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Academic focus: biomaterials activities at the University of Liverpool
Williams, D. F. (1980), J Biomed Mater Res 14(3): 325-7.

Academic focus: the biomaterials program at the University of Washington (Seattle)
Hoffman, A. S. (1982), J Biomed Mater Res 16(5): 735-40.

Accelerated ageing of metallic biomaterials: principle and results
Bellier, J. P., J. Lecoeur, et al. (1990), Biomaterials 11: 55-6.
Abstract: Electrochemical methods such as voltammetry and chronoamperometry are very useful in the study of biodegradation processes. Voltammetry gives qualitative information on the behaviour of a biomaterial in an electrolytic medium. Accelerated ageing of a metallic biomaterial can be obtained using chronoamperometry. Quantitative information on elements released in a solution is also obtained.

Accelerated functional maturation of isolated neonatal porcine cell clusters: in vitro and in vivo results in NOD mice
Luca, G., C. Nastruzzi, et al. (2005), Cell Transplant 14(5): 249-61.
Abstract: Neonatal porcine cell clusters (NPCCs) might replace human for transplant in patients with type 1 diabetes mellitus (T1DM). However, these islets are not immediately functional, due to their incomplete maturation/ differentiation. We then have addressed: 1) to assess whether in vitro coculture of islets with homologous Sertoli cells (SC) would shorten NPCCs' functional time lag, by accelerating the beta-cell biological maturation/differentiation; 2) to evaluate metabolic outcome of the SC preincubated, and microencapsulated NPCCs, upon graft into spontaneously diabetic NOD mice. The islets, isolated from < 3 day piglets, were examined in terms of morphology/viability/function and final yield. SC effects on the islet maturation pathways, both in vitro and in vivo, upon microencapsulation in alginate/poly-L-ornithine, and intraperitoneal graft into spontaneously diabetic NOD mice were determined. Double fluorescence immunolabeling showed increase in beta-cell mass for SC+ neonatal porcine islets versus islets alone. In vitro insulin release in response to glucose, as well as mRNA insulin expression, were significantly higher for SC+ neonatal porcine islets compared with control, thereby confirming SC-induced increase in viable and functional beta-cell mass. Graft of microencapsulated SC+ neonatal porcine islets versus encapsulated islets alone resulted in significantly longer remission of hyperglycemia in NOD mice. We have preliminarily shown that the in vitro NPCCs' maturation time lag can dramatically be curtailed by coincubating these islets with SC. Graft of microencapsulated neonatal porcine islets, precultured in Sertoli cells, has been proven successful in correcting hyperglycemia in stringent animal model of spontaneous diabetes.

Acceleration of wound healing in healing-impaired db/db mice with a photocrosslinkable chitosan hydrogel containing fibroblast growth factor-2
Obara, K., M. Ishihara, et al. (2005), Wound Repair Regen 13(4): 390-7.
Abstract: Application of ultraviolet light irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2) results within 30 seconds in an insoluble, flexible hydrogel. The FGF-2 molecules retained in the chitosan hydrogel remain biologically active and are released from the chitosan hydrogel upon in vivo biodegradation of the hydrogel. To evaluate the accelerating effect on wound healing of this hydrogel, full-thickness skin incisions were made in the backs of healing-impaired diabetic (db/db) mice and their normal (db/+) littermates. The mice were later killed, and histological sections of the wound were prepared. The degree of wound healing was evaluated using several histological parameters such as the rate of contraction, epithelialization, and tissue filling. Application of the chitosan hydrogel significantly advanced the rate of contraction on Days 0 to 2 in db/db and db/+ mice. Although the addition of FGF-2 into the chitosan hydrogel in db/+ mice had little effect, application of the chitosan hydrogel-containing FGF-2 further accelerated the adjusted tissue filling rate (Days 2 to 4 and Days 4 to 8) in db/db mice. Furthermore, the chitosan hydrogel-containing FGF-2 markedly increased the number of CD-34-positive vessels in the wound areas of db/db mice on Day 4. Thus, the application of chitosan hydrogel-containing FGF-2 onto a healing-impaired wound induces significant wound contraction and accelerates wound closure and healing.

