Vertebral augmentation with spinal implants: third-generation vertebroplasty.

This article is to review the different types of vertebral augmentation implants recently becoming available for the treatment of benign and malignant spinal compression fractures. After a detailed description of the augmentation implants, we review the available clinical data. We will conclude with a summary of the advantages and disadvantages of vertebral implants and how they can affect the future treatment options of compression fractures.

Spine Intervention-An Update on Injectable Biomaterials.

Back pain is the second most common reason for primary-care physician visits after the common cold. New understanding of the spine pathophysiology and biomechanics led to the development of novel injectable biomaterials to treat those pain generators. Although not all biomaterials are currently ready for common use, there is significant interest by the medical community to invest time, resources, and energy to optimize these injectables. This review introduces basic concepts and advancements in the field of bioinjectables tailored for the vertebral body. Also, we highlight advances in injectable biomaterials which were presented at the Groupe de Recherche Interdisciplinaire sur les Biomatériaux Ostéoarticulaires Injectables (GRIBOI) (Interdisciplinary Research Society for Injectable Osteoarticular Biomaterials) meeting in March 2018 in Los Angeles, CA. Indeed, multidisciplinary translational research and international meetings such as GRIBOI bring together scientists and clinicians with different backgrounds/expertise to discuss injectable biomaterials innovations tailored for the interventional pain management field.

Multimodal analysis of in vivo resorbable CaP bone substitutes by combining histology, SEM, and microcomputed tomography data.

This study introduced and demonstrated a new method to investigate the repair process of bone defects using micro- and macroporous beta-tricalcium phosphate (ß-TCP) substitutes. Specifically, the new method combined and aligned histology, SEM, and preimplantation microcomputed tomography (mCT) data to accurately characterize tissue phases found in biopsies, and thus better understand the bone repair process. The results included (a) the exact fraction of ceramic remnants (CR); (b) the fraction of ceramic resorbed and substituted by bone (CSB); and (c) the fraction of ceramic resorbed and not substituted by bone (CNSB). The new method allowed in particular the detection and quantification of mineralized tissues within the 1-10 µm micropores of the ceramic ("micro-bone"). The utility of the new method was demonstrated by applying it on biopsies of two ß-tricalcium phosphate bone substitute groups with two differing macropore sizes implanted in an ovine model for 6 weeks. The total bone deposition and ceramic resorption of the two substitute groups, having macropore sizes of 510 and 1220 µm, were 25.1 ± 8.1% and 67.5 ± 3.2%, and 24.4 ± 4.1% and 61.4 ± 6.5% for the group having the larger pore size. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1567-1577, 2018.

A novel method for segmenting and aligning the pre- and post-implantation scaffolds of resorbable calcium-phosphate bone substitutes.

Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional structure of bone graft scaffolds before and after implantation in order to assess changes occurring during implantation. The accurate processing of the microCT datasets of explanted ß-tricalcium phosphate (ß-TCP) scaffolds poses significant challenges because of (a) the overlap in the grey values distribution of ceramic remnants, bone, and soft tissue, and of (b) the resorption of the bone substitute during the implantation. To address those challenges, this article introduces and rigorously validates a new processing technique to accurately distinguish these three phases found in the explanted ß-TCP scaffolds. Specifically, the microCT datasets obtained before and after implantation of ß-TCP scaffolds were aligned in 3D, and the characteristic grey value distributions of the three phases were extracted, thus allowing for (i) the accurate differentiation between these three phases (ceramic remnants, bone, soft tissue), and additionally for (ii) the localization of the defect site in the post-implantation microCT dataset. Using the similarity matrix, a 94±1% agreement was found between algorithmic results and the visual assessment of 556,800 pixels. Moreover, the comparison of the segmentation results of the same microCT and histology section further confirmed the validity of the present segmentation algorithm. This new technique could lead to a more common use of microCT in analyzing the complex 3D processes and to a better understanding of the biological processes occurring after the implantation of ceramic bone graft substitutes. STATEMENT OF SIGNIFICANCE: Calcium-phosphate scaffolds are being increasingly used to repair critical bone defects. Methods for the accurate characterization of the repair process are still lacking. The present study introduced and validated a novel image-processing technique, using micro-computed tomography (mCT) datasets, to investigate material phases present in biopsies. Specifically, the new method combined mCT datasets from the scaffold before and after implantation to access the characteristic data of the ceramic for more accurate analysis of bone biopsies, and as such to better understand the interactions of the scaffold design and the bone repair process.

