Rapid prototyped porous titanium coated with calcium phosphate as a scaffold for bone tissue engineering

High strength porous scaffolds and mesenchymal stem cells are required for bone tissue engineering applications. Porous titanium scaffolds (TiS) with a regular array of interconnected pores of 1000 microm in diameter and a porosity of 50% were produced using a rapid prototyping technique. A calcium phosphate (CaP) coating was applied to these titanium (Ti) scaffolds with an electrodeposition method. Raman spectroscopy and energy dispersive X-ray analysis showed that the coating consisted of carbonated hydroxyapatite. Cross-sectioned observations by scanning electron microscopy indicated that the coating evenly covered the entire structure with a thickness of approximately 25 microm. The bonding strength of the coating to the substrate was evaluated to be around 25 MPa. Rat bone marrow cells (RBMC) were seeded and cultured on the Ti scaffolds with or without coating. The Alamar Blue assay provided a low initial cell attachment (40%) and cell numbers were similar on both the uncoated and coated Ti scaffolds after 3 days. The Ti scaffolds were subsequently implanted subcutaneously for 4 weeks in syngenic rats. Histology revealed the presence of a mineralized collagen tissue in contact with the implants, but no bone formation. This study demonstrated that porous Ti scaffolds with high strength and defined geometry may be evenly coated with CaP layers and cultured mesenchymal stem cells for bone tissue engineering.     

Porous titanium scaffolds fabricated using a rapid prototyping and powder metallurgy technique

One of the main issues in orthopaedic implant design is the fabrication of scaffolds that closely mimic the biomechanical properties of the surrounding bone. This research reports on a multi-stage rapid prototyping technique that was successfully developed to produce porous titanium scaffolds with fully interconnected pore networks and reproducible porosity and pore size. The scaffolds' porous characteristics were governed by a sacrificial wax template, fabricated using a commercial 3D-printer. Powder metallurgy processes were employed to generate the titanium scaffolds by filling around the wax template with titanium slurry. In the attempt to optimise the powder metallurgy technique, variations in slurry concentration, compaction pressure and sintering temperature were investigated. By altering the wax design template, pore sizes ranging from 200 to 400 microm were achieved. Scaffolds with porosities of 66.8 +/- 3.6% revealed compression strengths of 104.4+/-22.5 MPa in the axial direction and 23.5 +/- 9.6 MPa in the transverse direction demonstrating their anisotropic nature. Scaffold topography was characterised using scanning electron microscopy and microcomputed tomography. Three-dimensional reconstruction enabled the main architectural parameters such as pore size, interconnecting porosity, level of anisotropy and level of structural disorder to be determined. The titanium scaffolds were compared to their intended designs, as governed by their sacrificial wax templates. Although discrepancies in architectural parameters existed between the intended and the actual scaffolds, overall the results indicate that the porous titanium scaffolds have the properties to be potentially employed in orthopaedic applications.     

Peri- and intra-implant bone response to microporous Ti coatings with surface modification

Bone growth on and into implants exhibiting substantial surface porosity is a promising strategy in order to improve the long-term stable fixation of bone implants. However, the reliability in clinical applications remains a point of discussion. Most attention has been dedicated to the role of macroporosity, leading to the general consensus of a minimal pore size of 50–100 μm in order to allow bone ingrowth. In this in vivo study, we assessed the feasibility of early bone ingrowth into a predominantly microporous Ti coating with an average thickness of 150 μm and the hypothesis of improving the bone response through surface modification of the porous coating. Implants were placed in the cortical bone of rabbit tibiae for periods of 2 and 4 weeks and evaluated histologically and histomorphometrically using light microscopy and scanning electron microscopy. Bone with osteocytes encased in the mineralized matrix was found throughout the porous Ti coating up to the coating/substrate interface, highlighting that osseointegration of microporosities (<10 μm) was achievable. The bone trabeculae interweaved with the pore struts, establishing a large contact area which might enable an improved load transfer and stronger implant/bone interface. Furthermore, there was a clear interconnection with the surrounding cortical bone, suggesting that mechanical interlocking of the coating in the host bone in the long term is possible. When surface modifications inside the porous structure further reduced the interconnective pore size to the submicrometer level, bone ingrowth was impaired. On the other hand, application of a sol–gel-derived bioactive glass–ceramic coating without altering the pore characteristics was found to significantly improve bone regeneration around the coating, while still supporting bone ingrowth.     

