Improved bone anchorage of hydroxypatite coated implants compared with tricalcium-phosphate coated implants in trabecular bone in dogs

Tricalcium phosphate (TCP) and hydroxyapatite (HA) ceramic coatings are bioactive coatings that have been shown to stimulate bone apposition onto ceramic-coated implants. TCP and HA ceramics have well-documented differences in physical properties, but both types of ceramics are used for stimulation of bone ongrowth to cementless endo-prosthetic components clinically. However, little is known about the difference in osteoconductive properties between these coatings when inserted into trabecular bone in a controlled experimental situation. Unloaded cylindrical gritblasted titanium (Ti-6A1-4V) implants (6 x 10 mm) coated with either hydroxyapatite (HA) or tricalcium phosphate (TCP) ceramic were inserted into the proximal humerus of 20 skeletally mature dogs. The implants were initially surrounded by a 2 mm gap. Each animal received one HA-coated implant and one TCP-coated implant. All dogs were sacrificed 6 weeks after surgery. Results were evaluated by histomorphometry and mechanical push-out test. Push-out tests demonstrated that HA-coated implants were 10-fold stronger fixated in comparison to TCP-coated implant. Bone ongrowth was significantly higher for HA-coated implants compared to TCP-coated implants. Bone volume in the gap showed a tendency to less bone volume around HA-coated implants compared to TCP-coated implants but this difference was insignificant. As expected almost all of the TCP coating were resorbed after 6 weeks and almost none of the HA coating. HA-coated implants with a grit-blasted surface provide a favorable early mechanical implant anchorage most likely due to superior ceramic stability compared to TCP-coated implants.     

Cytological Evaluation of the Tissue-Implant Reaction Associated with S/C and I/P Implantation of ALCAP and HA Bioceramics in vivo

It is well documented that several ceramic materials are highly compatible and non-immunogenic with host tissues. Recent studies have demonstrated the need for further investigation of these devices in vivo to further elucidate the possible mechanisms involved in biocompatibility. The purpose of this investigation was to study the morphological characteristics of the fibrous tissue capsule resulting from the implantation of aluminum calcium phosphate (ALCAP) and hydroxyapetite (HA) bioceramics. Implants of ALCAP and HA were implanted into 10 adult male rats subcutaneously (S/C) and intraperitoneally (I/P). At 90 days post-implantation, the animals were euthanized, and the ceramic devices, the fibrous tissue, and vital organs were harvested. Evaluation of routine stained sections (5 m, hematoxylin & eosin) of the fibrous tissue capsule surrounding the HA and ALCAP ceramics revealed the following: 1) all the ceramic devices had fibrous connective tissue capsules of slightly varying degrees of thickness at the time of sacrifice, depending on the site of implantation and type of material, and 2) there were statistically significant differences (p < 0.05) in the numbers and types of cellular components with respect to implantation site. The number of macrophages, neutrophils, fibroblasts, degree of vascularity, and thickness of the fibrous tissue matrix was found to be statistically different between the S/C implanted ceramic groups. The number of macrophages, neutrophils, fibroblasts, and collagen content comparing the fibrous tissue surrounding the ALCAP and HA ceramics (I/P), was found to be statistically different.     

Cytological evaluation of the tissue-implant reaction associated with S/C and I/P implantation of ALCAP and HA bioceramics in vivo

