Ceramic Bone Research Articles

Preparation and properties of biodegradable polymer/nano-hydroxyapatite bioceramic scaffold for spongy bone regeneration

Abstract Biodegradable polymer/bioceramic composite scaffolds can overcome the limitations of conventional ceramic bone substitutes, such as brittleness and difficulty in shaping. To better mimic the mineral components and microstructure of natural bone, a novel nano-hydroxyapatite (nHAp)–chitosan composite scaffold including gelatin and polymer (poly(lactic acid)) with high porosity was developed using a sol-gel method and subsequently lyophilized for efficient bone tissue engineering. The nanocrystalline structure of hydroxyapatite was observed using X-ray diffraction analysis and the composite showed crystallinity due to the presence of nHAp. The pore diameter of the composite containing 5% nHAp was found to be 125 μm, while the composites with 10%, 15%, and 20% nHAp revealed a smaller pore size in the range of 15–28 μm. The highest compressive strength of 5.5 MPa was observed for the 10% nHAp-containing scaffold, whereas thermogravimetric analysis showed 90%–94% degradation at a temperature of 600°C, which demonstrated its excellent thermal stability. Antibacterial and cytotoxicity test results revealed that the composite is resistant toward microbial attack and has low sensitivity in cytotoxicity. The compressive strength data suggests that the composite does not have enough strength as that of human compact bone; however, the highly porous structure as observed in scanning electron microscopy makes it possible for use as an excellent substrate in the spongy bone of humans.

New investigations of early Neolithic layers (on the example of Rakushechny Yar)

R
 Rakushechny Yar has attracted interest for a long period of time. New questions arose around its materials and the site itself, which led to renewal of excavations and investigations of this site nowadays. New investigations of the place allowed the authors to distinguish early Neolithic layers, which were inaccessible before due to a high water level of the Don River. Particularities of Unio and Viviparus shells distribution show that these were different shell middens within several horizons. Also variety of spots full of bone debris and pits were uncovered here. New paleogeographical studies allowed reconstruction ancient landscape in the surroundings of this place. Shell tools, stone industry and ceramic assemblage, bone and antler tools are early Neolithic finds. The first time wooden artefacts and coprolites were found in a low watered layer. Finds of bones of domestic animals suggest even more complicated organization of this early Neolithic society.

Use of a biphasic cement bone substitute in the management of metaphyseal fractures

ObjectivesIn recent years, the increase in utilisation of bone substitutes in the reconstruction of bone defects has been fuelled by donor site complications associated with autologous bone harvesting. However the ability of bone substitute to stimulate bone union while maintaining fracture reduction has been a topic of debate. Cerament Bone Void Filler (CBVF) is a novel biphasic and injectable ceramic bone substitute that has high compressive strength and the ability to promote cancellous bone healing. Materials and MethodThis is a retrospective study to evaluate the surgical outcome of utilising CBVF in the treatment of depressed metaphyseal bone fractures over a two year period. The patients were followed up for at least six months after surgery and clinical parameters such as wound site complications were collated. Radiographic imaging was evaluated to determine loss of fracture reduction and rate of cement resorption. ResultsThirteen patients with depressed metaphyseal fractures were enrolled, which included: (i) one proximal humerus fracture; (ii) three tibial plateau fractures; and (iii) nine calcaneal fractures. None of the patients showed significant collapse in fracture reduction after six months of follow up. Cement resorption was noted in one patient as early as three weeks after surgery. There were no cases of cement leak or wound site complications. ConclusionCerament Bone Void Filler (CBVF) is a promising bone graft substitute in the management of depressed metaphyseal bone fractures, with the ability to maintain fracture reduction despite cement resorption.

Modulating Bone Regeneration in Rabbit Condyle Defects with Three Surface-Structured Tricalcium Phosphate Ceramics.

