PMC:2871132 / 209678-222990 JSONTXT

{"project":"2_test","denotations":[{"id":"20480036-11219722-52068966","span":{"begin":316,"end":319},"obj":"11219722"},{"id":"20480036-9697036-52068967","span":{"begin":513,"end":516},"obj":"9697036"},{"id":"20480036-8360216-52068968","span":{"begin":1316,"end":1319},"obj":"8360216"},{"id":"20480036-3356720-52068968","span":{"begin":1316,"end":1319},"obj":"3356720"},{"id":"20480036-8360216-52068969","span":{"begin":2129,"end":2132},"obj":"8360216"},{"id":"20480036-8360216-52068970","span":{"begin":2888,"end":2891},"obj":"8360216"},{"id":"20480036-8718930-52068971","span":{"begin":3966,"end":3969},"obj":"8718930"},{"id":"20480036-14566814-52068972","span":{"begin":6288,"end":6291},"obj":"14566814"},{"id":"20480036-14566814-52068973","span":{"begin":7041,"end":7044},"obj":"14566814"},{"id":"20480036-14566782-52068974","span":{"begin":7414,"end":7417},"obj":"14566782"},{"id":"20480036-14566783-52068975","span":{"begin":7418,"end":7421},"obj":"14566783"},{"id":"20480036-14566782-52068976","span":{"begin":8024,"end":8027},"obj":"14566782"},{"id":"20480036-14566783-52068977","span":{"begin":8028,"end":8031},"obj":"14566783"},{"id":"20480036-16106439-52068978","span":{"begin":8169,"end":8172},"obj":"16106439"},{"id":"20480036-16106439-52068979","span":{"begin":8878,"end":8881},"obj":"16106439"},{"id":"20480036-15890399-52068980","span":{"begin":8947,"end":8950},"obj":"15890399"},{"id":"20480036-15890399-52068981","span":{"begin":10002,"end":10005},"obj":"15890399"},{"id":"20480036-16368134-52068982","span":{"begin":10023,"end":10026},"obj":"16368134"},{"id":"20480036-16368134-52068983","span":{"begin":11424,"end":11427},"obj":"16368134"},{"id":"20480036-15603820-52068984","span":{"begin":11614,"end":11617},"obj":"15603820"},{"id":"20480036-15603820-52068985","span":{"begin":12599,"end":12602},"obj":"15603820"},{"id":"20480036-15664635-52068986","span":{"begin":12618,"end":12621},"obj":"15664635"},{"id":"20480036-15664635-52068987","span":{"begin":13307,"end":13310},"obj":"15664635"},{"id":"T50345","span":{"begin":316,"end":319},"obj":"11219722"},{"id":"T74567","span":{"begin":513,"end":516},"obj":"9697036"},{"id":"T17396","span":{"begin":1316,"end":1319},"obj":"8360216"},{"id":"T85495","span":{"begin":1316,"end":1319},"obj":"3356720"},{"id":"T16348","span":{"begin":2129,"end":2132},"obj":"8360216"},{"id":"T69522","span":{"begin":2888,"end":2891},"obj":"8360216"},{"id":"T29096","span":{"begin":3966,"end":3969},"obj":"8718930"},{"id":"T45481","span":{"begin":6288,"end":6291},"obj":"14566814"},{"id":"T86343","span":{"begin":7041,"end":7044},"obj":"14566814"},{"id":"T87124","span":{"begin":7414,"end":7417},"obj":"14566782"},{"id":"T26528","span":{"begin":7418,"end":7421},"obj":"14566783"},{"id":"T57077","span":{"begin":8024,"end":8027},"obj":"14566782"},{"id":"T7093","span":{"begin":8028,"end":8031},"obj":"14566783"},{"id":"T24704","span":{"begin":8169,"end":8172},"obj":"16106439"},{"id":"T89068","span":{"begin":8878,"end":8881},"obj":"16106439"},{"id":"T97250","span":{"begin":8947,"end":8950},"obj":"15890399"},{"id":"T53216","span":{"begin":10002,"end":10005},"obj":"15890399"},{"id":"T11518","span":{"begin":10023,"end":10026},"obj":"16368134"},{"id":"T97966","span":{"begin":11424,"end":11427},"obj":"16368134"},{"id":"T68584","span":{"begin":11614,"end":11617},"obj":"15603820"},{"id":"T15428","span":{"begin":12599,"end":12602},"obj":"15603820"},{"id":"T44113","span":{"begin":12618,"end":12621},"obj":"15664635"},{"id":"T28839","span":{"begin":13307,"end":13310},"obj":"15664635"}],"text":"5.3. Coating\nSurface modifications have been applied to metallic biomaterials in order to improve their wear properties, corrosion resistance, and biocompatibility. Methods of applying calcium phosphate-based materials are being actively investigated with the aim of enhancing osteoinduction on titanium materials [373,374]. This work is necessary because a plasma sprayed calcium phosphate coating has disadvantages, such as the need for a critical thickness to ensure complete coverage of the implant surface [375]. Another approach to enhancing osteoinduction is to promote the formation of hydroxyapatite on titanium in the human body. Calcium ion implantation [376] and a CaTiO3 coating [377] for titanium materials have been examined, and the improvement of biocompatibility with bone was confirmed.