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Tissue integration and tolerance to meshes used in gynecologic surgery: An experimental study
Boulanger, L., M. Boukerrou, et al. (2005), Eur J Obstet Gynecol Reprod Biol
Abstract: OBJECTIVE: To evaluate the tissue integration of and tolerance to five different mesh types used in genital prolapse surgery to provide mechanical support. STUDY DESIGN: We placed five different meshes (Vicryl((R)), Vypro((R)), Prolene((R)), Prolene soft((R)), and Mersuture((R))) on the peritoneums of 12 pigs. After 10 weeks, we used light microscopy to analyze the tissue integration of and tolerance to these meshes. We looked for inflammation, vascularization, fibroblasts, collagen fibers and the organization of connective tissue. RESULTS: The absorbable prostheses made of polyglactin 910 (Vicryl((R))) and the non-absorbable prostheses made of polypropylene (Prolene((R)) and Prolene soft((R))) induced the least severe inflammatory reactions. Tissue integration was best with the polypropylene meshes, which allowed the development of a well-organized, fibrous, mature, connective tissue. CONCLUSION: The tissue response to prosthetic meshes depends on the material used and its structure. This work highlights the feasibility of carrying out experimental studies to test the tolerance to and integration of biomaterials used in gynecology. Such studies need to be carried out whenever new prostheses become available to validate their use in common practice.

Tissue reaction to hydrophilic intraocular lenses
Tognetto, D., G. Sanguinetti, et al. (2005), Expert Rev Med Devices 2(1): 57-60.
Abstract: The implant of intraocular lenses (IOLs) following cataract surgery induces a foreign body reaction to the IOL and a lens epithelial cell reaction. The host response to the IOL is mainly influenced by biomaterial properties. With the increasing use of phacoemulsification and small incision cataract surgery, there is growing interest in the use of foldable IOLs made of different materials. Hydrophilic acrylic IOLs include a wide group of foldable biomaterials different in terms of water content. These lenses have been reported to show a good biocompatibility after implantation. Nevertheless, tissue reaction to the implant of hydrophilic lenses is variable and not directly related to the hydrophilicity of their surface. A different adsorption of proteins on the IOL optic surface might be responsible for the different cellular reaction and lens epithelial cell response. Other properties besides hydrophilicity should be taken into account to classify IOL biomaterials.

Tissue reaction to implanted biomaterials
Akagawa, Y., M. Hashimoto, et al. (1985), J Prosthet Dent 53(5): 681-6.
Abstract: Tissue reactions to the single-crystal sapphire, titanium, Co-Cr-Mo alloy, and PMMA were histologically evaluated after implantation into the subcutaneous tissue and tibia of rats. In subcutaneous tissue the reaction from early necrotic change and acute inflammation to final encapsulation by fibrous connective tissue was least pronounced around single-crystal sapphire implants. Tissue reactions of a slightly greater degree were found around titanium and Co-Cr-Mo alloy implants. The most prominent tissue reaction was observed around PMMA implants. In the tibia, single-crystal sapphire, titanium, and Co-Cr-Mo alloy implants were encapsulated by newly formed compact bone, but bone was not so evident around PMMA implants. These findings suggest that single-crystal sapphire implants have more favorable tissue compatibility than those of titanium, Co-Cr-Mo alloy, and PMMA.

