In vivo behavior of a novel injectable calcium phosphate cement compared with two other commercially available calcium phosphate cements

The aim of this study was to investigate the physicochemical and biological properties of a newly developed calcium phosphate cement (CPC). The novel cement was compared with two other commercially available CPCs. After mixing the powder and liquid phase, the CPCs were injected as a paste into a rabbit distal femoral defect model. The CPCs were evaluated after 24 h, 6 weeks, 26 weeks, and 52 weeks. The novel CPC was easy to handle and was fast setting. X-ray diffraction (XRD) and Fourier Transform Infrared Spectrometry (FTIR) at the different implantation periods showed that the cement had converted to carbonated hydroxyapatite and remained stable over time. Histological evaluation showed bone apposition on the cement surface without any inflammatory response or fibrous encapsulation. At later time points, all CPCs were completely covered by a thin layer of bone. Osteoclast-like cells present at the interface resorbed parts of the cement mass. Histological and histomorphometrical analyses did not show any significant differences between the three implanted CPCs. The results indicate that the investigated CPC is biocompatible, osteoconductive, as well as osteotransductive and seems to be both biologically safe and effective as a bone void filler.     

Histological evaluation of the bone response to calcium phosphate cement implanted in cortical bone

The aim of this study was to investigate the physicochemical and biological properties of a newly developed calcium phosphate cement (CaP cement) implanted in cortical bone. CaP cement was injected as a paste into tibia cortical bone defects in goats. Polymethylmethacrylate (PMMA) bone cement was used as a control. The animals were killed after 3 days, 2, 8, 16 and 24 weeks. X-ray diffraction and Fourier transform infrared spectroscopy performed at retrieved samples showed that the CaP cement had set as a carbonate apatite and remained stable over time. Light microscopic evaluation showed that after 2 weeks the cement was in tight contact with the bone without any inflammatory reaction or fibrous encapsulation. At later time points, the CaP cement implants were totally covered by a thin layer of bone and osteoclasts, present at the interface, which were clearly resorbing the cement. At locations where CaP cement was resorbed, new bone was deposited. Transmission electron microscopy revealed that indeed a seamless contact existed between CaP cement and bone, as characterized by the occurrence of an electron dense line of 50-60 nm thick that covered the CaP cement. Osteoblasts, in contact with the cement, were depositing new bone. Although the bulk of the material was still in situ after 24 weeks, the progressive osteoclast resorption of the cement followed by new bone formation suggests that all of the material may be replaced eventually. In contrast to the CaP cement, the PMMA reference cement was always surrounded by a thin fibrous capsule. The results indicate that the investigated CaP cement is biocompatible, osteoconductive as well as osteotransductive and is a candidate material for use as a bone substitute.     

Biocompatibility and degradation of poly(DL-lactic-co-glycolic acid)/calcium phosphate cement composites

Injectable calcium phosphate (Ca-P) cement materials exhibit favorable osteocompatible behavior but are resorbed slowly because of a lack of a bone ingrowth-enabling macroporosity. In this study, poly(DL-lactic-co-glycolic acid) (PLGA) microparticles (average size 66 +/- 25 microm) were incorporated into Ca-P cement to obtain a macroporous Ca-P cement scaffold after PLGA hydrolysis in vivo. Preset PLGA/Ca-P cement composite discs of various weight ratios (0/100, 15/85, 30/70, and 50/50) were implanted subcutaneously and in cranial defects in rats for 12 weeks. Histological analysis revealed that all macropores in the PLGA-containing composites (average pore size 73 +/- 27 microm) were filled with fibrous tissue and blood vessels (subcutaneous implants) and/or bone (cranial implants). Histologically, bone formation appeared most abundant and most consistent in the 30/70 PLGA/Ca-P cement composites. Histomorphometrical evaluation revealed a significant increase in defect fill in the 15/85 and 30/70 PLGA/Ca-P cement composites. Finally, subcutaneous and cranial 50/50 PLGA/Ca-P cement composites had degraded to a large extent, without adequate replacement by bone in the cranial implants. Therefore, we conclude that PLGA/Ca-P cement composites enable tissue ingrowth and show excellent osteocompatibility in weight ratios of 15/85 and 30/70 PLGA/Ca-P cement. In this model, 30/70 PLGA/Ca-P cement composites showed the most favorable biological response.     

