Preparation and property of a novel bone graft composite consisting of rhBMP-2 loaded PLGA microspheres and calcium phosphate cement

Calcium phosphate cement (CPC) is a highly promising bone substitute and an excellent carrier for delivering growth factors. Yet, the lack of macro-porosity and osteoinductive ability, limit its use. This study is aimed at developing a novel biodegradable biomaterial for bone repair with both highly osteoconductive and osteoinductive properties. RhBMP-2 loaded PLGA microspheres were incorporated into rhBMP-2/CPC for macropores for bone ingrowth. The compressive strength, crystallinity, microscopic structure, and bioactivity of the composites were investigated. The results showed that with the incorporation of rhBMP-2 loaded PLGA microspheres, the compressive strength was decreased from (29.48 ± 6.42) MPa to (8.26 ± 3.58) MPa. X-ray diffraction revealed that the crystallinity pattern of HA formed by CPC had no significant change. Inside the composite, the microspheres distributed homogeneously and contacted intimately with the HA matrix, as observed by scanning electron microscopy (SEM). When the PLGA microspheres dissolved after having been emerged in PBS for 56 days, macropores were created within the CPC. The rhBMP-2/PLGA/CPC composite, showing a 4.9% initial release of rhBMP-2 in 24 h, followed by a prolonged release for 28 days, should have a greater amount of rhBMP-2 released compared to the CPC delivery system. When rabbit marrow stromal cells were cocultured with the composite, the alkaline phosphatase (ALP) and osteocalcin (OC) showed a dose response to the rhBMP-2 released from the composite, indicating that the activity of rhBMP-2 was retained. This study shows that the new composite reveals more rhBMP-2 release and osteogenic activity. This novel BMP/PLGA/CPC composite could be a promising synthetic bone graft in craniofacial and orthopedic repairs.     

Effects of porous beta-tricalcium phosphate-based ceramics used as an E. coli-derived rhBMP-2 carrier for bone regeneration

Recombinant human bone morphogenetic protein-2 (rhBMP-2) requires carriers for clinical effectiveness. In this study, whether porous beta-tricalcium phosphate (β-TCP)-based ceramics are ideal carriers for rhBMP-2 was investigated. Hydroxyapatite (HA), β-TCP, TCP/HA (80 %/20 %), HA with rhBMP-2, TCP with rhBMP-2, and TCP/HA (80 %/20 %) with rhBMP-2 were manufactured by a sponge method with a pore size of 300 μm or more and macro-porosity of 83 %. The alkaline phosphatase (ALP) activity and ALP expression of the cells with 100 % β-TCP granules were more increased than the those of cells with 100 % HA and TCP/HA (80 %/20 %) at the baseline or when treated with 15 ng/ml of rhBMP-2. In an SD rat calvarial defect model, new bone formation was evidently shown in the TCP 100 %-rhBMP-2 and TCP/HA (80 %/20 %)-rhBMP-2 groups, showing that the most affected area was filled with newly-formed bone, that the percent bone volume and trabecular number were larger when compared to the groups without rhBMP-2 treatment at both 4 and 8 weeks after surgery using micro-CT and histology. Porous TCP-based ceramic granules enhanced the osteoblastic differentiation in the hMSC system when treated with 15 ng/ml of rhBMP-2 and accelerated bone-healing by trabecular number in a rat calvarial defect model. Thus, in this study it was proposed that TCP-based ceramics might be useful carriers of rhBMP-2.     

Delivery of a Therapeutic Protein for Bone Regeneration from a Substrate Coated with Graphene Oxide

The therapeutic efficacy of drugs often depends on the drug delivery carrier. For efficient delivery of therapeutic proteins, delivery carriers should enable the loading of large doses, sustained release, and retention of the bioactivity of the therapeutic proteins. Here, it is demonstrated that graphene oxide (GO) is an efficient carrier for delivery of therapeutic proteins. Titanium (Ti) substrates are coated with GO through layer‐by‐layer assembly of positively (GO‐NH₃⁺) and negatively (GO‐COO^?) charged GO sheets. Subsequently, a therapeutic protein (bone morphogenetic protein‐2, BMP‐2) is loaded on the GO‐coated Ti substrate with the outermost coating layer of GO‐COO^?(Ti/GO‐). The GO coating on Ti substrate enables loading of large doses and the sustained release of BMP‐2 with preservation of the structure and bioactivity of the drug. The extent of in vitro osteogenic differentiation of human bone marrow‐derived mesenchymal stem cells is higher when they are cultured on Ti/GO‐ carrying BMP‐2 than when they are cultured on Ti with BMP‐2. Eight weeks after implantation in mouse models of calvarial defects, the Ti/GO‐/BMP‐2 implants show more robust new bone formation compared with Ti, Ti/GO‐, or Ti/BMP‐2 implants. Therefore, GO is an effective carrier for the controlled delivery of therapeutic proteins, such as BMP‐2, which promotes osteointegration of orthopedic or dental Ti implants.     