Tissue reactions of 5 sling materials and tissue material detachment strength of 4 synthetic mesh materials in a rabbit model
Yildirim, A., E. K. Basok, et al. (2005), J Urol 174(5): 2037-40.
Abstract: PURPOSE: We evaluated tissue reactions to 5 sling materials used in tension-free vaginal tape (TVT), intravaginal slingplasty (IVS), polypropylene mesh hernia repair, the suprapubic approach to suburethral polypropylene tape (SPARC) and cadaveric fascia lata procedures. We also compared the mesh-to-tissue attachment strength of 4 sling mesh materials (TVT, IVS, surgical polypropylene mesh and SPARC) at on days 2, 7, 15 and 30 after implantation. MATERIALS AND METHODS: A total of 20 female New Zealand White rabbits were randomized to group 1-2 days, group 2-7 days, group 3-15 days and group 4-30 days. After the rabbits were anesthetized an 8 cm midline incision was made for rectus muscle access, and 0.5 x 1 cm pieces of TVT, IVS, SPARC, surgical polypropylene mesh and cadaveric fascia lata were sewn to the rectus muscle with direct contact. At the same time 4 subfascial tunnels in the medial surface of the upper extremities were prepared, and 1.0 x 0.5 cm strips of TVT, IVS, SPARC and polypropylene mesh were implanted in each tunnel. On days 2, 7, 15 and 30 after implantation mechanical testing was performed to define tissue detachment strength. The strips of 5 sling materials were then harvested with the surrounding tissue. Specimens were studied by light microscopy. RESULTS: Mean detachment strength, that is the minimum weight needed to move the mesh, of the synthetic meshes from days 2 to 30 were 291.6 to 2,390.0 gm for TVT, 178.4 to 2,160.0 gm for SPARC, 188.4 to 1,850.0 gm for hernia mesh and 92.8 to 1,510.0 gm for IVS (at all data points TVT vs IVS p < 0.05). Light microscopy revealed a quite uniform tissue reaction with a sign of marked acute inflammation in and around the mesh fibers on days 2 and 7 after implantation. All meshes showed stable fibrosis and muscle infiltration on day 30. CONCLUSIONS: All 5 synthetic sling materials produce similar tissue reactions beginning soon after implantation. Cadaveric fascia lata persisted in tissue with remarkable perifascial fibrosis at day 30. When comparing the 4 polypropylene mesh materials; the attachment capacity of TVT was superior and that of IVS was the least of the 4. TVT was statistically better than IVS at all data points. SPARC and hernia mesh provided results similar to those of TVT.

Tissue response and biomaterial integration: the efficacy of in vitro methods
Kirkpatrick, C. J., V. Krump-Konvalinkova, et al. (2002), Biomol Eng 19(2-6): 211-7.
Abstract: Implantation involves tissue trauma, which evokes an inflammatory response, coupled to a wound healing reaction, involving angiogenesis, fibroblast activation and matrix remodelling. Until now the type and extent of such reactions to give optimal integration of various biomaterials are practically unknown. Three principal fields of research can yield useful data to understand these phenomena better: studies on explanted biomaterials, animal models and relevant in vitro techniques. This paper will present examples of the latter field and the application of endothelial cell (EC) culture systems to study the effects of important tissue (e.g. pro-inflammatory cytokines, chemokines) and material (e.g. metal ions, particulate debris) factors on the regulation of the inflammatory and angiogenic response. A central feature is the use of microvascular endothelial cells (MEC), which can be used in both 2-and 3-dimensional (3-D) assays. We have also used genetic manipulation to develop a permanent MEC line from the human lung (HPMEC-ST1), which is being tested for its suitability to study cell-biomaterial interactions. In addition, suitable in vitro techniques are being developed in order to investigate drug delivery systems (DDS). Of particular interest is the targeting of the central nervous system, our approach being to establish a human model of the blood-brain barrier (BBB). A mainstay of our scientific philosophy is that such in vitro methods can make an important contribution to understanding biological reactions at the tissue-biomaterial interface and thus further a causal approach to tissue engineering (TE) and drug delivery applications.

Tissue response to biomaterials used for staple-line reinforcement in lung resection: a comparison between expanded polytetrafluoroethylene and bovine pericardium
Vaughn, C. C., P. L. Vaughn, et al. (1998), Eur J Cardiothorac Surg 13(3): 259-65.
Abstract: OBJECTIVE: A study in a canine model of lung-reduction surgery evaluated the tissue response to polytetrafluoroethylene (ePTFE) and bovine pericardium (BP) used for staple-line reinforcement. METHODS: In each of ten dogs, BP was placed in one lung and ePTFE in the other. The implants were retrieved at 30, 95, or 167 days after implantation and studied histologically. The connective tissue covering the implants was measured and analysis of variance was used to compare results with the two materials. RESULTS: At 30 days, the BP specimens showed focal chronic inflammation and thin tissue coverage, whereas the ePTFE specimens had no focal inflammation and thick tissue coverage. At 95 and 167 days, the inflammation in the BP specimens had resolved, but tissue coverage remained minimal, and there was no resorption of the BP. In the ePTFE specimens, tissue coverage had increased. Analysis of variance comparing representative tissue specimens showed that the tissue encapsulating the ePTFE was significantly thicker than that surrounding the BP (P < 0.0001). No air leaks, staple-line disruptions, or infections occurred in the study. CONCLUSIONS: Neither ePTFE nor BP is resorbable. Both materials have been used successfully, without resultant infections, for clinical staple-line reinforcement. The more favorable tissue response to ePTFE observed in this study may have clinical ramifications. Comparative clinical studies of the two materials are needed.

