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.     

Effects of local infusion of TGFbeta on bone ingrowth in rabbit chambers

The local delivery of exogenous growth factors may help achieve a stable, long-lasting prosthetic interface around primary and revision joint replacements. This study examines the effects of local infusion of transforming growth factor beta (TGFbeta) in an in vivo model of tissue differentiation within bone. The Drug Test Chamber was implanted in the proximal medial tibial metaphysis of 8 mature rabbits unilaterally. The chamber contained a 1 x 1 x 5 mm canal for tissue ingrowth. The chamber was connected to an osmotic diffusion pump via polyvinyl tubing. 3.5 microg of recombinant TGFbeta1 was infused for 1 day or 1 week with subsequent harvesting of the ingrown tissue after 3 weeks. Each TGFbeta treatment was followed by two, 3-week infusions of carrier alone and harvesting of the ingrown tissue. TGFbeta for 1 day increased, and TGFbeta for 1 week decreased the percentage of bone in the chamber, compared to the initial control harvest after carrier alone. These changes, however, did not reach statistical significance. The number of vitronectin receptor positive cells in total, adjacent to bone and away from bone was higher after treatment with TGFbeta for 1 day, compared to 1 week. In an "unperturbed" bone ingrowth system (i.e., if bone ingrowth is not initially suppressed by other stimuli), this dose of TGFbeta did not enhance bone ingrowth using the DTC model.     

Effects of bone ingrowth on the strength and non-invasive assessment of a coralline hydroxyapatite material

The dependence of strength on the amount of bone growth into a hydroxyapatite material made from coral was investigated. Block and granular forms of the material were implanted into cortical and trabecular regions of the skeletons of 16 dogs. The results were examined after 4, 8, 12 and 16 wk, with four dogs in each experimental group. When implanted into cortical bone, the bending strength of the implant material was found to be highly correlated with the amount of pore space which had become occupied by bone (r = 0.92, P less than 0.005 for the block form; r = 0.84, P less than 0.005 for the granular form). Multiple regression analysis showed that six histomorphometric measures of ingrowth accounted for 96% of the variability in bending strength of the block material, and there were no significant differences between block and granular forms of the material. On the other hand, when implanted into trabecular bone, the block form of the material achieved greater compressive strength than the granular form. While both strength and ingrowth increased with time, there were poor correlations between these two variables. Finally, when the material is implanted into trabecular bone, it becomes stronger in compression than the surrounding bone; when implanted in cortical bone, linear modelling suggests that resorption and replacement of the implant would be required to approximate the bending strength of the surrounding bone.     

MicroCT analysis of hydroxyapatite bone repair scaffolds created via three-dimensional printing for evaluating the effects of scaffold architecture on bone ingrowth

Recent studies have shown that it is now possible to construct tissue-engineered bone repair scaffolds with tight pore size distributions and controlled geometries using 3-D Printing techniques (3DP). This study evaluated two hydroxyapatite (HA) 8-mm diameter discs with controlled architectures in a rabbit trephine defect at 8 and 16 weeks using a 2 x 2 factorial design. Input parameters were time and scaffold void volume at two levels. Three output variables were extracted from MicroCT data: bone volume ingrowth with respect to total region of interest, bone volume ingrowth with respect to available ingrowth volume, and soft tissue volume. The experiment measured two groups--Group 1: 500-microm x 500-microm channels parallel to the scaffold's long axis and penetrating up 3-mm from the bottom. Group 2: 800-microm x 800-microm struts spaced 500 microm apart set perpendicularly to each other in each printed layer. Rendered 3-dimensional MicroCT scans and undecalcified histological slides of implants revealed good integration with the surrounding tissue, and a sizeable amount of bone ingrowth into the device. Factorial analysis revealed that the effects of time were the greatest determinant of soft tissue ingrowth, while time and its interaction with void volume were the greatest determinants of bone volume ingrowth with respect to both total and available volume.     