It is well documented that several ceramic materials are highly compatible and non-immunogenic with host tissues. Recent studies have demonstrated the need for further investigation of these devices in vivo to further elucidate the possible mechanisms involved in biocompatibility. The purpose of this investigation was to study the morphological characteristics of the fibrous tissue capsule resulting from the implantation of aluminum calcium phosphate (ALCAP) and hydroxyapetite (HA) bioceramics. Implants of ALCAP and HA were implanted into 10 adult male rats subcutaneously (S/C) and intraperitoneally (I/P). At 90 days post-implantation, the animals were euthanized, and the ceramic devices, the fibrous tissue, and vital organs were harvested. Evaluation of routine stained sections (5 microm, hematoxylin & eosin) of the fibrous tissue capsule surrounding the HA and ALCAP ceramics revealed the following: 1) all the ceramic devices had fibrous connective tissue capsules of slightly varying degrees of thickness at the time of sacrifice, depending on the site of implantation and type of material, and 2) there were statistically significant differences (p < 0.05) in the numbers and types of cellular components with respect to implantation site. The number of macrophages, neutrophils, fibroblasts, degree of vascularity, and thickness of the fibrous tissue matrix was found to be statistically different between the S/C implanted ceramic groups. The number of macrophages, neutrophils, fibroblasts, and collagen content comparing the fibrous tissue surrounding the ALCAP and HA ceramics (I/P), was found to be statisically different.     

不同口腔种植材料的应用及安全性评价

背景：目前临床应用的牙种植体材料种类繁多,各有其优缺点,哪种材料更具临床应用价值及良好的生物相容性呢？ 目的：综述不同口腔种植材料的研究进展,评价其种植后与宿主的相容性及临床应用前景。 方法：应用计算机检索CNKI和PubMed数据库中2000-01/2011-03关于口腔种植材料应用的文章,在标题和摘要中以“口腔种植体;牙种植体;合金;陶瓷;高分子材料;复合材料”或“dental implant;polymer alloy composite material;ceramic/aluminum alloy”为检索词进行检索。选择内容与不同口腔种植材料的应用特点及安全性相关文章。初检得到126篇文献,根据纳入标准选择30篇文章进行综述。 结果与结论：合金、陶瓷、高分子、复合材料及纳米材料在口腔种植方面发挥了重要作用。理想口腔植入材料的选择,需要对其生物相容性、生物力学性能、生物学形态、与周围组织的结合能力等各方面综合考虑,对细胞、组织等应无毒性、无刺激性、无致畸致突变性,同时与骨组织之间应形成骨性结合,具有良好的骨引导或骨诱导作用。     

Histological and histomorphometric investigations on bone integration of rapidly resorbable calcium phosphate ceramics

Resorbable ceramics can promote the bony integration of implants. Their rate of degradation should ideally be synchronized with bone regeneration. We report here the results of a histological study of implants with two resorbable calcium phosphate ceramic coatings: Ca(2)KNa(PO(4))(2)-(GB14) and Ca(10)[K/Na](PO(4))(7)-(602020). The results attained with these ceramic-coated implants show the benefits of these materials with regard to bioactive bone-healing stimulation, compared with uncoated implants. The GB14 ceramic coating exhibited greater bone regeneration and differentiation on its surface than the conventional hydroxyapatite coating and helped bone tissue achieve more extensive contact free of connective tissue. Not until the coating disintegrated did the histological features of GB14- and 602020-coated implants converge-both implant types were integrated into bone. Rapid disintegration of the coating material, as with 602020, supports osteoblast proliferation but has negative effects on bone mineralization. Both resorbable ceramics tested, GB14 and 602020, demonstrated bioactivity; even metal surfaces coated with these materials were populated by mature bone tissue without connective tissue after disintegration of their ceramic coating. The less rapidly degrading material, GB14, achieved better results. Degradable calcium phosphate coatings have the potential to stimulate bone regeneration. From the histological viewpoint, the resorbable ceramics examined here can be recommended as coating materials for clinical use.     

Enhancement of bone regeneration using resorbable ceramics and a polymer-ceramic composite material