Effect of nitinol implant porosity on cranial bone ingrowth and apposition after 6 weeks.

The present study addresses two aspects of the use of nitinol in cranial bone defect repair. The first is to verify that there is substantial bone ingrowth into the implant after 6 weeks; the second is to determine the effect of pore size on the ability of bone to grow into the implant during the early (6-week) postoperative period. Porous equiatomic (equal atomic masses of titanium and nickel) nickel-titanium (nitinol) implants with three different morphologies (differing in pore size and percent porosity) were implanted for 6 weeks in the parietal bones of New Zealand White rabbits. Ingrowth of bone into the implants and apposition of bone along the exterior and interior implant surfaces were calculated. The mean pore size (MPS) of implant type #1 (353 +/- 74 microm) differed considerably from implant types #2 (218 +/- 28 microm) and #3 (178 +/- 31 microm). There was no significant difference among implant types in the percentages of bone and void/soft tissue composition of the aggregate implants. The amount of bone ingrowth also was not significantly different among the implant types. Implant #1 was significantly higher in pore volume and thus had a significantly higher volume of ingrown bone (2.59 +/- 0.60 mm3) than implant #3 (1. 52 +/- 0.66 mm3) and a greater amount, but not significantly greater, than implant #2 (1.76 +/- 0.47 mm3). Pore size does not appear to affect bone ingrowth during the cartilaginous period of bone growth in the implant. This implies that within the commonly accepted range of implant porosities (150-400 microm), at 6 weeks bone ingrowth near the interface of nitinol implants is similar.     

Processing and biocompatibility evaluation of laser processed porous titanium

The Laser Engineered Net Shaping (LENS™) method was used to fabricate porous Ti implants. Porous Ti structures with controlled porosity in the range of 17–58 vol.% and pore size up to 800 μm were produced by controlling LENS™ parameters, which showed a broad range of mechanical strength of 24–463 MPa and a low Young’s modulus of 2.6–44 GPa. The effects of porous structure on bone cell responses were evaluated in vitro with human osteoblast cells (OPC1). The results showed that cells spread well on the surface of porous Ti and formed strong local adhesion. MTT assay indicated LENS™ processed porous Ti provides a preferential surface for bone cell proliferation. Porous Ti samples also stimulated faster OPC1 cell differentiation compared with polished Ti sheet, which could be due to the change in cell morphology within the pores of Ti samples. More extracellular matrix and a higher level of alkaline phosphatase expression were found on the porous samples than on the Ti sheet. This can be beneficial for faster integration of porous implant with host bone tissue. The results obtained also indicated that a critical pore size of 200 μm or higher is needed for cell ingrowth into the pores, below which OPC1 cells bridged the pore surface without any growth in the pores.     

电子束熔融快速成型技术在骨科植入物修复过程中的骨诱导能力

背景：电子束熔融快速成型技术(EBM RP)是一种新型金属粉末快速成型技术,它具有精准、复杂成型的特点,已在航空航天、汽车和医疗植入器材等领域显示独特的应用优势。 目的：探索电子束熔融快速成型技术用于骨科植入物时表现出的产品性能、个性化定制能力,尤其是诱导骨长入能力。 方法：计算机检索Pubmed数据库、中国期刊全文数据库、知网数据库,手工检索《东方早报》《世界科学》《中国骨科杂志》,以及相关的中英文会议论文集。所有检索时间均截止至2013年9月。纳入标准：①应用电子束熔融快速成型技术的文章。②外科植入物相关文章。最后选择50篇文献进行分析。 结果与结论：EBM态Ti6Al4V骨科植入物具有良好的产品综合性能;电子束熔融快速成型技术具有优良的个性化定制能力,尤其是生成的3D连通的孔隙结构,可提供诱导骨长入的结构性条件,在骨科植入物方面享有独特的优势。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程全文链接：     

Characteristics of hydroxyapatite coated titanium porous coatings on Ti-6Al-4V substrates by plasma sprayed method

