|Articles about Biomaterials|
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| Total hip replacement operation: biomaterials and indications
Derian, P. S., G. Truett, et al. (1972), J Miss State Med Assoc 13(8): 323-9.
| Toward a sutureless vasovasostomy: use of biomaterials and surgical sealants in a rodent vasovasostomy model
Schiff, J., P. S. Li, et al. (2004), J Urol 172(3): 1192-5.
Abstract: PURPOSE: With 500,000 to 800,000 vasectomies performed annually and a reversal rate of 3% to 8% vasectomy reversal has become a commonly performed procedure. Two-layer microsurgical vasovasostomy remains the gold standard for surgical reconstruction of the vas. However, this procedure is technically demanding and time-consuming. We determined the ability of biomaterials and surgical sealants to decrease the number of sutures used, enhance anastomosis watertightness and decrease operative time. MATERIALS AND METHODS: Adult male Wistar rats underwent vasectomy 2 weeks prior to vasovasostomy. Standard 2-layer microsurgical repair was performed in control animals. Experimental groups underwent 3-suture mucosal approximation and then completion of the anastomosis with a biomaterial membrane and/or synthetic sealant. The rats were sacrificed 9 weeks after vasovasostomy. Anastomotic patency was assessed functionally by the presence of motile sperm in the vas distal to the testes and anastomosis, and mechanically by methylene blue vasogram. The presence and size of sperm granulomas were also recorded. RESULTS: Microsurgical vasovasostomy required significantly less time when biomaterial (42.7 minutes) or sealant (40 minutes) was used compared to the standard sutured group (102.5 minutes, each p < 0.001). There was no difference in patency between the standard sutured and biomaterial groups (90% vs 92%). Patency was significantly lower in the sealant groups, that is 70% in the suture, biomaterial and sealant group, and 75% in the suture and sealant group. The biomaterial group had only 1 sperm granuloma in 12 procedures, which was significantly better than the 7 in the control group (p <0.001). CONCLUSIONS: Using a biomaterial wrap during vasovasostomy resulted in significantly decreased operative time and fewer sperm granulomas than in the control group. Sealants were not effective. Biomaterial wrap may support vasovasostomy and by decreasing leakage improve the outcome.
| Toward an understanding of biomaterial infections: a complex interplay between the host and bacteria
Proctor, R. A. (2000), J Lab Clin Med 135(1): 14-5.
| Toward new biomaterials
Montdargent, B. and D. Letourneur (2000), Infect Control Hosp Epidemiol 21(6): 404-10.
Abstract: Polymers are widely used for a large range of medical devices used as biomaterials on a temporary, intermittent, and long-term basis. It is now well accepted that the initial rapid adsorption of proteins to polymeric surfaces affects the performance of these biomaterials. However, protein adsorption to a polymer surface can be modulated by an appropriate design of the interface. Extensive study has shown that these interactions can be minimized by coating with a highly hydrated layer (hydrogel), by grafting on the surface different biomolecules, or by creating domains with chemical functions (charges, hydrophilic groups). Our laboratory has investigated the latter approach over the past 2 decades, in particular the synthesis and the biological activities of polymers to improve the biocompatibility of blood-contacting devices. These soluble and insoluble polymers were obtained by chemical substitution of macromolecular chains with suitable groups able to develop specific interactions with biological components. Applied to compatibility with the blood and the immune systems, this concept has been extended to interactions of polymeric biomaterials with eukaryotic and prokaryotic cells. The design of new biomaterials with low bacterial attachment is thus under intensive study. After a brief overview of current trends in the surface modifications of biocompatible materials, we will describe how biospecific polymers can be obtained and review our recent results on the inhibition of bacterial adhesion using one type of functionalized polymer obtained by random substitution. This strategy, applied to existing or new materials, seems promising for the limitation of biomaterial-associated infections.
| Toward the development of peptide nanofilaments and nanoropes as smart materials
Wagner, D. E., C. L. Phillips, et al. (2005), Proc Natl Acad Sci U S A 102(36): 12656-61.
Abstract: Protein design studies using coiled coils have illustrated the potential of engineering simple peptides to self-associate into polymers and networks. Although basic aspects of self-assembly in protein systems have been demonstrated, it remains a major challenge to create materials whose large-scale structures are well determined from design of local protein-protein interactions. Here, we show the design and characterization of a helical peptide, which uses phased hydrophobic interactions to drive assembly into nanofilaments and fibrils ("nanoropes"). Using the hydrophobic effect to drive self-assembly circumvents problems of uncontrolled self-assembly seen in previous approaches that used electrostatics as a mode for self-assembly. The nanostructures designed here are characterized by biophysical methods including analytical ultracentrifugation, dynamic light scattering, and circular dichroism to measure their solution properties, and atomic force microscopy to study their behavior on surfaces. Additionally, the assembly of such structures can be predictably regulated by using various environmental factors, such as pH, salt, other molecular crowding reagents, and specifically designed "capping" peptides. This ability to regulate self-assembly is a critical feature in creating smart peptide biomaterials.
| Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation
Zimmermann, H., D. Zimmermann, et al. (2005), J Mater Sci Mater Med 16(6): 491-501.
