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In Memory of Michael Brown
Demand President Obama and legislators across the country act now to address police use of lethal force across the USA
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October 7, 2014
A Bahraini man under sentence of death has lodged his final appeal and could be at risk of execution. He was sentenced to death in February 2014 and lost his first appeal in August.
October 7, 2014
Six men, including five convicted in a rape case, face execution in Afghanistan after an unfair trial. The men are due to be executed on 8 October.
October 3, 2014
Five media workers in Myanmar had their sentences reduced on appeal to seven years' imprisonment. They were jailed in connection with their journalistic activities and are prisoners of conscience....
October 3, 2014
Blasphemy prisoner Mohammad Asghar has been shot and wounded by a prison guard in Pakistan. He is recovering in a hospital, but his lawyers fear he is still in danger of being killed.


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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 1 Genetic Potential of Interfacial Guided Osteogenesis in Implant Devices Anka Letic-GavrilovicAnka Letic-Gavrilovic, Roberto Scandurra and Kimio Abe Department of Biochemistry, Faculty of Stomatology, University of Beograd, Beograd, Yugoslavia Corresponding author: Anka Letic-Gavrilovic, D.D.S.,Ph.D., International Clinic for Neo-Organs - Via Cardinal P. Parente 26 00030 San Cesareo, ROMA, ITALY Tel: +39 328 767 8623 Tel/Fax: +39 06 95 599697 e-mail: firstname.lastname@example.com Anka Letic-Gavrilovic, D.D.S.,Ph.D., International Clinic for Neo-Organs - Via Cardinal P. Parente 26 00030 San Cesareo, ROMA, ITALY Tel: +39 328 767 8623 Tel/Fax: +39 06 95 599697 e-mail: email@example.com
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 2Abstract The purpose of this review is to summarise recent advances in the design and composition of bioactive surface layers of implants and drug delivery devices. These advances improve biocompatibility, osseointegration and durability properties, which are required for long-term implantation in the living body. In this review, the implant-bone interface was evaluated and interpreted on the basis of osteoblast cell cultures. The interface formed by in vitro-grown osteoblasts may be used to identify components of the in vivo implant-bone interface. Over the years, a large number of implant systems consisting of many different biomaterials, have been introduced in dentistry and orthopaedics. This paper discusses the performance of currently used metals and other biomaterials, by focusing on the events which occur immediately after implantation and on their impact on the bone-implant interface. The review demonstrates that continuous improvements in composition, surface modality and design of implants may benefit osseointegration and clinical longevity of such implants. No load-bearing conditions or clinical status were discussed. Titanium (Ti) and calcium phosphate ceramics are regarded as the most biocompatible synthetic substances which are known to be used in hard tissue implantation. These biomaterials are osteoinductive and osteoconductive, and do not induce ectopic bone formation. Nonetheless, they provide a physical matrix which is suitable for the deposition of new bone and may guide both the growth and extension of the bone. Comparative investigation evaluated that Ti implant system, appear to be apposed by more bone than ceramic systems, although alternatives concerning the type of Ti alloy and bioactive surface layer engineering, generate extremely diverse results in osseointegration. It has been hypothesised that an increase in surface roughness will result in an increase in: i) calcium and phosphorus deposition after immersion in simulated physiological solutions; and ii) protein production and calcium uptake by osteoblast-like cells. Manufacturers created an extensive range of inorganic or ceramic coatings on Ti implants in order to achieve better bone healing and osteoconduction. Biologically active molecules, added to the implant surface, represent breakthroughs in guided interfacial osteogenesis. This methodology offers an enormous potential of in-situ controlling and promoting osteogenesis. The in-situ bone growth factors (BMPs, TGF β, PDGF, IGF-I, fibronectin, laminin, PGE2, ALP ) relevant to the implant material osseointegration, are not fully understood, but most researchers agree that the contact between the bioactive surface layer of the implant and bone is not static but dynamic and above factors may maximise the implant osseointegration.
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 3Introduction The surface of implantable biomaterials is in direct contact with the host bone and soft tissue and it plays a critical role in determining its biocompatibility, functional compatibility, osteoinduction of bone and osseointegration of implants.The goal of regenerative therapy around orthopedic and dental implant devices is to create a suitable environment in which the natural biological potential for functional regeneration of the bone and of the periodontal ligament can be stimulated and maximised. In implantology, a wide array of biomaterials have been used so far with variable success rates (Table 1). The mechanical and chemical properties of metals (cobalt-based alloys, titanium, titanium based alloys) and ceramics (Bioglass and calcium phosphate and so on,) generally make them suitable for implant applications. Among these biomaterials, titanium (Ti) is the most widely used in medical applications, even if its long-term clinical success is questionable. This paper reviews available data on the evolution of implantable devices, by dwelling on the extensive range of manipulations on their surface layer, which were made to ensure better osseointegration. The paper also covers the possible clinical applications of biologically active molecules, growth factors and cytokines as well as of functional carriers and implantabile devices, because their combination may accelerate bone formation and bone healing and open new prospects for reconstructive bone therapy. Placing of implants into bone tissue should in principle lead to bone-implant osseointegration. Osseointegration in biology and medicine was both macro- and microscopically defined by different authors. Albrektsson [1] defined osseointegration as a process whereby, clinically asymptomatic rigid fixation of alloplastic materials is achieved and maintained in a bone during its functional loading. Branemark [2,3] stated that osseointegration is: i) the process whereby new and reformed bone perfectly fixes to the implant (including the surface irregularities), to such an extent that the light microscope does not show any interposition between connective and physiological fibrous tissue; and ii)when a direct, structural and functional connection is established between the bone and the implant, the bone can carry normal physiological loads without excessive deformation and without initiating rejecting mechanisms [4]. The concept of osseointegration was developed largely from the work of Branemark. Today, by definition, osseointegration requires the absence of a fibrous layer [4-6] and implies that the biological response of the bone is not one of inertness towards a foreign material but rather one of active integration of the material with the bone[7], as part of the body. At present, the transmission electron microscope (TEM) is commonly used to determine whether actual osseointegration has occurred i.e. whether calcified bone is within 100 A of the implant material [18]. Recently, a new concept of biointegration has hypothesised a chemical bond between the implant and the bone. Accordingly, the concept of biointegration and the use of ceramic materials such as hydroxyapatite (HA) or beta tricalcium phosphate (βTCP), leaving no space between calcified tissue and the material, were developed [7-9,12]. Ceramics are osteoconductive biomaterials (Table 3 and 4A), but in some cases also bone graft proteins, which are usually osteoinductive, can influence osteoconduction [217]. Ceramics are not osteoinductive, but serve as an active participatory template in the formation of new bone. However, they can induce osteogenic phenotype on osteoblasts (expression of noncollagenous bone related proteins - osteonectin, osteopontin, alkaline phosphatase and osteocalcin) followed by proliferation, differentiation, extracellular matrix (ECM)