\nThe development of a post-operative infection following the implantation, such as a Ti-6Al-4V alloy total joint prosthesis, is a severe complication in many orthopedic surgeries. Preventing these bacterial infections could theoretically be accomplished by administering therapeutic doses of antibiotics as close to the implant site as possible. Mixing antibiotics with PMMA (polymethylmetaacrylate) bone cements has been shown to provide adequate local antibiotic concentrations for extended periods of time [378–380]. Because metallic materials dominate orthopedic bioprosthetic devices, there exists a definite need for developing methods to attach antibiotics to metallic surfaces. Since the naturally forming passive surface oxide layer of Ti-6Al-4V is thought to be responsible for the excellent biocompatibility and corrosion resistance of this alloy, this oxide layer would be a natural choice for facilitating antibiotic attachment and retainment. By carefully controlling the surface chemistry of the oxide and utilizing the pH dependence of surface charge characteristics of the oxide, the attachment of charged antibiotics may be facilitated at suitable pH values. Such a concept has already been successfully tested with macroporous oxides (1–10 μm pores) formed in sulfuric acid solutions [381]. Dunn et al. [378] also studied the microporous (about 1.5 μm) anodized oxides formed on Ti-6Al-4V alloy to facilitate the attachment and sustained release of antibiotics for longer times. The degree of entamicin sulfate attachment and retainment to microporous oxide layers created on the surface of Ti-6Al-4V materials was determined to be a function of the oxide morphology and surface chemistry. Sulfuric (5–10%) anodized samples were observed to retain the electrostatically attached antibiotic for a period of 13 days when washed in saline at a pH of 7.4. It was found that a longer retention of gentamicin by potentiostatically anodized surfaces in phosphoric acid may be attributed to the lower isoelectric point and more negative zeta potential of these surfaces [378]. Similar studies were conducted by Kato et al. [382,383] to evaluate the applicability of the titanium material as a carrier or a substratum. Spongy titanium adsorbed bone morphogenetic protein (BMP) was implanted in muscle pouches in the thighs of mice. It was found that the quantity of new bone induced was somewhat less than that of the control.\nThe adsorption of bovine serum albumin (BSA) on titanium powder has been studied as a function of protein concentration and pH, and in the presence of calcium and phosphate ions. Isotherm data have shown that the adsorption process does not follow the Langmuir model (inflection points). For the pH dependence of adsorption, it was found that (i) the amount adsorbed increased with decreasing pH, indicating that hydration effects are important, and (ii) adsorption increases and decreases in the presence of calcium and phosphate ions, indicating that electrostatic effects are important. The time dependence, isotherm, and desorption data provide indirect evidence of possible conformational changes in the BSA molecule [384]. Hence, protein adsorption is a dynamic event with proteins adsorbing and desorbing as a function of time. McAlarney et al. [385] investigated the role of complement C3 in the competitive adsorption of proteins from diluted human plasma (the Vroman effect) onto TiO2 surfaces. Ti oxide surfaces were made: (1) four anatase surfaces (70 nm, 140 nm, 70 nm aged and solid anatase), (2) three rutile surfaces (70 nm, 140 nm, and solid rutile), and (3) one electropolished Ti. It was found that (i) in both rutile and anatase surfaces, there was an increase in adsorption with increasing oxide film thickness and/or crystallinity, and (ii) anatase surfaces had greater C3 concentration than the equivalent rutile surfaces [385].