Tissue restoration after resorption of polyglycolide and poly-laevo-lactic acid screws
Bostman, O. M., O. M. Laitinen, et al. (2005), J Bone Joint Surg Br 87(11): 1575-80.
Abstract: Despite worldwide clinical use of bio-absorbable devices for internal fixation in orthopaedic surgery, the degradation behaviour and tissue replacement of these implants are not fully understood. In a long-term experimental study, we have determined the patterns of tissue restoration 36 and 54 months after implantation of polyglycolic acid and poly-laevo-lactic acid screws in the distal femur of the rabbit. After 36 months in the polyglycolic acid group the specimens showed no remaining polymer and loose connective tissue occupied 80% of the screw track. Tissue restoration remained poor at 54 months, the amounts of trabecular bone and haematopoietic elements being significantly lower than those in the intact control group. The amount of trabecular bone within the screw track at 54 months in the polyglycolic acid group was less than in the empty drill holes (p = 0.04). In the poly-laevo-lactic acid group, polymeric material was present in abundance after 54 months, occupying 60% of the cross-section of the core area of the screw track. When using absorbable internal fixation implants we should recognise that the degradation of the devices will probably not be accompanied by the restoration of normal trabecular bone.

Tissue/biomaterial interface characteristics of four elastomers. A transmission electron microscopical study
Bakker, D., C. A. van Blitterswijk, et al. (1990), J Biomed Mater Res 24(3): 277-93.
Abstract: The tissue/biomaterial interface reactions of four elastomers--selected as candidates for scaffolding for tympanic membrane tissue in a total alloplastic middle ear prosthesis--were studied at the electron microscopical level after implantation in the rat middle ear. Time-dependent changes in the phagocyte/polymer interface suggested degradation of porous implants made of Estane polyether urethane, polypropylene oxide, and a poly(ethylene oxide hydantoin) and poly(tetramethylene terephthalate) segmented polyether polyester copolymer (HPOE/PBT copolymer), but not of dense Silastic silicone rubber implants. Silastic was always encapsulated in fibrous tissue. Contact between fibrous tissue and HPOE/PBT copolymer or Estane was established in the third month, but fibrous tissue was never seen close to polypropylene oxide. Bone made contact only with Estane and HPOE/PBT copolymer implants. The bone/copolymer interface showed an electron-dense layer morphologically similar to that seen between bone and hydroxyapatite ceramic, suggesting that with respect to bone HPOE/PBT copolymer behaves like a bioactive implant material. The electron-dense layer was absnet at the bone/Estane interface. Estane and especially HPOE/PBT copolymer seem to be suitable as alloplastic tympanic membrane because of their interface behavior with respect to fibrous tissue and bone.

Tissue-derived biomaterials and their use in cardiovascular prosthetic devices
Hilbert, S. L., V. J. Ferrans, et al. (1988), Med Prog Technol 14(3-4): 115-63.
Abstract: A variety of tissues and tissue components, ranging from allograft and xenograft tissues to albumin- and collagen-coated synthetic materials, have been used to fabricate cardiovascular prosthetic devices. Tissue-derived biomaterials include both viable and non-viable tissues as well as individual tissue components which have undergone some degree of preimplantation processing. A review of the biochemistry, immunogenicity, mechanical properties, physicochemical properties, preimplantation processing and the morphology of the following cardiovascular prostheses are discussed: heart valve bioprostheses and allografts; blood vessel allografts; biologic vascular grafts; and, protein-coated vascular prostheses. This review focuses on the generic aspects of prosthetic device fabrication using tissue-derived biomaterials, realizing that specific differences between various commercially available prostheses may exist.