Access to biomaterials: a growing health policy concern
Morgan, A. (1998), Pacing Clin Electrophysiol 21(9): 1822-3.

Accumulation of cyclic AMP in Swiss 3T3 cells adhering to a cellulose biomaterial substratum through interaction with adenylyl cyclase
Faucheux, N., C. Correze, et al. (2001), Biomaterials 22(22): 2993-8.
Abstract: Controlling cell shape induced by cell-substrata interaction appears of prime importance to influence subsequent biological processes such as cell migration, proliferation, differentiation or apoptosis. Studies on Swiss 3T3 fibroblasts have recently provided evidence that cell spreading is mediated by integrins and RhoA. Our previous studies showed that on Cuprophan, a cellulose membrane (CU) to which vitronectin adhesive protein is poorly adsorbed, Swiss 3T3 cells are rounded and undergo cAMP-dependent aggregation. In contrast, on a polyacrylonitrile membrane (AN69) that favours the adsorption of vitronectin and fibronectin, cells spread out and contain low concentrations of cAM P. We have now examined the parts played by the three components in the cAMP pathway (receptors, G-proteins and adenylyl cyclase itself) in cAM P-dependent cell aggregation on CU. Experiments with intact cells showed no interaction between the CU and receptors, or between the CU and G-proteins. Assays on membrane preparations plus the Mn-ATP substrate, which uncouples G-proteins and adenylyl cyclase, demonstrated that activation of the cAMP pathway by CU depends primarily on the catalytic activity of the adenylyl cyclase. These investigations provide essential data for the development of biomaterials that favour cell functionality.

Accumulation of organochlorine pesticides from water using triolein embedded cellulose acetate membranes
Xu, Y., Z. Wang, et al. (2005), Environ Sci Technol 39(4): 1152-7.
Abstract: A new type of composite membrane, triolein embedded cellulose acetate membrane (TECAM), was produced by embedding triolein drops in the matrix of cellulose acetate polymers. The distribution of six organochlorine pesticides (OCPs) between water and TECAM was investigated in a static water system. Its field application was tested in Taihu Lake (China). Results from both laboratory and field experiments indicate that TECAM quickly and efficiently accumulated hydrophobic OCPs from water. Under laboratory conditions, uptake equilibrium was achieved within 24 h for all of the six OCPs. Significant correlations were obtained between log Kp TECAM (TECAM-water partition coefficient) and log Kow (octanol-water partition coefficient); between log Ktw (triolein-water partition coefficient, triolein in TECAM) and log Kow; and between log Ktw and log BCF (bioconcentration factor in rainbow trout calculated from literatures). Triolein in TECAM significantly increased the accumulation of strongly hydrophobic OCPs when compared to the use of cellulose acetate polymers alone. Temperature had only slight effects on the Kp TECAM values of the strongly hydrophobic OCPs. The partition coefficient obtained by measuring OCP concentrations in TECAM under field conditions could be successfully applied to estimate OCPs concentrations in surface water.

