Resorbable Calcium Research Articles

Successful treatment of multi-resistant Pseudomonas aeruginosa osteomyelitis after allogeneic bone marrow transplantation with a combination of colistin and tigecycline

A case of osteomyelitis caused by multidrug-resistant Pseudomonas aeruginosa is reported in a patient who underwent allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. The patient was successfully treated by prolonged administration of a full dose of colistin and tigecycline, and surgical curettage with the positioning of resorbable calcium sulfate pellets loaded with colistin.

Calcium Phosphate Ceramic Blasting on Titanium Surface Improve Bone Ingrowth

Surface roughness modulates the osseointegration of orthopaedic and dental titanium implants. High surface roughness is currently obtained by blasting of titanium implants with silica or aluminium abrasive particles. This process includes into the surface abrasive particles and may cause the release of cytotoxic silica or aluminium ions in the peri implant tissue. To overcome this drawback, we currently develop an innovative gridblasting process using Biphasic Calcium Phosphate (BCP) particles (RBBM Resorbable and Biocompatible Blast Media) to generate biocompatible roughened titanium surface. This work present the technique of blasting using RBBM particles to provide a roughened surface which does not release cytotoxic elements and (ii) to assess the effects of such a roughened surface for bone osteointegration in critical size rabbit defect. Our results demonstrate that resorbable biphasic calcium phosphate abrasive particles can be used to create titanium surface roughness. This grid blasting process increases surface roughness of titanium implants and offers a non cytotoxic surface for rapid and efficient osteointegration.

Repairing Segmental Defect with a Composite Associating Collagen Membrane and MBCP® Combined with Total Bone Marrow Graft in Irradiated Bone Defect: an Experimental Study in Rabbit

The aim of this study was to study bone marrow quality from various location and species for reconstruction of segmental critical size defect in irradiated weigh bearing bone. Sample of bone marrow aspirates from rabbits and Beagle dog were analyzed. Rabbits were implanted with a composite associating resorbable collagen membrane plus micro macroporous biphasic calcium phosphate (MBCP®) and autologous bone marrow (BM) injected after irradiation. Bone marrow samples were found to be significantly less rich in tibia than in humerus and ilium in Dog and less rich in Dog than in Rabbit (p<0,05). Successful osseous colonization bridging of the defect were obtain at 16 weeks in all animals. Identical repartition of bone ingrowth and residual ceramic at the different levels of the implant suggest an osteoinduction role of the bone marrow graft in the center of the defect. This model succeeded in reconstruct a large segmental defect in weight bearing and irradiated bone in rabbit.

Histological and histomorphometric investigations on bone integration of rapidly resorbable calcium phosphate ceramics

Resorbable ceramics can promote the bony integration of implants. Their rate of degradation should ideally be synchronized with bone regeneration. We report here the results of a histological study of implants with two resorbable calcium phosphate ceramic coatings: Ca(2)KNa(PO(4))(2)-(GB14) and Ca(10)[K/Na](PO(4))(7)-(602020). The results attained with these ceramic-coated implants show the benefits of these materials with regard to bioactive bone-healing stimulation, compared with uncoated implants. The GB14 ceramic coating exhibited greater bone regeneration and differentiation on its surface than the conventional hydroxyapatite coating and helped bone tissue achieve more extensive contact free of connective tissue. Not until the coating disintegrated did the histological features of GB14- and 602020-coated implants converge-both implant types were integrated into bone. Rapid disintegration of the coating material, as with 602020, supports osteoblast proliferation but has negative effects on bone mineralization. Both resorbable ceramics tested, GB14 and 602020, demonstrated bioactivity; even metal surfaces coated with these materials were populated by mature bone tissue without connective tissue after disintegration of their ceramic coating. The less rapidly degrading material, GB14, achieved better results. Degradable calcium phosphate coatings have the potential to stimulate bone regeneration. From the histological viewpoint, the resorbable ceramics examined here can be recommended as coating materials for clinical use.