Tissue-engineered cartilage using fibrin/hyaluronan composite gel and its in vivo implantation
Park, S. H., S. R. Park, et al. (2005), Artif Organs 29(10): 838-45.
Abstract: The importance of scaffold biomaterials has been emphasized for in vitro culture of tissue-engineered cartilage in a three-dimensional (3D) environment. In this study, we examined the feasibility of fibrin glue, mixed with hyaluronic acid (HA) as a composite scaffold. Fibrin glue has been a useful cell delivery matrix for cartilage tissue engineering and HA is a key component of normal articular cartilage. Our hypothesis is that compared to fibrin itself, a fibrin/HA composite can have significantly enhanced properties, due mainly to the added benefits of HA in the matrix. Pieces of cartilage were isolated from rabbit knees and the chondrocytes were harvested through enzymatic digestion. Both fibrin and fibrin/HA composite were prepared and subsequently implanted in nude mice (n = 9, each group) for 1, 2, and 4 weeks, respectively. The retrieved specimens were then analyzed and the results were compared. Cartilage-like tissue formation was detected earlier with fibrin/HA specimens. They produced significantly higher amounts of the extracellular matrix (ECM) molecules, GAG, and collagen at each time point than those in fibrin. Interestingly, the fibrin/HA composite was also competent in maintaining its initial size. Histology--Safranin O/fast green and Alcian blue--of the retrieved specimens found more intense, uniform staining in the fibrin/HA composites. Analysis of the gene expression of the ECM molecules also confirmed the benefits of the composite with added HA in the maintenance of phenotypic stability. The present study suggests that fibrin/HA composite may serve as a dependable cell delivery vehicle as well as a structural basis for tissue-engineered cartilage.

Tissue-engineered hybrid tooth and bone
Young, C. S., H. Abukawa, et al. (2005), Tissue Eng 11(9-10): 1599-610.
Abstract: Tooth loss accompanied by alveolar bone resorption presents a significant clinical problem. We have investigated the utility of a tissue-engineering approach to provide corrective therapies for tooth-bone loss. Hybrid tooth-bone tissues were bioengineered as follows. Tooth implants were generated from pig third molar tooth bud cells seeded onto polyglycolide (PGA) and polyglycolide-colactide (PLGA) scaffolds, and grown for 4 weeks in the omenta of adult rat hosts. Bone implants were generated from osteoblasts induced from bone marrow progenitor cells obtained from the same pig, seeded onto PLGA fused wafer scaffolds, and grown for 10 days in a rotational oxygen-permeable bioreactor system. The tooth and bone implants were harvested, sutured together, reimplanted, and grown in the omenta for an additional 8 weeks. Histological and immunohistochemical analyses of the excised hybrid tooth-bone constructs revealed the presence of tooth tissues, including primary and reparative dentin and enamel in the tooth portion of hybrid tooth-bone implants, and osteocalcin and bone sialoprotein-positive bone in the bone portion of hybrid tooth-bone constructs. Collagen type III-positive connective tissue resembling periodontal ligament and tooth root structures were present at the interface of bioengineered tooth and bone tissues. These results demonstrate the utility of a hybrid tooth-bone tissue-engineering approach for the eventual clinical treatment of tooth loss accompanied by alveolar bone resorption.

Tissue-engineering approaches for axonal guidance
Zhang, N., H. Yan, et al. (2005), Brain Res Brain Res Rev 49(1): 48-64.
Abstract: Owing to the profound impact of nervous system damage, extensive studies have been carried out aimed at facilitating axonal regeneration following injury. Tissue engineering, as an emerging and rapidly growing field, has received extensive attention for nervous system axonal guidance. Numerous engineered substrates containing oriented extracellular matrix molecules, cells or channels have displayed potential of supporting axonal regeneration and functional recovery. Most attempts are focused on seeking new biomaterials, new cell sources, as well as novel designs of tissue-engineered neuronal bridging devices, to generate safer and more efficacious neuronal tissue repairs.