Percutaneous Dorsal Instrumentation of Vertebral Burst Fractures: Value of Additional Percutaneous Intravertebral Reposition-Cadaver Study.

PURPOSE: The treatment of vertebral burst fractures is still controversial. The aim of the study is to evaluate the purpose of additional percutaneous intravertebral reduction when combined with dorsal instrumentation. METHODS: In this biomechanical cadaver study twenty-eight spine segments (T11-L3) were used (male donors, mean age 64.9 ± 6.5 years). Burst fractures of L1 were generated using a standardised protocol. After fracture all spines were allocated to four similar groups and randomised according to surgical techniques (posterior instrumentation; posterior instrumentation + intravertebral reduction device + cement augmentation; posterior instrumentation + intravertebral reduction device without cement; and intravertebral reduction device + cement augmentation). After treatment, 100000 cycles (100-600 N, 3 Hz) were applied using a servohydraulic loading frame. RESULTS: Overall anatomical restoration was better in all groups where the intravertebral reduction device was used (p < 0.05). In particular, it was possible to restore central endplates (p > 0.05). All techniques decreased narrowing of the spinal canal. After loading, clearance could be maintained in all groups fitted with the intravertebral reduction device. Narrowing increased in the group treated with dorsal instrumentation. CONCLUSIONS: For height and anatomical restoration, the combination of an intravertebral reduction device with dorsal instrumentation showed significantly better results than sole dorsal instrumentation.

Vertebral augmentation with nitinol endoprosthesis: clinical experience in 40 patients with 1-year follow-up.

PURPOSE: This study was designed to assess the clinical outcomes of patients treated by vertebral augmentation with nitinol endoprosthesis (VNE) to treat painful vertebral compression fractures. METHODS: Forty patients with one or more painful osteoporotic VCF, confirmed by MRI and accompanied by back-pain unresponsive to a minimum 2 months of conservative medical treatment, underwent VNE at 42 levels. Preoperative and postoperative pain measured with Visual Analog Scale (VAS), disability measured by Oswestry Disability Index (ODI), and vertebral height restoration (measured with 2-dimensional reconstruction CT) were compared at last follow-up (average follow-up 15 months). Cement extravasation, subsequent fractures, and implant migration were recorded. RESULTS: Long-term follow-up was obtained in 38 of 40 patients. Both VAS and ODI significantly improved from a median of 8.0 (range 5-10) and 66 % (range 44-88 %) to 0.5 (range 0-8) and 6 % (range 6-66 %), respectively, at 1 year (p < 0.0001). Vertebral height measurements comparing time points increased in a statistically significant manner (ANOVA, p < 0.001). Overall cement extravasation rate was 9.5 %. Discal and venous leakage rates were 7.1 and 0 % respectively. No symptomatic extravasations occurred. Five of 38 (13.1 %) patients experienced new spontaneous, osteoporotic fractures. No device change or migration was observed. CONCLUSIONS: VNE is a safe and effective procedure that is able to provide long-lasting pain relief and durable vertebral height gain with a low rate of new fractures and cement leakages.

Height restoration and maintenance after treating unstable osteoporotic vertebral compression fractures by cement augmentation is dependent on the cement volume used.

BACKGROUND: Two different procedures, used for percutaneous augmentation of vertebral compression fractures were compared, with respect to height restoration and maintenance after cyclic loading. Additionally the impact of the cement volume used was investigated. METHODS: Wedge compression fractures were created in 36 human cadavaric vertebrae (T10-L3). Twenty-seven vertebrae were treated with the SpineJack® with different cement volumes (maximum, intermediate, and no cement), and 9 vertebrae were treated with Balloon Kyphoplasty. Vertebral heights were measured pre- and postfracture as well as after treatment and loading. Cyclic loading was performed with 10,000cycles (1Hz, 100-600N). FINDINGS: The average anterior height after restoration was 85.56% for Kyphoplasty; 96.20% for SpineJack® no cement; 93.44% for SpineJack® maximum and 96% for the SpineJack® intermediate group. The average central height after restoration was 93.89% for Kyphoplasty; 100.20% for SpineJack® no cement; 99.56% for SpineJack® maximum and 101.13% for the SpineJack® intermediate group. The average anterior height after cyclic loading was 85.33 % for Kyphoplasty; 87.30% in the SpineJack® no cement, 92% in the SpineJack® maximum and 87% in the SpineJack® intermediate group. The average central height after cyclic loading was 92% for Kyphoplasty; 93.80% in the SpineJack® no cement; 98.56% in the SpineJack® maximum and 94.25% in the SpineJack® intermediate group. INTERPRETATION: Height restoration was significantly better for the SpineJack® group compared to Kyphoplasty. Height maintenance was dependent on the cement volume used. The group with the SpineJack® without cement nevertheless showed better results in height maintenance, yet the statistical significance could not be demonstrated.