Fabrication of an rhBMP-2 loaded porous β-TCP microsphere-hyaluronic acid-based powder gel composite and evaluation of implant osseointegration

Methods to improve osseointegration that include implantation of rhBMP-2 with various kinds of carriers are currently of considerable interest. The present study was conducted to evaluate if the rhBMP-2 loaded β-TCP microsphere-hyaluronic acid-based powder-like hydrogel composite (powder gel) can act as an effective rhBMP-2 carrier for implantation in host bone with a bone defect or poor bone quality. The release pattern for rhBMP-2 was then evaluated against an rhBMP-2-loaded collagen sponge as a control group. Dental implants were also inserted into the tibias of three groups of rabbits: an rhBMP-2 (200 µg) loaded powder gel composite implanted group, an implant only group, and a powder gel implanted group. Micro-CT and histology of the implanted areas were carried out four weeks later. The rhBMP-2 powder gel released less rhBMP-2 than the collagen sponge, but it continued a slow release for more than 7 days. The rhBMP-2 powder gel composite improved osseointegration of the dental implant by increasing the amount of new bone formation in the implant pitch and it improved the bone quality and bone quantity of new bone. The histology results indicated that the rhBMP-2 powder gel composite improved the osseointegration in the cortical bone as well as the marrow space along the fixture. The bone-to-implant contact ratio of the rhBMP-2 (200 µg) loaded powder gel composite implanted group was significantly higher than those of the implant only group and the powder gel implanted group. The powder gel appeared to be a good carrier and could release rhBMP-2 slowly to promote the formation of new bone following implantation in a bone defect, thereby improving implant osseointegration.     

Use of an osteoinductive biomaterial as a bone morphogenetic protein carrier

A porous calcium phosphate ceramic, which induced bone formation in soft tissues of dogs, was termed as osteoinductive biomaterial and studied as a carrier of bone morphogenetic protein (rhBMP-2). Cylinder implants (ø 4×5 mm) impregnated with 0, 1, 10 and 40 g rhBMP-2 were implanted in dorsal muscles of rabbits for five weeks. Histological observation and histomorphometric analysis were performed on thin un-decalcified sections. No bone formation was detected in the implants without rhBMP-2, while mature lamellar bone was found inside the implants with 1 g rhBMP-2, both on the outer surface and inside the implants with 10 g and 40 g rhBMP-2. Little difference in formed bone was found between 1 g and 10 g rhBMP-2, but no difference was found between 10 g and 40 g rhBMP-2. A significant difference in bone marrow formation was found among 1, 10 and 40 g rhBMP-2. The more rhBMP-2, the more bone marrow formed. The present results indicate that osteoinductive biomaterial is a good carrier of BMP and high dose of BMP is not necessary for bone formation in clinic. © 2001 Kluwer Academic Publishers     

Promotion of osteogenic differentiation of stem cells and increase of bone-bonding ability in vivo using urease-treated titanium coated with calcium phosphate and gelatin

Abstract

Because of its excellent biocompatibility and low allergenicity, titanium has been widely used for bone replacement and tissue engineering. To produce a desirable composite with enhanced bone response and mechanical strength, in this study bioactive calcium phosphate (CaP) and gelatin composites were coated onto titanium (Ti) via a novel urease technique. The cellular responses to the CaP/gelatin/Ti (CaP/gel/Ti) and bone bonding ability were evaluated with proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) on CaP/gel/Ti and CaP/Ti in vitro. The results showed that the optical density values, alkaline phosphatase expression and genes expression of MSCs on CaP/gel/Ti were similar to those on CaP/Ti, yet significantly higher than those on pure Ti (p < 0.05). CaP/gel/Ti and CaP/Ti rods (2 mm in diameter, 10 mm in length) were also implanted into femoral shaft of rabbits and pure Ti rods served as control (n = 10). Histological examination, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) measurements were performed at 4 and 8 weeks after the operation. The histological and SEM observations demonstrated clearly that more new bone formed on the surface of CaP/gel/Ti than in the other two groups at each time point. The CaP/gel/Ti bonded to the surrounding bone directly with no intervening soft tissue layer. An interfacial layer, containing Ti, Ca and P, was found to form at the interface between bone and the implant on all three groups by EDS analysis. However, the content of Ca, P in the surface of CaP/gel/Ti implants was more than in the other two groups at each time point. The CaP/gel/Ti modified by the urease method was not only beneficial for MSCs proliferation and osteogenic differentiation, but also favorable for bone bonding ability on Ti implants in vivo, suggesting that Ti functionalized with CaP and gelatin might have a great potential in clinical joint replacement or dental implants.     