A porous metal coating applied to solid substrate implants has been shown, in vivo, to anchor implants by bone ingrowth. Calcium phosphate ceramics, in particular hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2), HA], are bioactive ceramics, which are known to be biocompatible and osteoconductive, and these ceramics deposited on to porous-coated devices may enhance bone ingrowth and implant fixation. In this study, bi-feedstock of the titanium powder and composite (Na(2)CO(3)/HA) powder were simultaneously deposited on a Ti-6Al-4V substrate by a plasma sprayed method. At high temperature of plasma torch, the solid state of Na(2)CO(3) would decompose to release CO(2) gas and then eject the molten Ti powder to induce the interconnected pores in the coatings. After cleaning and soaking in deionized water, the residual Na(2)CO(3) in the coating would dissolve to form the open pores, and the HA would exist at the surface of pores in the inner coatings. By varying the particle size of the composite powder, the porosity of porous coating could be varied from 25.0 to 34.0%, and the average pore size of the porous coating could be varied to range between 158.5 and 202.0 microm. Using a standard adhesive test (ASTM C-633), the bonding strength of the coating is between 27.3 and 38.2 MPa. By SEM, the HA was observed at the surface of inner pore in the porous coating. These results suggest that the method exhibits the potential to manufacture the bioactive ceramics on to porous-coated specimen to achieve bone ingrowth fixation for biomedical applications.     

Porous Ti6Al4V scaffold directly fabricating by rapid prototyping: preparation and in vitro experiment

Three-dimensional (3D) fiber deposition (3DF), a rapid prototyping technology, was successfully directly applied to produce novel 3D porous Ti6Al4V scaffolds with fully interconnected porous networks and highly controllable porosity and pore size. A key feature of this technology is the 3D computer-controlled fiber depositing of Ti6Al4V slurry at room temperature to produce a scaffold, consisting of layers of directionally aligned Ti6Al4V fibers. In this study, the Ti6Al4V slurry was developed for the 3D fiber depositing process, and the parameters of 3D fiber depositing were optimized. The experimental results show how the parameters influence the structure of porous scaffold. The potential of this rapid prototyping 3DF system for fabricating 3D Ti6Al4V scaffolds with regular and reproducible architecture meeting the requirements of tissue engineering and orthopedic implants is demonstrated.     

3D打印钛合金孔隙支架骨长入影响因素的分析

BACKGROUND: With the development of three-dimensional (3D) printing technology, 3D printed porous titanium scaffolds as bone substitutes have become a research hotspot. OBJECTIVE: To introduce and discuss the effects of each parameter of 3D printed porous titanium scaffolds on bone ingrowth, and to sum out the optimal parameters for bone ingrowth. METHODS: The first author retrieved PubMed, Springerlink and Medline databases with “three-dimensional (3D) printing, scaffold, titanium, bone ingrowth” as keywords for relevant articles published from 2006 to 2016. 125 articles were retrieved initially, and finally 42 eligible articles were included for analysis. RESULTS AND CONCLUSION: Pore size, porosity, pore structures and surface modifications of 3D printed porous titanium scaffolds all make effects on bone ingrowth or osteoblasts in scaffolds. Scaffolds with appropriate pore size and porosity can promote the vascularization and provide adequate nutrition and oxygen supplement, to ensure high cell viability. Regulations of cell performances, such as cell attachment, proliferation and differentiation, are also affected by pore structures and nano-scale surface modification. Herein, a detailed combination of the parameters, as mentioned above, can create a better porous scaffold for better bone ingrowth. Hence, the high-stability interface between bone and scaffolds may be obtained through the parameter adjustment.     

Porous titanium and silicon-substituted hydroxyapatite biomodification prepared by a biomimetic process: Characterization and in vivo evaluation

Porous titanium with a pore size of 150–600 μm and a porosity of 67% was prepared by fiber sintering. The porous titanium had a complete three-dimensional (3D) interconnected structure and a high yield strength of 100 MPa. Si-substituted hydroxyapatite (Si-HA) was coated on the surface by a biomimetic process to improve the surface bioactivity. X-ray diffraction results showed that Si-HA coating was not well crystallized. New bone tissue was found in the uncoated porous titanium after 2 weeks of implantation and a significant increase (p < 0.05) in the bone ingrowth rate (BIR) was found after 4 weeks of implantation, indicating the good osteoconductivity of the porous structure. The HA-coated and Si-HA-coated porous titanium exhibited a significantly higher BIR than the uncoated titanium at all intervals, highlighting the better surface bioactivity and osteoconductivity of the HA- and Si-HA coatings. Also, the Si-HA-coated porous titanium demonstrated a significantly higher BIR than the HA-coated porous titanium, showing that silicon plays an active role in the surface bioactivity. For Si-HA-coated porous titanium, up to 90% pore area was covered by new bone tissue after 4 weeks of implantation in cortical bone. In the bone marrow cavity, the pore spaces were filled with bone marrow, displaying that the interconnected pore structure could provide a channel for body fluid. It was concluded that both the 3D interconnected pore structure and the Si-HA coating contributed to the high BIR.     