Synthesis of spherical calcium phosphate particles for dental and orthopedic applications.

Calcium phosphate materials have been used increasingly in the past 40 years as bone graft substitutes in the dental and orthopedic fields. Accordingly, numerous fabrication methods have been proposed and used. However, the controlled production of spherical calcium phosphate particles remains a challenge. Since such particles are essential for the synthesis of pastes and cements delivered into the host bone by minimally-invasive approaches, the aim of the present document is to review their synthesis and applications. For that purpose, production methods were classified according to the used reagents (solutions, slurries, pastes, powders), dispersion media (gas, liquid, solid), dispersion tools (nozzle, propeller, sieve, mold), particle diameters of the end product (from 10 nm to 10 mm), and calcium phosphate phases. Low-temperature calcium phosphates such as monetite, brushite or octacalcium phosphate, as well as high-temperature calcium phosphates, such as hydroxyapatite, ß-tricalcium phosphate or tetracalcium phosphate, were considered. More than a dozen production methods and over hundred scientific publications were discussed.

Mechanical variables affecting balloon kyphoplasty outcome--a finite element study.

It is still unclear how a vertebral fracture should be stabilised and strengthened without endangering the remaining intact bone of the augmented vertebra or the adjacent vertebrae. Numerical modelling may provide insight. To date, however, few finite element (FE) spine models have been developed which are both multi-segmental and capture a more complete anatomy of the vertebrae. A 3-D, two-functional unit, CT-based, lumbar spine, FE model was developed and used to predict load transfer and likelihood of fracture following balloon kyphoplasty. The fractured anterior wall and injected cement were modelled in a two-functional spinal unit model with osteoporotic bone properties. Parameters investigated included: cement stiffness, cement volume and height restoration. Models were assessed based on stresses and a user-defined fracture-predicting field. Augmentation altered the stress distribution; shielding was dependent on positioning of the cement; and fracture algorithm found incomplete height restoration to increase the likelihood of fracture, particularly in adjacent vertebrae.

Cement interdigitation and bone-cement interface after augmenting fractured vertebrae: A cadaveric study.

BACKGROUND: The treatment of painful osteoporotic vertebral compression fractures with transpedicular cement augmentation has grown significantly over the last 20 years. There is still uncertainty about long-term and midterm effects of polymethyl methacrylate in trabecular bone. Preservation of the trabecular structures, as well as interdigitation of the cement with the surrounding bone, therefore has been gaining increasing attention. Interdigitation of cement is likely relevant for biological healing and the biomechanical augmentation process. In this study a cutting and grinding technique was used to evaluate the interdigitation for 4 augmentation techniques. METHODS: By use of a standardized protocol, wedge fractures were created in vertebrae taken from a fresh-frozen spine. Thereafter the vertebrae were assigned to 1 of 4 similar groups with regard to the vertebral size and force required to produce the fracture. The 4 groups were randomized to the following augmentation techniques: balloon kyphoplasty, radiofrequency (RF) kyphoplasty, shield kyphoplasty, and vertebral stenting. Histologic analysis was designed to examine the bone structure and interdigitation after the augmentation. RESULTS: For the void-creating procedures, the distance between bone and cement was 341.4 ± 173.7 µm and 413.6 ± 167.6 µm for vertebral stenting and balloon kyphoplasty, respectively. Specifically, the trabecular bone was condensed around the cement, forming a shield of condensed bone. The procedures without a balloon resulted in shorter distances of 151.2 ± 111.4 µm and 228.1 ± 183.6 µm for RF and shield kyphoplasty, respectively. The difference among the groups was highly significant (P < .0001). The percentage of interdigitation was higher for the procedures that did not use a balloon: 16.7% ± 9.7% for balloon kyphoplasty, 20.5% ± 12.9% for vertebral stenting, 66.45% ± 12.35% for RF kyphoplasty, and 48.61% ± 20.56% for shield kyphoplasty. The difference among the groups was highly significant (P < .00001). CONCLUSIONS: Cavity-creating procedures reduce the cement interdigitation significantly and may accordingly reduce the effectiveness of the augmentation procedures.