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 4production and mineralisation of new bone. Osteoinductive biomaterials (listed in Table 4B) can induce bone formation starting with early stages of mesenchymal cells - osteoblast (Fig. 2). Many bone-related biological active molecules are osteoinductive (Table 4B and 6). Under the influence of these biomolecules - nondifferentiated mesenchymal cells may differentiate into early stages of osteoblasts and subsequently into committed and mature osteoblast (Fig. 2). A common model for investigating aspects of osseointegration in vitro is an osteoblast cell culture [10,11,13,14], offering unique opportunities to study bone formation [rev. in 10]. The bone formation that occurs during osseointegration may be an osteoblast activity which is affected by the implant surface. Osteoblasts are ideally positioned to function as cellular mediators of skeletal metabolism, and increasing evidence suggests that the effects of different biomolecules (osteotropic hormones, cytokines and prostaglandins) on the skeleton, including osteoclast activation, are osteoblast-mediated [13-17]. The interaction of the osteoblasts with different implant substrates, leading to osteoinduction or osteoconduction, can be measured in terms of attachment, proliferation and differentiation or expression of osteocalcin, osteopontin and fibronectin, i.e. antigens which play a vital part in the integrity and functioning of the bone and of the soft connective tissue, respectively. In this review, the interaction at the implant-bone interface is reported as evaluated and interpreted by authors on the basis of osteoblast cell cultures. The interface formed by in vitro-cultured osteoblasts may be used to identify molecular components of the in vivo implant-bone interface [10]. 1. Biomaterials for implant devices Over the years, a large number of implant systems, composed of many different biomaterials, have been introduced in dentistry and orthopaedics [18]. In this review, the performance of currently used metals and other biomaterials is discussed by focusing on the events which occur immediately after implantation and on their impact on the bone-implant interface. The review demonstrates that the improvements which have been made to composition, surface modality and design of implants (Fig. 1) over the years promote beneficial conditions for their osseointegration and clinical longevity. Based on the literature, the strength and properties of the material-bone interface, the amount of bone apposition onto the implant surface, and the extent of a new bone formation around implants depend on their composition and surface properties (references listed in Tables 2,3,4). In this review, the biofunctionality of currently used heterologous artificial biomaterials (polymers, metals, metal alloys, ceramics and composites) is discussed by paying attention to their capability of subsequently inducing variable-scale osseointegration. No load-bearing conditions or clinical status are discussed. Metals are probably the oldest form of materials used for dental implants and the most common type of materials used so far [19]. Superior fracture and fatigue resistance caused them to become the materials of choice in traditional load-bearing applications. A large spectrum of metals and alloys were used as endosseous implants, in orthopaedics, cranio-maxillofacial surgery and dentistry (Table 1 and 2). Gold-based alloys were among the first alloys to be used for implants, probably because these alloys were available in dentistry, but they promoted the fibrous interface with a bone [20], i. e. a distant osteogenesis with a short lifespan. Cobalt-chromium alloys were also developed and used as endosseous implants. However, the fundamental problem with these metals and alloys was the fibrous response which they promoted with the bone [21]. By today's standards, none of these materials
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 5achieve osseointegration, probably because of their corrosion effected by the living tissue and the release of elements into the tissue. Today, these metals have largely been replaced by titanium and titanium alloys (Table 2,3,4). Ultrahigh molecular weight (UHMW) polyethylene has long been used as a component for implantology. Polymers are classified as biotolerant materials but they were shown to be involved in the formation of a fibrous layer at the bone-implant interface (Table 1). Disintegration of polyethylene and acrylic cement was associated with chronic soft tissue inflammation [22] and bone resorption in the area close to the polymeric debris, leading to implant failure [23-28], probably stimulating focal adhesion of fibroblasts [30] through dose-dependent release of cytokines: IL-1α, IL-6, TNFα, PGE2, bFGF, PDGF and TGF β [32,33]. Bioactive ceramic materials, such as calcium phosphate (CaP) or hydroxy-apatite (HA) and glass ceramics or composites of special composition (12,29,39,40) are osteoconductive (Table 4) [34-39] or bioactive, because they allow the formation of a new bone on their surfaces and provide a unique strong interface with the host bone [37,40-49]. They were used in the form of a bioceramic (dense or porous), bioactive glass and glass-ceramics, as coatings of metal prosthesis or in some form of composites. Methods of manufacturing, properties and applications of these biomaterials were reviewed [50-54]. The bioactivity of ceramics depends not only on their chemical composition, but mostly on their surface topology [7,31,38,40,47,56-58]. The evaluation of histological and biochemical parameters evidenced that cells cultured on a bioactive glass generally have better osteoblast character than on the other tested materials, such as commercially pure titanium (cpTi) or titanium alloys [38,39]. By comparing Bioglass with titanium (Ti-6Al-4V), Co-Cr-Mo alloys [21], or polystyrene surfaces, the osteoblast cell line MG63 (human bone cells), recovered more viable cells, greater DNA synthesis, but had no influence of the osteocalcin production [58]. Commercial calcium phosphate ceramics, e.g. hydroxyapatite (HA), β-tricalcium phosphate (β-TCP), and biphasic calcium phosphate (BCP), are usually prepared by precipitation [7] and sintering at 950-1200° C. They are available in microporous and macroporous forms, or block forms depending on their applications - fillers in bone defects, augmentation of alveolar ridges or as plasma-sprayed coatings on metal implants. β-TCP is used as a resorbable material encouraging bone ingrowth, but is replaced over time with native bone. HA is used as a non-resorbable implant material [59] and in different forms, frequently as a coating on the Ti implants [7,44,60-63]. Calcium phosphate ceramics (HA and β-TCP) are considered as the most biocompatible synthetic substance which are known to be used in hard tissue implantation [12,29,39,40]. These biomaterials are not osteogenic per se, in that they do not induce ectopic bone formation. However, they provide a physical matrix suitable for deposition of new bone and display growth-guiding properties causing the bone to extend into otherwise non-occupied spaces. Consequently, they are osteoconductive. The key features of ceramics, such as chemical composition (being primarily composed of calcium and phosphate ions), physical properties and geometric topology, caused them to be frequently resorted to as coatings of titanium implants or carriers for a variety of biomolecules (Table 4 and 5) [64-66]. Various geometric forms of a HA were analysed, revealing that porous HA (average pore size of 300-400 µm) induced the highest amount of bone around the implant [66]. Experiments with sintered HA compared to as-received HA and calcined HA, showed an increased osteoblast-like activity on the sintered HA surface, suggesting that the crystallite size of HA surface may play an important role in governing cellular response [31,67]. It was reported an increased osteoblast-like cell activity on sintered HA surfaces in the presence of different TGF β dosage, suggested that sintering of HA
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 6surfaces may play an important role in determining of cellular response [112]. Other authors reported that osteoblasts cultured on bioactive glass and HA have a better morphology and higher proliferation rate, leading to confluent cultures with high cell density and, generally, to a better expression of the osteoblast phenotype in comparison with other substrates [31,38,68,9]. Besides the reported excellent results, there are disappointing data on bone resorption around HA implants, based on both clinical observations and histological research [44,46,70]. HA endosseal implants gain rigid biointegration with surrounding bone, impairing its mechanical integrity and causing a stressful tissue response at the interface. Supraosseous HA implants are plaque-attractant, leading to peri-implantitis. 