Pore throat size and connectivity determine bone and tissue ingrowth into porous implants: three-dimensional micro-CT based structural analyses of porous bioactive titanium implants

A porous structure comprises pores and pore throats with a complex three-dimensional (3D) network structure, and many investigators have described the relationship between average pore size and the amount of bone ingrowth. However, the influence of network structure or pore throats for tissue ingrowth has rarely been discussed. Four types of bioactive porous titanium implants with different pore sizes and porosities (6mm in diameter and 15 mm long) were analyzed using specific algorithms for 3D analysis of interconnectivity based on a micro focus X-ray computed tomography system. In vivo histomorphometric analysis was performed using the very same implants implanted into the femoral condyles of male rabbits for 6 and 12 weeks. This matching study revealed that more poorly differentiated pores tended to have narrow pore throats, especially in their shorter routes to the outside. In addition, for assessment of the entire implant, we proposed new two indices that represent the degree of bone and tissue ingrowth into an implant by considering the effect of narrow pore throats. Data obtained suggest that this sort of novel analysis is useful for evaluating bone and tissue ingrowth into porous biomaterials.     

Porous poly(DL-lactic-co-glycolic acid)/calcium phosphate cement composite for reconstruction of bone defects

Calcium phosphate (Ca-P) cements are injectable, self-setting ceramic pastes generally known for their favorable bone response. Ingrowth of bone and subsequent degradation rates can be enhanced by the inclusion of macropores. Initial porosity can be induced by CO(2) foaming during setting of the cement, whereas secondary porosity can develop after hydrolysis of incorporated poly(DL-lactic- co-glycolic acid) (PLGA) microparticles. In this study, we focused on the biological response to porous PLGA/Ca-P cement composites. Pre-set composite discs of four formulations (4 wt% or 15 wt% PLGA microparticles and low or high CO(2) induced porosity) were implanted subcutaneously and in cranial defects in rats for 12 weeks. Histological analysis of the explanted composites revealed that bone and fibrous tissue ingrowth was facilitated by addition of PLGA microparticles (number average diameter of 66 +/- 25 microm). No adverse tissue reaction was observed in any of the composites. Significant increases in composite density due to bone ingrowth in cranial implants were found in all formulations. The results suggest that the PLGA pores are suitable for bone ingrowth and may be sufficient to enable complete tissue ingrowth without initial CO(2) induced porosity. Finally, bone-like mineralization in subcutaneous implants suggests that, under appropriate conditions and architecture, porous PLGA/Ca-P cement composites can exhibit osteoinductive properties. These PLGA/Ca-P composites are a promising scaffolding material for bone regeneration and bone tissue engineering.     

Mechanics considerations for microporous titanium as an orthopedic implant material

This article investigates mechanics issues related to potential use of a recently developed porous titanium (Ti) material for load-bearing implants. This material may have advantages over solid Ti of enhancing the bone-implant interface strength by promoting bone and soft tissue ingrowth and of reducing the bone-implant modulus mismatch, which can lead to stress shielding. Experimental data from ultrasound experiments and uniaxial compression testing on microporous Ti are presented. Analytic models to predict its elastic modulus and Poisson's ratio are discussed, including "structural" approaches (Gibson and Ashby's cellular solids) and a "composite material" approach (Mori-Tanaka). Finally, two-dimensional finite element models based on optical micrographs of the material are presented. Simulations were performed for different conditions and levels of approximation. Results demonstrate that simple analytic models provide good estimates of the elastic properties of the porous Ti and that the moduli can be significantly reduced to decrease the mismatch between solid Ti and bone. The finite element simulations show that bone ingrowth will dramatically reduce stress concentrations around the pores.     