Synthesis,Characterization and Bioactivity Evaluation of Porous Barium Titanate with Nanostructured Hydroxyapatite Coating for Biomedical Application

Nano phase hydroxyapatite (HA) bioceramics have gained importance in the biomedical field due to their superior biological properties. In this study, nanostructured HA coating was used to increase the bioactivity of a piezoelectric bioceramic, barium titanate (BT). Early reports on the influence of collagen piezoelectricity in remodeling of bone have attracted many researchers to piezoelectric bioceramics such as BT. Hence; porous BT was used as the matrix of a new bone graft composite and then coated with nanostructured HA. BT ceramic was foamed via a direct foaming method with a spray of polyurethane foam. The surface of the foam voids was coated with HA via sol–gel and dip‐coating methods. X‐ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) techniques were used to characterize the prepared coated foam. XRD and TEM analysis showed that the HA coating had a nanostructure with crystallite size of 20–30 nm. SEM images of the prepared samples showed that the HA coating has about 25 µm thickness. The bioactivity of the prepared composite was evaluated in an in vitro study. The variation of Ca²⁺ and PO₄^3? ions versus time in simulated body fluid (SBF) solution were measured by inductively coupled plasma (ICP) analysis during 1 month and the results showed that the mineralization of calcium phosphate (Ca‐P) on HA coated porous samples was much more than that in non‐coated sample. The SEM micrographs and energy‐dispersive X‐ray spectroscopy (EDS or EDX) analysis of the samples after 1 month of immersing in SBF confirm that Ca‐P phase (bone‐like apatite) was significantly mineralized on HA coated porous BT samples. It was concluded that the nanostructured HA coating would improve the bioactivity of BT foam.     

An exploratory study on the efficacy of rat dedifferentiated fat cells (rDFATs) with a poly lactic-co-glycolic acid/hydroxylapatite (PLGA/HA) composite for bone formation in a rat calvarial defect model

In the last two decades, tissue-engineering approaches using scaffolds, growth factors, and cells, or their combination, have been developed for the regeneration of periodontal tissue and bone. The aim of this study was to examine the effects of rat dedifferentiated fat cells (rDFATs) with a poly lactic-co-glycolic acid/hydroxylapatite (PLGA/HA) composite on bone formation in rat calvarial defects. Twenty animals surgically received two calvarial defects (diameter, 5 mm) bilaterally in each parietal bone. The defects were treated by one of the following procedures: PLGA/HA+osteo-differentiated rDFATs implantation (PLGA/HA+rDFATs (OD)); PLGA/HA+rDFATs implantation (PLGA/HA+rDFATs); PLGA/HA implantation (PLGA/HA); no implantation as a control. The animals were euthanized at 8 weeks after the surgery for histological evaluation. The PLGA/HA composite was remarkably resorbed and the amounts of residual PLGA/HA were very slight at 8 weeks after the surgery. The PLGA/HA-implanted groups (PLGA/HA+rDFATs (OD), PLGA/HA+rDFATs and PLGA/HA) showed recovery of the original volume and contour of the defects. The newly formed bone area was significantly larger in the PLGA/HA group (42.10 ± 9.16 %) compared with the PLGA/HA+rDFATs (21.35 ± 13.49 %) and control (22.17 ± 13.08 %) groups (P < 0.05). The percentage of defect closure (DC) by new bone in the PLGA/HA+rDFATs (OD) group (83.16 ± 13.87 %) was significantly greater than that in the control group (40.61 ± 29.62 %) (P < 0.05). Furthermore, the PLGA/HA+rDFATs (OD) group showed the highest level of DC among all the groups. The present results suggest that the PLGA/HA composite is a promising scaffold and that PLGA/HA+DFATs (OD) may be effective for bone formation.     