Segmental bone repair by tissue-engineered periosteal cell transplants with bioresorbable fleece and fibrin scaffolds in rabbits

The biological bone healing depends on the presence of osteochondral progenitors and their ability for proliferation. Isolated periosteal cells were seeded into biodegradable PGLA polymer fleece or fibrin beads and cultivated for 14 days after prior monolayer culture. On 12 New Zealand white rabbits 8 mm metadiaphyseal ulna defects were created bilaterally and subsequently filled with cell-fibrin beads, with polymers seeded with cells compared to controls with fibrin beads and polymers alone and untreated defects. A semiquantitative grading score was applied for histomorphological and radiological analysis after 28 days. Histologically intense bone formation was observed in both experimental groups with cell transplants only. The histological and radiological scoring was superior for both experimental groups. Control groups revealed only poor healing indices and untreated defects did not heal. The highest histological score was noted in the group with polymer fleeces containing periosteal cells. Applying the radiographic score system we determined a significant difference between experimental groups and controls without cells. The radiographic and histological scores for both experimental groups containing periosteal cells differed not significantly. The results strongly encourage the approach of the transplantation of pluripotent mesenchymal cells within a suitable carrier structure for the reconstruction of critical size bone defects.     

Effects of local infusion of OP-1 on particle-induced and NSAID-induced inhibition of bone ingrowth in vivo

Excessive polyethylene wear particles from joint replacements may lead to periprosthetic osteolysis and loosening. Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease fracture healing and bone ingrowth. We hypothesized that continuous local infusion of OP-1 (BMP-7) would increase local bone formation in the presence of two different adverse stimuli, polyethylene particles, and an oral NSAID. The Drug Test Chamber (DTC) was implanted in the proximal tibia of mature rabbits. The tissue growing into the chamber was exposed to OP-1 solution (110 ng/day), which was infused via an osmotic pump. Infusion of OP-1 alone for 6 weeks enhanced local bone formation in the chamber by 80% (p < 0.05) over infusion of carrier alone. In the presence of polyethylene particles, infusion of OP-1 increased local bone formation by 38% (p < 0.05) over treatment with particles and carrier. Oral administration of NSAID reduced local bone formation by 58% (p < 0.05); this suppressive effect caused by NSAIDS was completely reversed by the infusion of OP-1 (p < 0.05). These findings underline a potential role for local treatment with OP-1 to increase bone formation in the presence of potentially adverse stimuli such as polyethylene wear particles or NSAID use.     

Effects of a p38 MAP kinase inhibitor on bone ingrowth and tissue differentiation in rabbit chambers

The effects of an oral p38 mitogen-activated protein kinase (MAPK) inhibitor and polyethylene particles separately and together on tissue differentiation in the bone harvest chamber (BHC) in rabbits over a 3-week treatment period were investigated. The harvested tissue was analyzed histomorphometrically for markers of bone formation (percentage of bone area), osteoblasts (alkaline phosphatase staining), and osteoclasts (CD51, the alpha chain of the vitronectin receptor). Polyethylene particles decreased the percentage of bone ingrowth and staining for alkaline phosphatase. The p38 MAPK inhibitor alone decreased alkaline phosphatase staining. When the oral p38 MAPK inhibitor was given and the chamber contained polyethylene particles, there was a suppression of bone ingrowth and alkaline phosphatase staining. In contrast to oral non-steroidal anti-inflammatory drugs (NSAIDs) and local Interleukin-1 receptor antagonist (IL-1ra) administration, the oral p38 MAPK inhibitor alone did not suppress bone formation when given during the initial phase of tissue differentiation. Particle-induced inflammation and the foreign body reaction were not curtailed when the p38 MAPK inhibitor was given simultaneously with particles. Additional experiments are needed to establish the efficacy of p38 MAPK inhibitor administration on mitigating an established inflammatory and foreign body reaction that parallels the clinical situation more closely.     

Effect of spaceflight on periosteal bone formation in rats

Male Wistar rats were placed in orbit for 18.5 days aboard the Soviet COSMOS 1129 biological satellite. Tetracycline was administered before and after spaceflight to label areas of bone formation. An inhibition of periosteal bone formation occurred during spaceflight in the tibial and humeral diaphyses, but this defect was corrected during the postflight period. The increased extent of arrest lines at these skeletal sites suggested that periosteal bone formation may have even ceased during spaceflight. The rib exhibited a small but nonsignificant decrease in periosteal bone formation. Endosteal bone resorption was not affected markedly by spaceflight conditions. The observed inhibition of periosteal bone formation may be a result of mechanical unloading, but endocrine factors cannot be ruled out.     

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.     

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.     