The aim of this experimental study was to evaluate the use of resorbable implants for the repair of nonloaded skeletal defects. Porous ceramic implants of alpha-TCP, of glass-ceramic, and of solid composite implants of glass-ceramic/polylactic acid 8 mm in diameter and 2 mm in thickness were fabricated and implanted pressfit into biparietal, full-thickness defects of the calvaria of 60 adult rats. Twenty rats received unfilled defects and served as controls. Fluorochrome labeling of bone formation was performed during the observation period. Five animals from each group were evaluated after 6, 13, 26, and 52 weeks. The control defects showed incomplete regeneration, with bone formation extending 1.66 mm, on average, into the defect after 52 weeks. In the group of alpha-TCP implants, histologic evaluation indicated that the bone formed during initial stages had undergone resorption later on, so that bone repair after 52 weeks was not significantly enhanced, with an average depth of 1.83 mm of bone ingrowth. The glass-ceramic implants exhibited extensive bone formation and nearly complete repair of the calvarial defect, with 3.90 mm of bone ingrowth into the implant pores. Degradation of the ceramic was nearly complete, with a few remaining particles surrounded by soft tissue. The composite implants showed a negligible bone ingrowth of 0.63 mm, on average. Soft tissue had invaded the polylactic acid implant body, but no bone formation had taken place at the surface of the embedded ceramic particles. Degradation of the polymer was not complete after 52 weeks. It is concluded that the balance between degradation and bone formation is delicate and that chemical events and cellular reaction during degradation may counteract complementary bone ingrowth.     

Long-term implantation of zinc-releasing calcium phosphate ceramics in rabbit femora

Zinc is an essential trace element that has stimulatory effects on bone formation. Recently, we developed zinc-releasing calcium phosphate ceramics in order to add the pharmacologic effect of zinc to calcium phosphate ceramics. In our previous study, we showed that the optimum zinc content for promoting bone formation was 0.316 wt %. Therefore a zinc composite ceramic of zinc-containing beta-tricalcium phosphate and hydroxyapatite, with a zinc content of 0.316 wt %, was chosen for long-term implantation. Cylindrical rods of the zinc composite ceramic were implanted in rabbit femora for 2 to 60 weeks. Using computer-aided image analysis, a histomorphometric study was carried out to investigate bone formation and resorption around the implants. The control was a composite ceramic of beta-tricalcium phosphate and hydroxyapatite without zinc. The addition of zinc to the implant demonstrated both favorable and unfavorable effects on bone remodeling. The favorable effect was enhanced bone apposition to the implant surface, demonstrated by a significant increase in intramedullary bone apposition rate at 6 weeks and in cortical bone apposition rate at 24 and 60 weeks (p < 0.05). The unfavorable effect was increased bone resorption, demonstrated by a significant increase in medullary cavity area at 60 weeks (p < 0.05). In order to utilize the favorable effect and avoid the unfavorable effect of zinc, either a reduction in zinc content in the zinc composite ceramic or the selection of implantation sites that do not have excessive exposure to bone marrow are required.     

Histological findings in titanium implants coated with calcium phosphate ceramics installed in rabbit''s tibias

Oral reconstruction using osteointegrated implants are widely indicated nowadays. The implant bone anchorage is very important for its functional stability. Thus, ceramic biomaterials are widely used as coatings of the implant surfaces to accelerate local osteogenesis. The purpose of this study is to assess the biocompatibility and the osteoconduction of two types of calcium phosphate ceramics used as titanium dental implant coatings. These implants were installed in rabbit tibia during an 8-week healing period. The light and fluorescent microscopy observations showed that the materials are biocompatible and that they have osteoconductive activities.     

Ectopic bone formation in rats: the importance of the carrier

Much research has been done to develop the ideal bone graft substitute (BGS). One approach to develop this ideal BGS is the use of growth factors, but for this approach osteoprogenitor cells are needed at the site of reconstruction. An alternative is a cell-based approach, where enough cells are provided to form bone in a carrier material. In previous studies of our group, titanium (Ti) carriers have been used, because of the excellent mechanical properties and the bone-compatibility of this material. On the other hand, calcium phosphate (CaP) ceramics are known for their excellent osteoconductivity. The aim of this study is to investigate the influence of the carrier in a cell-based bone regeneration approach, whereby we hypothesize that CaP-ceramic implants will induce more bone formation than Ti-fiber implants, in the same animal model as our previous experiment. Ti-fiber mesh implants and ceramic implants were seeded with rat bone marrow cells (RBM) and implanted subcutaneously. Histological analysis after one, three and six weeks showed differences in the way of bone formation in the two groups: bone appeared to grow from the center to the periphery of the implant in the titanium group, while bone formation in the ceramic group occurred through the whole implant. Histomorphometrical analysis after one week showed very limited bone formation for both the titanium and ceramic group. At three weeks, the amount of bone formation was increased till about 10% for the titanium group and 18% for the ceramic group. No significant difference between the two groups could be observed. In the six week group, the bone formation was 6% (Ti) and 23% (CaP), respectively (P < 0.001). Further, bone formation started earlier in the CaP-ceramic scaffolds than in the Ti scaffolds. Our hypothesis could be confirmed: ceramic implants induce more bone formation than titanium implants.     