Trabecular bone response to surface roughened and calcium phosphate (Ca-P) coated titanium implants.

The influence of calcium phosphate (Ca-P) coating and surface roughness on the trabecular bone response of titanium implants was investigated. Four types of titanium implants, i.e. blasted with titanium powder, sintered with titanium beads, titanium powder blasted and provided with an additional Ca-P coating, and titanium beads with Ca-P coating, were prepared. The Ca-P coating was deposited by ion beam dynamic mixing method. The Ca-P coating was rapid heat-treated with infrared radiation at 700 degrees C. The implants were inserted into the trabecular bone of the left and right femoral condyles of 16 rabbits. After implantation periods of 2, 3, 4 and 12 weeks, the bone-implant interface was evaluated histologically and histomorphometrically. Histological evaluation revealed new bone formation around different implant materials after already 3 weeks of implantation. After 12 weeks, mature trabecular bone surrounded all implants. At 3 and 4 weeks of implantation, no difference existed in bone contact to the various implant materials. On the other hand, after 12 weeks of implantation the highest percentage of bone contact was found around the Ca-P coated beads implants. Supported by the results, we concluded that the combination of surface geometry and Ca-P coating benefits the implant-bone response during the healing phase.     

Bone inductive properties of rhBMP-2 loaded porous calcium phosphate cement implants inserted at an ectopic site in rabbits

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is known for its osteoinductive potential in bone tissue engineering. Calcium phosphate (Ca-P) cements are injectable, osteoconductive ceramic materials in which a macroporous structure can be induced during the setting reaction. In this study, the osteoinductive capability of rhBMP-2 loaded porous Ca-P cement was evaluated. Porous Ca-P cement discs were made and loaded with rhBMP-2 in vitro and implanted subcutaneously in the back of New Zealand white rabbits. The implantation period was either 2 or 10 weeks. Histological analysis of retrieved specimens revealed evident bone formation in the rhBMP-2 loaded Ca-P cement discs (pore fill: 18+/-6%) after 10 weeks of implantation. Bone formation occurred only in rhBMP-2 loaded porous Ca-P cement discs. Degradation of the Ca-P cement could not be confirmed after 10 weeks of implantation. The scaffold maintained its shape and stability during this time period. We conclude that porous Ca-P cement is a suitable carrier material for ectopic bone engineering.     

Tissue response to a newly developed calcium phosphate cement containing succinic acid and carboxymethyl-chitin

We developed a new calcium phosphate cement containing succinic acid and carboxymethyl-chitin in the liquid component. In this study, the biocompatibility and osteoconductivity of this new cement were investigated. After mixing, cement in putty form was implanted immediately between the periosteum and parietal bone and in the subcutaneous tissues of rats. In control cement, distilled water was used instead of the liquid component. In addition to histological evaluations, analyses with X-ray diffraction and Fourier transform infrared were performed for the subcutaneously implanted cements. Histological examination showed slight inflammation around the new cement on the bone and in the subcutaneous tissue at 1 week after surgery. At 2 weeks, the cement was partially bound to the parietal bone. The extent of the surface of the new cement directly in contact with the bone increased with time, and most of the undersurface of the new cement bound to the host parietal bone by 8 weeks. Analysis by X-ray diffraction showed that the new cement in the subcutaneous tissue was transformed into hydroxyapatite by 8 weeks. These results indicate that this new calcium phosphate cement is useful as a bone substitute material.     