Abstract: The concept of encapsulated-cell therapy is very appealing, but in practice a great deal of technology and know-how is needed for the production of long-term functional transplants. Alginate is one of the most promising biomaterials for immunoisolation of allogeneic and xenogeneic cells and tissues (such as Langerhans islets). Although great advances in alginate-based cell encapsulation have been reported, several improvements need to be made before routine clinical applications can be considered. Among these is the production of purified alginates with consistently high transplantation-grade quality. This depends to a great extent on the purity of the input algal source as well as on the development of alginate extraction and purification processes that can be validated. A key engineering challenge in designing immunoisolating alginate-based microcapsules is that of maintaining unimpeded exchange of nutrients, oxygen and therapeutic factors (released by the encapsulated cells), while simultaneously avoiding swelling and subsequent rupture of the microcapsules. This requires the development of efficient, validated and well-documented technology for cross-linking alginates with divalent cations. Clinical applications also require validated technology for long-term cryopreservation of encapsulated cells to maintaining a product inventory in order to meet end-user demands. As shown here these demands could be met by the development of novel, validated technologies for production of transplantation-grade alginate and microcapsule engineering and storage. The advances in alginate-based therapy are demonstrated by transplantation of encapsulated rat and human islet grafts that functioned properly for about 1 year in diabetic mice.
| Towards a methodology for the effective surface modification of porous polymer scaffolds
Safinia, L., N. Datan, et al. (2005), Biomaterials 26(36): 7537-47.
Abstract: A novel low-pressure radio-frequency plasma treatment protocol was developed to achieve the effective through-thickness surface modification of large porous poly (D,L-lactide) (PDLLA) polymer scaffolds using air or water: ammonia plasma treatments. Polymer films were modified as controls. Scanning electron micrographs and maximum bubble point measurements demonstrated that the PDLLA foams have the high porosity, void fraction and interconnected pores required for use as tissue engineering scaffolds. The polymer surface of the virgin polymer does contain acidic functional groups but is hydrophobic. Following exposure to air or water: ammonia plasma, an increased number of polar functional groups and improved wetting behaviour, i.e. hydrophilicity, of wet surfaces was detected. The number of polar surface functional groups increased (hence the decrease in water contact angles) with increasing exposure time to plasma. The change in surface composition and wettablility of wet polymer constructs was characterised by zeta potential and contact angle measurements. The hydrophobic recovery of the treated PDLLA polymer surfaces was also studied. Storage of the treated polymer constructs in ambient air caused an appreciable hydrophobic recovery, whereas in water only partial hydrophobic recovery occurred. However, in both cases the initial surface characteristics decay as function of time.
| Towards automated 3D finite element modeling of direct fiber reinforced composite dental bridge
Li, W., M. V. Swain, et al. (2005), J Biomed Mater Res B Appl Biomater 74(1): 520-8.
Abstract: An automated 3D finite element (FE) modeling procedure for direct fiber reinforced dental bridge is established on the basis of computer tomography (CT) scan data. The model presented herein represents a two-unit anterior cantilever bridge that includes a maxillary right incisor as an abutment and a maxillary left incisor as a cantilever pontic bonded by adhesive and reinforced fibers. The study aims at gathering fundamental knowledge for design optimization of this type of innovative composite dental bridges. To promote the automatic level of numerical analysis and computational design of new dental biomaterials, this report pays particular attention to the mathematical modeling, mesh generation, and validation of numerical models. To assess the numerical accuracy and to validate the model established, a convergence test and experimental verification are also presented.
| Towards practical soft X-ray spectromicroscopy of biomaterials
Hitchcock, A. P., C. Morin, et al. (2002), J Biomater Sci Polym Ed 13(8): 919-37.