Histological analysis of bone/heteroplastic implant interfaces in dog tibia.

This work presents histological analysis of interfaces between bone and heteroplastic implants in dog tibias. The study was performed in four tibias (of four mongrel dogs) into which cylindrical implants were inserted. One ceramic (titania) implant and three grit-blasted titanium implants (with sandblasted and acid-corroded surfaces) were chosen for histological analysis of the implant surface/bone tissue interface. The implants remained in the tibias for eight months and none were loaded during this period. The animals were subsequently sacrificed and the samples were processed for analysis. Light microscope analysis revealed a large amount of osteoid tissue and proximity of osteoblasts and osteocytes to the implant surfaces. In addition, little or no fibrous tissue was observed between the bone and implant surfaces. The titanium implants presented better osseointegration than did the ceramic implant.     

Elongation of brachymetatarsy with ceramic implant: a roentgenographic evaluation of its utility

The metatarsal bone was elongated by intercalary implantation of a single-crystal alumina ceramic in 7 patients with brachymetatarsy. The implants were encased with new bone 24 months after surgery and resulted in 5.2 to 9.2 mm elongation of the metatarsal bone. The response of the bone to the ceramic implant was observed roentgenographically. No resorption or pseudoarthrosis of the bones, nor loosening or breakage of the implants, were observed. The alumina ceramic implant proved to be a useful substitute for a bone graft, because of its biocompatibility and strength.     

多孔羟基磷灰石陶瓷诱导成骨的作用

多孔羟基磷灰石陶瓷种植体埋植于狗背部肌肉内,分别于植入后1、2、4和8月处死动物,取出种植体,将其固定,脱钙,切片、HE染色,在光镜下作组织形态学观察发现:一月的种植体孔隙内充满了血管丰富的结缔组织;二、四和八月的种植体孔隙内有较多量的新骨组织形成,种植体固有完整的纤维结缔组织包膜。本研究从组织形态学说明了多孔羟基磷灰石陶瓷具有诱导骨形成的能力。     

Material-dependent bone induction by calcium phosphate ceramics: a 2.5-year study in dog

Bone induction by different calcium phosphate biomaterials has been reported previously. With regard to (1) whether the induced bone would disappear with time due to the absence of mechanical stresses and (2) whether this heterotopically formed bone would give rise to uncontrolled growth, a long-time investigation of porous hydroxyapatite ceramic (HA), porous biphasic calcium phosphate ceramic (TCP/HA, BCP), porous alpha-tricalcium phosphate ceramic (alpha-TCP) and porous beta-tricalcium phosphate ceramic (beta-TCP) was performed in dorsal muscles of dog, for 2.5 years. Histological observation, backscattered scanning electron microscopy observation and histomorphometric analysis were made on thin un-decalcified sections of retrieved samples. Normal compact bone with bone marrow was found in all HA implants (n = 4) and in all BCP implants (n = 4), 48 +/- 4% pore area was filled with bone in HA implants and 41 +/- 2% in BCP implants. Bone-like tissue, which was a mineralised bone matrix with osteocytes but lacked osteoblasts and bone marrow, was found in all beta-TCP implants (n = 4) and in one of the four alpha-TCP implants. Both normal bone and bone-like tissues were confined inside the pores of the implants. The results show that calcium phosphate ceramics are osteoinductive in muscles of dogs. Although the quality and quantity varied among different ceramics, the induced bone in both HA and BCP ceramics did neither disappear nor grow uncontrollably during the period as long as 2.5 years.     