Influence of porosity on mechanical properties and in vivo response of Ti6Al4V implants

Metallic biomaterials are widely used to restore the lost structure and functions of human bone. Due to the large number of joint replacements, there is a growing demand for new and improved orthopedic implants. More specifically, there is a need for novel load-bearing metallic implants with low effective modulus matching that of bone in order to reduce stress shielding and consequently increase the in vivo lifespan of the implant. In this study, we have fabricated porous Ti6Al4V alloy structures, using laser engineered net shaping (LENS?), to demonstrate that advanced manufacturing techniques such as LENS? can be used to fabricate low-modulus, tailored porosity implants with a wide variety of metals/alloys, where the porosity can be designed in areas based on the patient’s need to enhance biological fixation and achieve long-term in vivo stability. The effective modulus of Ti6Al4V alloy structures has been tailored between 7 and 60 GPa and porous Ti alloy structures containing 23–32 vol.% porosity showed modulus equivalent to human cortical bone. In vivo behavior of porous Ti6Al4V alloy samples in male Sprague–Dawley rats for 16 weeks demonstrated a significant increase in calcium within the implants, indicating excellent biological tissue ingrowth through interconnected porosity. In vivo results also showed that total amount of porosity plays an important role in tissue ingrowth.     

Bone response to a novel highly porous surface in a canine implantable chamber

Long-term survival of uncemented hip components is dependent upon successful biological fixation. This study examined a new prosthetic surface treatment consisting of a highly porous open structure of commercially pure titanium, Tritanium Dimensionalized Metal; its overall porosity is approximately 65-70%. With the use of an implantable chamber in dogs, the effects of this treatment on bone ingrowth and strength of attachment were compared to both titanium (overall porosity of 30-35%) and cobalt chrome beads (overall porosity of 35-40%), with and without hydroxyapatite coating. At 6 and 12 weeks, chambers were explanted and specimens underwent high-resolution radiographic imaging and mechanical testing. At 12 weeks, Tritanium surfaces had greater bone penetration and tensile strength than remaining surface types. Over 40% of the Tritanium specimens had a tensile strength greater than 500 N, exceeding the testing capability of the servohydraulic equipment. The highly porous Tritanium surfaces allow for a far greater amount of bone ingrowth than beaded surfaces, and may create a geometry that enhances mechanical strength. Tritanium Dimensionalized Metal surface treatment may result in a clinically valuable implant fixation surface to induce rapid ingrowth and a strong bone-implant interface, contributing to increased implant survivorship.     

The structure of the bond between bone and porous silicon-substituted hydroxyapatite bioceramic implants

The significance of micrometer-sized strut porosity in promoting bone ingrowth into porous hydroxyapatite (HA) scaffolds has only recently been noted. In this study, silicon-substituted HA (0.8 wt % Si-HA) with approximately 8.5% of the total porosity present as microporosity within the struts of the implant was prepared for high-resolution transmission electron microscopy (HR-TEM) via both ultramicrotomy and focused ion beam milling. Between the struts of the porous Si-HA, pores with varying shapes and sizes (1-10 microm in diameter) were characterized. Within the struts, the Si-HA contained features such as grain boundaries and triple-junction grain boundaries. Bone ingrowth and dissolution from a Si-HA implant were studied using HR-TEM after 6 weeks in vivo. Minor local dissolution occurred within several pores within the struts. Organized, mineralized collagen fibrils had grown into the strut porosity at the interface between the porous Si-HA implant and the surface of the surrounding bone. In comparison, deeper within the implant, disorganized and poorly mineralized fibers were observed within the strut porosity. These findings provide valuable insight into the development of bone around porous Si-HA implants.     

Quantification of bone ingrowth into porous block hydroxyapatite in humans.

This study sought to quantify bone ingrowth from a single bone-implant surface into porous block hydroxyapatite used in maxillofacial applications. Seventeen maxillary hydroxyapatite implants (implant time of 4-138 months, 39-month mean) were harvested for analysis from 14 patients. The implants had been placed into the lateral maxillary wall during orthognathic surgery, juxtapositioned to the maxillary sinus. Ingrowth was measured in 100-microm increments from a bone-implant interface to a depth of 1500 microm. Bone ingrowth averaged over the 14 patients (0-1100 microm depth) is described by the equation % ingrowth - 20% * (depth in millimeters) + 41.25% (R2 = 0.98, n = 10 incremental depths). Beyond 1100 microm, the average ingrowth remained constant at 15.0 +/- 0.7%. The duration of implantation also showed as affect on the percent ingrowth into the implants at the incremental depths, and the percent ingrowth asymptotically approached a maximum. Overall, the composite average data from all depths is best described by the logarithmic function % ingrowth = 15% * ln(implantation time in months) - 24.0% (R2 = 0.71, n = 14 patients). Several factors may come into play in determining bone ingrowth including the mechanical environment, the osteoconductivity of the implant material, and the osteogenic capability of the tissues in the pore spaces. Measurements of bone ingrowth are most influenced by the depth into the implant and the time the implant was in the body; the age of the patient had little affect on bone ingrowth.     