Evaluation of the ultrasonication process for injectability of hydraulic calcium phosphate pastes.

This study examined the use of ultrasonication to improve the injectability of an aqueous calcium phosphate paste. Ultrasonication was applied to the paste through the plunger of the delivery syringe. A factorial design of experiments with three investigated factors, liquid to powder ratio (LPR) (38%, 39% and 40%), the size of the delivery syringe (5 and 10 ml) and the amplitude of the 20 kHz power ultrasonication (0-30 µm), was used in this study. The volume fraction of the extruded paste was used to quantify injectability. Small injectability improvements were observed with an increase in LPR and decrease in syringe size, which is consistent with previously published results. The improvements due to ultrasonication were significant and remarkable. For example, when using the 5 ml syringe the injected volume fraction of the 38% LPR paste improved from 63.4 ± 2.3% without ultrasonication to 97.3 ± 2.4% with 30%. This result shows that ultrasonication is an effective solution to improve injectability.

Simulation of the in vivo resorption rate of ß-tricalcium phosphate bone graft substitutes implanted in a sheep model.

A few years ago, a model was proposed to predict the effect of the pore architecture of a bone graft substitute on its cell-mediated resorption rate. The aim of the present study was to compare the predictions of the model with the in vivo resorption rate of four ß-tricalcium phosphate bone graft substitutes implanted in a sheep model. The simulation algorithm contained two main steps: (1) detection of the pores that could be accessed by blood vessels of 50 µm in diameter, and (2) removal of one solid layer at the surface of these pores. This process was repeated until full resorption occurred. Since the pore architecture was complex, µCT data and fuzzy imaging techniques were combined to reconstruct the precise bone graft substitute geometry and then image processing algorithms were developed to perform the resorption simulation steps. The proposed algorithm was verified by comparing its results with the analytical results of a simple geometry and experimental in-vivo data of ß-TCP bone substitutes with more complex geometry. An excellent correlation (r(2)>0.9 for all 4 bone graft substitutes) was found between simulation results and in-vivo data, suggesting that this resorption model could be used to (i) better understand the in vivo behavior of bone graft substitutes resorbed by cell-mediation, and (ii) optimize the pore architecture of a bone graft substitute, for example to maximize its resorption rate.

Cement filling control and bone marrow removal in vertebral body augmentation by unipedicular aspiration technique: an experimental study using leakage model.

STUDY DESIGN: Experimental design using a laboratory leakage model. OBJECTIVE: To examine that a new aspiration technique, with a double conduit cannula design, improves the uniformity of cement filling, thus significantly reducing the risk of extraosseous leakage. SUMMARY OF BACKGROUND DATA: In vertebral augmentation, understanding the forces governing the intravertebral cement flow is essential for controlling the cement formation. A path of least resistance posed by the irregularities in the bone matrix or vertebral shell increases the risk of leak. We have previously shown that using viscous cement reduces the leakage risk. However, this may damage the already weak bone due to the high forces required for the cement to enter the bone cavities. METHODS: An experimental leakage model for vertebral augmentation was used-with a path, simulating a blood vessel, to provoke leakage. A novel cannula with 2 concentric conduits was used. The inner conduit is used for cement delivery and the outer conduit for aspiration. A mixed level with 2 factors (2 x 2(2)) experiment design was used to examine the ability of aspiration to direct the cement flow in both low and high viscous cement regimes. RESULTS: Aspiration significantly enhanced the filling uniformity and reduced the risk of leakage. The reduction in leak with the suction simultaneous to the injection for low viscosity cement, elapsed time 4 minutes, was 1.5 cc (alpha = 0.05). In the suction experiments, the reduction in leakage as compared with the reference condition for the 8 minutes elapsed time was 0.5 cc, (alpha = 0.05). CONCLUSION: The aspiration technique combined with a new cannula design improved the uniformity of filling. The aspiration technique helps in removal of the displaced bone marrow or tumor tissue. The aspiration applied with the new cannula requires only a single incision. Thus, it does not result in an increased invasiveness.

Cement leakage and filling pattern study of low viscous vertebroplastic versus high viscous confidence cement.