Electrically Active Bioceramics: A Review of Interfacial Responses

Electrical potentials in mechanically loaded bone have been implicated as signals in the bone remodeling cycle. Recently, interest has grown in exploiting this phenomenon to develop electrically active ceramics for implantation in hard tissue which may induce improved biological responses. Both polarized hydroxyapatite (HA), whose surface charge is not dependent on loading, and piezoelectric ceramics, which produce electrical potentials under stress, have been studied in order to determine the possible benefits of using electrically active bioceramics as implant materials. The polarization of HA has a positive influence on interfacial responses to the ceramic. In vivo studies of polarized HA have shown polarized samples to induce improvements in bone ingrowth. The majority of piezoelectric ceramics proposed for implant use contain barium titanate (BaTiO₃). In vivo and in vitro investigations have indicated that such ceramics are biocompatible and, under appropriate mechanical loading, induce improved bone formation around implants. The mechanism by which electrical activity influences biological responses is yet to be clearly defined, but is likely to result from preferential adsorption of proteins and ions onto the polarized surface. Further investigation is warranted into the use of electrically active ceramics as the indications are that they have benefits over existing implant materials.     

Personalized implant for high tibial opening wedge: combination of solid freeform fabrication with combustion synthesis process

In this work a new generation of bioceramic personalized implants were developed. This technique combines the processes of solid freeform fabrication (SFF) and combustion synthesis (CS) to create personalized bioceramic implants with tricalcium phosphate (TCP) and hydroxyapatite (HA). These porous bioceramics will be used to fill the tibial bone gap created by the opening wedge high tibial osteotomy (OWHTO). A freeform fabrication with three-dimensional printing (3DP) technique was used to fabricate a metallic mold with the same shape required to fill the gap in the opening wedge osteotomy. The mold was subsequently used in a CS process to fabricate the personalized ceramic implants with TCP and HA compositions. The mold geometry was designed on commercial 3D CAD software. The final personalized bioceramic implant was produced using a CS process. This technique was chosen because it exploits the exothermic reaction between P?O? and CaO. Also, chemical composition and distribution of pores in the implant could be controlled. To determine the chemical composition, the microstructure, and the mechanical properties of the implant, cylindrical shapes were also fabricated using different fabrication parameters. Chemical composition was performed by X-ray diffraction. Pore size and pore interconnectivity was measured and analyzed using an electronic microscope system. Mechanical properties were determined by a mechanical testing system. The porous TCP and HA obtained have an open porous structure with an average 400?μm channel size. The mechanical behavior shows great stiffness and higher load to failure for both ceramics. Finally, this personalized ceramic implant facilitated the regeneration of new bone in the gap created by OWHTO and provides additional strength to allow accelerated rehabilitation.     

Priming the Surface of Orthopedic Implants for Osteoblast Attachment in Bone Tissue Engineering

The development of better orthopedic implants is incessant. While current implants can function reliably in the human body for a long period of time, there are still a significant number of cases for which the implants can fail prematurely due to poor osseointegration of the implant with native bone. Increasingly, it is recognized that it is extremely important to facilitate the attachment of osteoblasts on the implant so that a proper foundation of extracellular matrix (ECM) can be laid down for the growth of new bone tissue. In order to facilitate the osseointegration of the implant, both the physical nanotopography and chemical functionalization of the implant surface have to be optimized. In this short review, however, we explore how simple chemistry procedures can be used to functionalize the surfaces of three major classes of orthopedic implants, i.e. ceramics, metals, and polymers, so that the attachment of osteoblasts on implants can be facilitated in order to promote implant osseointegration.     