\nTitanium dental implants are widely used with success, but their rejection is not rare. One of the causes for implant failure may be due to biofilms created by interactions between the implant material and the surrounding tissues and fluids. The study described the selective adsorption of a specific salivary protein to Ti-oxide and the mechanism of adsorption. Klinger et al. [386] treated enamel powder, CpTi powder, as well as Ti powder by Ca, Mg, or K, which were suspended in vitro in human clarified whole saliva, or in various concentrations of purified salivary constituents, at pH 3.0 and 7.0. The powders were then suspended in EDTA solution in order to release proteins that may have adsorbed to their surfaces. It was found that (i) Ti powders adsorbed considerably less salivary proteins as compared with the enamel powder, (ii) human salivary albumin was identified by Western-immunoblot as the main protein that adsorbed to Ca-treated Ti powder, (iii) the Ca effect was not evident at pH 3.0 due to a neutral-basic shift of the protein at a pH level lower than its isoelectric point, and (iv) the in vivo investigation of salivary proteins adsorbing to Ti parts confirmed these results. Based on these findings, it was concluded that albumin was shown to be the main salivary protein adsorbing to Ti via a selective calcium and pH-dependent mechanism, and these findings are important for the understanding of Ti biocompatibility properties, as well as patterns of bacterial dental plaque accumulation on Ti implants, and the consequent implant success [386].\nHayakawa et al. [387] investigated to attach fibronectin directly to a titanium surface treated with tresyl chloride (2,2,2-trifluoroethanesulfonyl chloride) for the development of a strong connection of a dental implant to subepithelial connective tissues and/or peri-implant epithelia. Basic terminal OH groups of mirror polished titanium were allowed to react with tresyl chloride at 37 °C for 2 days. After the reaction of fibronectin with titanium, the X-ray photoelectron spectroscopy revealed the remarkable effect of the activation of terminal OH groups with the tresyl chloride treatment. It was mentioned that fibronectin, a well-known cell-adhesive protein, could easily be attached to the titanium surface by use of the tresyl chloride activation technique [387]. Studies in developmental and cell biology have established the fact that responses of cells are influenced to a large degree by morphology and composition of the extracellular matrix. In order to use this basic principle for improving the biological acceptance of implants by modifying the surfaces with components of the extracellular matrix (ECM), Bierbaum et al. [388,389] modified titanium surfaces with the collagen types I and III in combination with fibronectin. It was reported that (i) increasing the collagen type III amount resulted in a decrease of fibril diameter, while no significant changes in adsorption could be detected, (ii) the amount of fibronectin bound to the heterotypic fibrils depended on fibrillogenesis parameters, such as ionic strength or concentration of phosphate, and varied with the percentage of integrated type III collagen, and (iii) the initial adhesion mechanism of the cells depended on the substrate (titanium, collagen, fibronectin) [388,389].\nCollagen, as a major constituent of human connective tissues, has been regarded as one of the most important biomaterials. Kim et al. [390] investigated the fibrillar self-assembly of collagen by incubating acid-dissolved collagen in an ionic-buffered medium at 37 °C. It was reported that (i) the degree of assembly was varied with the incubation time and monitored by the turbidity change, (ii) the partially assembled collagen contained fibrils with varying diameters, as well as nonfibrillar aggregates, while the fully assembled collagen showed the complete formation of fibrils with uniform diameters of approximately 100–200 nm with periodic stain patterns within the fibrils, which are typical of native collagen fibers, and (iii) without the assembly, the collagen layer on Ti adversely affected the cell attachment and proliferation [390].