Effect of porosity on the osteointegration and bone ingrowth of a weight-bearing nickel-titanium bone graft substitute

Porous nickel-titanium (NiTi) alloy is a promising new material for a bone graft substitute with good strength properties and an elastic modulus closer to that of bone than any other metallic material. The purpose of this study was to evaluate the effect of porosity on the osteointegration of NiTi implants in rat bone. The porosities (average void volume) and the mean pore size (MPS) were 66.1% and 259+/-30 microm (group 1, n=14), 59.2% and 272+/-17 microm (group 2, n=4) and 46.6% and 505+/-136 microm (group 3, n=15), respectively. The implants were implanted in the distal femoral metaphysis of the rats for 30 weeks. The proportional bone-implant contact was best in group 1 (51%) without a significant difference compared to group 3 (39%). Group 2 had lower contact values (29%) than group 1 (p=0.038). Fibrotic tissue within the porous implant was found more often in group 1 than in group 3 (p=0.021), in which 12 samples out of 15 showed no signs of fibrosis. In conclusion, porosity of 66.1% (MPS 259+/-30 microm) showed best bone contact (51%) of the porosities tested here. However, the porosity of 46.6% (MPS 505+/-136 microm) with bone contact of 39% was not significantly inferior in this respect and showed lower incidence of fibrosis within the porous implant.     

Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes

Previous investigations have shown that both the early biological response and the mechanical properties of a porous hydroxyapatite bone graft substitute are highly sensitive to its pore structure. The objective of this study was to evaluate whether the pore structure continued to influence bone integration in the medium to long term. Two screened batches of porous hydroxyapatite (PHA) designated as batch A and batch B, with porosities of approximately 60 and 80%, respectively, were selected for this study and implanted for periods of 5, 13, and 26 weeks into the lower femur of New Zealand White rabbits. Histomorphometric analysis of the absolute volume of bone ingrowth within batch A and B implants from 5 to 26 weeks showed that the absolute volume of bone ingrowth was consistently lower in batch A (10-21%), compared to batch B implants (24-31%). However, when the volume of bone ingrowth was normalised for the available pore space, this difference was reduced (23-47% and 32-42% for batches A and B, respectively). These observations suggest that differences in the volume of bone ingrowth initially depended on pore interconnectivity rather than pore size, whereas the volume or morphology of the PHA influenced the volume and morphology of bone ingrowth at later time points. Compression testing showed that bone ingrowth had a strong reinforcing effect on PHA bone graft substitutes, and a strong correlation was identified between mechanical properties and the absolute volume of ingrowth for both batches A and B. Furthermore, at 13 and 26 weeks, there was no significant variation in the ultimate compressive strength of integrated batch A and B implants. This similarity in ultimate mechanical properties indicated that the absolute volume of ingrowth may be mediated by the PHA structure through its impact on the dynamics of the local biomechanical environment. The results of push-out testing showed that fixation of PHA bone graft substitutes was independent of density within the range studied, with no significant difference in the interfacial shear stress between batches A and B at each time point throughout the study.     

Bone response to endosseous titanium implants surface-modified by blasting and chemical treatment: a histomorphometric study in the rabbit femur

This study evaluated the effects of the addition of oxide structure with submicron-scale porous morphology on the periimplant bone response around titanium (Ti) implants with microroughened surfaces. Hydroxyapatite-blasted Ti implants with (experimental) and without (control) a porous oxide structure produced by chemical treatment were investigated in a rabbit femur model. Surface characterizations and in vivo bone response at 4 and 8 weeks after implantation were compared. The experimental implants had submicron-scale porous surface structure consisted of anatase and rutile phase, and the original R(a) values produced by blasting were preserved. The histomorphometric evaluation demonstrated statistically significantly increased bone-to-implant contact (BIC) for experimental implants, both in the three best consecutive threads (p < 0.01) and all threads (p < 0.05) at 4 weeks. There was no remarkable difference in the BIC% or bone area percentage between the two groups at 8 weeks. The porous Ti oxide surface enhanced periimplant bone formation around the Ti implants with microroughened surfaces at the early healing stage. Based on the results of this study, the addition of crystalline Ti oxide surface with submicron-sized porous morphology produced by chemical treatment may be an effective approach for enhancing the osseointegration of Ti implants with microroughened surfaces by increasing early bone-implant contact.