Abstract: Scanning transmission X-ray microscopy (STXM) is being developed as a new tool to study the surface chemical morphology and biointeractions of candidate biomaterials with emphasis on blood compatible polymers. STXM is a synchrotron based technique which provides quantitative chemical mapping at a spatial resolution of 50 nm. Chemical speciation is provided by the near edge X-ray absorption spectral (NEXAFS) signal. We show that STXM can detect proteins on soft X-ray transparent polymer thin films with monolayer sensitivity. Of great significance is the fact that measurements can be made in situ, i.e. in the presence of an overlayer of the protein solution. The strengths, limitations and future potential of STXM for studies of biomaterials are discussed.
| Toxicity evaluation of a novel filler free silicone rubber biomaterial by cell culture techniques
Chawla, A. S. (1982), J Biomed Mater Res 16(4): 501-8.
Abstract: Cytotoxicity of a novel filler free silicone rubber (FFSR) was evaluated by studying its effect on mouse L929 cells. Silastic and a laboratory rubber tubing (RT) were used as control materials. Three different experimental methods were used. In method A, after six days of cell culturing in the sample extracts, there were 95, 80, and 50% of control viable cells for FFSR, Silastic, and RT, respectively. Similarly, in method B, after six days of direct contact between samples and the cells, there were 80, 40, and 20% of control viable cells for FFSR, Silastic, and RT, respectively. For the Agar Overlay Test, method C, the cells under the FFSR samples were normal and healthy compared to those under Silastic and RT. From these studies it was concluded that FFSR had the least cytotoxicity of the three materials studied.
| Toxicogenic potentials of biomaterials and methods for evaluating toxicity
Autian, J. and E. Dillingham (1973), Med Instrum 7(2): 125-30.
| Toxicological evaluation of biomaterials: primary acute toxicity screening program
Autian, J. (1977), Artif Organs 1(1): 53-60.
| Trabecular metal in hip reconstructive surgery
Stiehl, J. B. (2005), Orthopedics 28(7): 662-70.
Abstract: Biological ingrowth surfaces have become a standard prosthetic element in reconstructive hip surgery. A material's properties, three-dimensional architecture, and surface texture all play integral parts in its biological performance. Trabecular metal is an important new biomaterial that has been introduced to enhance the potential of biological ingrowth as well as provide a structural scaffold in cases of severe bone deficit. Initial clinical applications have focused on bone restoration in tumor and salvage cases and in primary and revision reconstructive cases where the increased biological fixation would be of clinical benefit. The bone ingrowth potential and mechanical integrity of this material offer exciting options for orthopedic reconstructive surgeons.
| Traditional and Modern Biomedical Prospecting: Part II-the Benefits: Approaches for a Sustainable Exploitation of Biodiversity (Secondary Metabolites and Biomaterials from Sponges)
Muller, W. E., H. C. Schroder, et al. (2004), Evid Based Complement Alternat Med 1(2): 133-144.
Abstract: The progress in molecular and cell biology has enabled a rational exploitation of the natural resources of the secondary metabolites and biomaterials from sponges (phylum Porifera). It could be established that these natural substances are superior for biomedical application to those obtained by the traditional combinatorial chemical approach. It is now established that the basic structural and functional elements are highly conserved from sponges to the crown taxa within the Protostomia (Drosophila melanogaster and Caenorhabditis elegans) and Deuterostomia (human); therefore, it is obvious that the molecular etiology of diseases within the metazoan animals have a common basis. Hence, the major challenge for scientists studying natural product chemistry is to elucidate the target(s) of a given secondary metabolite, which is per se highly active and selective. After this step, the potential clinical application can be approached. The potential value of some selected secondary metabolites, all obtained from sponges and their associated microorganisms, is highlighted. Examples of compounds that are already in medical use (inhibition of tumor/virus growth [arabinofuranosyl cytosine and arabinofuranosyl adenine]), or are being considered as lead structures (acting as cytostatic and anti-inflammatory secondary metabolites [avarol/avarone], causing induction of apoptosis [sorbicillactone]) or as prototypes for the interference with metabolic pathways common in organisms ranging from sponges to humans (modulation of pathways activated by fungal components [aeroplysinin], inhibition of angiogenesis [2-methylthio-1,4-napthoquinone], immune modulating activity [FK506]) are discussed in this study. In addition, bioactive proteins from sponges are listed (antibacterial activity [pore-forming protein and tachylectin]). Finally, it is outlined that the skeletal elements-the spicules-serve as blueprints for new biomaterials, especially those based on biosilica, which might be applied in biomedicine. These compounds and biomaterials have been isolated/studied by members of the German Center of Excellence BIOTECmarin. The goal for the future is to successfully introduce some of these compounds in the treatment of human diseases in order to raise the public awareness on the richness and diversity of natural products, which should be sustainably exploited for human benefit.
| Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes
Kim, J. H., B. Kim, et al. (2005), Nature 434(7035): 921-6.