Acellular collagen matrix as a possible "off the shelf" biomaterial for urethral repair
Chen, F., J. J. Yoo, et al. (1999), Urology 54(3): 407-10.
Abstract: OBJECTIVES: To determine whether a naturally derived collagen-based tissue substitute developed for urethral reconstruction would be suitable for urethral repair in an animal model. Several urethral conditions often require nongenital tissues for reconstruction, such as skin grafts or mucosal grafts from the bladder or buccal regions. However, the use of these tissues for urethroplasty may be associated with additional procedures for graft retrieval, prolonged hospitalization, and morbidity. METHODS: A ventral urethral defect was created in 10 male rabbits. The acellular collagen matrix, obtained and processed from porcine bladder submucosa, was trimmed and used to replace the urethral defect in an onlay fashion. Serial urethrography was performed pre- and postoperatively at 0.5, 1, 2, 3, and 6 months. The animals were sacrificed 0.5, 1, 2, 3, and 6 months after surgery. The retrieved implants were analyzed grossly, histologically, and with immunocytochemistry. RESULTS: All animals survived until being sacrificed without any noticeable voiding dysfunction. Serial urethrograms confirmed the maintenance of a wide urethral caliber without any signs of strictures. Gross examination at retrieval showed normally appearing tissue without any evidence of fibrosis. Histologically, the implanted matrices contained host cell infiltration and generous angiogenesis by 2 weeks after surgery. The presence of a confluent transitional cell layer was confirmed by immunocytochemical analyses using pancytokeratin antibodies. Anti-alpha actin antibodies demonstrated the migration of unorganized muscle fiber bundles 2 months after implantation and organized muscle bundles 6 months after implantation. CONCLUSIONS: The acellular collagen matrix appears to be a useful material for urethral repair in the rabbit. The matrix can be processed easily, has good characteristics for tissue handling and urethral function, and has the advantage of being an "off the shelf" material.

Acellular dermal matrix and hydroxyapatite in prevention of ridge deformities after tooth extraction
Luczyszyn, S. M., V. Papalexiou, et al. (2005), Implant Dent 14(2): 176-84.
Abstract: The aim of this study was to evaluate the role of acellular dermal matrix graft (ADMG) acting as a membrane, associated with a resorbable hydroxyapatite (RHA) in bone regeneration to prevent ridge deformities after tooth extraction. Fifteen patients who had at least 2 noncontiguous, uniradicular teeth indicated for extraction were selected. In group I, the extraction sockets were covered by ADMG alone; and in group II, the alveoli were filled with RHA before the placement of the ADMG. After 6 months, re-entry surgeries and biopsies were performed. Although ridge thickness had been preserved in both groups, the means were significantly greater (P < 0.05) for group II when compared to group I (6,8 +/- 1.26 and 5.53 +/- 1.06). The histologic analysis showed small bone formation in some samples for group II, where the presence of a highly vascularized fibrous connective tissue surrounding the particles was a common finding. Based on the results, it can be concluded that the ADMG was able to preserve ridge thickness and that the additional use of RHA favored the preservation of the ridges along with an increase in the width of keratinized tissue.

Acellular dermal tissue study: an ultrastructural evaluation of human and porcine derived tissues in a rat model
Hoyama, E., S. A. Schellini, et al. (2004), J Submicrosc Cytol Pathol 36(3-4): 305-8.
Abstract: The purpose of this study was to evaluate the host response of a human and a porcine derived acellular dermal tissue (ADT) implanted in the subcutaneous tissue of a rat model. Two subcutaneous pockets were surgically created along the dorsal midline of 25 rats (5 rats/group). The human ADT was placed superiorly and the porcine ADT, inferiorly. The animals were sacrificed at 07, 15, 30, 60 and 180 postoperative days (PO) and the ADTs and surrounding soft tissues were assessed for ultrastructural evaluation by transmission electron microscopy. The ultrastructural findings were similar in both materials. Normal collagen and elastic fibers bundles were observed during all experimental moments, as well as macrophages presenting cytoplasmic enlargements digesting cellular portions after 15 PO. From 30 until 180 PO, vacuolar structures filled with an amorphous, electron-transparent substance, were present inside and outside the fibroblasts. Both human and porcine ADT showed similar pattern of ultrastructural response when implanted in the subcutaneous tissue of rats. The porcine ADT appears as a good alternative to be used as a biomaterial.