Differentiation of preosteoblasts using a delivery system with BMPs and bioactive glass microspheres

Bone morphogenetic proteins (BMPs) and 45S5 Bioglass microspheres (bioactive GM) can increase the differentiation of osteoblasts. Recombinant human BMP-2 (rhBMP-2) is presently the BMP most frequently used in delivery systems and it has already been used in clinical bone healing studies. We have developed a delivery system that combines a collagen Type I gel, BMP and bioactive GM. Since BMP-9 seems to be more osteogenic than BMP-2, we compared the differentiation of MC3T3-E1 preosteoblasts induced by our delivery system containing either a peptide derived from BMP-9 (pBMP-9), or rhBMP-2, both at 100 ng/mL. After 5 days, alkaline phosphatase staining showed that pBMP-9 induced more differentiation than rhBMP-2 in all experimental conditions. Also, bioactive GM increased this BMP effect. Since preosteoblasts secreted matrix metalloproteinases (MMPs) that can degrade collagen, we then studied the influence of the delivery system on MMPs production. We observed that MMP-2 was the major MMP involved in all experimental conditions. In addition, pBMP-9 with bioactive GM generated less MMP-2 than did rhBMP-2 on days 3 and 5. Thus, a delivery system using collagen Type I gel with pBMP-9 and bioactive GM seems to be a promising system for bone regeneration.     

Preparation of an electrodeposited hydroxyapatite coating on titanium substrate suitable for in-vivo applications

In this paper the porous hydroxyapatite coating on Ti implant materials was prepared by the process of electrodeposition, hydrothermal and sinter. The surface morphology, bond strength and thickness of HA coatings were investigated by SEM, AFM, and its biocompatibility was evaluated by cytotoxicity experiments and implant experiments, respectively. Results showed that (1) The HA coatings was 50 μm thickness and adhered on the Ti substrate strongly, which bond strength reached 38MPa. AFM analysis showed that the HA coating was porous structure, in which the mean pore size was 236.5 μm, (2) Cytotoxicity experiments and implant experiments showed that HA-coated Ti implant materials has little cytotoxicity in vitro and little inflammatory reaction in vivo, and there were no statistically disparity between HA-coated Ti implant and titanium implant materials of clinical application (p > 0.05), which demonstrated that HA-coated Ti has a good biocompatibility.     

中空羟基磷灰石微球作为rhBMP-2缓释载体的研究

利用锂钙硼玻璃在磷酸盐溶液中的原位转化反应制备表面多孔且中空的羟基磷灰石(HA)微球, 将重组人骨形态发生蛋白2(rhBMP-2)装载到微球中, 研究了微球中rhBMP-2的体外缓释行为, 并采用体外细胞培养技术, 将载有rhBMP-2的微球和大鼠骨髓间充质干细胞(MSCs)一起培养, 测定细胞的碱性磷酸酶(ALP)活性, 并与单纯rhBMP-2的作用进行比较. 结果显示, 微球中所装载的rhBMP-2具有明显的缓释效应, 体外释放周期达到1000h以上, 该微球缓释系统具有一定的生物活性, 其作用效果优于单纯使用rhBMP-2.     

射频磁控溅射TiO2/HA复合生物膜的制备与表征

将水热合成的羟基磷灰石(HA)粉与20 wt%Ti粉混合,冷压烧结成靶材。采用射频磁控溅射方法,在工业纯钛基体上沉积TiO₂/HA生物薄膜,通过扫描电镜(SEM)及其能谱(EDS)、X射线衍射(XRD)和差热分析仪(TDA)对膜层进行了表征,探讨了溅射膜的晶化工艺。结果表明:由于选择溅射和OH-损失,溅射膜由TiO₂晶体颗粒和非晶钙磷化合物组成,且其Ca/P比降低。经700℃,0.5 h水蒸气处理,非晶钙磷化合物结晶度大大提高,并部分转化为HA晶体,且处理后的溅射膜与基体间无裂纹。     

A new growth factor controlled drug release system to promote healing of bone fractures: nanospheres of recombinant human bone morphogenetic-2 and polylactic acid