Influence of Platelet-Rich Plasma on Osteogenic Differentiation of Mesenchymal Stem Cells and Ectopic Bone Formation in Calcium Phosphate Ceramics

Platelet-rich plasma (PRP) contains a mixture of growth factors that play an important role in wound and fracture healing. While PRP enhanced bone formation by autogenous cancellous bone grafts, its influence in combination with different bone substitutes remained unknown. This study evaluated the effect of PRP on osteogenic differentiation and ectopic bone formation of human mesenchymal stem cells (MSC) in distinct resorbable calcium phosphate ceramics. Calcium-deficient hydroxyapatite (CDHA) blocks with a large specific surface area (48 m²/g) and β-tricalcium phosphate (β-TCP) with a low specific surface area (<0.5 m²/g) were loaded with 2 × 10⁵ bone marrow-derived MSC. Half of the specimens were treated with 5-fold concentrated PRP. Biocomposites were implanted subcutaneously into SCID mice or kept under osteogenic culture conditions for 2 weeks before implantation. The addition of PRP increased the specific alkaline phosphatase (ALP) activity (p = 0.012) in undifferentiated MSC/CDHA composites but not in MSC/β-TCP composites. Osteogenic preinduction was ineffective for CDHA and reduced ALP activity of β-TCP composites significantly at explantation. Ectopic bone formation was stronger in MSC/CDHA (7/32) compared to MSC/β-TCP (2/30) composites, but no influence of PRP was evident. In conclusion, the effect of PRP depended on the type of ceramic and the differentiation status of the MSC, and enhanced ALP activity of MSC on the high surface scaffold CDHA only, but PRP did not improve osteogenesis in our setting.

Calcium Phosphate‐Based Resorbable Ceramics: Influence of MgO, ZnO, and SiO2 Dopants

Resorbable calcium phosphate (CaP)‐based biomaterials are important because they can significantly improve health care by shortening the time necessary for restoration of functional loading of grafted bones. Although synthetic CaPs show exceptional similarities to natural bone, however, they are deficient in one major area, in that they do not have the same mineral content of bone. The focus of our work is to understand the influence of dopants on the physical, mechanical, and biological properties of tricalcium phosphate (TCP) resorbable ceramics with special emphasis toward in vitro strength degradation and cell–materials interactions as a function of time. For this purpose, β‐TCP was doped with magnesia (MgO), zinc oxide (ZnO), and silica (SiO2). Those dopants were added as individual dopants, and their binary and ternary compositions. It was found that these dopants significantly influenced densification behavior and as sintered microstructures of TCP. In vitro mineralization studies in simulated body fluids (SBF) for 12 weeks showed apatite growth on the highly porous compositions either on the surface or inside. From scanning electron microscopic analysis it was evident that surface degradation occurred on all compositions in SBF. Compression strengths for samples up to 12 weeks in SBF showed that it is possible to tailor strength loss behavior through compositional modifications. The highest compression strength was found for binary MgO–ZnO doped TCP. Overall, samples showed either a similar strength level during the 12 weeks test period, or a continuous decrease or a continuous increase in strength depending on dopant chemistry or amount. In vitro human osteoblast cell culture was used to determine influence of dopants on cell‐materials interactions. All samples were non‐toxic and biocompatible. Dopant chemistry also influenced adhesion, proliferation, and differentiation of osteoblastic precursor cell line 1 (OPC1) cells on these matrices.

Composition and crystal structure of resorbable calcium phosphate thin films

Silicon stabilized tricalcium phosphate (Si-TCP) is formed, among other phases, as a result of sintering hydroxyapatite (HA) in the presence of silica (SiO2) at >800°C. Calcium phosphate films sintered at 1000°C on quartz substrates are examined with and without additional SiO2 added to the starting precipitate. Data from transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) separate the undoped film morphology into a surface layer with a monoclinic crystal structure P21/a characteristic of α or Si-tricalcium phosphate and grain size in the range 100–1000 nm and a substrate layer with a crystal structure which is predominantly apatitic P63/m and grain size in the range 30–100 nm. The silicon content is greatest in the substrate layer. The addition of SiO2 to the film material during fabrication induces a more uniform grain size of 10–110 nm and a higher Si content. The structural and phase evolution of these films suggests the nucleation of α-TCP by the local formation of Si-TCP at a SiO2-hydroxyapatite interface. The results are consistent with X-ray diffraction studies and are explained by a model of nucleation and growth developed for bulk powders.