\nA unique surface treatment on Ti was developed by Wang et al. [391]. Titanium screws and titanium flat sheets were implanted into the epithelial mantle pearl sacs of a fresh water bivalve by replacing the pearls. After 45 days of cultivation, the implant surfaces were deposited with a nacre coating with iridescent luster. The coating could conform, to some extent, to the thread topography of the screw implant, and was about 200–600 μm in thickness. It was found that (i) the coating was composed of a laminated nacreous layer and a transitional non-laminated layer that consisted mainly of vaterite and calcite polymorphs of calcium carbonate, and (ii) the transitional layer was around 2–10 μm thick in the convex and flat region of the implant surface, and could form close contact with titanium surface while the transitional layer was much thicker in the steep concave regions, and could not form close contact with the titanium surface. It was hence concluded that it was possible to fabricate a biologically active and degradable, and mechanically tough and strong nacre coating on titanium dental implants [391].\nFrosch et al. [392] evaluated the partial surface replacement of a knee with stem cell-coated titanium implants for a successful treatment of large osteochondral defects. Mesenchymal stem cells (MSCs) were isolated from bone marrow aspirates of adult sheep. Round titanium implants were seeded with autologous MSC and inserted into an osteochondral defect in the medial femoral condyle. As controls, defects received either an uncoated implant or were left untreated. Nine animals with 18 defects were sacrificed after six months. It was reported that (i) the quality of regenerated cartilage was assessed by in situ hybridization of collagen type II and immunohistochemistry of collagen types I and II, (ii) in 50% of the cases, defects treated with MSC-coated implants showed a complete regeneration of the subchondral bone layer, (iii) a total of 50% of MSC-coated and uncoated implants failed to osseointegrate, and formation of fibrocartilage was observed, (iv) untreated defects, as well as defects treated with uncoated implants, demonstrated incomplete healing of subchondral bone and formation of fibrous cartilage. It was, therefore, concluded that in a significant number of cases, a partial joint resurfacing of the knee with stem cell-coated titanium implants occurs, and a slow bone and cartilage regeneration and an incomplete healing in half of the MSC-coated implants are limitations of the method [392]. The osseointegration of four different kinds of bioactive ceramic-coated Ti screws were compared with uncoated Ti screws by biomechanical and histomorphometric analysis by Lee et al. [152]. Calcium pyrophosphate, 1:3 patite-wollastonite glass ceramic, 1:1 apatite-wollastonite glass ceramic, and bioactive CaO-SiO2-B2O3 glass ceramic coatings were prepared and coated by the dipping method. Coated and uncoated titanium screws were inserted into the tibia of 18 adult mongrel male dogs for 2, 4, and 8 weeks. It was reported that (i) at 2 and 4 weeks after implantation, the extraction torque of ceramic-coated screws was significantly higher than that of uncoated screws, (ii) at 8 weeks, the extraction torques of calcium pyrophosphate coated and both apatite-wollastonite glass ceramics-coated screws were significantly higher than those of CaO-SiO2-B2O3 glass-coated and uncoated screws, and (iii) the fixation strength was increased by the presence of osteoconductive coating materials, such as calcium pyrophosphate, and apatite-wollastonite glass ceramic, which enabled the achievement of higher fixation strength even as early as 2–8 weeks after the insertion [152].\nBigi et al. [393] performed a fast biomimetic deposition of hydroxyapatite (HA) coatings on Ti-6Al-4V substrates using a slightly supersaturated Ca/P solution, with an ionic composition simpler than that of simulated body fluid (SBF) to fabricate nanocrystalline HA. It was found that (i) soaking in supersaturated Ca/P solution results in the deposition of a uniform coating in a few hours, whereas SBF, or even 1.5 × SBF, requires 14 days to deposit a homogeneous coating on the same substrates, (ii) the coating consists of HA globular aggregates, which exhibit a finer lamellar structure than those deposited from SBF, and (iii) the extent of deposition increases on increasing the immersion time [393]."}