Abstract: Defining the molecular strategies that integrate diverse signalling pathways in the expression of specific gene programmes that are critical in homeostasis and disease remains a central issue in biology. This is particularly pertinent in cancer biology because downregulation of tumour metastasis suppressor genes is a common occurrence, and the underlying molecular mechanisms are not well established. Here we report that the downregulation of a metastasis suppressor gene, KAI1, in prostate cancer cells involves the inhibitory actions of beta-catenin, along with a reptin chromatin remodelling complex. This inhibitory function of beta-catenin-reptin requires both increased beta-catenin expression and recruitment of histone deacetylase activity. The coordinated actions of beta-catenin-reptin components that mediate the repressive state serve to antagonize a Tip60 coactivator complex that is required for activation; the balance of these opposing complexes controls the expression of KAI1 and metastatic potential. The molecular mechanisms underlying the antagonistic regulation of beta-catenin-reptin and the Tip60 coactivator complexes for the metastasis suppressor gene, KAI1, are likely to be prototypic of a selective downregulation strategy for many genes, including a subset of NF-kappaB target genes.
| Transcriptional response of Saccharomyces cerevisiae to the plasma membrane-perturbing compound chitosan
Zakrzewska, A., A. Boorsma, et al. (2005), Eukaryot Cell 4(4): 703-15.
Abstract: Chitosan is a plasma membrane-perturbing compound consisting of linear chains of beta-1,4-linked glucosamine residues, which at acidic pHs become positively charged. It is extensively used as an antimicrobial compound, yet its mode of action is still unresolved. Chitosan strongly affected the growth of the yeast Saccharomyces cerevisiae, the food spoilage yeast Zygosaccharomyces bailii, and two human-pathogenic yeasts, Candida albicans and Candida glabrata. Microarray analysis of yeast cells treated with sublethal concentrations of chitosan revealed induction of the environmental stress response and three more major transcriptional responses. The first was a rapid and stable Cin5p-mediated response. Cin5p/Yap4p is a transcription factor involved in various stress responses. Deletion of CIN5 led to increased chitosan sensitivity. The second was a Crz1p-mediated response, which is delayed compared to the Cin5p response. Crz1p is a transcription factor of the calcineurin pathway. Cells deleted for CRZ1 or treated with the calcineurin inhibitor FK506 became hypersensitive to chitosan, supporting the notion that the Crz1p-controlled response offers protection against chitosan. The third was a strong Rlm1p-mediated response which ran parallel in time with the Crz1p-regulated response. Rlm1p is a transcription factor of the cell wall integrity pathway, which is activated by cell wall stress. Importantly, chitosan-treated cells became more resistant to beta-1,3-glucanase, which is a well-known response to cell wall stress. We propose that the transcriptional response to chitosan may be representative of other plasma membrane-perturbing compounds.
| Transfection efficiency of chitosan vectors: effect of polymer molecular weight and degree of deacetylation
Huang, M., C. W. Fong, et al. (2005), J Control Release 106(3): 391-406.
Abstract: Chitosans of defined molecular weight (Mw 10-213 kDa) and degree of deacetylation (DD 46-88%) were synthesized, complexed with pEGFP-C2 plasmid into nanoparticles (NP) and evaluated for cellular uptake and transfection efficiency in the A549 cell model. DNA condensation of >90% was achieved at the N/P ratio of 6, independent of the chitosan Mw and DD. However, chitosan vectors of lower Mw or DD were less efficient at retaining the DNA upon dilution, and consequentially, less capable of protecting the condensed DNA from degradation by DNase and serum components. A549 cellular uptake of the NP was also significantly reduced by decreasing the Mw or DD of the chitosan vector. These factors contributed to the low transfection efficiencies for chitosan vectors of low Mw or DD. There was good correlation between transfection efficiency, cellular uptake and zeta potential of the NP, suggesting that cellular uptake mediated by electrostatic interactions with the cell membrane preceded efficient transfection. NP produced with chitosan of Mw 213 kDa and DD of 88% showed the highest zeta potential (+23 mV), cellular uptake (4.1 microg/mg protein) and transfection efficiency (12.1%), while chitosan vector with Mw of 213 kDa and DD of 46% showed the lowest cellular uptake (0.4 microg/mg protein) and transfection efficiency (0.05%). Confocal microscopy images suggested that the chitosan-complexed DNA successfully escaped from the endo-lysosomal compartment for nuclear translocation and expression. Intracellular DNA disassembly appeared to occur at different locations depending on the retentive capacity of the chitosan vector.
| Transforming growth factor-beta 1 (TGF-beta1) prevents the age-dependent decrease in bone formation in human osteoblast/implant cultures
Zhang, H., M. S. Aronow, et al. (2005), J Biomed Mater Res A 75(1): 98-105.