Elevated extracellular calcium stimulates secretion of bone morphogenetic protein 2 by a macrophage cell line

It has been suggested that macrophages and multinucleated giant cells are responsible for phagocytosis of resorbable calcium phosphate (CaP) compounds implanted in bone defects. However, function of macrophages around the CaP, if continuously exposed to various concentration of extracellular calcium ions ([Ca 2+] o), is still unknown. The present study showed that when resorbable octacalcium phosphate was implanted in mouse calvaria, macrophage-like cells were observed around the implant during bone formation. Then, experiments were designed to investigate whether secretion of bone morphogenetic protein 2 (BMP-2) is enhanced by extracellular calcium ions in a macrophage cell line (J774A.1) in vitro. The mRNA expression and the secretion of BMP-2 in J774A.1 cells were significantly increased when incubated in the medium with [Ca 2+] o up to 14 mM. The promotion of mRNA expression was maintained even when incubated with a small amount of minute CaP crystals. The present results suggest that [Ca 2+] o above physiological concentration may stimulate macrophages to induce osteogenic cytokine, such as BMP-2, for bone formation by osteoblasts.

Strength of Calcium Phosphate Cements

ABSTRACTCalcium phosphates materials are widely used to treat the bones defects. HA bioceramics traditionally used in medicine has some serious disadvantage – week resorbility properties. Calcium phosphate cements seems to be promising compounds to replace conventional ceramics. High macroporosity of hardened materials leads to low mechanical strength. The main objective of present work was a development of new chemically bonded materials based on α-tricalcium phosphate (α-TCP) and hydroxylapatite phase. The main idea was to combine the benefit of ceramics technology (compacting of powders to reduce the starting macroporosity) to improve the materials strength with advantages of cement product (small resorbable calcium phosphate particles). α-Ca3(PO4)2-based biocements were synthesized with initial composition of HA, α- and β-TCP containing 80% wt. of TCP phase. The rate of α-TCP transformation to apatite phase during setting reaction was about 20% wt. in case of cylindrical samples (8mm × 8 mm) at 60°C for 50 hours. The fabricated TCP – bio-composites demonstrated high mechanical strength and stiffness characteristic. Most efficient results were achieved with chitosan biopolymer containing samples (σc = 120 MPa).

Comparison of Carbonate Apatite and .BETA.-tricalcium Phosphate (Resorbable Calcium Phosphates) Implanted Subcutaneously into the Back of Rats

Bioresorption and biocompatibility of carbonate apatites, both sintered and non-sintered (S-CAP and N-CAP), and of sintered beta-tricalcium phosphate (beta-TCP) were compared by implanting particles of these materials into the back of adult rats. Bioresorption--when evaluated non-destructively with non-decalcified tissues using microfocus X-ray tomography--was essentially the same for N-CAP and beta-TCP, while S-CAP exhibited statistically lower bioresorption at 2, 4, and 12 weeks postoperatively. Biocompatibility--when evaluated by ED1 immunostaining--was in the order of beta-TCP > N-CAP > S-CAP. The intensity of ED1 immunostaining decreased with time, but persisted longer in beta-TCP than in S-CAP and N-CAP, indicating that beta-TCP produced the strongest and most enduring stimulation of macrophages. Although no statistical differences were found in tartrate-resistant acid phosphatase (TRAP) staining among the materials at each implantation period, the degree of TRAP staining for S-CAP was statistically greater at 12 weeks than at 2 and 4 weeks, indicating that osteoclast-like cells were in part responsible for the resorption of the carbonate apatite.

Evaluation of an osteoconductive resorbable calcium phosphate cement and polymethylmethacrylate for augmentation of orthopedic screws in the pelvis of canine cadavers

To evaluate the effect of an osteoconductive resorbable calcium phosphate cement (CPC) on the holding power of bone screws in canine pelvises and to compare the effect with that for polymethylmethacrylate (PMMA). 35 pelvises obtained from canine cadavers. Each pelvis was sectioned longitudinally. Within each pair of hemipelvises, one 4.0-mm cancellous screw was placed in the sacroiliac (SI) region and another in the iliac body. Similar regions on the contralateral-matched hemipelvis were assigned 1 of 3 augmentation techniques (CPC-augmented 4.0-mm cancellous screws, PMMA-augmented 4.0-mm cancellous screws, and CPC-augmented 3.5-mm cortical screws). Pullout force was compared between matched screws and between treatment groups prior to examination of cross sections for evaluation of cement filling and noncortical bone-to-cortical bone ratio. CPC and PMMA augmentation significantly increased pullout force of 4.0-mm screws inserted in the SI region by 19.5% and 33.2%, respectively, and CPC augmentation significantly increased pullout force of 4.0-mm cancellous screws inserted in the iliac body by 21.2%. There was no difference in the mean percentage augmentation between treatment groups at either location. Cement filling was superior in noncortical bone, compared with filling for cortical bone. Noncortical bone-to-cortical bone ratio was significantly greater in the sacrum (6.1:1) than the ilium (1.3:1). CPC and PMMA improve the ex vivo holding strength of 4.0-mm cancellous screws in the SI and iliac body regions and SI region, respectively. Cement augmentation may be more effective in areas with greater noncortical bone-to-cortical bone ratios.

Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier

Bone substitute materials can induce bone formation in combination with mesenchymal stem cells (MSC). The aim of the current study was to examine ectopic in vivo bone formation with and without MSC on a new resorbable ceramic, called calcium deficient hydroxyapatite (CDHA). Ceramic blocks characterized by a large surface (48 m 2/g) were compared with β -tricalcium phosphate ( β -TCP), hydroxyapatite (HA) ceramics (both ca. 0.5 m 2/g surface) and demineralized bone matrix (DBM). Before implantation in the back of SCID mice carriers were freshly loaded with 2×10 5 expanded human MSC or loaded with cells and kept under osteogenic conditions for two weeks in vitro. Culture conditions were kept free of xenogenic supplements. Deposits of osteoid at the margins of ceramic pores occurred independent of osteogenic pre-induction, contained human cells, and appeared in 4 16 MSC/CDHA composites compared to 2 16 MSC/ β -TCP composites. ALP activity was significantly higher in samples with MSC versus empty controls ( p < 0.001 ). Furthermore, ALP was significantly ( p < 0.05 ) higher for all ceramics when compared to the DBM matrix. Compared to previous studies, overall bone formation appeared to be reduced possibly due to the strict human protocol. Ectopic bone formation in the novel biomaterial CDHA varied considerably with the cell pool and was at least equal to β -TCP blocks.

Periodontal healing in one‐wall intra‐bony defects in dogs following implantation of autogenous bone or a coral‐derived biomaterial

Autogenous bone grafts and bone biomaterials are being used as part of protocols aiming at reconstruction of periodontal defects. There is a limited biologic information on the effect of such materials on periodontal healing, in particular aberrant healing events that may prevent their general use. The objective of this study was, using histological techniques, to evaluate periodontal healing with focus on root resorption and ankylosis following implantation of autogenous bone and a coral-derived biomaterial into intra-bony defects in dogs. One-wall intra-bony periodontal defects were surgically created at the distal aspect of the second and the mesial aspect of the fourth mandibular premolars in either right or left jaw quadrants in four Beagle dogs. Each animal received particulated autogenous bone and the resorbable calcium carbonate biomaterial into discrete one-wall intra-bony defects. The mucoperiosteal flaps were positioned and sutured to their pre-surgery position. The animals were euthanized 8 weeks post-surgery when block sections of the defect sites were collected and prepared for qualitative histological analysis. There were no significant differences in periodontal healing between sites receiving autograft bone and the coral-derived biomaterial. A well-organized periodontal ligament bridging new bone and cementum regeneration was observed extending coronal to a notch prepared to delineate the apical extent of the defect. Osteoid and bone with enclosed osteocytes were formed onto the surface of both autograft and coral particles. Although small resorption pits were evident in most teeth, importantly none of the biomaterials provoked marked root resorption. Ankylosis was not observed. Particulated autogenous bone and the coral-derived biomaterial may be implanted into periodontal defects without significant healing aberrations such as root resorption and ankylosis. The histopathological evaluation suggests that the autogenous bone graft has a limited osteogenic potential as demonstrated in this study model.

In Vivo Behavior of Calcium Phosphate Glasses with Controlled Solubility

Resorbable calcium phosphate glasses offer interesting solutions in the biomedical field, as bone cavity fillers, drug delivery systems, biodegradable reinforcing phase in the case of composites for bone fixation devices and tissue engineering scaffolds. In this work, two different glass formulations in the systems 44.5CaO-44.5P2O5-(11-X)Na2O-XTiO2 (X=0or 5) have been elaborated. It is known that the incorporation or TiO2 into the vitreous system reduces considerably the solubility of the glasses. To study the material solubility effect on the in vivo response, glass particles of the two formulations were implanted in rabbits. Results showed that both glasses elicited a similar biological response and good biocompatibility. The percentage of new bone formation in the glasses was comparable to that obtained for the autologous bone (control) after 12 weeks of implantation. The materials showed to have an osteoconductive potential. Finally, this study showed that in spite of the solubility difference of the studied glasses, there were no significant differences in the in vivo response.