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Coating\nSurface modifications have been applied to metallic biomaterials in order to improve their wear properties, corrosion resistance, and biocompatibility. Methods of applying calcium phosphate-based materials are being actively investigated with the aim of enhancing osteoinduction on titanium materials [373,374]. This work is necessary because a plasma sprayed calcium phosphate coating has disadvantages, such as the need for a critical thickness to ensure complete coverage of the implant surface [375]. Another approach to enhancing osteoinduction is to promote the formation of hydroxyapatite on titanium in the human body. Calcium ion implantation [376] and a CaTiO3 coating [377] for titanium materials have been examined, and the improvement of biocompatibility with bone was confirmed.\nThe development of a post-operative infection following the implantation, such as a Ti-6Al-4V alloy total joint prosthesis, is a severe complication in many orthopedic surgeries. Preventing these bacterial infections could theoretically be accomplished by administering therapeutic doses of antibiotics as close to the implant site as possible. Mixing antibiotics with PMMA (polymethylmetaacrylate) bone cements has been shown to provide adequate local antibiotic concentrations for extended periods of time [378–380]. Because metallic materials dominate orthopedic bioprosthetic devices, there exists a definite need for developing methods to attach antibiotics to metallic surfaces. Since the naturally forming passive surface oxide layer of Ti-6Al-4V is thought to be responsible for the excellent biocompatibility and corrosion resistance of this alloy, this oxide layer would be a natural choice for facilitating antibiotic attachment and retainment. By carefully controlling the surface chemistry of the oxide and utilizing the pH dependence of surface charge characteristics of the oxide, the attachment of charged antibiotics may be facilitated at suitable pH values. Such a concept has already been successfully tested with macroporous oxides (1–10 μm pores) formed in sulfuric acid solutions [381]. Dunn et al. [378] also studied the microporous (about 1.5 μm) anodized oxides formed on Ti-6Al-4V alloy to facilitate the attachment and sustained release of antibiotics for longer times. The degree of entamicin sulfate attachment and retainment to microporous oxide layers created on the surface of Ti-6Al-4V materials was determined to be a function of the oxide morphology and surface chemistry. Sulfuric (5–10%) anodized samples were observed to retain the electrostatically attached antibiotic for a period of 13 days when washed in saline at a pH of 7.4. It was found that a longer retention of gentamicin by potentiostatically anodized surfaces in phosphoric acid may be attributed to the lower isoelectric point and more negative zeta potential of these surfaces [378]. Similar studies were conducted by Kato et al. [382,383] to evaluate the applicability of the titanium material as a carrier or a substratum. Spongy titanium adsorbed bone morphogenetic protein (BMP) was implanted in muscle pouches in the thighs of mice. It was found that the quantity of new bone induced was somewhat less than that of the control.\nThe adsorption of bovine serum albumin (BSA) on titanium powder has been studied as a function of protein concentration and pH, and in the presence of calcium and phosphate ions. Isotherm data have shown that the adsorption process does not follow the Langmuir model (inflection points). For the pH dependence of adsorption, it was found that (i) the amount adsorbed increased with decreasing pH, indicating that hydration effects are important, and (ii) adsorption increases and decreases in the presence of calcium and phosphate ions, indicating that electrostatic effects are important. The time dependence, isotherm, and desorption data provide indirect evidence of possible conformational changes in the BSA molecule [384]. Hence, protein adsorption is a dynamic event with proteins adsorbing and desorbing as a function of time. McAlarney et al. [385] investigated the role of complement C3 in the competitive adsorption of proteins from diluted human plasma (the Vroman effect) onto TiO2 surfaces. Ti oxide surfaces were made: (1) four anatase surfaces (70 nm, 140 nm, 70 nm aged and solid anatase), (2) three rutile surfaces (70 nm, 140 nm, and solid rutile), and (3) one electropolished Ti. It was found that (i) in both rutile and anatase surfaces, there was an increase in adsorption with increasing oxide film thickness and/or crystallinity, and (ii) anatase surfaces had greater C3 concentration than the equivalent rutile surfaces [385].