BACKGROUND: Vertebral augmentation has recently evolved as a medical procedure for the treatment of vertebral compression fractures, the most common type of skeletal fractures related to osteoporosis. METHODS: This study compared the cement leakage and filling behavior of 2 existing delivery systems (Confidence and Vertebroplastic; DePuy Spine, Raynham, MA). The Confidence system with the high viscosity cement has been recently introduced in an attempt to curtail cement leakage. RESULTS: The comparison was performed using an established benchmark model wherein the cement leakage, filling behavior can be assessed. A double-conduit introducer needle was used to deliver the cement and to measure the intravertebral pressure while delivering the cement. There were 5 experimental groups in this study: 3 low-viscosity groups, whose cement was injected at 3.5, 6.5, and 9.5 minutes after admixing the powder and monomer, and 2 high-viscosity groups injected at 3.5 and 6.5 minutes. The mass of leaked cement generally decreased with delaying the start of the injection. Specifically, for the low-viscosity, the average smallest leakage mass obtained was 2.6 ± 1.2g when the cement was delivered at 9.5 minutes. If delivered after 3.5 minutes, the mass of cement leak was 4.0 ± 1.2g. The high-viscosity system has showed improved results in curtailing cement leakage, as compared to low-viscosity. Specifically, if injected after 3.5 and 6.5 minutes, the cement leakage amounts were 1.5 ± 1.2g and 0.92 ± 0.6g, respectively. Similarly, the uniformity of cement filling increased when the delivery was delayed and when the high-viscosity system was applied. Furthermore, there were no significance changes in the intravertebral pressures between the low- and high-viscous groups. No correlation between the leakage mass and the IV pressures was noted. CONCLUSION: The cement thickness and timing of delivery are key in controlling the intravertebral cement filling and physician may want to explore the use of low- or high-viscous cement for different fractures. The thickness of the cement has no significant impact on the intravertebral pressures.

A physical approach to modify the hydraulic reactivity of alpha-tricalcium phosphate powder.

A microsized alpha-tricalcium phosphate (alpha-TCP) powder was calcined at various temperatures (350 degrees C

Mechanisms underlying the limited injectability of hydraulic calcium phosphate paste.

Calcium phosphate (CaP) cements are being increasingly used for minimally invasive hard tissue implantation. Possible approaches to improve the bad injectability of hydraulic calcium phosphate pastes have been discussed and investigated in a number of recent publications. However, the liquid-phase separation mechanism leading to the limited injectability has not yet been addressed. Liquid-phase separation means that the liquid-to-powder ratio (LPR) of the extruded paste is higher than the LPR of the paste left in the syringe. The goal of this paper was to remedy this situation by looking at the liquid-phase migration occurring during the injection of a paste from a syringe through a cannula. Experimentally, it was seen that the liquid content of both the syringe paste and the extrudate decreased during the paste injection. Moreover, a high extrusion velocity, small syringe size, short cannula and high LPR favored a good injectability. These results could be partly explained in light of rheological measurements performed with the investigated paste.

Long-term effects of vertebroplasty: adjacent vertebral fractures.

In today's aging population, osteoporosis-related fractures are an ever-growing concern. Vertebroplasty, a promising yet cost-effective treatment for vertebral compression fractures, has an increasing role. The first vertebroplasty procedures were reported by Deramond and Galibert in France in 1987, and international interest grew with continued development of clinical techniques and augmentation materials in Europe and the United States. Initial publications and presentations at peer review meetings demonstrated 60-90% success rates in providing immediate and significant pain relief. The objective of this review is to assemble experimental and computational biomechanical research whose goal is determining and preventing the negative long-term effects ofvertebroplasty, with a specific focus on adjacent vertebral fractures. Biomechanical studies using isolated cancellous bone cylinders have shown that osteoporotic cancellous bone samples augmented by the rigid bone cement were at least 12 times stiffer and 35 times stronger than the untreated osteoporotic cancellous bone samples. The biomechanical efficacy of the procedure to repair the fractured vertebrae and prevent further collapse is determined using single-vertebra models. The strength or load-bearing capacity of a single vertebra is significantly increased following augmentation when compared to the intact strength. However, there is no dear result regarding the overall stiffness of the single vertebra, with studies reporting contradictorily that the stiffness increases, decreases, or does not significantly alter following augmentation. The effects of vertebroplasty on adjacent structures are studied via multisegment models, whose results plainly oppose the findings of the single-vertebra and intravertebral models. Here, augmentation was shown to decrease the overall segment strength by 19% when compared to the matched controls. As well, there is a significant increase in disc pressure compared to the pre-augmentation measurements. This translates to a high hydrostatic pressure adjacent to the augmented vertebra, representing the first evidence of increased loading. Computational finite element (FE) models have found that the rigid cement augmentation results in an increase in loading in the structures adjacent to the augmented vertebra. The mechanism of the increase of the loading is predicted to be the pillar effect of the rigid cement. The cement inhibits the normal endplate bulge into the augmented vertebra and thus pressurizes the adjacent disc, which subsequently increases the loading of the untreated vertebra. The mechanism for adjacent vertebral fractures is still unclear, but from experimental and computational studies, it appears that the change in mechanical loading following augmentation is responsible. The pillar effect of injected cement is hypothesized to decrease the endplate bulge in the augmented vertebra causing an increase in adjacent disc pressure that is communicated to the adjacent vertebra. To confirm the viability of the pillar effect as the responsible mechanism, endplate bulge and disc pressure should be directly measured before and after augmentation. Future studies should be concerned with quantifying the current and ideal mechanical response of the spine and subsequently developing cements that can achieve this optimum response.

