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.     

Cell-based resorption assays for bone graft substitutes

The clinical utilization of resorbable bone substitutes has been growing rapidly during the last decade, creating a rising demand for new resorbable biomaterials. An ideal resorbable bone substitute should not only function as a load-bearing material but also integrate into the local bone remodeling process. This means that these bone substitutes need to undergo controlled resorption and then be replaced by newly formed bone structures. Thus the assessment of resorbability is an important first step in predicting the in vivo clinical function of bone substitute biomaterials. Compared with in vivo assays, cell-based assays are relatively easy, reproducible, inexpensive and do not involve the suffering of animals. Moreover, the discovery of RANKL and M-CSF for osteoclastic differentiation has made the differentiation and cultivation of human osteoclasts possible and, as a result, human cell-based bone substitute resorption assays have been developed. In addition, the evolution of microscopy technology allows advanced analyses of the resorption pits on biomaterials. The aim of the current review is to give a concise update on in vitro cell-based resorption assays for analyzing bone substitute resorption. For this purpose models using different cells from different species are compared. Several popular two-dimensional and three-dimensional optical methods used for resorption assays are described. The limitations and advantages of the current ISO degradation assay in comparison with cell-based assays are discussed.     

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.     

Enhanced bone ingrowth into hydroxyapatite with interconnected pores by Electrical Polarization

Hydroxyapatite (HA) ceramics are used as implants to repair damaged/removed bone, and negative or positive electrical polarization enhances osteoblast and decreases osteoclast activity, respectively, in vivo. We compared the ability of electrically polarized and non-polarized HA with interconnected pores (IPHA) implants to promote bone growth. Polarized or non-treated IPHAs were implanted into the right or left femoral condyle of rabbits (N = 10 in each group), and we performed histological examination, including enzymatic staining for osteoblasts and osteoclasts, 3 and 6 weeks after implantation. We observed improved bone ingrowth and increased osteoblast activity in polarized implants with complete bone penetration into polarized implants occurring as early as 3 weeks after surgery. In contrast, non-polarized implants were not fully ossified at 6 weeks after surgery. Furthermore, positively charged implant regions had decreased osteoclast activity compared to negatively charged or uncharged regions. We propose two different models to explain these observations.     

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.     

Bioactive glass and autogenous bone as bone graft substitutes in benign bone tumors

In a prospective randomized study, 25 patients with benign bone tumors were surgically treated with either bioactive glass S53P4 (BG) or autogenous bone (AB) as bone graft material. X-rays were taken preoperatively and postoperatively at 2 weeks and at 3, 8, 12, 18, 24, and 36 months. In addition, for most of the patients, CT scans were performed at the same time-points. No infections or material-related adverse reactions occurred in any patient. The filled cavity was replaced faster by new bone in the AB group than in the BG group (p = 0.0001). However, at 36 months, no statistical difference in cavity volume between the two groups was observed on X-rays (p = 0.7881) or on CT scans (p = 0.9117). In the BG group at 3 years, the filled cavity appeared, however, dense on X-rays, and glass granules on CT scans were observed. During the follow-up period, the cortical thickness seemed to increase more in the BG group than in the AB group (p < 0.0001).     

Fabrication and mechanical and tissue ingrowth properties of unidirectionally porous hydroxyapatite/collagen composite

This study investigated the effects of the three-dimensional (3-D) pore structure of a porous hydroxyapatite/collagen (HAp/Col) composite on their mechanical properties and in vivo tissue ingrowth. The unique 3-D pore structure, comprising unidirectionally interconnected pores, was fabricated by the unidirectional growth of ice crystals by using a cooling stage and a subsequent freeze-drying process. The unidirectional pores had a spindle-shaped cross section, and their size gradually increased from the bottom to the upper face. The porous composite showed an elastic property and anisotropic compressive strength for the pore directions. While the strength and modulus parallel to the pore axis were 1.3- and twofold higher than those of the porous composite with spherical pores formed randomly, the strength and modulus perpendicular to the pore axis showed the lowest values. The subcutaneous implantations revealed that when compared with the random pores, the unidirectional pores promote the ingrowth of the surrounding tissues into the pores.     

Bone ingrowth in bFGF-coated hydroxyapatite ceramic implants

This experimental study was performed to evaluate angiogenesis, bone formation, and bone ingrowth in response to osteoinductive implants of bovine-derived hydroxyapatite (HA) ceramics either uncoated or coated with basic fibroblast growth factor (bFGF) in miniature pigs. A cylindrical bone defect was created in both femur condyles of 24 miniature pigs using a saline coated trephine. Sixteen of the 48 defects were filled with HA cylinders coated with 50 microg rhbFG, uncoated HA cylinders, and with autogenous transplants, respectively. Fluorochrome labelled histological analysis, histomorphometry, and scanning electron microscopy were performed to study angiogenesis, bone formation and bone ingrowth. Complete bone ingrowth into bFGF-coated HA implants and autografts was seen after 34 days compared to 80 days in the uncoated HA group. Active ring-shaped areas of fluorochrome labelled bone deposition with dynamic bone remodelling were found in all cylinders. New vessels could be found in all cylinders. Histomorphometric analysis showed no difference in bone ingrowth over time between autogenous transplants and bFGF-coated HA implants. The current experimental study revealed comparable results of bFGF-coated HA implants and autogenous grafts regarding angiogenesis, bone synthesis and bone ingrowth.     