2. Titanium, titanium alloys and modifications of implant devices Titanium is used in implantology because its chemical, physical and biological properties provide good biocompatibility. As titanium has a unique combination of properties (light weight, high strength to weight ratio, low modulus of elasticity, and excellent corrosion resistance), titanium and some of its alloys are important materials in medicine [rev. 71,72,63]. Nowadays, titanium and its alloys, with additional advantages (excellent biocompatibility, good local spot wettability, and easy shaping, weldability and finishing via a number of mechanical and electrochemical processes) have become mandatory in implantology. Although more research is needed in such areas as development of optimum casting investments, device design and control of biological responses, the future holds bright prospects of use of titanium in implantology. Cp Ti (Table 2A) and titanium alloys, such as Ti-6Al-4V [42,73,60,58,74] or as NiTi [75,76,] or TiNbZr, Ti-6Al-7Nb [77,33] and others (Table 2 B), have been used for manufacturing implants for the last 25 years. However, in spite of their excellent mechanical and physical properties, the worldwide medical use was hindered by their alleged toxicity [76,24,55], carcinogenicity or genotoxicity [76], hard metal disease by TiN and TiC [78,79], fibroblast-mediated osteolysis [32,27,28], or merely by their highly questionable longevity in vivo [4,23]. An immunocytochemical study demonstrated [80] that lysosomal cathepsins B and D are related to tissue degradation at the bone-Ti interface. An extensive and excellent metanalytic review on biological factors contributing to failures of osseointegrated oral implants of Branemark type was published by Esposito et al. [4]. Most of the reports indicates excellent biocompatibility of either pure titanium (cpTi) or titanium alloys with osteoblasts and surrounding tissue [81-84,73,43]. Nevertheless, data on titanium implant failures [4,41,23,24,81,46] suggest that it is far from being ideal material. Comparative investigation found that Ti implant system, apposes more bone than ceramic systems [84], although alternatives concerning the type of Ti alloy and bioactive surface layer engineering, generate extremely diverse results in osseointegration (references listed in Table 2). From the biocompatibility point of view, the two critical success factors for inductive osteogenesis i.e. osteoinduction that we expect from titanium or other implants, are: i) chemical composition and reactivity of bioactive surface layer; and ii) topography i.e. roughness of the surface in contact with the bone. Lately, the Ti implant surface has been the focus of multitechnical approaches and manipulations (both mechanical and physico-chemical), which were targeted to enhance the responsiveness of the host tissue to the implant, to promote in situ osteoinduction and thus
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 7to prolong the longevity of the implant (Table 2,3,4). Pure titanium (cpTi) is available in four grades: 1-4. Ti contains dissolved oxygen, N, H, C and Fe in various amounts and forms a strong and tightly-bound oxide over the surface (TiO2). This oxide forms instantaneously and spontaneously at all temperature. Its thickness is 5-10 nm, with tendency to grow up to 200 nm. This layer, described as passive, is capable of withstanding a saline, physiological environment without disintegrating., and is believed to give Ti its biocompatibility [71]. This oxide layer (TiO2) makes Ti casting difficult, largely is responsible for the outstanding corrosion resistance of cpTi and Ti alloys of any known implant material. Recently, many biotechnological improvements were made to the surface layer of Ti (Table 2 and 3). The question which arises is whether the efforts that scientist have undertaken thus far, for upgrading both the quality of the composition of the implant and the quality of its bioactive surface layer, are sufficient to achieve a desirable control of tissue response, i..e. to have a better osteogenesis. Combination of chemical and mechanical manipulations were reported to improve the surface layer. For instance: polished cpTi was acid-etched in two ways: i) the natural oxide was dissolved with hydrofluoric acid and a new oxide layer was grown by oxidation in nitric acid (HF/HNO3) [85,86]; or ii) Ti was pre-treated with HF/HNO3 and then machined [86], HF/HNO3 etched, fine or coarse sand-blasted and then HCl/H2SO4 etched [87], HF/HNO3 etched and electropolished [87] and HF/HNO3 etched and Ti plasma-sprayed [87]. The different chemical treatments resulted in distinct differences in surface roughness when examined by light microscopy, i.e., roughness was changed from the smoothest to the roughest. Subsequently, the effects of surface roughness on the function of osteoblast-like cells were measured. Acid-etching pre-treatment were used for covalent attachment of selected biological molecules as alkaline phosphatase and albumin [88]. These developments generated different kinds of interfaces between Ti and bone tissue [89], as described later. Subsequent chemical procedures on Ti were: deposition of thin polymeric film from ethylene plasma [90], alkali- and heat-treated Ti [43, 60], biomimetic method for apatite nucleation for bone-like apatite-formed Ti [92] or electrochemical apatite deposition [91]. These chemical manipulations have two key results in common: changes on TiO2 layer reactivity and surface fine topography. The implant surface roughness is essential for interfacial interaction with local tissue around implant, particularly for osteoblast. Osteoblasts, osteoblast-like osteosarcoma cells, macrophages, fibroblasts, bone marrow cells, nicely grow on polished Ti surfaces [10,31,61,81,93,94]. However, they need not only excellent chemical conditions, but also particular topographic conditions of the surface layer to create an environment conducive to optimum cell morphology and activity [9,81,61,56]. Optimum roughness of Ti implants (e.g. 4000-4500 nm, or 600 grit, or 300 A) was shown to significantly affect osteoblast cell response [31,86,81,87]. For instance, it can decrease the cell number, but increase the expression of more mature cellular phenotype such as: alkaline phosphatase (ALP), osteocalcin (OC), transforming growth factor β and prostanglandin E2 and the response of MG63 osteoblast-like cells to 1,25-(OH)2D3 [86,95]. After testing indicative parameters of biocompatibility (primary cell adherence, cell number, cell proliferation, production of extracellular matrix, cell viability, and cell differentiation), Wilke et al. [81] showed a lower level of Ti alloys biocompatibility vs. HA ceramics. Goldberge et al. [74] compared the osseointegration of surface-blasted Ti and CoCr implants, recording good biocompatibility, both radiographically and histologically. Both types of blasted implants have osteoconductive effects in vivo [74]. Increased surface roughness was assumed to cause an increase in
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 8calcium and phosphorus deposition after immersion in simulated physiological solutions [40], as well as higher protein production and calcium uptake by osteoblast-like cells [96]. Surface roughness modulates the local production of growth factors and cytokines such as prostanglandin (PGE2) and transforming growth factor β 1 (TGF-β 1) by osteoblast-like MG-63 cells [86,87,98]. Significant high levels of cellular attachment were observed when using rough, sand-blasted surfaces with irregular morphologies [86,61,81,56,17]. Experiments with grooved surface topography-induced changes in cell shape and matrix metal proteinases (MMP)-2 gene expression in normal human gingival fibroblasts [97], also support the above findings. Interestingly, the reaction of bone marrow-derived osteoblastic cells to rough Ti surface was suggested to be basically different from the one of calvaria-derived osteoblasts, even though both cells are from bone tissue. Ti roughness decreased protein synthesis of cultured osteoblast-like MG63 cells, measured by collagenase-digestible proteins, noncollagenase-digestible proteins and proteoglycans [99]. By analysing bone-Ti interface, Ayukawa et al., [100] identified an amorphous zone (20-50 nm) interposed between Ti and cells labelled strongly for osteocalcin and weakly for osteopontin. They suggested that osteoblasts secrete osteocalcin which, together with osteopontin, acts as a regulator of mineralisation, and as a mediator of cell-matrix and matrix-matrix/mineral adhesion along the Ti surface. These and other reports [83,60,61,38,58,57], made it clear that osteogenic-like cells have a specific, case- or model-oriented response to the surface roughness of implantable materials. This is probably the reason why manufacturers created varieties of inorganic or ceramic coatings onto titanium implants, aiming at achieving better bone healing and osteoconduction (Table 4A). 3. Coatings on implant devices Bone formation on the bioactive surface layer of the implant may be directly influenced by effects of the quality of the surface layer on osteogenic cells behaviour (Figs.1 and 2) [7,17,57,18 ,101,96]. From the character and amount of bone formation around different implants, it can be concluded whether the used materials are biocompatibile. This is why we should fully understand the process of bone growth around implants, as well as the reaction of the bone to trauma or to various properties of the implant surface layer [57,18 ,9,101,89]. The classical protocol of osseointegration was based on the success of the uncoated cpTi, treaded root-form implant. Long-term clinical data support the use of this material as an ideal dental implant. Ti is osteoinductive and it may create physico-chemical bonds with the bone. However, current data substantiate the use of a variety of implant surface biomodifications, coatings, as well as geometries to attain osseointegration. Therefore, the next step in the upgrading of the quality of implant surfaces was the addition of coatings onto the implant in the following ways: a) metal to metal (Table 3); b) ceramic to metal (Table 4A); and c) biological active molecules on metal (Table 4B), on ceramics (Table 5) or diverse functional carriers (Table 5). Ti has been used to date as a biological substrate of many osteoconductive and osteoinductive, inorganic or organic coatings (listed with references in Table 4): ceramics of different kind, glass, adhesion proteins, extracellular bone matrix proteins, growth factors and cytokines. The primary goal of coated implants was to combine the benefit of a bioactive surface layer with the properties of the substrate i.e. the strength of the underlining metal. The application of