\nTitanium dental implants are widely used with success, but their rejection is not rare. One of the causes for implant failure may be due to biofilms created by interactions between the implant material and the surrounding tissues and fluids. The study described the selective adsorption of a specific salivary protein to Ti-oxide and the mechanism of adsorption. Klinger et al. [386] treated enamel powder, CpTi powder, as well as Ti powder by Ca, Mg, or K, which were suspended in vitro in human clarified whole saliva, or in various concentrations of purified salivary constituents, at pH 3.0 and 7.0. The powders were then suspended in EDTA solution in order to release proteins that may have adsorbed to their surfaces. It was found that (i) Ti powders adsorbed considerably less salivary proteins as compared with the enamel powder, (ii) human salivary albumin was identified by Western-immunoblot as the main protein that adsorbed to Ca-treated Ti powder, (iii) the Ca effect was not evident at pH 3.0 due to a neutral-basic shift of the protein at a pH level lower than its isoelectric point, and (iv) the in vivo investigation of salivary proteins adsorbing to Ti parts confirmed these results. Based on these findings, it was concluded that albumin was shown to be the main salivary protein adsorbing to Ti via a selective calcium and pH-dependent mechanism, and these findings are important for the understanding of Ti biocompatibility properties, as well as patterns of bacterial dental plaque accumulation on Ti implants, and the consequent implant success [386].\nHayakawa et al. [387] investigated to attach fibronectin directly to a titanium surface treated with tresyl chloride (2,2,2-trifluoroethanesulfonyl chloride) for the development of a strong connection of a dental implant to subepithelial connective tissues and/or peri-implant epithelia. Basic terminal OH groups of mirror polished titanium were allowed to react with tresyl chloride at 37 °C for 2 days. After the reaction of fibronectin with titanium, the X-ray photoelectron spectroscopy revealed the remarkable effect of the activation of terminal OH groups with the tresyl chloride treatment. It was mentioned that fibronectin, a well-known cell-adhesive protein, could easily be attached to the titanium surface by use of the tresyl chloride activation technique [387]. Studies in developmental and cell biology have established the fact that responses of cells are influenced to a large degree by morphology and composition of the extracellular matrix. In order to use this basic principle for improving the biological acceptance of implants by modifying the surfaces with components of the extracellular matrix (ECM), Bierbaum et al. [388,389] modified titanium surfaces with the collagen types I and III in combination with fibronectin. It was reported that (i) increasing the collagen type III amount resulted in a decrease of fibril diameter, while no significant changes in adsorption could be detected, (ii) the amount of fibronectin bound to the heterotypic fibrils depended on fibrillogenesis parameters, such as ionic strength or concentration of phosphate, and varied with the percentage of integrated type III collagen, and (iii) the initial adhesion mechanism of the cells depended on the substrate (titanium, collagen, fibronectin) [388,389].\nCollagen, as a major constituent of human connective tissues, has been regarded as one of the most important biomaterials. Kim et al. [390] investigated the fibrillar self-assembly of collagen by incubating acid-dissolved collagen in an ionic-buffered medium at 37 °C. It was reported that (i) the degree of assembly was varied with the incubation time and monitored by the turbidity change, (ii) the partially assembled collagen contained fibrils with varying diameters, as well as nonfibrillar aggregates, while the fully assembled collagen showed the complete formation of fibrils with uniform diameters of approximately 100–200 nm with periodic stain patterns within the fibrils, which are typical of native collagen fibers, and (iii) without the assembly, the collagen layer on Ti adversely affected the cell attachment and proliferation [390].