Bioresorption behavior of tetracalcium phosphate-derived calcium phosphate cement implanted in femur of rabbits

One primary focus of the present study was to clarify the crucial resorption-location relationship of a recently developed single-phase TTCP-derived calcium phosphate cement (CPC) implanted in rabbit femur in a systematic and quantitative way. Gross examination of retrieved CPC/bone composite samples indicated that the CPC implant did not evoke inflammatory response, necrosis or fibrous encapsulation in surrounding bony tissues. Histological examination revealed excellent CPC-host bone bonding. At 4 weeks, the resorption-induced voids between terminals of bone defects and implants were largely filled with new bone. CPC resorption, new blood vessels, osteocytes, osteons and osteoblast-like cells lining up with active new bone were observed at remodeling sites. At 12 weeks, a new bone network was developed within femoral defect, while CPC became islands incorporated in the new bone. At this stage, crevices filled with lamellar new bone structure were frequently observed. At 24 weeks, bone ingrowth and remodeling activities became so extensive that the interface between residual cement and new bone became less identifiable. In general, at all implant locations the resorption ratio values increased with implantation time, while at all implantation times the resorption ratios decreased from the exterior (cortical site) to the interior (cancellous site) of implants. At the end of 24 weeks, CPC was almost completely resorbed and bone remodeling almost finished at the cortical site.     

In vivo bone response to porous calcium phosphate cement

We conducted an in vivo experiment to evaluate the resorption rate of a calcium phosphate cement (CPC) with macropores larger than 100 microm, using the CPC called Biocement D (Merck Biomaterial, Darmstadt, Germany), which after setting only shows pores smaller than 1 microm. The gas bubble method used during the setting process created macroporosity. Preset nonporous and porous cement implants were inserted into the trabecular bone of the tibial metaphysis of goats. The size of the preset implants was 6 mm and the diameter of the drill hole was 6.3 mm, leaving a gap of 0.3 mm between implant surface and drill wall. After 2 and 10 weeks, the animals were euthanized and cement implants with surrounding bone were retrieved for histologic evaluation. Light microscopy at 2 weeks revealed that the nonporous implants were surrounded by connective tissue. On the cement surface, we observed a monolayer of multinucleated cells. Ten weeks after implantation, the nonporous implants were still surrounded by connective tissue. However, a thin layer of bone now covered the implant surface. No sign of cement resorption was observed. In contrast, the porous cement evoked a completely different bone response. At 2 weeks, bone formation had already occurred inside the implant porosity. Bone formation even appeared to occur as a result of osteoinduction. Also, at their outer surface, the porous implants were completely surrounded by bone. At 2 weeks, about 31% of the initial cement was resorbed. After 10 weeks, 81% of the initial phosphate cement was resorbed and new bone was deposited. On the basis of these observations, we conclude that the creation of macropores can significantly improve the resorption rate of CPC. This increased degradation is associated with almost complete bone replacement.     

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.     

Bone inductive properties of rhBMP-2 loaded porous calcium phosphate cement implants in cranial defects in rabbits

In this study, the osteoinductive properties of porous calcium phosphate (Ca-P) cement loaded with bone morphogenetic protein 2 (rhBMP-2) were evaluated and compared with rhBMP-2 loaded absorbable collagen sponge (ACS). Discs with a diameter of 8mm were loaded with a buffer solution with or without 10 microg rhBMP-2 and inserted in 8mm full thickness cranial defects in rabbits for 2 and 10 weeks of implantation. Histological analysis revealed excellent osteoconductive properties of the Ca-P material. It maintained its shape and stability during the implantation time better than the ACS but showed no degradation like the ACS. Quantification of the Ca-P cement implants showed that bone formation was increased significantly by administration of rhBMP-2 (10 weeks pore fill: 53.0+/-5.4%), and also reached a reasonable amount without rhBMP-2 (43.1+/-10.4%). Remarkably, callus-like bone formation outside the implant was observed frequently in the 2 weeks rhBMP-2 loaded Ca-P cement implants, suggesting a correlation with the presence of growth factor in the surrounding tissue. However, an additional in vitro assay revealed an accumulative release of no more than 9.7+/-0.9% after 4 weeks. We conclude that: (1). Porous Ca-P cement is an appropriate candidate scaffold material for bone engineering. (2). Bone formation can be enhanced by lyophilization of rhBMP-2 on the cement. (3). Degradation of porous Ca-P cement is species-, implantation site- and implant dimension-specific.     