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 9different types of ceramics onto titanium surface (Table 4A), was aimed at gaining two advantages: bonding osteogenesis and connective tissue osteogenesis. Ceramic coatings on titanium-based implants combine osteoconductivity and osteoinductivity , and additionally improve the strength of chemical bonds of the implant-bone interface. Various Ti implant coating methods were developed (Table 3): plasma spraying [86,44,62,87,56,99], chemical vapour deposition process (CVD) and physical vapour deposition process (PVD) (Table 3), slip casting/sintering, electrophoretic deposition/sintering, electrochemical deposition, and sputter coating, but plasma spraying is most commonly used one [86,90,44,87,102]. Chemical vapour deposition (CVD) process with high temperature (500-1000°C) of the substrate is not very suitable for dental alloys. In dentistry, the more recent physical vapour deposition (PVD) process may be used. For example, under vacum conditions, evaporated Ti is applied on thoroughly-cleaned metal surfaces, while feeding nitric or carbon gas in order to produce TiN [103] or TiC [104] (Table 3). Substrate temperature vary from 200-500°C. Coatings have a paramount clinical importance in the following cases: a) big defects and poorly supportive bone; b) when a very small or very big implant should be applied; c) repeated surgical procedure or re-implantation; d) type III and IV bone [57]; and e) in fresh extraction site. In each of this cases, given the adverse local conditions, the use of an implant with a coating or a sol-coated biomaterial, as a carrier of biologically active molecules, is recommended. Ceramic coatings appear to have better biological response than cpTi or Ti alloy alone [7,105,106], even if their clinical predictability remains controversial [62]. Coatings seem to promote faster bone adaptation [107,43,108,68], higher bone implant strength [105], better osteoblast precursor activity [67,96], bone growth around dental implants [48] and thus bonding of the bone to the implants, i.e. osseointegration (Fig.2). Coatings were reported to considerably change biological response around the implant and accelerated bone attachment comparing to their uncoated counterparts. The difference between osseointegration (bone-to-implant contact under the light microscope) and biointegration (chemical bond under the scanning electron microscope) was studied by analysing HA-coated surface in comparison with smooth and plasma-sprayed metal surfaces, titanium and titanium alloy surfaces [41,86,44,105,62,109]. HA coatings were highly considered because they enhance osseointegration [106], and they lead to the formation of more mineralised extracellular matrix (ECM) and to faster bone formation with respect to Ti substrates alone [61]. The philosophy was that HA has an advantage over smooth Ti surfaces having: 1) bioactive surface versus an inert Ti surface; 2) higher bond strength of the bone to the implant; and 3) increased bone-to-implant contact [101]. In spite of reports about overstressing, rapid, bone-resorption adjacent to HA-coated implants [46], short-term survival rates (from 6 months to 6 years) [62], or other causes of failures [6,57,11,106], there are still evidence of positive effects of HA coatings on osseointegration [96,106,83]. A review of literature about coated versus uncoated substrates was made by Biesbrock at al. [62] and others [18,105,106]. Meffert [101] wondered whether the implant surface induces a difference in osseointegration versus biointegration. The author posed a question: Do the epithelium and connective tissue attach or adapt to synthetic surfaces? Is one surface better than any other? The literatures offers plenty of evidence validating the hypothesis that coating engineering of the bioactive surface layer of the implant enhances bone healing (references listed in Table 4). Recently, ceramic coatings, such as titanium nitride (TiN) and titanium carbide (TiC) [103,78], have been proposed for implantology. In general, biocompatibility of TiN in cell culture and animal tests was evaluated positively [114]. Aesthetic appearance (gold-
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 10coloured layer) is questionable and probably culture dependent. However, longitudinal clinical studies have been scarce so far. In total joint arthroplasty, a diamond-like carbon coating was applied onto Ti [115-118]. TiC coatings were developed to fit straight stems and cementless accetabular implants [104]. Subsequent studies questioned the biocompatibility of TiC on grounds of toxicity or hard metal disease [79]. Also vitreous carbon, pyrolytic carbon, pyrolytic graphite/silicon-carbide were occasionally used as Ti coating on implants [103,104,119,47]. When testing their biocompatibility on mandibular tissues of rabbits, the implants elicited similar reactions, including fibrous connective tissue capsule formation, multinucleated phagocytic cells, mild inflammatory infiltrate and reactive bone [119]. By contrast, amorphous alumina and silicon carbide, applied as coatings onto Ti, combine the good mechanical properties of the alloy with good cytocompatibility of coatings [47]. 4. Implant devices as functional carriers of biologically active molecules Devices for drug or biologically active molecule delivery aroused considerable interest in the field of implant engineering, due to the advent of proteins that can induce proliferation and differentiation of various cells, so as to form specific tissues and organs, for example BMP-2 for osteogenesis. Drug-delivery devices or carriers (Table 5) for various bone promoting growth factors (Table 4B and 6) have been investigated as physiologic delivery system in the earlier 1990s. Most of the listed carriers have recently been used in routine bone regeneration, as mechanical barriers obstructing epithelial ingrowth and as osteo-promoters, used separately or in combination [57,120-123]. These reports showed that the repair of bone defect and the induction of ectopic bone with BMP is significantly facilitated by a suitable carrier, particularly when the unique geometry of the carrier provides microenvironmetal conditions for an excellent cell differentiation and vascularization [64-66,124,102,125]. Natural and synthetic resorbable carriers (Table 5A) and ceramic nonresorbable carriers (Table 5B) have recently been reported as possible delivery devices for bone growth factors. The outstanding affinity of CaPs for selective adsorption of peptides and proteins is a major advantage for ceramics. As a matter of fact, by selecting proteins to be adsorbed, CaP ceramics can have a direct influence on interfacial interaction. Undifferentiated cells were shown to recognise the physico-chemical properties of adsorbed proteins on the substrate carrier with which they are associated through cell-ECM interactions. For example, glass fibres may favour the expression of chondrogenic phenotypes, whereas collagen fibres may allow the progenitors to differentiate directly into osteogenic cells [64]. Main carrier, i.e. ceramics such as: HA, Ti, beta-TCP, are often combined with a second carrier: collagen [120,126,127-129] or allogeneic demineralized bone matrix (DBM) [129-131] prior to impregnation with growth factors: BMPs (Table 6) [64-66,132], or IGF-I [133], bFGF [134], PDGF [137] or non-collagen proteins [135]. However, biphasic calcium phosphate (BCP) combined with rhBMP-2 was shown to induce ectopic bone formation without additional (second) carrier [136]. Anyhow, HA ceramic-collagen-BMP complex is frequently recommended for clinical applications [138-140,128,120]. This complex stimulates faster bone formation. Given its porosity, the ceramic is thought to entrap collagen-BMP within its micro-pores, and thus, the intrinsically diffusible BMP is retained and its action consequently prolonged. This complex also demonstrated to offer increased surface contact