Beta-TCP bone graft substitutes in a bilateral rabbit tibial defect model

The use of artificial bone graft substitutes has increased as the surgical applications widen and the availability of allograft bone decreases. The ideal graft substitute should reabsorb with time to allow and encourage new bone formation whilst maintaining its properties as an osteoconductive scaffold until it is no longer required. A potential disadvantage of some synthetic substitutes is their long dissolution time. Beta-tricalcium phosphates (beta-TCPs) have some advantages when compared to hydroxyapatite (HA), when used as a filler, in that it is more rapidly reabsorbed. Three commercially available and clinically used beta-TCP bone graft substitutes with the same chemistry (Vitoss, Osferion, Chronos) but with varying macro and microscopic characteristics were investigated using a bilateral tibial metaphyseal defect model in New Zealand white rabbits. When placed into tibial defects all three materials performed similarly in terms of mechanical properties of the healing defects. A decrease in properties was found at 12 weeks where implant resorption was nearly achieved while remodelling of the anteromedial cortex had yet to be completed. All materials were osteoconductive and supported new bone formation while implant resorption with time differed between materials. Vitoss resorbed faster than the other materials and is likely to differences in particle geometry, pore structure and interconnectivity.     

Increasing strut porosity in silicate-substituted calcium-phosphate bone graft substitutes enhances osteogenesis

Synthetic, porous silicate-substituted calcium phosphate bone graft matrices (SiCaP; 0.8 wt % Si) with varying strut porosity were applied to ovine critical-sized defect sites as either 1-2 mm microgranules (SiCaP-23G, SiCaP-32G, and SiCaP-46G) or 1-2 mm microgranules in an aqueous poloxamer carrier (SiCaP-23P, SiCaP-32P, and SiCaP-46P). Defect sites treated with SiCaP-23G or SiCaP-23P showed evidence of bone formation at 8 and 12 weeks in central zones. More advanced neovascularization and increased bone contact was observed for graft materials with higher strut porosities. At 12 weeks, graft materials with higher strut porosities (32% and 46%) had statistically significantly higher absolute bone volumes (p < 0.05) versus those with a strut porosity of 23%. Absolute bone volume in defects treated with grafts of matched strut porosities as microgranules, or microgranules with poloxamer carrier, were similar at 12 weeks. Absolute graft volume for SiCaP-46 reduced over 12 weeks (not statistically significant). In conclusion, bone formation patterns in critically-sized defects confirm strut porosity to be a clinically relevant property of porous silicate-substituted calcium phosphate bone grafts in promoting osteogenesis. Increasing graft matrix strut porosity encouraged earlier neovascularization and increased the absolute equilibrium volume of bone growth within the graft without compromising graft stability.     

In vitro corrosion study of porous metal fibre coatings for bone ingrowth

As a first part of a biocompatibility testing programme, in vitro corrosion tests were carried out on porous stainless steel AISI 316L and titanium compacts made of 100 microns thick fibres. The present porous metal structures are used as coatings on permanent orthopaedic implants; with osseous tissue invading the pores, the implant becomes securely anchored to the surrounding bone. The results show that no inadvertent reactions occur with porous titanium. It can probably be used with no greater risk of localized electrochemical attack than the parent bulk material.     

Comparison of hydroxyapatite and beta tricalcium phosphate as bone substitutes after excision of bone tumors

Long-term results are reported in 23 patients and short-term results in 30 patients presenting with bone tumors treated by curettage or resection followed by implantation of hydroxyapatite (HA) or highly purified beta-tricalcium phosphate (beta-TCP), respectively. Mean follow-up was 97 and 26 months in cases involving HA implantation and beta-TCP implantation, respectively. Radiographs revealed HA incorporation into host bone in all but two cases; moreover, no obvious evidence of HA biodegradation was observed. A single patient exhibited late deformity following implantation of HA. All grafted beta-TCP was, at least partially, absorbed and replaced by newly formed bone. The mean period required for the disappearance of radiolucent zones between the ceramics and host bone was 17 weeks in HA and 9.7 weeks in beta-TCP. Highly purified beta-TCP appears to be advantageous relative to HA for surgical intervention in bone tumors consequent to the nature of remodeling and superior osteoconductivity.     