Biomimetic nano-apatite coating capable of promoting bone ingrowth

Nano-apatite coating closely mimicking bone mineral was grown directly on titanium soaked in an aqueous solution containing all major inorganic components present in the body, mainly, HCO3(-), Ca(2+), HPO4(2-), and Mg(2+) ions. The removal of HCO3(-) ions from the solution in the form of CO2 resulted in the increase of solution pH. As a consequence of this reaction, the nano-apatite coating was formed on the surface of titanium with composition and structure equivalent to those of bone mineral. The biomimetic nano-apatite was demonstrated to be capable of conducting bone formation and promoting direct bone apposition. This bioactive coating also affected the behavior of human osteoblasts as indicated by their morphologies observed in cell culture study.     

Temporal effects of a COX-2-selective NSAID on bone ingrowth

The effects of a short course of a COX-2 inhibitor on bone healing when the drug is discontinued are unknown. We examined the effects of rofecoxib on bone ingrowth over a 6-week period using a well-defined animal model. The Bone Harvest Chamber was implanted bilaterally in mature rabbits. After osseointegration of the chamber, the following treatments were given for 6 weeks each, followed by a harvest in each case: control-no drug; oral rofecoxib (12.5 mg/day) for the first 2 of 6 weeks; washout period-no drug; oral rofecoxib for the last 2 of 6 weeks; washout period-no drug; rofecoxib given continuously for all 6 weeks. Harvested specimens were snap-frozen, cut into serial 6-microm sections, and stained with hematoxylin and eosin and alkaline phosphatase (osteoblast marker), and processed using immunohistochemistry to identify the vitronectin receptor (osteoclast-like cells). Rofecoxib given continuously for 6 weeks yielded statistically less bone ingrowth compared to the control treatment. Rofecoxib given during the initial or final 2 weeks of a 6-week treatment did not appear to interfere with bone ingrowth. This suggests that the effects of COX-2 inhibitors on bone are less profound when the drug is administered for a short period of time.     

Preliminary observations of bone ingrowth into porous materials.

A preliminary investigation has been performed (a) to determine the kinetics of bone ingrowth into porous materials and to determine if this ingrowth could be catalyzed by the presence of a foreign substrate; and (b) to measure the bonding capability of bone with a porous-surfaced metallic implant. Tests on porous-surfaced implants corroborate the work of other investigators in showing that bony tissue will grow into a porous substance that has pores large enough to support tissue nourishment. The shear strength of the bone-implant interface appears to increase with pore size and time of healing. Furthermore, it may be possible to catalyze this tissue ingrowth by the introduction into the fracture site of a foreign substance; in this experiment, glass beads 200-290mu in diameter were used.     

The rate of bone ingrowth into porous metal.

Experiments have been devised to study the rate of ingrowth of bone into porous metal with pore sizes up to 100 mu and to study the significance of a gap between the porous metal surface and bone. When the porous coat was in direct apposition with bone, the implant was firmly locked in place after a three week period and the plateau value of implant-tissue shear strength was reached at four weeks. A gap of 1.5 mm between the bone and the implant was bridged by new bone within four weeks.     

Assessment of bone ingrowth into porous biomaterials using MICRO-CT

The three-dimensional (3D) structure and architecture of biomaterial scaffolds play a critical role in bone formation as they affect the functionality of the tissue-engineered constructs. Assessment techniques for scaffold design and their efficacy in bone ingrowth studies require an ability to accurately quantify the 3D structure of the scaffold and an ability to visualize the bone regenerative processes within the scaffold structure. In this paper, a 3D micro-CT imaging and analysis study of bone ingrowth into tissue-engineered scaffold materials is described. Seven specimens are studied in this paper; a set of three specimens with a cellular structure, varying pore size and implant material, and a set of four scaffolds with two different scaffold designs investigated at early (4 weeks) and late (12 weeks) explantation times. The difficulty in accurately phase separating the multiple phases within a scaffold undergoing bone regeneration is first highlighted. A sophisticated three-phase segmentation approach is implemented to develop high-quality phase separation with minimal artifacts. A number of structural characteristics and bone ingrowth characteristics of the scaffolds are quantitatively measured on the phase separated images. Porosity, pore size distributions, pore constriction sizes, and pore topology are measured on the original pore phase of the scaffold volumes. The distribution of bone ingrowth into the scaffold pore volume is also measured. For early explanted specimens we observe that bone ingrowth occurs primarily at the periphery of the scaffold with a constant decrease in bone mineralization into the scaffold volume. Pore size distributions defined by both the local pore geometry and by the largest accessible pore show distinctly different behavior. The accessible pore size is strongly correlated to bone ingrowth. In the specimens studied a strong enhancement of bone ingrowth is observed for pore diameters>100 microm. Little difference in bone ingrowth is measured with different scaffold design. This result illustrates the benefits of microtomography for analyzing the 3D structure of scaffolds and the resultant bone ingrowth.     