Titanium as a biomaterial for ossicular replacement: results after implantation in the middle ear of the rabbit
Schwager, K. (1998), Eur Arch Otorhinolaryngol 255(8): 396-401.
Abstract: The middle ear poses unique challenges when finding suitable materials for ossicular reconstruction, primarily because of its link to the external environment via the eustachian tube and, hence, its greater exposure to infectious agents. In this study, the biocompatability of titanium was examined in the middle ear of rabbits by using light and scanning electron microscopy. Implants were placed as middle ear prostheses or as free implants. These were inspected at 28 days, 84 days, 168 days, 336 days and 504 days following implantation for mucosal coverage, percent epithelization and any sign of foreign-body reaction. After 28 days, the prostheses were covered by regular mucosa. Although a majority of the free implants took up to 336 days for complete epithelialization, some of the free implants were not epithelialized even at day 504. There were no inflammatory cells observed on the surface of the material, nor were unusual amounts of fibrous tissue seen. In addition, the titanium material exhibited an affinity toward bone. The results of this animal experiment indicate that titanium is a favorable material for ossicular replacement prostheses.

Titanium dioxide nanoparticles-coated column for capillary electrochromatographic separation of oligopeptides
Hsieh, Y. L., T. H. Chen, et al. (2005), Electrophoresis 26(21): 4089-97.
Abstract: A novel column made through the condensation reaction of TiO2 nanoparticles (TiO2 NPs) with silanol groups of the fused-silica capillary is described. EOF measurements under various buffer constitutions were used to monitor the completion of reactions. The results indicated that the EOF was dependent on the interactions between buffers and the bonded TiO2 NPs. With formate/Tris buffer, EOF reversal at pH below 5 and cathodic EOF at pH above 5 were indicated. The pI of the bonded TiO2 NPs was found at approximately ph 5. Only cathodic EOF was illustrated by substituting the mobile phase with either glutamate or phosphate buffer. It was elucidated that both glutamate and phosphate buffer yield a negative charge layer on the surface of TiO2 NPs attributable to the formation of a titanium complex. The CEC performance of the column was tested with angiotensin-type oligopeptides. Some parameters that would affect the retention behavior were investigated. The interactions between the bonded phases and the analytes were explicated by epitomized acid-base functional groups of the oligopepetides and the speciation of the surface oxide in different pH ranges. The average separation efficiencies of 3.1 x 10(4) plates/m is readily achieved with a column of 70 cm (50 cm) x 50 mum ID under an applied voltage of 15 kV, phosphate buffer (pH 6.0, 40 mM), and UV detection at 214 nm.

Titanium is a highly thrombogenic biomaterial: possible implications for osteogenesis
Hong, J., J. Andersson, et al. (1999), Thromb Haemost 82(1): 58-64.
Abstract: Titanium has superior osteointegrating properties compared to other biomaterials. The mechanism for this is unknown. During the initial phase of bone implantation the biomaterial comes into direct contact with whole blood. In this study we use a newly developed in vitro chamber model to compare different commonly used biomaterials in contact with whole blood. These materials were selected with respect to their different osteointegrating properties in order to correlate these properties with the response to whole blood. In the presence of 3 IU/ml of heparin only titanium induced macroscopic clotting. This was reflected by the generation of thrombin-antithrombin which was much increased in blood in contact with titanium compared with steel and PVC. The coagulation activation caused by titanium was triggered by the intrinsic pathway because the generation of FXIIa-AT/C1 esterase inhibitor paralleled that of thrombin-antithrombin, and both thrombin-antithrombin complex and FXIIa-AT/C1 esterase inhibitor generation were abrogated by corn trypsin inhibitor, which is a specific inhibitor of FXIIa. The binding of platelets was increased on the titanium surface compared to the other biomaterial surfaces and the state of platelet activation was much more pronounced as reflected by the levels of beta-thromboglobulin and PDGF. This study indicates that titanium is unsuitable as a biomaterial in devices which are in direct contact with blood for a prolonged period. Furthermore, PDGF and other alpha-granule proteins e.g. TGF-beta, are known to be potent promotors of osteogenesis which suggests that the pronounced thrombogenic properties of titanium might contribute to the good osteointegrating properties.