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 11between BMP and mesenchymal cells, which induce bone formation more rapidly than BMP alone [138,141]. 5. Resorbable and non resorbable membranes 1) Osteopromotive membranes of expanded polytetrafluoroethylene (ePTFE; GORE-TEX) facilitate guided bone regeneration, are not resorbable and require a second procedure to be removed. The combination of membrane placement with rhBMP-2 may be of value in the clinical applications for bone regeneration purposes [132]. This finding is also valuable for choosing carrier materials for delivery of other growth-stimulatory substances, in combination with membranes. ePTFE membrane plus BMP can be combined with Ti implants [137,142], demineralized freeze-dried bone (DFDB) [137], and with the growth factors PDGF-BB, PDGF/IGF-I [137] or rhBMP [132]. Clinical results, demonstrated that ePTFE membranes plus PDGF/IGF-I, had the -highest bone density compared with controls receiving membranes alone [137] and they also allow the bone to grow directly around the implant [142]. 2) Basically there are two types of biologically resorbable biomaterials: a) synthetic polymers of lactide-/glycolide- and polylactic acid [143-145]; and b) collagen. Collagen plays an important role in wound healing since it is present in connective tissue capsules which lie around implanted materials. The influence of collagens, including collagen I, III and IV on in vitro cell proliferation [146,147] greatly depends on the cell cultures. Collagen membranes are used in clinical applications because their compact layer protects against soft tissue invasion and their porous texture enables the integration of newly formed bone tissue. The amount of collagen type I and III during soft tissue capsule formation varies, depending on the type of metal implants [147]. The properties of collagen favour cell attachment. Collagen I was reported to inhibit cell proliferation, whereas collagen IV had no effect. Moreover, highly differentiated osteoblasts were cultured on Matrigel [146]. Matrigel is a reconstituted basement membrane gel, whose components include such growth factors as laminin, collagen I and IV, and factor VIII antigen. It can be used independently [146] or in association with various biomaterials, such as polystyrene, low and high crystallinity HA and rough Ti [148], for investigation the interaction of primary calvarial bone cells of rats and osteoblast-like cells of mice. Matrigel significantly enhanced mitogenicity of calvaria cells, and eliminated differences between two HA coatings of different cristallinity [148]. 6. Genetic potential of osteopromotivve growth factors on implant devices Polypeptide growth factors are a class of natural biological bone mediators regulating the critical cellular events which are involved in wound healing: cell proliferation, chemotaxis, differentiation, and matrix synthesis. Growth factors elicit their effects by binding
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 12to specific cell surface receptors, which transduce signals to the nucleus via complex signal transduction pathways. Examples of growth factors found in bone, cementum and healing tissues include platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β), acidic and basic fibroblast growth factors (a- and b-FGF), insulin-like growth factors (IGF-I and II), cementum-derived growth factor (CGF) and the bone morphogenetic proteins (BMPs) [rev. 149]. The in situ factors which induce osseointegration of the implant material are not fully understood, but most researchers agree that the contact between the bioactive surface layer of the implant and the bone is not static but dynamic [150,7]. As in vivo osseointegration reactions are governed by molecular mediators, it makes biological sense to suppose that such mediators might play a role in the interfacial reactions leading to implant integration, encapsulation or rejection. When an implant is inserted into a body environment, it is exposed to host cells and molecules that ultimately determine the course of underlying events (Fig.2). The first event is the absorption of proteins within the first 10 to 60s after the contact [151,89,152], long before the cells get access to the surface. This means that any cell interacting with the implant surface can only do so indirectly, through the bioactive layer of the adsorbed proteins. Obviously, adsorbed protein coatings depend on the physico- and electrochemical- properties of a given surface [153,89,154]. And it is conceivable that the type of the adsorbed protein [153] (adsorbed naturally or pre-adsorbed commercially) may determine the type of cells interacting with the implant surface. In order to maximise and control the osseointegration of implants, an array of peptides with osteoinductive potential, together with implant devices, have lately been introduced (Table 4B) and in vitro tested. Since these biomolecules are responsible for cell anchorage, attachment, spreading, adhesion, migration and all other events connected to biointegration, implants should be capable of releasing these peptides in a controllable way, under strict clinical conditions, in order to maximise implant osseointegration. 7. Bone morphogenetic proteins (BMPs) The three main ingredients for bone regeneration are regulatory signals, responding stem cells, and extracellular matrix proteins (ECMs) [155-158]. The osteoinductive signals are the bone morphogenetic proteins [155,157] (Table 6). BMPs are members of the transforming growth factor beta (TGF β) superfamily, which consist of almost 15 secreted signalling proteins (Table 6), which are present in vertebrate and invertebrates [rev. in 156-160]. They are responsible for a broad range of biological and developmental effects and control processes during tissue development and repair. These factors affects mesenchimal cells recruitment, proliferation, differentiation and secretion of extracellular matrix components [110, 113,161-167], a cascade of cellular events that are involved in the initiation of in vivo bone morphogenesis. Recombinant human BMPs (rhBMPs) were shown to induce new bone formation in vivo and to heal a large segments of bone defects by fostering chondrogenesis [113,167]. When implanted in ectopic sites, they can also induce intramembranous ossification, i.e. direct bone formation without pre-existing cartilage [168]. However, little is known about their mode of action. The biological functions of individual BMP molecules were reported to be different depending on cell lines [165,156]. Multipotent cell types respond to BMPs by increasing or decreasing their proliferation, because their inductive properties highly depend on the nature of carrier material used for implantation [169]. The geometry of the substrate appeared to
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 13have a profound influence on bone induction by BMP [135]. The effects of BMPs on osteoblastic cell lines were indicated to depend on the Ti surface roughness [170], or surface TiO2 contaminants, such as carbon and nitrogen. In the later study, microgeometry of Ti was shown to affect the activity of BMP-2-treated osteoblast cells, which expressed significantly higher alkaline phosphatase and produce more vitamin D-stimulated osteocalcin [171]. Interestingly, the production of osteocalcin (marker of mature osteoblasts) was not stimulated by rhBMP on any of the tested biomaterials [145] and osteogenin did not induce bone cells differentiation when combined with granules of porous HA with identical pore size [135]. BMP-2 may be regulator of cell adhesion [172]. In addition to a direct action on responding cells, BMPs may enhance their effects on osteoblast cell lines by stimulating the local production of paracrine and autocrine factors [165,156,173,174,175]. The combination of membrane placement with rhBMP-2 may be of value in the clinical applications for bone regeneration purposes [132]. This finding is also valuable for choosing carrier materials for delivery of other growth-stimulatory substances in combination with membranes. The effects of rhBMP 2 [45,170,171,176,125] and BMP 3 [102], applied with collagen sponges in Ti chamber [176], with HA (Interpore 200) [125] or coated on plasma-sprayed titanium Ti-6Al-4V [102] were tested in vivo and in vitro. Kawai et al. [177] used Ti sponges infused with BMP to measure osteoinductivity. Recently, many efforts have been undertaken to develop delivery systems for BMPs (Table 5), such as natural and synthetic carriers and various ceramics (discussed above). Recently, the function of individual BMPs on various cell types, cultured with various biomaterials has been extensively tested [45,113,171,170,102,176,125,177]. In vivo experiments surprisingly showed that BMP-2 (probably model-related) can inhibit [176] or increase [125] bone ingrowth. Sailer et al. described their clinical experience with the BMP that they had prepared and used in compromised cranio-maxillo-facial patients [178]. The authors demonstrated that concentrated BMP preparations can induce bone areas with seemingly lost implants. In their patients (all with Branemark type implants), the two most critical aspects were an incomplete bone bed around implant, and a bone mostly of poor quality and of doubtful vitality. Accordingly, they emphasised the excellent results obtained from the application of BMP together with Ti implants in surgical reconstruction. BMP-2 and the effects of surface topography and chemistry of titanium on human bone marrow cells [45] or osteoblast progenitor cells 2T9 of mice [170,171] were tested in vitro. Ong et al. [171] showed that the expression of osteoblast phenotypes was enhanced when osteoblast progenitor cells were stimulated with BMP-2 on polished and rough Ti surfaces. BMP-2 stimulated more phenotypic expression of alkaline phosphatase-specific activity and osteocalcin production on rough Ti surfaces than on polished Ti surfaces [170,171]. Kim et al. [45] tested carrier for rhBMP-2, as well as cpTi, Ti alloy, cobalt alloys and HA. They concluded that grafts of porous Ti implants, combined with rhBMP-2, may act as good osteoinductive composite for bone defects. rhBMPs-2 have not only a potent effect on bone formation but they also promote re-osseointegration of peri-implantitis defects [179]. 8. Transforming growth factor β β (TGF β β) BMPs and TGF β belong to the TGF β superfamily. TGF β is present in most tissue and is known to play an important regulatory role in cell growth, migration and differentiation. TGF β has stimulatory effects on proliferation and extracellular matrix