Supercritical carbon dioxide processed resorbable polymer nanocomposite bone graft substitutes

The development of synthetic bone graft substitutes is an intense area of research due to the complications associated with the harvest of autogenous bone and concerns about the supply of allogenic bone. Porous resorbable polymers have been used extensively in hard tissue engineering applications, but currently lack load-bearing capacity. Supercritical carbon dioxide (scCO(2)) processing is used as a novel method to simultaneously impart a porous structure and disperse a nano-clay in a resorbable polymer matrix suitable for load-bearing applications. Porous resorbable polylactic acid (PLA)/cloisite clay nanocomposite constructs prepared using scCO(2) processing exhibit a 2.5-fold increase in compressive strength compared with pure polymer constructs. The resulting mechanical properties are comparable with human cancellous and cortico-cancellous bone. In addition to the significant improvements in mechanical properties, the nanocomposite constructs display a biocompatibility greater than that of polystyrene culture plate controls. Furthermore, calcium phosphate-rich deposits could clearly be seen on the surface of the constructs, as well as at the center of the cultured constructs, indicating that osteoblasts are able to penetrate the porous network of the nanocomposite constructs. Cellular infiltration of these constructs is important for their in vivo use as bone graft substitutes. The diameter of the pores suggests that these constructs would also support neovascularization, which is integral for nutrient transport.     

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.     

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.     

Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength.

The effect of a plasma-sprayed hydroxylapatite (HA) coating on the degree of bone ingrowth and interface shear attachment strength was investigated using a canine femoral transcortical implant model. Cylindrical implants were fabricated by sintering spherical Co-Cr-Mo particles 500-710 microns in diameter; the nominal implant dimensions were 5.95 +/- 0.05 mm diameter by 18 mm in length. One half of each implant was coated with hydroxylapatite, 25-30 microns in thickness, by a plasma-spray technique. Using strict aseptic technique, the implants were placed through both femoral cortices into defects approximately 0.05 mm undersized. After 2, 4, 6, 8, 12, 18, 26, and 52 weeks, the implants were harvested and subjected to mechanical pullout testing and undecalcified histologic evaluation. The application of the HA coating to porous implants enhanced both the amount of bone ingrowth and the interface attachment strength at all time periods. These differences were statistically significant for the percent of bone ingrowth at the 4-, 6-, 12-, 18-, 26-, and 52-week time periods, and interface shear strength values were significantly different at the 6-, 8-, 12-, 18-, and 26-week time periods. The rate of development of interface strength and bone ingrowth was also more rapid for the HA-coated implants. No evidence of any disruption, mechanical failure, or biologic resorption of the HA coating was observed. The results of the present study--demonstrating a beneficial effect of the HA coating at all time periods--are believed to be due to the use of paired comparisons, which allow assessment of subtle differences that might otherwise have been obscured by normal biological variability.     

Biodegradable polyurethane cancellous bone graft substitutes in the treatment of iliac crest defects

Porous scaffolds were produced from newly designed biodegradable, segmented aliphatic polyurethanes of various chemical compositions and hydrophilic-to-hydrophobic segment ratios. The scaffolds were implanted into monocortical defects in the iliac crest of healthy sheep for 6 months. The resected cortex was not repositioned. The ilium defects, which were not implanted with polyurethane scaffolds, were used as controls. In none of the control defects was there bone regeneration at the time of euthanasia. The defects implanted with porous scaffolds from polyurethanes were healed to varying extents with cancellous bone. The structure of the regenerated cancellous bone was radiographically denser than the structure of native bone. New bone that was formed in the scaffolds with a higher amount of hydrophilic component contained more calcium phosphate deposit than the bone formed in the scaffolds with a lower amount of the hydrophilic component. There was no new cortex formed over the defect, but a thin layer of soft tissue covered the newly formed cancellous bone.     

Evaluation of bone healing with eggshell-derived bone graft substitutes in rat calvaria: a pilot study

The purpose of this study was to investigate the potential effectiveness of a surface-modified natural calcium carbonate, hen eggshell (ES) as a bone graft substitute. The surface characteristics, cell viability on, and osteoconductivity of, particulated ES with and without hydrothermal treatment in phosphate solutions were evaluated. Hydrothermal treatment partially converted ES to calcium-deficient hydroxyapatite (HA) with surface microstructure. MTT assay indicated higher osteoblast viability on surface-modified ES compared with a commercially available bone substitute, anorganic bovine bone (Bio-Oss, BO) (p < 0.001). Histological and histomorphometric analysis showed significantly greater new bone formation and mineralized bone-to-graft contact of surface-modified ES, especially with hydrothermally treated ES, compared with BO in 5-mm diameter calvarial defects in rats at 4 and 8 weeks of healing (p < 0.01). Complete bony bridging was more frequently found with hydrothermally treated ES. The results of this pilot study indicate the potential efficacy of surface-modified particulated hen eggshell as an osteoconductive bone substitute in a rat calvarial defect model.