Bone marrow genesis after subcutaneous delivery of rat osteogenic cell‐seeded biodegradable scaffolds into nude mice

This study describes the generation of an active hematopoietic marrow within the confines of a biodegradable, macroporous polyester scaffold, seeded with rat osteogenic cells, after subcutaneous implantation in nude mice. A macroporous, poly(DL-lactide-co-glycolide) polymer scaffold, into which resorbable calcium phosphate particles were incorporated, was seeded with rat bone marrow-derived cells. Scanning electron microscopy of the cell-seeded scaffold demonstrated confluent cell colonization. Scaffolds seeded with cells were implanted under the dorsum of immunocompromised mice for 5 weeks. Histological analysis revealed bone formation along the scaffold pores creating bony cavities within which a host-derived, hematopoietic marrow was observed which included hematopoietic precursors, megakaryocytes, fat cells, and numerous marrow sinusoids. In those areas where bone was not elaborated on the scaffold surface, no marrow genesis was observed and the scaffold interstices were filled with fibrous tissue. These results demonstrate the utility of this biodegradable scaffold in delivery of a phenotypically functional cell population for bone tissue and bone marrow engineering applications. Moreover, the recapitulation of hematopoietic marrow tissue within the engineered bony cavities also provides a new experimental environment with which to further investigate the interactions of hematopoietic and nonhematopoietic compartments of the marrow microenvironment.

Analytical technique for quantification of selected resorbable calcium phosphate bone void fillers with the use of polarized-light microscopy.

Synthetic calcium phosphate bone void fillers promote varying rates of bone formation and material resorption depending on chemistry, porosity, pore structure, and implant site. The objective of this study was to quantify the resorption of a novel ultraporous beta-tricalcium phosphate cancellous bone void filler with simultaneous quantification of bone formation in a canine humerus model. Potential measurement error involved in conventional histomorphometry using Von Kossa stains inspired the development of a new technique. This technique utilizes bright-field and polarized-light microscopy in conjunction with image analysis software, allowing more accurate histomorphometry. This technique was validated with two separate controlled experiments. Scanning electron microscopy further supported the results. The findings suggest that the use of polarized-light microscopy combined with image analysis software can be an effective tool in simultaneously quantifying calcium phosphate resorption and bone formation.

Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections

The use of polymethylmetacrylate beads for local delivery of antibiotics requires a second surgical procedure for their removal and resorbable calcium sulphate exhibits cytotoxic effects. In this work, a bioresorbable composite of calcium sulphate and nanoparticulate hydroxyapatite (PerOssal®) was studied regarding its antibiotic release properties and biocompatibility.Material characteristics of plain PerOssal® and pure calcium sulphate pellets were studied using scanning and electron microscopy and X-ray methods. Pellets were soaked with gentamicin and vancomycin, respectively. Release properties of both antibiotics from both materials were investigated over 10 days. Quantitative and qualitative cytotoxic assays were performed for biocompatibility testing.Specific surface was 106m2/g for PerOssal® and 2.2m2/g for pure calcium sulphate. Almost complete elution of gentamicin was found for both carrier materials (94.7% for PerOssal® vs. 95.8% for calcium sulphate) within 10 days, whereas vancomycin release was higher for PerOssal® (96.3% vs. 74.8%). PerOssal® showed higher initial and lower release after approximately 5 days compared to calcium sulphate. No significant in vitro cytotoxic differences were found between PerOssal® and nontoxic cell culture medium. Calcium sulphate showed cytotoxic effects in two out of four tests. PerOssal® exhibits excellent properties regarding resorption, biocompatibility, and antibiotic release.

Percutaneous injection of recombinant human bone morphogenetic protein-2 in a calcium phosphate paste accelerates healing of a canine tibial osteotomy.