To prepare a new drug control release system, which can markedly promote the healing of bone fractures. Optimized water-in-oil-in-water multiple emulsion evaporation method, prepared nanospheres of recombinant human bone morphogenetic-2 and polylactic acid (rhBMP-2-PLA-Ns). Its physical character was determined by the enzyme linked immunosorbent assay method. Its bioactivity was measured with the microculture tetrazolium test immunohistochemical analyses, alizarin red staining and western blot analysis. rhBMP-2-PLA-Ns exhibited an even and uniform spherical appearance without adhesion, with a particle size distribution between 35 and 65 nm, and a mean size of 45 nm. The drug loading volume and encapsulation efficiency reached ([124.73 +/- 0.41] x 10(-3))% and (90.54 +/- 1.32)%, respectively. The drug release in vitro persisted for 14 days, with a mean concentration of 73.44 +/- 5.38 ng/ml, and corresponded to the Higuichi equation (r = 0.9962). The microculture tetrazolium test showed that 4 days later, the optical density value ranking was rhBMP-2-PLA-N group > rhBMP-2 group > blank control group. Fluorescence immunocytochemical analysis showed that 10 days later the fluorescent density of the rhBMP-2-PLA-N group was significantly higher than the other two groups. Western blot analysis confirmed that the amount of vascular endothelial growth factor in the rhBMP-2-PLA-N group was the greatest. This study showed that rhBMP-2-PLA-Ns have excellent biological activity, can promote proliferation, differentiation and mineralization of osteoblasts. The drug release time is suitable for fracture healing and is an ideal delivery system for fracture healing.     

纳米羟基磷灰石/聚碳酸酯复合生物材料Ⅱ:体外生物活性

研究了纳米羟基磷灰石/聚碳酸酯(n-HA/ PC)生物复合材料在模拟体液(SBF)中的表面变化,并用傅里叶红外光谱(FTIR) 、X射线衍射仪(XRD)和扫描电子显微镜(SEM)对材料的表面变化进行了分析。结果表明,n-HA/PC生物复合材料在模拟体液(SBF)中浸泡后,表面会沉积碳酸化羟基磷灰石(CHA),随着浸泡时间的延长,沉积层变厚,CHA晶体形貌变得规整。对n-HA/PC复合材料进行了细胞实验,通过四唑盐(MTT)检测和扫描电镜观察,表明n-HA/PC复合材料无细胞毒性,细胞形态正常,是一种有应用前景的可承力骨修复替代材料。      

Biomimetic synthesis of the composites of hydroxyapatite and chitosan–phosphorylated chitosan polyelectrolyte complex

A polyelectrolyte complex (PEC) composed of chitosan (CS) and phosphorylated chitosan (PCS) was used to encapsulate a calcium phosphate by a biomimetic method. An acidic CS (polycation) solution containing calcium and phosphate ions (Ca²⁺: 6 mM, Ca/P = 1.67) was added into a PCS (polyanion) solution leading to the formation of a polyelectrolyte complex (PEC) with nanoscopic carbonate-containing, low-crystallinity hydroxyapatite (HA) distributed evenly in the fibrils of the PEC by controlled crystal growth. The resulting composite material, PEC–HA, has a complicated porous structure that is expected to have high biocompatibility and that may be of use as materials for bone replacement and a carrier for controlled-release therapeutic agents.     

Silicon-substituted hydroxyapatite composite coating by using vacuum-plasma spraying and its interaction with human serum albumin

The incorporation of silicon can improve the bioactivity of hydroxyapatite (HA). Silicon-substituted HA (Ca₁₀(PO₄)_6−x (SiO₄) _x (OH)_2−x , Si-HA) composite coatings on a bioactive titanium substrate were prepared by using a vacuum-plasma spraying method. The surface structure was characterized by using XRD, SEM, XRF, EDS and FTIR. The bond strength of the coating was investigated and XRD patterns showed that Ti/Si-HA coatings were similar to patterns seen for HA. The only different XRD pattern was a slight trend toward a smaller angle direction with an increase in the molar ratio of silicon. FTIR spectra showed that the most notable effect of silicon substitution was that –OH group decreased as the silicon content increased. XRD and EDS elemental analysis indicated that the content of silicon in the coating was consistent with the silicon-substituted hydroxyapatite used in spraying. A bioactive TiO₂ coating was formed on an etched surface of Ti, and the etching might improve the bond strength of the coatings. The interaction of the Ti/Si-HA coating with human serum albumin (HSA) was much greater than that of the Ti/HA coating. This might suggest that the incorporation of silicon in HA can lead to significant improvements in the bioactive performance of HA.     