Acellular matrix: a biomaterials approach for coronary artery bypass and heart valve replacement
Wilson, G. J., D. W. Courtman, et al. (1995), Ann Thorac Surg 60(2 Suppl): S353-8.
Abstract: We have developed a multistep detergent-enzymatic extraction process (involving hypotonic and hypertonic solutions, the detergents octyl-phenoxy-polyethoxyethanol and sodium dodecyl sulfate, as well as DNAse and RNAse) which, while inhibiting autolysis, removes all cells from tissues and, with them, cellular antigens together with lipids and more soluble glycosaminoglycans. What remains is acellular matrix with the structural proteins well conserved and normally arranged. Canine arteries extracted to acellular matrix were implanted as coronary artery bypass allografts in a canine model, without the use of cardiopulmonary bypass, and compared with autogenous saphenous veins. Of nine pilot acellular matrix implants, four were patent, as compared with four of seven saphenous vein grafts. All occlusions in both graft types occurred acutely soon after implantation, with almost all patent grafts followed up for 6 months. The acellular matrix allografts showed no inflammation and only minimal cellular repopulation. This model needs further development, but appears promising for preclinical evaluation. Canine aortic and pulmonic valves extracted to acellular matrix using a modification of our extraction process, eliminating the detergent sodium dodecyl sulfate, were implanted heterotopically as allografts in the left main pulmonary artery in dogs, a location chosen to avoid the need for cardiopulmonary bypass. At 1 month, two-dimensional echocardiography of six implants showed leaflet motion and 3- to 5-mm Hg transvalvular gradients. Explant histology of four valves at 1 month showed no inflammation, cellular repopulation at the base of the valve, and partial endothelialization.(ABSTRACT TRUNCATED AT 250 WORDS)

Acellular mineral deposition in collagen-based biomaterials incubated in cell culture media
Andre-Frei, V., B. Chevallay, et al. (2000), Calcif Tissue Int 66(3): 204-11.
Abstract: Rapid developments in tissue engineering have renewed interest in biodegradable three-dimensional structures such as collagen-based biomaterials. Collagen matrices seeded in vitro with fibroblasts, osteoblasts, and chondrocytes can form tissues resembling skin, bone, and cartilage that could be used as functional substitutes for damaged tissues. Collagen is associated with both dystrophic calcification of collagenous implants and bone mineralization. We report here the calcification properties of collagen sponges incubated in cell-free media. Mineral deposited in sponges was identified by X-ray and electron diffraction, Fourier transform infrared spectroscopy, and the molar ratio of calcium:phosphorus (Ca:P) as a poorly crystalline apatite similar to bone. The degree of calcification increased with length of incubation and the Ca and P content of the media, with 10-15% Ca (dry weight) after 21 days' incubation in media containing 1.6-3 mM Ca and a Ca x P molar product of 2-3 mM(2), but only 2% Ca after incubation in medium with 1.33 mM Ca and a 1.7 mM(2) Ca x P molar product. Mineral deposition was completely inhibited in sponges that were washed extensively and initially contained less than 0.01% P. Readdition of phosphate in these sponges and subsequent freeze drying and sterilization restore their mineralization capacity, suggesting that collagen per se cannot initiate calcification and that the inorganic phosphate content associated with the collagen preparation process is in the solid state a potential nucleator. Addition of chondroitin 4-sulfate to the sponges partially or totally inhibited mineral deposition, even though 80-90% of the compound was released within 24 hours. These results indicate that acellular calcification of collagen-based biomaterials can occur under the culture conditions currently used in tissue engineering.

Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering
Schmidt, C. E. and J. M. Baier (2000), Biomaterials 21(22): 2215-31.
Abstract: Various research groups around the world are actively investigating cardiovascular prostheses of biological origin. This review article discusses the need for such bioprosthetics and the potential role for natural tissues in cardiovascular applications such as cardiac valves and vascular grafts. Upon implantation, unmodified natural materials are subject to chemical and enzymatic degradation, seriously decreasing the life of the prosthesis. Therefore, methods such as glutaraldehyde and polyepoxide crosslinking treatments and dye-mediated photooxidation have been developed to stabilize the tissue while attempting to maintain its natural mechanical properties. Also, residual cellular components in a bioprosthetic material have been associated with undesired effects, such as calcification and immunological recognition, and thus have been the motivation for various decellularization processes. The effects of these stabilization and decellularization treatments on mechanical, biological and chemical properties of treated tissues have been investigated, specifically with regard to calcification, immunogenicity, and cytotoxicity concerns. Despite significant advances in the area of cardiovascular prostheses, there has yet to be developed a completely biocompatible, long-lasting implant. However, with the recent advent of tissue engineering, the possibility of applying selective cell seeding to naturally derived bioprosthetics moves us closer to a living tissue replacement.

Acetylecholinesterase-based biosensor electrodes for organophosphate pesticide detection. II. Immobilization and stabilization of acetylecholinesterase
Vakurov, A., C. E. Simpson, et al. (2005), Biosens Bioelectron 20(11): 2324-9.
Abstract: The dry and wet stability of Drosophila acetylcholinesterase non-covalently immobilized onto polyethyleneimine modified screen-printed carbon electrodes was improved when compared to non-immobilized acetylcholinesterase, and acetylcholinesterase covalently immobilized onto dialdehyde and polyethyleneimine modified electrodes. Stabilizer mixtures were characterized for additional stabilization of acetylcholinesterase during storage in the dry state, with dextran-sulphate/sucrose and polygalacturonic acid/sucrose mixtures proving highly effective for long-term storage of biosensor electrodes.

Achieving quality esthetic dentistry and integrated comprehensive care with new generation techniques and materials
Malament, K. A. (2005), J Okla Dent Assoc 95(7): 26-9.
Abstract: BACKGROUND: Prosthodontics is the dental specialty responsible for diagnosis, rehabilitation and maintenance of patients with complex clinical conditions involving missing or deficient teeth and/or craniofacial tissues. The essence of the specialty is expert treatment planning. OVERVIEW/LITERATURE REVIEWED: In recent years, new approaches and technology have been introduced as a result of research performed in universities and by industry. The field of prosthodontics continues to evolve owing to a better understanding of the biology of the oral cavity and the introduction of new techniques and improved biomaterials. Improvements in periodontal and oral surgical techniques, implant procedures and materials, esthetic restorative materials, and jaw tracking recorders and articulators have led to enhanced functional and esthetic oral and maxillofacial prostheses. CONCLUSIONS AND CLINICAL IMPLICATIONS: The complexities of today's technical and clinical procedures and the higher expectations for more esthetically pleasing dentistry by the general patient population have placed a premium on teamwork involving general dentists, specialists and dental technicians.

Acoustic and visual characteristics of cavitation induced by mechanical heart valves
Sohn, K., K. B. Manning, et al. (2005), J Heart Valve Dis 14(4): 551-8.
Abstract: BACKGROUND AND AIM OF THE STUDY: A sudden pressure drop and recovery can induce cavitation in liquids. Mechanical heart valves (MHVs) generate such a pressure drop at closure, and cavitation generation around MHVs has been demonstrated many times. Cavitation is suspected as being a cause of blood and valve material damage. METHODS: In this in-vitro experiment, visual images and acoustic signals associated with MHV cavitation were studied to reveal cavitation characteristics. Bjork-Shiley Convex-Concave valves, one with a pyrolytic carbon occluder and one with a Delrin occluder, were installed in a single-shot valve chamber. Cavitation intensity was controlled by load (dP/dt) and air content of water. The acoustic signal was measured using a hydrophone and visual images recorded with a high-speed digital camera system. RESULTS: Cavitation images showed that 10 ppm water rarely developed cavitation, unlike the 16 ppm water. A distinct peak pressure was observed at cavitation collapse that was a good indicator of MHV cavitation intensity. The average of the peak pressures revealed that cavitation intensity increased faster with increasing load for the 16 ppm water. CONCLUSION: The use of the peak pressure may be the preferred method for correlating cavitation intensity in structures for which the separation of valve closure noise and cavitation signal is difficult, as for the valves studied here.