In this study, we evaluated the capacity of a single percutaneous injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a rapidly resorbable calcium phosphate paste (alpha-BSM) to accelerate bone-healing in a canine tibial osteotomy model. We hypothesized that the osteotomy sites would heal faster after percutaneous delivery of rhBMP-2/alpha-BSM than they would after injection of alpha-BSM alone or after no treatment. Bilateral tibial osteotomy was performed and the sites were stabilized with external fixators in sixteen dogs. Four hours after the surgery, one limb of each dog was treated with a single percutaneous injection of rhBMP-2/alpha-BSM paste or an equal volume of alpha-BSM alone. There were eight limbs in each group, and the osteotomy site in the contralateral limb served as an untreated control. The results were evaluated with serial radiography and force-plate analysis at four and eight weeks after surgery and with mechanical testing and histologic examination at eight weeks after the surgery. At four and eight weeks after the osteotomy and treatment, the scores for radiographic union were significantly greater for the rhBMP-2/alpha-BSM-treated limbs than they were for the alpha-BSM-treated or untreated, control limbs (p < 0.05). The callus area in the rhBMP-2/alpha-BSM-treated limbs was significantly greater than that in the alpha-BSM-treated and untreated, control limbs at four and eight weeks postinjection (p < 0.05). The time-integrated vertical force for the rhBMP-2-treated limbs was significantly greater than that for their contralateral controls at four weeks and significantly greater than that for the treated and control limbs of the alpha-BSM-treated dogs at four and eight weeks after the surgery (p </= 0.05). The rhBMP-2-treated limbs were significantly stiffer in bending and in torsion (p < 0.05) compared with the alpha-BSM-treated and control limbs. Histologic analysis demonstrated increased bone formation and more mature bone at the osteotomy site in the rhBMP-2-treated limbs compared with that in the alpha-BSM-treated and control limbs. This study demonstrates the capacity of a single percutaneous injection of rhBMP-2 delivered in a resorbable calcium phosphate paste (alpha-BSM) four hours after surgery to accelerate the healing of tibial osteotomy sites in a canine model.

Effect of rapidly resorbable calcium phosphates and a calcium phosphate bone cement on the expression of bone-related genes and proteins in vitro.

The use of biodegradable bone substitutes is advantageous for alveolar ridge augmentation because it avoids second-site surgery for autograft harvesting. This study examines the effect of novel, rapidly resorbable calcium phosphates and a calcium phosphate bone cement on the expression of bone-related genes and proteins by human bone-derived cells (HBDCs) and compares this behavior to that of tricalciumphosphate (TCP). Test materials were alpha-TCP, two materials with a crystalline phase Ca(2)KNa(PO(4))(2) and with a small amorphous portion containing either magnesium potassium phosphate (material denominated GB14) or silica phosphate (material denominated GB9), and a calcium phosphate bone cement (material denominated Biocement D). HBDCs were grown on the substrata for 3, 7, 14, and 21 days, counted, and probed for various mRNAs and proteins (type I collagen, osteocalcin, osteopontin, osteonectin, alkaline phosphatase, and bone sialoprotein). All substrates supported continuous cellular growth for 21 days. In the presence of GB14 and Biocement D specimens cell proliferation was reduced and cell differentiation increased. At day 21, the greatest number of cells was found on GB9 expressing significantly higher levels of bone-related proteins than cells grown on all other surfaces. Because all novel materials facilitated the expression of the osteoblastic phenotype at least as much as TCP and the polystyrene control, these biomaterials can be regarded as excellent candidate bone substitute materials. GB9 induced the highest proliferation and cellular differentiation after 21 days of incubation, suggesting that this material may possess a higher potency for enhancing osteogenesis than TCP.

Bone Substitution and Augmentation in Trauma Surgery with a Resorbable Calcium Phosphate Bone Cement

Synthetically manufactured bone substitute materials are widely used to fill cancellous bone defects in fracture treatment. By using these materials, complications occurring with the harvesting of autologous bone such as inflammation, hemorrhage and pain are prevented. Ideally, after osteointegration, the bone substitute resorbs, and complete restoration of bone architecture is achieved. Until now, clinical experience is limited to non-fully resorbable calcium phosphates, e. g., hydroxyapatite. Previous studies have revealed a fully resorbable pure calcium phosphate, which is applied in a paste form as a bone implant and results in complete resorption and biocompatibility. The purpose of this prospective, uncontrolled clinical study was to investigate the safety and performance of this new resorbable bone substitute material. In 107 patients, bone defects were filled with 1.0–27.5 g (median 5.45 g) of the bone substitute material. From 15 patients, biopsy samples for histological examination could be taken during secondary surgery, mostly when implants for osteosynthesis had to be removed. On clinical, radiologic and histological examination, the bone substitute material studied appeared safe and efficient for filling bone defects in fracture treatment, showing resorption and osseous integration during remodeling of bone. No clinical signs of allergic reactions or inflammation did occur. When using calcium phosphate bone cement, a second surgical procedure to harvest autologous bone is not necessary and complications at the donor site are avoided.