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 14synthesis in many types of skeletal tissue cells, probably in combination with other osteogenic growth factors. TGF β may be synergistic in promoting bone formation either with BMP-2 [110,113,139,149] or BMP-7 [180], probably by inducing BMP genes expression during endochondral bone formation in baboon [180], or both at the stage of intramembranous bone formation and early chondrogenesis in the rabbit mandible [110]. OP-1/BMP-7 may have an opposite effect, with respect to TGF β, on fetal rat calvaria cells [181]. TGF β and PDGF-BB had the strongest chemotactic and proliferative effects on human osteoblasts [149], whereas PDGF-AA, IGF-I and IGF-II had less but significant chemotactic effects on osteoblasts [149]. The addition of PGE2 to the culture media stimulated the release of TGF β peptides in primary osteoblastic cells of mice in vitro [182]. The metal substrate reduced the activity of TGF β, measured by using IL-1 assay method [183]. Combined effect of TGF β and HA on osteoblast response in vitro shown that protein production by osteoblast cells was not different comparing sintered, as-received and calcined HA samples, but TGF β synergistically with sintered HA increases ALP and osteocalcine production [112]. Following mechanical stress, TGF β 1 down-regulated IL-6 expression, which induces mitogenesis in periodontal ligament cells and simultaneously reducing IL-6-induced bone resorption [184]. TGF β exogenously applied directly to calvariae increases bone mass in mice and rats. TGF β has complex effects upon ECM production: for the most part, it enhances the accumulation of various matrix components by increasing their synthesis and decreasing their turnover [183]. Implants treated with human recombinant TGF β 1 achieve a more rapid and higher percentage surface of osseointegration than in comparable sites without TGF β 1, but the rate of osseointegration was not accelerated [185,112]. Local administration or implantation of materials that release TGF β might be useful for increasing the skeletal matrix after pathological bone loss or for enhancing matrix formation and bonding between residual bone and allografts or synthetic bone substitutes. 9. PDGF and IGF-I and II Bone and cementum contain high concentrations of growth factors such as insulin growth factors (IGF-I, -II), TGF-β, and platelet derived growth factor (PDGF) which may be released following injuries. Moreover, activated platelets, plasma exudate and other cells adjacent to the injured site provide a variety of growth factors which regulate the repair and regenerative process of bone and periodontal tissue [rev. in 186]. PDGF-AA, -AB and –BB isoforms have potent effects on the periodontium in vitro and in vivo. In osteogenic cells culture, PDGF stimulate DNA synthesis and chemotaxis, as well as collagen and non-collagen protein synthesis. In osteoblast-like cells, ALP and osteocalcin are down regulated by PDGF [186]. PDGF-BB stimulate proliferation and chemotaxis but not differentiation of osteoblast. IGF-I and -II are found in large amounts in bone, with BMP being the most abundant growth factors in bone matrix. IGF-I is produced by osteoblasts and stimulates bone formation by inducing cellular proliferation, differentiation, and type I collagen biosynthesis [187]. Both IGF-I and -II are incorporated into the mineralised bone matrix and retain their activity when extracted from bone. PDGF-BB and IGF-I were tested when incorporated into expanded polytetrafluoroethylene (ePTFE) nonresorbable membrane and in combination with demineralised freeze-dried bone (Table 4). They were placed over Ti implant and inserted into
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Dental Material Journal Vol. 19, No.2, 99-132, May,2000 15fresh sockets. Clinically and histologically, significant gains in bone density around Ti implants were reported [137]. 10. Genetic markers of adhesive interactions with implant devices Cell adhesion is fundamental cellular process which directly influences cell growth, differentiation as well as tissue morphogenesis, integrity and repair [188-191,172,17] and adhesion proteins were associated with wound healing. Adhesive biomolecules in the extracellular matrix are presumably responsible for much of the strength and stability of implant junctures. These data were often interpreted to suggest that adhesive biomolecules permeate a thin, collagen-free zone at the most intimate contact points with implant surface [192]. Klinger et al. [192] reported a thin layer of proteoglycans at the bone-implant interface. In their model, the Ti surface accelerates osseointegration by causing the rapid degradation of a hyaluronan meshwork, which develops as a part of the wound healing response [192]. Furthermore, enhancement of epithelial cell attachment was attributed to Ti-6Al-4V alloy coated with laminin-5 [73]. Protein analysis showed that Ti-6Al-4V has a high affinity for laminin-5 and adsorbed significantly more laminin-5 than laminin-1. Bagambise et al. [89] compared the adsorption of fibronectin on different ceramic or metal surfaces, evidencing an active molecular and cellular interaction between the cells and metal surfaces where fibronectin was adsorbed. They concluded that the surfaces of implants should not be designed to be mere bystanders, but rather active subjects in wound healing and tissue repair. Additionally, different orthopaedic implant materials were reported to affect osteoblast integrin expression [17]. 11. Integrins Integrins are the largest and best-studied family of osteoblast cell surface receptors for specific amino acid sequences in ECM proteins [193,194,17,195], which thus regulate osteoblast attachment to metal implants, such as Ti or Co, in vitro [21]. The profile of osteoblast integrin expression in vivo and in vitro were also studied by several investigators [196,197,198,199]. Sinha and Tuan [17] have showed that the Ti implant material composition and surface texture influence the appearance of integrin subunits, α 2,3,4,5,6, β1 and 2 [17]. Since those integrin subunits represent receptors for collagen, fibronectin and laminin [200,201], osteoblasts are likely to have differing capabilities to use integrin-mediated mechanisms for attachment to implantabile materials, possibly by depositing different ECM proteins on these surfaces. This finding may explain the differences in clinical performance of these materials [202-204]. The results of Gronowicz and McCarthy [191] have shown that β 1 integrin subunit can bind directly to Ti and Co, but not to glass and plastic. Antibodies to fibronectin receptor α 5β 1, inhibit the binding of cells to Ti and Co, but antibodies to vitronectin receptor α v β 3/β5, did not alter cell adhesion [191]. When Ti coated with diamond-like carbon, and cultured with osteoblasts, was pre-treated with fibronectin, it increased cell binding. Conversely, when it was pre-treated with fibrinogen, vitronectin and laminin, it did not enhance cell adhesion [118]. Ti surface texture may also
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Quoizel Cooper COR901 Post LanternItem # HN-QUO1035
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Gaige House, a Four Sisters Inn, Glen Ellen
- Free WiFi and free parking
Main amenities
- 23 smoke-free guestrooms
- Outdoor pool
- Terrace
- Coffee/tea in the lobby
- Air conditioning
- Daily housekeeping
- Garden
- Library
- Computer station
- Lobby fireplace
- Front desk safe
- Meeting room
What's around
- Quarryhill Botanical Garden (0.9 mi / 1.5 km)
- Jack London State Historic Park (1.6 mi / 2.5 km)
- Mayo Family Winery (0.5 mi / 0.8 km)
- Bouverie Preserve (0.9 mi / 1.4 km)
- Sonoma Valley Regional Park (1 mi / 1.7 km)
Very romantic. We stayed in the Poolside Suite which was fantastic.