Characterization of electrolytic HA/ZrO2 double layers coatings on Ti–6Al–4V implant alloy

Hydroxyapatite (HA) coating was proved having bioactive property and hence improving the bonding strength on bone tissue without inducing the growth of fiber tissue. However, the weak adhesion between HA and metal implants is still the major problem. In this study, a novel method of electrolytic HA/ZrO₂ double layers coating was successfully conducted on F-136 Ti–6Al–4V implant alloy in ZrO₂(NO₃)₂ aqueous solution and subsequently in the mixed solution of Ca(NO₃)₂ and NH₄H₂PO₄. After annealing at 400 °C, 500 °C and 600 °C for 4 h in air, the coated specimens were evaluated by X-ray diffraction analyses, surface morphology observations, scratch tests, dynamic polarization tests, immersion tests and cell culture assays. In addition to corrosion resistance, the adhesion strength of electrolytic deposited HA on Ti alloy was dramatically improved from the critical scratch load 2 N to 32 N by adding the intermediate electrolytic deposition of ZrO₂, which showed the strong bonding effects between Ti alloy substrate and HA coating. Based on the cell morphology and cell proliferation data, HA/ZrO₂ double layers coating revealed the better substrate for the adhesion and proliferation of osteoblasts than the others. It was also found that the crystallization of HA had positive effect on the proliferation of osteoblasts.     

Effect of titanium and titania on chemical characteristics of hydroxyapatite plasma-sprayed into water

HA and its composite particles (HA/Ti, HA/TiO₂) were plasma-sprayed into water as well as on the Ti substrate, respectively. The microstructure and phase compositions of the sprayed HA and its composite particles before and after impinging on the substrate were studied by using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. The results showed that the HA in the composite particles sprayed into water had a higher crystallinity than that in the composite coating. The addition of Ti or TiO₂ could both influence the decomposition of HA, but no chemical reacting product between them was formed before and after impinging on the substrate. However, EDS analyses showed the occurrence of interdiffusion of elements between HA and TiO₂, which was favorable to enhance the cohesive strength of particles in the composite coating. The post heat treatment at 650 °C for 2 h can effectively improve the crystallinity of coating by transforming amorphous phases into HA.     

Formation of hydroxyapatite coating using novel chemo-biomimetic method

A novel chemo-biomimetic method was developed to deposit hydroxyapatite (HA), simulating the porous nano-scale structure and chemical composition of natural bone. Electrochemical activation in NaOH solution, a prerequisite process to heterogeneously nucleate hydroxyapatite in this investigation, creates nano-scale porous structure on the surface of Ti6Al4V alloy. XPS analysis confirmed that the surface of activated Ti6Al4V substrate converted to TiO(2) during activation, existing in the form of hydrated TiO(2). Benefiting from the biocompatible top-layer of hydrated TiO(2) and the favorable alkaline surface chemistry created through the electrochemical activation, the HA coating nucleates heterogeneously and grows continuously on the activated substrate resembling the nano-scale porous bone-like structure. The coating was characterized using XRD, SEM/FESEM/EDX, TEM and FTIR, and was confirmed as pure hydroxyapatite. A coating thickness of 50 mum was achieved, which is preferable and acceptable for medical implant application to promote bone ingrowth, thus enhancing fixation and biocompatibility of implant surface.     

Bone tissue reactions to biomimetic ion-substituted apatite surfaces on titanium implants

The aim of this study was to evaluate the bone tissue response to strontium- and silicon-substituted apatite (Sr-HA and Si-HA) modified titanium (Ti) implants. Sr-HA, Si-HA and HA were grown on thermally oxidized Ti implants by a biomimetic process. Oxidized implants were used as controls. Surface properties, i.e. chemical composition, surface thickness, morphology/pore characteristics, crystal structure and roughness, were characterized with various analytical techniques. The implants were inserted in rat tibiae and block biopsies were prepared for histology, histomorphometry and scanning electron microscopy analysis. Histologically, new bone formed on all implant surfaces. The bone was deposited directly onto the Sr-HA and Si-HA implants without any intervening soft tissue. The statistical analysis showed significant higher amount of bone–implant contact (BIC) for the Si-doped HA modification (P = 0.030), whereas significant higher bone area (BA) for the Sr-doped HA modification (P = 0.034), when compared with the non-doped HA modification. The differences were most pronounced at the early time point. The healing time had a significant impact for both BA and BIC (P < 0.001). The present results show that biomimetically prepared Si-HA and Sr-HA on Ti implants provided bioactivity and promoted early bone formation.