Biomimetic porous scaffolds with high elasticity made from mineralized collagen--an animal study

Histological investigations of a new hydroxyapatite-collagen composite material were carried out to evaluate its possible suitability as a bone substitute. The three-dimensional scaffolds made from biomimetically mineralized collagen exhibit an interconnecting pore structure and elastic mechanical properties. They were implanted into the subcutaneous tissue and bone defects made in the femur of rats and harvested with the surrounding tissue at 1, 2, 4, 8, and 12 weeks after surgery. The materials implanted in the subcutaneous tissue were covered by fibrous connective tissue with a slight inflammatory response, and many foreign-body giant cells were observed on the surface of the scaffolds. Most of the material implanted in the subcutaneous tissue was resorbed at 8 weeks by phagocytosis. In the bone defects, new bone formation was observed on the surface of the material at 1 week. New bone increased with time, and osteoclasts were seen on the surface of the scaffolds at 2 weeks. Resorption and replacement by new bone of many parts of the materials implanted in the femur were observed by 12 weeks. These responses occurred faster than those of other hydroxyapatite-collagen composites. The results suggested that the new biomimetically mineralized collagen scaffolds were suitable as an implant material for bone-tissue reconstruction.     

In vivo testing of a new in situ setting beta-tricalcium phosphate cement for osseous reconstruction

A new in situ setting tricalcium phosphate cement was implanted in 1.5-mm trepanation defects in rat femurs. Empty cavities and autologous bone grafts were used as controls. Cement resorption and new bone formation were evaluated in undecalcified sections with histologic examination, contact microradiographies, radiodensitometry, and scanning electron microscopy after 1 and 3 weeks. The mechanical integrity was tested in a three-point bending test. The amount of new bone formation over time was determined by intravital fluorescence staining. With the in situ setting substance, a good filling of the whole trepanation defect was achieved without leakage of the paste-like cement. Slow resorption of the cement and new bone formation beginning at the edge of the defect were seen after 1 week. After 3 weeks, resorption was advanced and there was ingrowth of new bone, with close contact between cement particles and bone, as shown in histologic sections and with a calcium/phosphorus analysis by quantitative line scans of an electron microanalysis (SEM-EPMA). This new self-hardening cement is bioactive, resorbable, and osteotransductive. It may be usable for the filling of stable defects, such as cysts or benign tumors, or for bone supplementation in revision arthroplasty.     

Development of calcium phosphate cement using chitosan and citric acid for bone substitute materials.

We developed a calcium phosphate cement that could be molded into any desired shape due to its chewing-gum-like consistency after mixing. The powder component of the cement consists of alpha-tricalcium phosphate and tetracalcium phosphate, which were made by decomposition of hydroxyapatite ceramic blocks. The liquid component consists of citric acid, chitosan and glucose solution. In this study, we used 20% citric acid (group 20) and 45% citric acid (group 45). The mechanical properties and biocompatibility of this new cement were investigated. The setting times of cements were 5.5 min, in group 20 and 6.4 min, in group 45. When incubated in physiological saline, the cements were transformed to hydroxyapatite at 3, and 6 weeks, the compressive strengths were 15.6 and 20.7 MPa, in group 45 and group 20, respectively. The inflammatory response around the cement implanted on the bone and in the subcutaneous tissue in rats was more prominent in group 45 than in group 20 at 1 week after surgery. After 4 weeks, the inflammation disappeared and the cement had bound to bone in both groups. These results indicate that this new calcium phosphate cement is a suitable bone substitute material and that the concentration of citric acid in the liquid component affects its mechanical properties and biocompatibility.     

Bone formation in calcium-phosphate-coated titanium mesh

The osteogenic activity of porous titanium fiber mesh and calcium phosphate (Ca-P)-coated titanium fiber mesh loaded with cultured syngeneic osteogenic cells was compared in a syngeneic rat ectopic assay model. In 30 syngeneic rats, (Ca-P)-coated and non-coated porous titanium implants were subcutaneously placed either without or loaded with cultured rat bone marrow (RBM) cells. Fluorochrome bone markers were injected at 2, 4, and 6 weeks. The rats were sacrificed, and the implants were retrieved at 2, 4, and 8 weeks post-operatively. Histological analysis demonstrated that none of the (Ca-P)-coated and non-coated meshes alone supported bone formation at any time period. In RBM-loaded implants, bone formation started at 2 weeks. At 4 weeks, bone formation increased. However, at 8 weeks bone formation was absent in the non-coated titanium implants, while it had remained in the (Ca-P)-coated titanium implants. Also, in (Ca-P)-coated implants more bone was formed than in non-coated samples. In general, osteogenesis was characterized by the occurrence of multiple spheres in the porosity of the mesh. The accumulation sequence of the fluorochrome markers showed that the newly formed bone was deposited in a centrifugal manner starting at the center of a pore. Our results show that the combination of Ti-mesh with RBM cells can indeed generate bone formation. Further, our results confirm that a thin Ca-P coating can have a beneficial effect on the bone-generating properties of a scaffold material.     