Reduced responses of macrophages on nanometer surface features of altered alumina crystalline phases

Extensive prolonged interactions of inflammatory cells (such as macrophages) at the host–implant interface may lead to implant failure. While previous studies have shown increased in vitro and in vivo bone cell adhesion, proliferation and mineralization on nanophase compared to currently implanted ceramics, few studies have been conducted to elucidate inflammatory cell responses on such nanophase ceramics. Controlling surface feature size and corresponding surface roughness on implants may clearly alter immune cell responses, which would be an extremely important consideration for the use of nanostructured materials as improved biomaterials. In this study, reduced macrophage density was observed on alumina (Al₂O₃) compacts with greater nanometer surface roughness accompanied by changes in crystallinity for up to 24 h in culture. Since alumina is a commonly used ceramic in orthopedic applications, this in vitro study continues to support the use of nanophase ceramics as improved orthopedic implants by demonstrating reduced macrophage responses.     

Alkali- and heat-treated porous titanium for orthopedic implants

This study was carried out to investigate the effects of the alkali and heat treatments on the bone-bonding behavior of porous titanium implants. Porous titanium implants had a 4.6 mm solid core and a 0.7 mm thick porous outer layer using pure titanium plasma-spray technique. Three types of porous implants were prepared from these pieces: 1.control implant (CL implant) as manufactured 2.AW-glass ceramic bottom-coated implant (AW implant) in which AW-glass ceramic was coated on only the bottom of the pore of the implant 3.alkali- and heat-treated implant (AH implant), where implants were immersed in 5 mol/L NaOH solution at 60 degrees C for 24 h and subsequently heated at 600 degrees C for 1 h. The implants were inserted into bilateral femora of six dogs hemi-transcortically in a randomized manner. At 4 weeks, push-out tests revealed that the mean shear strengths of the CL, AW, and AH implants were about 10.8, 12.7, and 15.0 MPa, respectively. At 12 weeks there was no significant difference between the bonding strengths of the three types of the porous implants (16.0-16.7 MPa). Histologically and histomorphologically, direct bone contact with the implant surface was significantly higher in the AH implants than the CL and AW implants both at 4 and 12 weeks. Thus, the higher bonding strength between bone and alkali- and heat-treated titanium implants was attributed to the direct bonding between bone and titanium surface. In conclusion, alkali and heat treatments can provide porous titanium implants with earlier stable fixation.     

Analysis of primary bone formation in porous alumina: a fluorescence and scanning electron microscopic study of marrow cell induced osteogenesis.

Porous alumina ceramics alone and combined with rat marrow cells were implanted subcutaneously in the back of syngeneic Fischer rats. Fluorochrome-labeling was performed post operatively and the ceramics were harvested 6 and 8 weeks after implantation. Undecalcified sections of the implants were observed under fluorescence microscopy and the de novo bone-ceramic interfacial areas were analyzed by a scanning electron microscope equipped with an electron probe microanalyzer. Alumina ceramics alone did not show any bone formation, while all marrow cell loaded ceramics showed new bone formation 6 and 8 weeks after implantation. Bone formation was first observed in the center of the pores and proceeded in a centrifugal direction, leading to contact with the ceramic. These results suggest that bone marrow cells have inherent osteogenic capacity and in the pore region of alumina ceramics progression of the osteogenesis causes the dissipation of intervening fibrous tissue between the de novo bone and alumina ceramic surface.     

Bioactivation of inert alumina ceramics by hydroxylation

Alumina ceramics (Al(2)O(3)) are frequently used for medical implants and prostheses because of the excellent biocompatibility, and the high mechanical reliability of the material. Inauspiciously alumina is not suitable for implant components with bone contact, because the material is bioinert and thereby no bony ongrowth, and subsequently loosening of the implant occurs. Here, we present a new method to bioactivate the surface of the material. Specimens made of high purity alumina were treated in sodium hydroxide. Cell culture tests with osteoblast-like cells as well as spectroscopical and mechanical tests were performed. Aluminium hydroxide groups were detected on the surface of the treated specimens. Enhanced cell adhesion, proliferation and secretion of osteocalcin were determined after hydroxylation. The bioactivating treatment had no deteriorating effect on the short- and long-term strength behaviour. Our results indicate that the described surface technique could be used to develop a new class of osseointegrative high-strength ceramic implants.