interface for the MgTiO implant and mainly occurred at the bone to implant interface for the TiO implant that consisted mainly of TiO2 chemistry and significantly rougher surface as compared to the MgTiO implant. Between bone and the Mg- incorporated implant surface, ionic movements and ion concentrations gradient were detected. The current in vivo experimental data may provide positive evidence for the surface chemistry-mediated biochemical bonding theory of oxidized bioactive implants. However, the present study does not rule out potential synergy effects of the oxide thickness, micro-porous structure, crystal structure and surface roughness on improvements of bone responses to oxidized bioactive implants.

The cell and molecular biological approach to biomaterial research: a perspective
Kirkpatrick, C. J., M. Wagner, et al. (1997), J Mater Sci Mater Med 8(3): 131-41.
Abstract: The past two decades have witnessed a revolution in our understanding of chemical processes in living organisms. This is mainly a result of the massive advances in the fields of cell and molecular biology. These techniques are highly relevant to the biomaterials sector, as they offer the scientist the possibility to better understand the mechanisms involved in the interactions between cells and a material surface-a prerequisite for the rational development of medical devices with optimal biocompatibility. The purpose of the present article is to explain the rationale of the cell and molecular biological approach to biomaterial research and to present typical examples from the authors' laboratory, as well as from the literature, to illustrate its application. Important aspects of interfacial biology, including the underlying biological mechanisms and methodology, are presented. Of the latter the combination of morphological techniques with methods of cell and molecular biology as well as molecular genetics (so-called "combinative techniques") are particularly useful. The applicability of this approach is illustrated from a study on the pathomechanisms of metal ion-induced inflammation. In addition, the approach is essential to the development of targeted intervention strategies, as for example in the luminal surface modification of vascular prostheses to permit endothelial cell seeding.

The cell as a biomaterial
Pollack, G. H. (2002), J Mater Sci Mater Med 13(9): 811-21.
Abstract: For materials scientists, the cell is evidently a biomaterial - rich with polymers, surface forces, solvent-solute interactions, liquid-crystalline structures, etc. Yet, the language of the materials scientist is as foreign to the biological world as French is to Chinese. Little of the materials scientists' perspective has been brought to bear on the question of biological function. This review aims to begin bridging the gap between the two disciplines-to show that a materials-oriented approach has power to bring fresh insights into an otherwise impenetrably complex maze. In this approach the cell is treated as a polymer gel. If the cell is a gel, then a logical approach to the understanding of cell function is through an understanding of gel function. Great strides have been made recently in understanding the principles of polymer-gel dynamics. It has become clear that a central mechanism is the phase-transition - a major structural change prompted by a subtle change of environment. Phase-transitions are capable of doing work and such work could be responsible for much of the work of the cell. Here, we pursue this approach. We set up a polymer-gel-based foundation for cell behavior, and explore the extent to which this foundation explains how the cell achieves its everyday tasks.

The cellular response to transglutaminase-cross-linked collagen
Chau, D. Y., R. J. Collighan, et al. (2005), Biomaterials 26(33): 6518-29.
Abstract: Collagen, type I, is a highly abundant natural protein material which has been cross-linked by a variety of methods including chemical agents, physical heating and UV irradiation with the aim of enhancing its physical characteristics such as mechanical strength, thermal stability, resistance to proteolytic breakdown, thus increasing its overall biocompatibility. However, in view of the toxicity of residual cross-linking agents, or impracticability at large scales, it would be more useful if the collagen could be cross-linked by a milder, efficient and more practical means by using enzymes as biological catalysts. We demonstrate that on treating native collagen type I (from bovine skin) with both tissue transglutaminase (TG2; tTG) and microbial transglutaminase (mTG; Streptoverticillium mobaraense) leads to an enhancement in cell attachment, spreading and proliferation of human osteoblasts (HOB) and human foreskin dermal fibroblasts (HFDF) when compared to culture on native collagen. The transglutaminase-treated collagen substrates also showed a greater resistance to cell-mediated endogenous protease degradation than the native collagen. In addition, the HOB cells were shown to differentiate at a faster rate than on native collagen when assessed by measurement of alkaline phosphatase activity and osteopontin expression.

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Last Modified: 8 February 2006