We can't say enough good things about this hotel! It is a historic old house, that has…
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Hotel Info: 866-539-8117from $206
- Deluxe Room, 1 King Bed (Spa Tub)
- Zen Suite (Garden)
- Gaige House Suite
- Zen Suite (Creekside)
- Creekside Suite
- King Deluxe
- Deluxe Room, 1 Queen Bed
- Studio Suite
- Zen Suite
- Suite
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Key facts
Hotel size
- This hotel has 23 rooms
- This hotel is arranged over 3 floors
- Check-in time 3 PM-9 PM
- Check-out time is 11 AM
- Express check-in/out
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
- Minimum check-in age is 21
Travelling with others
- Children (5 years old and younger) stay free when occupying the parent or guardian's room, using existing bedding
- No cribs (infant beds)
- Pets not allowed
- Free WiFi in public areas
- Free WiFi in rooms
- Free self parking
Other information
- Smoke-free property
Nearby Four Star Glen Ellen hotels
In the hotel
- Free reception
- Coffee/tea in the lobby
- Outdoor pool
- Pool sun loungers
- Spa tub
- Pool umbrellas
- Conference space size (feet) - 500
- One meeting room
- Computer station
- Front desk (limited hours)
- Concierge services
- Tours/ticket assistance
- Free newspapers in lobby
- Luggage storage
- Wedding services
- Number of buildings/towers - 4
- Safe-deposit box at front desk
- Garden
- Picnic area
- Terrace
- Library
- Fireplace in lobby
In the room
- Climate control
- Air conditioning
- Ceiling fan
- Minibar
- Coffee/tea maker
- Bathrobes
- Iron/ironing board
- Down comforter
- Blackout drapes/curtains
- Premium bedding
- Pillowtop mattress
- In-room massage available
- Individually decorated
- Individually furnished
- Private bathroom
- Bathtub or shower
- Designer toiletries
- Hair dryer
- 32-inch flat-screen TV
- Cable TV channels
- DVD player
- Desk
- Free newspaper
- Free WiFi
- Free local calls
- Free bottled water
- Daily housekeeping
- In-room safe
- Access via exterior corridors
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Special features
Awards and affiliations
- Gaige House, a Four Sisters Inn is listed in the 2011 Condé Nast Traveler Gold List of the world's best places to stay.
Gaige House, a Four Sisters Inn, Glen Ellen's small print
Also known as
- Gaige
- Gaige House
- Gaige House Four Sisters
- Gaige House Four Sisters Glen Ellen
- Gaige House Four Sisters Inn
- Gaige House Four Sisters Inn Glen Ellen
- Gaige House Inn
- Gaige Inn
Only registered guests are allowed in the guestrooms.
The name on the credit card used at check-in to pay for incidentals must be the primary name on the guestroom reservation.
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


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We are looking for fictional stories about people's experience with life crisis', problems, struggling with hanging on to faith. It will be incorporated into a fictional novel, so the stories must be written as if Person A was telling a story to Person B about something that happened in their life and how God's presence or their faith got them through. We are looking for specific stories not generalities (so ie a story about an individual who has a condition and at the 11th hour is saved, or an individual who prays to God to take over their life and how their world is transformed) The stories can be true stories that you write as fictional, or they can be legitimately fictional. Looking for stories that are about 2000-3000 word short stories. If you have a longer story, please let us know in advance the premise and we can discuss additional compensation. We are willing to take more than one story from a single contractor.
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post #31 of 34 Old 05-02-2014, 03:13 AM
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Good question, i'll be in the same boat pretty soon. Have gone with Yamaha, HK, Denon and Pioneer. The Yamy and Denon have had their issues but i've actually liked the Audyssey feature.
I should rule out Denon because that HDMI handshake issue is annoying and Onkyo has had iffy reviews for a long time now.
I should rule out Denon because that HDMI handshake issue is annoying and Onkyo has had iffy reviews for a long time now.
post #32 of 34 Old 05-02-2014, 06:51 AM - Thread Starter
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So the Yamaha is pretty awesome so far in my opinion. The sound seems super clear and plenty powerful. I haven't gone near the max volume yet. YPAO works just like Audyssey although I'm only finding the option for setting the mic up for one listening position at this point. Still sounds good all around my listening area. The Denon offered 5 listening positions I believe. No HDMI handshake issues with my Blu Ray player, TiVo box, or AppleTV, with the Yamaha, which is an improvement over the Denon. Just seems to work and do a real nice job. After owning both the Denon E300, and the Yamaha 375, I think it's safe to say they are both very capable, high quality receivers that will do a great job for those that don't need all of the fancy extra stuff that an AppleTV/Roku/Amazontv already offer. Other than the HDMI handshake issues I really liked the Denon. The Yamaha fixes that issue and I like it as well. Works for me.
post #33 of 34 Old 05-02-2014, 07:01 AM
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The best receiver is the one that works properly. Good sound is pretty much a given. Ypao jumps from one mic position to eight when you step up to the 775. Now you know why I suggested that model. Just kidding. Ypao doesn't do much eq even with 8 position version. I measured it myself to be sure. It won't make the sound worse though. If you want flat bass response an external eq is required. Behringer feedback destroyer $100 is the cheapest.
post #34 of 34 Old 11-30-2014, 08:12 PM
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I am about to buy the RX-V377. For the last 2 or 3 years I'd been using the RX-V661. It never gave me any issues.
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- Yamaha RX-V375 5.1 Channel 3D A/VDolby TrueHD, DTS-HD Master Audio, Dolby Digital Plus, DTS-HD High Resolution, Dolby Digital, DTS,...
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$299.95$219.95Yamaha RX-V377 5.1-Channel A/VHigh Quality, New RECEIVER,5.1CH,100W/CHNNL...
1 ReviewMore on Yamaha RX-V377 5.1-Channel A/VYamaha RX-V373 5.1-Channel AVYamaha's RX-V373 entry level receiver provides simple operation yet includes essential capabilities...
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The Macon County precincts of Smith Bridge and Flats met to organize and energize democratic and independent voters over breakfast on Saturday. Guest speakers included candidate for the 50th Senate District, John Snow, and John deVille, vice-president of the Macon County chapter of the North Carolina Association of Educators.
Senate hopeful John Snow discussed that he believes incumbent Jim Davis isn't working for the people of Western North Carolina. Snow highlighted how he was an independent-minded advocate for WNC, while Davis was towing the party-line, whether it was to benefit WNC or not.


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Christmas evening to benefit Interfaith
First Christian Church has invited the community to A Merry Christmas Evening Dec. 10 to benefit Interfaith Ministries.
The informal evening will include dinner and musical entertainment starting at 7 p.m. at the church, 3701 Taft Blvd. Tickets are $25, and reservations should be made by Dec. 9. For tickets, call Interfaith Ministries at 322-1365.
Organizers promise a "cozy, homey, informal, traditional Christmas party" featuring food and favorite Christmas music.