TNF and IL-1 generation by human monocytes in response to biomaterials
Cardona, M. A., R. L. Simmons, et al. (1992), J Biomed Mater Res 26(7): 851-9.
Abstract: The biocompatibility of surgically implanted materials may be compromised as a consequence of inflammatory reactions associated with phagocyte activation. Two important mediators of the inflammatory response are Interleukin-1 (IL-1) and tumor necrosis factor (TNF), both of which exert a wide range of biologic effects on many cells. This study was designed to evaluate the release of these cytokines by human monocytes (HM) brought into contact with four biomaterials utilized in clinical practice: polyurethane, expanded polytetrafluorethylene (ePTFE), Dacron velour, and woven Dacron. In vitro cultures for the generation of IL-1 and TNF by HM in the presence of the above biomaterials were established by exposing cells to each biomaterial in the presence and absence of lipopolysaccharide (LPS) with harvest of supernatants after 6 or 18 h. These studies showed that in the absence of LPS, IL-1 was released only by Dacron velour and woven Dacron associated monocytes while TNF was secreted in response to all of the materials. When LPS was present, however, monocytes associated with all of the materials released IL-1; and TNF release was greatly augmented. Further, the quantity of released cytokine was directly related to the duration of the association time. This study demonstrated that HM in association with various biomaterials were activated to produce both TNF and IL-1 and that the addition of nanogram quantities of LPS, such as would be produced if infection were present, greatly increased the amount of cytokines released.

Tooth extraction, immediate replacement and loading of an implant
Cloyd, S. (2005), Dent Today 24(6): 74, 76-9; quiz 79.

Tooth preparation for post-retained restorations
Ricketts, D. N., C. M. Tait, et al. (2005), Br Dent J 198(8): 463-71.
Abstract: Failure of root canal treatment and/or post crowns can be avoided in many cases if appropriate tooth preparation is carried out. This paper discusses the rationale for the timing of post placement following root canal treatment and appropriate methods for removal of gutta-percha prior to post space preparation. The basic principles of post space preparation are described, which should reduce the risk of weakening the root unnecessarily, causing damage to the periodontium and post perforation.

Topographic and dynamic radioisotopic investigations of interactions between biomaterials and blood components
Baquey, C., B. Basse-Cathalinat, et al. (1986), Artif Organs 10(6): 481-8.
Abstract: Functional investigations using radionuclides to study protein adsorption and platelet adhesion onto biomaterials are described. The authors' novel methods use radiotracers with a dynamic technique. This allows direct observation of the interaction between blood, or simpler biological substances, and artificial materials. Several radiotracers were used in this study, including 111In-platelets, 123I-fibrinogen, 123I-antithrombin III, and 99mTc-tagged red blood cells. The detectors employed were a semiconductor diode or gamma-camera equipped with special collimators. The acquisition and treatment of data were performed with an original device. These methods allowed precise comparisons, especially between platelet adhesion upon different materials in the form of tubes and also protein adsorption and desorption. The results are discussed in terms of materials to be used for work in vivo.

Topographically modified surfaces affect orientation and growth of hippocampal neurons
Dowell-Mesfin, N. M., M. A. Abdul-Karim, et al. (2004), J Neural Eng 1(2): 78-90.
Abstract: Extracellular matrix molecules provide biochemical and topographical cues that influence cell growth in vivo and in vitro. Effects of topographical cues on hippocampal neuron growth were examined after 14 days in vitro. Neurons from hippocampi of rat embryos were grown on poly-L-lysine-coated silicon surfaces containing fields of pillars with varying geometries. Photolithography was used to fabricate 1 microm high pillar arrays with different widths and spacings. Beta(III)-tubulin and MAP-2 immunocytochemistry and scanning electron microscopy were used to describe neuronal processes. Automated two-dimensional tracing software quantified process orientation and length. Process growth on smooth surfaces was random, while growth on pillared surfaces exhibited the most faithful alignment to pillar geometries with smallest gap sizes. Neurite lengths were significantly longer on pillars with the smallest inter-pillar spacings (gaps) and 2 microm pillar widths. These data indicate that physical cues affect neuron growth, suggesting that extracellular matrix topography may contribute to cell growth and differentiation. These results demonstrate new strategies for directing and promoting neuronal growth that will facilitate studies of synapse formation and function and provide methods to establish defined neural networks.

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