High-viscosity cement significantly enhances uniformity of cement filling in vertebroplasty: an experimental model and study on cement leakage.

STUDY DESIGN: Experimental study using a laboratory leakage model. OBJECTIVE: To examine the working hypothesis that high-viscosity cements will spread uniformly, thus significantly reducing the risk of leakage. SUMMARY OF BACKGROUND DATA: In vertebroplasty, forces that govern the flow of bone cement in the trabecular bone skeleton are an essential determinant of the uniformity of cement filling. Extraosseous cement leakage has been reported to be a major complication of this procedure. Leakage occurs due to the presence of a path of least resistance caused by irregularities in the trabecular bone or shell structure. Ideally, cement uniformly infiltrates the trabecular bone skeleton and does not favor specific paths. Cement viscosity is believed to affect the infiltration forces and flow during the procedure. Clinically, altering the time between cement mixing and delivery modifies the viscosity of bone cement. METHODS: An experimental model of the leakage phenomenon of vertebroplasty was developed. A path, simulating a blood vessel, was created in the model to perturb the forces underlying cement flow and to favor leakage. Cement of varying viscosities was injected in the model, and, thereafter, the filling pattern, cement mass that has leaked, time at which leakage occurred, and injection pressure were measured. RESULTS: A strong relationship was found between the uniformity of the filling pattern and the elapsed time from cement mixing and viscosity, respectively. Specifically, 3 distinct cement leakage patterns were observed: immediate leakage was observed when cement was injected 5-7 minutes following mixing. The cement was of a low viscosity and more than 50% of the total cement injected leaked. Moderate leakage was observed when injection occurred 7-10 minutes following mixing. Less than 10% of the cement leaked, and the viscosity was at a transient state between the low viscosity of immediate leakage and a higher viscosity, doughy cement. Cement leakage ceased completely when cement was delivered after 10 minutes. The viscosity of the cement in this case was high, and the cement was of a dough-like consistency. CONCLUSIONS: High-viscosity cement seems to stabilize cement flow. However, the forces required for the delivery of high-viscosity cement may approach or exceed the human physical limit of injection forces. Although the working time of the cement is about 17 minutes, it may not be manually injectable with a standard syringe and cannula after 10 minutes, at which time cement leakage ceased completely.

In vivo behavior of calcium phosphate scaffolds with four different pore sizes.

The goal of the present study was to assess the effect of macropore size on the in vivo behavior of ceramic scaffolds. For that purpose, beta-tricalcium phosphate (beta-TCP) cylinders with four different macropore sizes (150, 260, 510, and 1220 microm) were implanted into drill hole defects in cancellous bone of sheep and their resorption behavior was followed for 6, 12 and 24 weeks. The scaffolds were evaluated for biocompatibility, and new bone formation was observed macroscopically, histologically and histomorphometrically. Histomorphometrical measurements were performed for the whole defect area and for the area subdivided into three concentric rings (outer, medial, and inner ring). All implants were tolerated very well as evidenced by the low amount of inflammatory cells and the absence of macroscopic signs of inflammation. Resorption proceeded fast since less than 5% ceramic remained at 24-week implantation. Hardly any effect of macropore size was observed on the in vivo response. Samples with an intermediate macropore size (510 microm) were resorbed significantly faster than samples with smaller macropore sizes (150 and 260 microm). However, this fast resorption was associated with a lower bone content and a higher soft tissue content. At 12 and 24 weeks, the latter differences had disappeared. Bone was more abundant in the outer ring than in the rest of the blocks at 6 weeks, and in the outer and medial ring compared to the inner ring at 12 weeks.