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eos Lip Balm Sphere - Summer Fruit
1233 reviews
55% would repurchase
Package Quality: 4.1
Price: $$
Package Quality: 4.1
Price: $$
INGREDIENTSOlea Europaea (Olive) Fruit Oil, Beeswax (Cire D'abeille), Cocos Nucifera (Coconut) Oil, Simmondsia Chinensis (Jojoba) Seed Oil, Natural Flavor, Butyrospermum Parkii (Shea Butter), Stevia Rebaudiana Leaf/Stem Extract, Tocopherol, Helianthus Annuus (Sunflower) Seed Oil, Vaccinium Angustifolium (Blueberry) Fruit Extract, Fragaria Vesca (Strawberry) Fruit Extract, Prunus Persica (Peach) Fruit Extract, Linalool
on 7/2/2012 9:18:00 PM
Age: 19-24
Skin: Combination, Fair-Medium, Not Sure
Hair: Brown, Other, Other
Eyes: Brown
I really wanted to like this lip balm, but it didn't moisturize my lips. It was simply a waxy residue on my lips. I thought it was a unique concept and the packaging is cute but once it got to the bottom, it gets awkward to use, yet there's still alot of product left!
on 7/2/2012 7:29:00 PM
Age: 18 & Under
Skin: Combination, Fair, Warm
Hair: Blond, Wavy, Medium
Eyes: Green
I admitI originally bought this product because of the adorable packaging (which I still love) but it's great stuff! First off it smells AMAZING kind of like peaches even though it says summer fruit. The formula itself kind of waxy but after using it for a couple days I noticed an improvement in my lips and I prefer it to other lip treatments like carmax, blistex and vasilene because it isn't glossy and it's light weight. I will repurchase and I want to try all the different colors they've come out with!
on 7/2/2012 6:47:00 AM
Age: 25-29
Skin: Combination, Medium, Not Sure
Hair: Black, Straight, Other
Eyes: Brown
I like the juicy smell of this product. I have never been attached to any specific lip balm but I have changed my ways after this product. Chapstick, Burts bees or Blistex, I find myself not really reaching for any one in particular, but this EOS seems to have grown on me. I actually find myself at the end of my EOS lip balm. In the past I have always lost my lip balms, but this bright RED color/Shape is a bit hard to lose. I leave it in my purse mostly and I find myself using it time and time again. For a non lip balm person, I really like this one. I even ordered the sweet mint to try it out. I really like the packaging, the spherical application and the texture of this balm. It makes my lips feel moisturized without being Oily or mediciney or thick (Burts bees).
on 6/30/2012 5:17:00 PM
Age: 18 & Under
Skin: Combination, Tan, Not Sure
Hair: Black, Other, Other
Eyes: Brown
This lip balm is ultra moisturizing for me, but the scent is NASTY! It smells like fruit mixed in with cheese wax and sweat. My mom and sister can't stand the smell, but it's something I can tolerate. Only using it for night time since it locks in the moisture until I wake up. Maybe I'll try another flavor since the summer fruit one is bad. I love the packaging and the actual product's effects!
on 6/30/2012 9:38:00 AM
Age: 18 & Under
Skin: Other, Olive, Not Sure
Hair: Brown, Straight, Other
Eyes: Brown
I use this lipbalm everyday because i'm addicted to the smell of it. It moisturises my lips and makes it nice and smooth. I wear this under my lipsticks and it works great. I love how cute the packaging is. It does not dry out my lips. I think that it works great. I really recommend this to anyone who have dry lips or for people who wants to make their lips smooth.
on 6/28/2012 2:30:00 AM
Age: 18 & Under
Skin: Normal, Fair-Medium, Not Sure
Hair: Brunette, Other, Other
Eyes: Brown
Personally i love this product. I have all the eos lip balm eggs, and they are totally amazing. this eos egg lip balm happens to be my favorite. I use it daily, and i must admit at first it is waxy, but after a few uses it is nice smooth and creamy. The packaging is soo adorable! the smell is great, and it keeps lips healthy. I've actually read a lot of reviews for this product, and i must say i disagree. I would sooo buy this again! I've actually bought this like 5 times already since i used it up so many times, because i love this one sooo much. so yeah. i love this lip balm egg thing in summer fruit. :) kay then. bye. i guess..... :D
on 6/27/2012 11:22:00 AM
Age: 18 & Under
Skin: Acne-prone, Fair, Neutral
Hair: Brunette, Curly, Coarse
Eyes: Blue
Overall, a great product. I use this every day, and reapply a lot, just because I love how it feels on my lips. It's extremely moisturizing, and it smells and tastes great. The only downside to it is I once had one in Honeysuckle Honeydew, but I threw it in my full backpack, and the cover twisted off and the product and a few other things were ruined, but haven't had this problem since repurcasing.
on 6/27/2012 10:57:00 AM
Age: 18 & Under
Skin: Normal, Tan, Not Sure
Hair: Brunette, Wavy, Medium
Eyes: Brown
This is a really cool lip balm! I love the unique packaging, in a sphere, and the yummy 'flavors'! My favorite, personally, would have to be the strawberry sorbet. However, it appears they did not think the sphere packaging completely through because when you use the whole top, you'll have to apply the rest with your fingers, which is a big pet peeve for me. Another thing is, they don't fit into small purses without showing a big lump. Overall, a fairly great product.
on 6/26/2012 10:31:00 PM
Age: 19-24
Skin: Combination, Olive, Warm
Hair: Black, Straight, Fine
Eyes: Black
I saw this in my local drugstore and I was so drawn to it, because I liked the packaging! I love the rounded shape, and how it looks like a jawbreaker, or a giant gumball. The lip balm formula is quite nice. It's creamy, a moisturizing. But, when you run out of the lip balm, ughh...There's so much product left in the bottom half! I'm quite dissapointed about that. But all in all, I really like this!
on 6/25/2012 1:53:00 PM
Age: 18 & Under
Skin: Combination, Fair-Medium, Not Sure
Hair: Black, Straight, Other
Eyes: Brown
Okay, so a few days after I used this my lips started becoming dry to the point that they began cracking and bleeding. I didn't know that it was the EOS lip balm until I stopped using it, and my lips miraculously healed.
I thought that maybe it was a mistake. I tried using it again, and just like last time, my lips began cracking. I tried a third time, and I got the same results. I'm glad that this product worked out for a lot of people, but for me it was a total nightmare. I can still remember how much the corners of my mouth would sting every time I opened or closed my mouth. Ouch!
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I pray that out of his glorious riches he may strengthen you with power through his Spirit in your inner being, so that Christ may dwell in your hearts through faith. —Ephesians 3:16-17 read more
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{ Day 58 }
Therefore, I urge you, brothers, in view of God's mercy, to offer your bodies as living sacrifices, holy and pleasing to God—this is your spiritual act of worship. Do not conform any longer to the pattern of this world, but be transformed by the renewing of your mind. Then you will be able to test and approve what God's will is—his good, pleasing and perfect will. —Romans 12:1-2 read more
{ Day 59 }
Now therefore, be wise, O kings; be instructed, you judges of the earth. Serve the Lord with fear, and rejoice with trembling. —Psalm 2:10-11, NKJV read more
{ Day 60 }
Kiss the Son, lest He be angry, and you perish in the way, when His wrath is kindled but a little. Blessed are all those who put their trust in Him. —Psalm 2:12, NKJV read more
{ Day 61 }
When Jesus entered Jerusalem, the whole city was stirred and asked, "Who is this?" The crowds answered, "This is Jesus, the prophet from Nazareth in Galilee." —Matthew 21:10-11 read more
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I will proclaim the decree of the Lord: He said to me, "You are my Son; today I have become your Father. Ask of me, and I will make the nations your inheritance, the ends of the earth your possession. You will rule them with an iron scepter; you will dash them to pieces like pottery." —Psalm 2:7-9 read more
{ Day 63 }
For he has rescued us from the dominion of darkness and brought us into the kingdom of the Son he loves, in whom we have redemption, the forgiveness of sins. He is the image of the invisible God, the firstborn over all creation. —Colossians 1:13-15 read more
{ Day 64 }
Some people are like seed along the path, where the word is sown. As soon as they hear it, Satan comes and takes away the word that was sown in them. —Mark 4:15 read more
{ Day 65 }
Do not lie to each other, since you have taken off your old self with its practices and have put on the new self, which is being renewed in knowledge in the image of its Creator. —Colossians 3:9-10 read more
{ Day 66 }
The god of this age has blinded the minds of unbelievers, so that they cannot see the light of the gospel of the glory of Christ, who is the image of God. —2 Corinthians 4:4 read more
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