Biocompatibility and resorption of a brushite calcium phosphate cement

A hydraulic calcium phosphate cement with beta-tricalcium phosphate (TCP) granules embedded in a matrix of dicalcium phosphate dihydrate (DCPD) was implanted in experimentally created defects in sheep. One type of defect consisted of a drill hole in the medial femoral condyle. The other, partial metaphyseal defect was located in the proximal aspect of the tibia plateau and was stabilized using a 3.5 mm T-plate. The bone samples of 2 animals each per group were harvested after 2, 4, 6 and 8 weeks. Samples were evaluated for cement resorption and signs of immediate reaction, such as inflammation, caused by the cement setting in situ. Differences regarding these aspects were assessed for both types of defects using macroscopical, radiological, histological and histomorphometrical evaluations. In both defects the brushite matrix was resorbed faster than the beta-TCP granules. The resorption front was followed directly by a front of new bone formation, in which residual beta-TCP granules were embedded. Cement resorption occurred through (i) extracellular liquid dissolution with cement disintegration and particle formation, and (ii) phagocytosis of the cement particles through macrophages. Signs of inflammation or immunologic response leading to delayed new bone formation were not noticed at any time. Cement degradation and new bone formation occurred slightly faster in the femur defects.     

The biodegradation mechanism of calcium phosphate biomaterials in bone

This study was undertaken to understand the biodegradation mechanisms of calcium phosphate (Ca-P) biomaterials with different crystallization. Two types of sintered Ca-P porous ceramic (HA and beta-TCP) and a Ca-P bone cement (CPC) were implanted into cavities drilled in rabbit femoral and tibiae condyles. The results have shown that a material biodegradation was rapid in the beta-TCP and the CPC, but very weak in the HA. This biodegradation presented a decrease of material volume from the periphery to the center as well as a particle formation causing phagocytosis by numerous macrophages and multinucleated giant cells in the CPC. In the beta-TCP, there was a peripheral and central decrease of material volume as well as an absence of particle formation or visible phagocytosis. The process of biodegradation is considered to be directly influenced by the type of material crystallization. The sintered bioceramics processed at a high temperature exhibit good crystallization and are primarily degraded by a process dependent on interstitial liquids. However, the bone cement is formed by physicochemical crystallization and is degraded through a dissolution process associated with a cellular process.     

Healing of segmental bone defects in rats induced by a beta-TCP-MCPM cement combined with rhBMP-2.

A beta-tricalcium phosphate-monocalcium phosphate monohydrate (beta-TCP-MCPM) cement was evaluated as an effective carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2) in rat femoral critical-size defects. Hard cement cylinders (4 x 5 mm) impregnated with two different doses of rhBMP-2 (1.26 or 6.28 microg) were implanted into each defect, and the results were compared with those in rats that had implantations of cylinders only. Implantation of the 6.28 microg dose of rhBMP-2 caused a large bone shell to form around the defect, resulting in osseous union in all cases within 3 weeks. Except for beta-TCP granules, the cement was resorbed and replaced by bone tissue at 6 weeks. A torsion test at 9 weeks showed that the failure torque and bone stiffness had recovered 99% and 141%, respectively, compared with the intact contralateral femur. The defects that received 1.26 microg of rhBMP-2 resulted in 40% union and 41% of the failure torque at 9 weeks. However, no instances of union were observed in the defects implanted with cylinders only. In conclusion, the beta-TCP-MCPM cement was shown to be effective as a rhBMP-2 carrier. Combined with rhBMP-2, this cement was rapidly resorbed and completely healed the defects.     