Abstract: Titanium implants have been extensively used in orthopedic surgery and dentistry. Most of the patients who receive such implants are elderly with a compromised ability to heal and form new bone. By using an in vitro osteoblast/implant culture system, the potency of TGF-beta1 in enhancing mineralization of human osteoblast cultures from elderly subjects was investigated in this study. Primary human osteoblast (HOB) cells obtained from different age group human subjects [Young (Y), Middle (M), and Old (O)] were cultured on Ti alloy (Ti-6Al-4V) disks with or without continuous administration of 0.2 ng/mL TGF-beta1 in the medium for 2 or 4 weeks. TGF-beta1 significantly (p < 0.05) increased calcium content and the size of calcified nodules on implant disks in the O group, but had no effect on the Y or M groups. The number of calcified nodules was not different with or without TGF-beta1 in all age groups. As measured by Northern blot analysis and RT-PCR, TGF-beta1 significantly increased the expression of bone-specific extracellular matrix proteins, including alkaline phosphatase, Type I collagen, bone sialoprotein and osteocalcin, after both 2 and 4 weeks in the O group but not in the Y group. In conclusion, TGF-beta1 enhances mineralization on implant materials of osteoblast cultures from elderly human subjects.
| Transglutaminase-mediated gelatin matrices incorporating cell adhesion factors as a biomaterial for tissue engineering
Ito, A., A. Mase, et al. (2003), J Biosci Bioeng 95(2): 196-9.
Abstract: The goal of this work was to develop a novel biomaterial to be used for either wound dressing or as a scaffold for tissue engineering. The biodegradable hydrogels were prepared through cross-linking of gelatin with transglutaminase (TGase) in an aqueous solution. We found that the concentrations of 5 wt% gelatin and 1 unit/ml TGase were optimum for the proliferation of NIH/3T3 fibroblasts. Then, we investigated whether the cell proliferation was enhanced by incorporation of cell adhesion factors into the gelatin hydrogels. Since vitronectin and fibronectin can bind with gelatin by the action of TGase, we added these cell adhesion proteins into the gelatin hydrogels. The hydrogels incorporating these cell adhesion proteins significantly enhanced cell proliferation compared with the gelatin hydrogels without these proteins (p<0.05). Two types of synthetic Arg-Gly-Asp (RGD) peptides, RGDLLQ and RGDLLG were also added to the gelatin solution where RGDLLQ is a substrate of TGase by virtue of a glutamine (Q) residue with an epsilon-amino group and RGDLLG is not. These two RGD peptides enhanced cell proliferation, but RGDLLQ significantly enhanced the proliferation compared with RGDLLG (p<0.05). These results suggest that T-Gase-mediated incorporation of cell adhesion factors into gelatin matrices enhanced cell proliferation and this novel biomaterial is a potent tool for wound dressing or tissue engineering.
| Transient in vivo protein adsorption onto polymeric biomaterials
Ihlenfeld, J. V. and S. L. Cooper (1979), J Biomed Mater Res 13(4): 577-91.
Abstract: The adsorption of albumin, gamma-globulin, and fibrinogen was measured on three ex vivo polymeric shunt surfaces [polyvinyl chloride (PVC), Silastic, and segmented polyether urethane (Biomer)] exposed to flowing heparinized, canine blood in vivo. Small amounts of radiolabeled proteins were infused into anesthetized mongrel dogs and the deposition of radioactivity on the walls of femoral arteriovenous shunts was followed with time for two hours following initial blood-polymer contact. Previously, transient in vivo platelet and fibrin deposition onto PVC, Silastic, and Biomer was measured by a similar technique in the absence of anticoagulant. A time-dependent phase of thrombus deposition followed by thromboembolism was observed on the PVC and Silastic shunt surfaces but not on the Biomer surface. In the studies reported here on PVC and Silastic, fibrinogen adsorption was found to predominate initially, though it subsequently desorbed somewhat and was replaced by albumin and gamma-globulin. On Biomer, the adsorption of all three proteins increased with time following initial blood contact and fibrinogen was less prominent initially. The PVC surface was found to become passivated with respect to further thrombogenesis after 60-min exposure to flowing blood, at which time a higher fraction of albumin was present on the surface compared to that at earlier blood contact times. These results indicate that rearrangement of adsorbed protein species occurs with time on polymer surfaces exposed to flowing blood in vivo. Early and predominant fibrinogen adsorption appears to be an important factor in the thrombogenic and embolic events observed on the PVC and Silastic shunt surfaces in vivo.
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