Acoustic emission and nondestructive evaluation of biomaterials and tissues
Kohn, D. H. (1995), Crit Rev Biomed Eng 23(3-4): 221-306.
Abstract: Acoustic emission (AE) is an acoustic wave generated by the release of energy from localized sources in a material subjected to an externally applied stimulus. This technique may be used nondestructively to analyze tissues, materials, and biomaterial/tissue interfaces. Applications of AE include use as an early warning tool for detecting tissue and material defects and incipient failure, monitoring damage progression, predicting failure, characterizing failure mechanisms, and serving as a tool to aid in understanding material properties and structure-function relations. All these applications may be performed in real time. This review discusses general principles of AE monitoring and the use of the technique in 3 areas of importance to biomedical engineering: (1) analysis of biomaterials, (2) analysis of tissues, and (3) analysis of tissue/biomaterial interfaces. Focus in these areas is on detection sensitivity, methods of signal analysis in both the time and frequency domains, the relationship between acoustic signals and microstructural phenomena, and the uses of the technique in establishing a relationship between signals and failure mechanisms.

Acoustic microscopy--principles and applications in the studies of biomaterial microstructure
Hafsteinsson, H. and S. S. Rizvi (1984), Scan Electron Microsc(Pt 3): 1237-47.
Abstract: The acoustic microscopy is based on totally different physical concepts than both the optical and electron microscopes. Therefore, the information obtained with an acoustic microscope is significantly different from those obtainable by the other two. By employing elastic waves, detailed microscopic information regarding biomaterial properties like density, elasticity, viscosity and viscoelasticity are obtained with an acoustic microscope. Live tissue can be examined without fixing or chemical staining. The Scanning Laser Acoustic Microscope (SLAM) and the Scanning Acoustic Microscope (SAM) are the only acoustic microscopes commercially available today. The SAM operates at as high as 4.2 GHz frequency providing at least five times better resolution than the optical limit. The SLAM, however, operates generally at 100 or 500 MHz and can therefore examine thicker samples than the SAM, but at lower resolutions. For optically translucent samples, the SLAM can also provide an optical image simultaneously with the acoustical one. A laser beam is employed in the scanning mechanism in the SLAM, compared to mechanically translating the sample in the SAM. Consequently, the scanning rate is much faster in the SLAM at about 30 frames per second, compared to several seconds per frame for the SAM. Both qualitative as well as quantitative information is obtainable about the material under examination. As a qualitative tool, the information is used to classify and sort materials and detect and localize flaws and defects in optically opaque samples. A microscopic map of the specimen's mechanical properties can be produced using information from the acoustic image. This information may then lead to better understanding of biomaterial microstructure and also can be a valuable aid in characterization of certain subtle morphological differences.

Acrylic scaffolds with interconnected spherical pores and controlled hydrophilicity for tissue engineering
Diego, R. B., M. P. Olmedilla, et al. (2005), J Mater Sci Mater Med 16(8): 693-8.
Abstract: Polymer scaffolds are obtained in which the geometric characteristics (pore size, connectivity, porosity) and the physico-chemical properties of the resulting material can be controlled in an independent way. The interconnected porous structure was obtained using a template of sintered PMMA microspheres of controlled size. Copolymerization of hydrophobic ethyl acrylate and hydrophilic hydroxyethyl methacrylate comonomers took place in the free space of the template, different comonomer ratio gave rise to different hydrophilicity degrees of the material keeping the same pore architecture. The morphology of the resulting scaffolds was investigated by scanning electron microscopy (SEM), the porosity of the material calculated, and the mechanical properties compared with those of the bulk (non porous) material of the same composition.


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