注射型可吸收聚氨基酸/硫酸钙复合材料动物体内降解吸收及促成骨作用*

背景：注射型人工骨可经皮穿刺注射植入体内,对机体创伤较小,同时该型材料可以任意塑形,能较好地充填骨缺损,但目前临床上尚无在体内能完全降解吸收且具有较好促成骨作用的注射型人工骨产品。 目的：评估注射型可吸收聚氨基酸/硫酸钙复合材料(硫酸钙含量70%)动物体内的降解吸收及促成骨作用,观察其修复骨缺损的能力。 方法：取48只新西兰大白兔,在股骨外髁处制备直径为5 mm、深10 mm的骨缺损模型,以随机数字表法分为实验组和对照组,实验组将注射型可吸收聚氨基酸/硫酸钙复合材料植入骨缺损处,对照组未予干预。 结果与结论：X射线平片示：实验组骨缺损逐渐被骨痂填充,术后16周,骨缺损处恢复正常松质骨密度,塑形完成;对照组骨缺损处修复不明显。组织学检查(苏木精-伊红、MASSON染色)示：术后4周,材料开始降解,新生原始骨小梁长入材料内;术后12周,编织骨开始转化为板层骨;术后16周,材料完全被降解吸收,新生骨组织完全修复骨缺损。结果显示注射型聚氨基酸/硫酸钙复合材料在动物内能够完全降解、吸收,具备一定的成骨活性,可望用作骨修复材料。     

改性纳米羟基磷灰石/聚乳酸-聚羟乙酸复合骨髓基质干细胞修复兔桡骨缺损*

背景：前期试验证实骨髓基质干细胞能够在改性纳米羟基磷灰石/聚乳酸-聚羟乙酸材料表面黏附、增殖,该材料具有良好的生物安全性。 目的：观察骨髓基质干细胞与改性纳米羟基磷灰石/聚乳酸-聚羟乙酸材料复合修复兔桡骨缺损的效果。 方法：建立兔15 mm桡骨缺损模型,随机分为3组：空白对照组不进行任何处理,实验组植入改性纳米羟基磷灰石/聚乳酸-聚羟乙酸+骨髓基质干细胞组织工程化骨,对照组植入单纯改性纳米羟基磷灰石/聚乳酸-聚羟乙酸支架材料。 结果与结论：①X射线评价：术后1~12周,实验组骨缺损修复程度及速度明显优于空白对照组与对照组(P < 0.05)。②组织学检测：实验组术后4周即可观察到新生骨和纤维组织长入材料空隙,局部形成陷窝结构;8周时新生骨组织增多,部分可观察到成熟的骨小梁结构;12周时可见大量成熟骨细胞,骨小梁排列紧密,移植材料逐步被新生骨取代,与正常骨组织形态基本一致,且骨小梁出现时间早于空白对照组与对照组。说明骨髓基质干细胞复合改性纳米羟基磷灰石/聚乳酸-聚羟乙酸构建的组织工程化骨能够促进骨缺损处新骨的生成,较单纯支架材料具有明显优势。     

Evaluation of a resorbable, in situ setting bone substitute in a sheep model

The gold standard for bone substitution is the autologous bone graft, but because of its limited supply and the associated morbidity, the search for synthetic alternatives is necessary. A new in situ setting tricalcium phosphate cement was implanted in a trepanation defect (9.4 mm diameter, 10 mm depth) in the distal femoral epiphysis of sheep. Empty cavities and autologous bone graft were used as controls. Histologic and histomorphometric examinations were carried out after 12 weeks. Nearly 90% of the implanted cement was resorbed and replaced by ingrown bone with close contact between surrounding bone, new bone, and remaining cement particles. The amount of bone in the defect area was significantly higher in defects filled with cement relative to defects filled with autologous bone graft (mean 27 vs. 21%, 95% confidence intervals 23 to 31 and 18 to 23, p = 0.026). In conclusion, this new in situ setting cement is bioactive, resorbable, and osteoconductive. It will be useful as an alternative to autologous bone graft to fill stable defects.