\nA unique surface treatment on Ti was developed by Wang et al. [391]. Titanium screws and titanium flat sheets were implanted into the epithelial mantle pearl sacs of a fresh water bivalve by replacing the pearls. After 45 days of cultivation, the implant surfaces were deposited with a nacre coating with iridescent luster. The coating could conform, to some extent, to the thread topography of the screw implant, and was about 200–600 μm in thickness. It was found that (i) the coating was composed of a laminated nacreous layer and a transitional non-laminated layer that consisted mainly of vaterite and calcite polymorphs of calcium carbonate, and (ii) the transitional layer was around 2–10 μm thick in the convex and flat region of the implant surface, and could form close contact with titanium surface while the transitional layer was much thicker in the steep concave regions, and could not form close contact with the titanium surface. It was hence concluded that it was possible to fabricate a biologically active and degradable, and mechanically tough and strong nacre coating on titanium dental implants [391].\nFrosch et al. [392] evaluated the partial surface replacement of a knee with stem cell-coated titanium implants for a successful treatment of large osteochondral defects. Mesenchymal stem cells (MSCs) were isolated from bone marrow aspirates of adult sheep. Round titanium implants were seeded with autologous MSC and inserted into an osteochondral defect in the medial femoral condyle. As controls, defects received either an uncoated implant or were left untreated. Nine animals with 18 defects were sacrificed after six months. It was reported that (i) the quality of regenerated cartilage was assessed by in situ hybridization of collagen type II and immunohistochemistry of collagen types I and II, (ii) in 50% of the cases, defects treated with MSC-coated implants showed a complete regeneration of the subchondral bone layer, (iii) a total of 50% of MSC-coated and uncoated implants failed to osseointegrate, and formation of fibrocartilage was observed, (iv) untreated defects, as well as defects treated with uncoated implants, demonstrated incomplete healing of subchondral bone and formation of fibrous cartilage. It was, therefore, concluded that in a significant number of cases, a partial joint resurfacing of the knee with stem cell-coated titanium implants occurs, and a slow bone and cartilage regeneration and an incomplete healing in half of the MSC-coated implants are limitations of the method [392]. The osseointegration of four different kinds of bioactive ceramic-coated Ti screws were compared with uncoated Ti screws by biomechanical and histomorphometric analysis by Lee et al. [152]. Calcium pyrophosphate, 1:3 patite-wollastonite glass ceramic, 1:1 apatite-wollastonite glass ceramic, and bioactive CaO-SiO2-B2O3 glass ceramic coatings were prepared and coated by the dipping method. Coated and uncoated titanium screws were inserted into the tibia of 18 adult mongrel male dogs for 2, 4, and 8 weeks. It was reported that (i) at 2 and 4 weeks after implantation, the extraction torque of ceramic-coated screws was significantly higher than that of uncoated screws, (ii) at 8 weeks, the extraction torques of calcium pyrophosphate coated and both apatite-wollastonite glass ceramics-coated screws were significantly higher than those of CaO-SiO2-B2O3 glass-coated and uncoated screws, and (iii) the fixation strength was increased by the presence of osteoconductive coating materials, such as calcium pyrophosphate, and apatite-wollastonite glass ceramic, which enabled the achievement of higher fixation strength even as early as 2–8 weeks after the insertion [152].\nBigi et al. [393] performed a fast biomimetic deposition of hydroxyapatite (HA) coatings on Ti-6Al-4V substrates using a slightly supersaturated Ca/P solution, with an ionic composition simpler than that of simulated body fluid (SBF) to fabricate nanocrystalline HA. It was found that (i) soaking in supersaturated Ca/P solution results in the deposition of a uniform coating in a few hours, whereas SBF, or even 1.5 × SBF, requires 14 days to deposit a homogeneous coating on the same substrates, (ii) the coating consists of HA globular aggregates, which exhibit a finer lamellar structure than those deposited from SBF, and (iii) the extent of deposition increases on increasing the immersion time [393]."}