Effects of gentamicin and gentamicin-RGD coatings on bone ingrowth and biocompatibility of cementless joint prostheses: an experimental study in rabbits

Antimicrobial coatings are of interest as a means to improve infection prophylaxis in cementless joint arthroplasty. However, those coatings must not interfere with the essential bony integration of the implants. Gentamicin-hydroxyapatite (gentamicin-HA) and gentamicin-RGD (arginine-glycine-aspartate)-HA coatings have recently been shown to significantly reduce infection rates in a rabbit infection prophylaxis model. The purpose of the current study was to investigate the in vitro elution kinetics and in vivo effects of gentamicin-HA and gentamicin-RGD-HA coatings on new bone formation, implant integration and biocompatibility in a rabbit model. In vitro elution testing showed that 95% and 99% of the gentamicin was released after 12 and 24 h, respectively. The in vivo study comprised 45 rabbits in total, with six animals for each of the gentamicin-HA, gentamicin-RGD-HA group and control pure HA coating groups for the 4 week time period, and nine animals for each of the three groups for the 12 week observation period. A 2.0 mm steel K-wire with one of the coatings under test was placed in the intramedullary canal of the tibia. After 4 and 12 weeks the tibiae were harvested and three different areas (proximal metaphysis, shaft area, distal metaphysis) were assessed by quantitative and qualitative histology for new bone formation, direct implant-bone contact and the formation of multinucleated giant cells. The results exhibited high standard deviations in all subgroups. There was a trend towards better bone formation and better direct implant contact in the pure HA coating group compared with both gentamicin coatings after 4 and 12 weeks, which was, however, not statistically significant. The number of multinucleated giant cells did not differ significantly between the three groups at both time points. In summary, both gentamicin coatings with 99% release of gentamicin within 24 h revealed good biocompatibility and bony integration, which was not statistically significant different compared with pure HA coating. Limitations of the study are the high standard deviation of the results and the limited number of animals per time point.     

Effect of calcium phosphate coating characteristics on early post-operative bone tissue ingrowth

The synthesis of model porous metal-CPC materials, and their use in one-parametric studies of bone tissue ingrowth enhancement were considered. By using the same starting calcium-deficient hydroxyapatite powder, three different coatings, CAP1, CAP2 and CAP3, were obtained of thicknesses 50 +/- 5, 75 +/- 5 and 75 +/- 5 microns, respectively. CAP1 and 2 were either the starting powder mixed in a 3:1 ratio CPC: poly(lactic acid) or the powder by itself. The CAP3 coating was the result of a thermal treatment producing a mixture of oxyhydroxyapatite, alpha- and beta-tricalcium phosphate. Orderly oriented wire mesh porous coated specimens were implanted, along with the same specimens lined with CAP 1, 2 or 3. Subsequently, the total of 156 specimens was retrieved at 2, 4 or 6 wk, and tested mechanically and processed for histomorphometry. The data produced considerable evidence for the CPC-dependent enhancement of bone tissue ingrowth in porous metals immediately after implantation. They prove that the materials processing of CPC coatings influences the resulting biological behaviour substantially. Furthermore, they support the hypothesis that ceramic dissolution is a causative factor on the bone tissue growth enhancement mechanisms.     

Development of a large titanium bone chamber to study in vivo bone ingrowth

In the bone conduction chamber (BCC) various materials and factors have been tested for their effect on bone graft incorporation and bone healing. However, biomaterials often have to be crushed to fit in this small chamber. Since cellular responses to biomaterials are influenced by the size and shape of particles, research concerning the evaluation of biomaterials is limited by the dimensions of this bone chamber. We enlarged and modified the BCC in order to be able to investigate the in vivo influences of biomaterials, growth factors and bone graft processing on tissue and bone ingrowth. Seven goats received four bone chambers each, three modified models and a BCC. The first model (BCC+) had two ingrowth openings, similar to that of the BCC. The second model had two round ingrowth openings (ROU). The third model had a open bottom for bone ingrowth (BOT). After 12 weeks, bone ingrowth distances were measured on histological sections and using muCT. Bone ingrowth was significantly higher (p=0.009 and 0.008) in the ROU compared to the BCC+ and the BOT, respectively. Similar results were found using muCT. The ROU model performed most similar to the BCC (gold standard) and is considered to be a promising new tool in biomaterials research.     

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.