Tricalcium phosphate (TCP) ceramics are used as bone void fillers because of their bioactivity and resorbability, while their performance in bone regeneration and material resorption vary with their physical properties (e.g., the dimension of the crystal grain). Herein, three TCP ceramic bone substitutes (TCP-S, TCP-M, and TCP-L) with gradient crystal grain size (0.77 ± 0.21 μm for TCP-S, 1.21 ± 0.35 μm for TCP-M and 4.87 ± 1.90 μm for TCP-L), were evaluated in a well-established rabbit lateral condylar defect model (validated with sham) with respect to bone formation and material resorption up to 26 weeks. Surface structure-dependent bone regeneration was clearly shown after 4 weeks implantation with TCP-S having most mineralized bone (20.2 ± 3.4%), followed by TCP-M (14.0 ± 3.5%), sham (8.1 ± 4.2%), and TCP-L (6.6 ± 2.6%). Afterward, the amount of mineralized bone was similar in all the three groups, but bone marrow and material resorption varied. After 26 weeks, TCP-S induced most bone tissue formation (mineralized bone + bone marrow) (61.6 ± 7.8%) and underwent most material resorption (80.1 ± 9.0%), followed by TCP-M (42.9 ± 5.2% and 61.4 ± 8.0% respectively), TCP-L (28.3 ± 5.5% and 45.6 ± 9.7% respectively), and sham (25.7 ± 4.2%). Given the fact that the three ceramics are chemically identical, the results indicate that the surface structure (especially, the crystal grain size) of TCP ceramics can greatly tune their bone regeneration potential and the material resorption in rabbit condyle defect model, with the submicron surface structured TCP ceramic performing the best.

Sinus augmentation using rhBMP-2/ACS in a mini-pig model: Influence of an adjunctive ceramic bone biomaterial.

Recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support significant bone formation when used to augment the maxillary sinus for implant dentistry. Nevertheless, bone biomaterials have been suggested to extend rhBMP-2/ACS with limited support of the merits of such approaches. To evaluate local bone formation/dental implant osseointegration following implantation of rhBMP-2/ACS combined with a ceramic bone biomaterial using a mini-pig sinus augmentation model. Twelve adult Göttingen mini-pigs received rhBMP-2/ACS (rhBMP-2 adjusted to 0.43mg/cc) alone or combined with an off-the-shelf biphasic ceramic (15%/85% HA/ß-TCP) biomaterial at 3:1, 1:1 and 1:3 ratios randomized to contra-lateral maxillary sinus sites yielding rhBMP-2/ACS fractions of 100%, 75%, 50% and 25%, respectively. A 4-cc implant volume was used for all sites. Two threaded dental implants (ø4.0×11.5mm) were placed at each site. The animals were euthanized at 8weeks for histologic analysis. Surgical execution and healing were generally uneventful, infraorbital local swelling was observed in all animals until suture removal. rhBMP-2/ACS combined with the ceramic biomaterial did not significantly enhance local bone formation (range 9.0±1.5 to 9.7±2.1mm) compared with rhBMP-2/ACS alone (8.6±1.1mm; p>0.05). Variations in rhBMP-2/ACS to ceramic matrix ratios yielding rhBMP-2 doses approximating 0.4, 0.9, 1.3 and 1.7mg/sinus did not appreciably influence bone formation/osseointegration. Whereas rhBMP-2/ACS supports significant bone formation/osseointegration in the mini-pig sinus augmentation model and thus appears an effective alternative for sinus augmentation procedures, adding a ceramic biomaterial to rhBMP-2/ACS does not produce meaningful biological advantages.

Endogenous Platelet-Rich Plasma Supplements/Augments Growth Factors Delivered via Porous Collagen-Nanohydroxyapatite Bone Substitute for Enhanced Bone Formation

Polymer (acrylate) and ceramic bone cements are extensively used as bone void fillers and for implant fixation in orthopedics. These materials have micro- to nonporous architectures. Postimplantation, they may cause hypoxic and exothermic injuries to already compromised damage site. These materials also have limited interaction with surrounding tissue. In this work we have developed composite collagen-nanohydroxyapatite (CS) bone filler, mimicking porous architecture of trabecular bone. It was functionalized with clinically available bone active agents like bone morphogenetic protein-2 (rhBMP-2) and zoledronic acid (ZA). We investigated synergistic effects of the bone active molecules and endogenous platelet rich plasma (PRP), a source of growth factors on mineralization. Porous CS and collagen/gelatin/chiotosan polymer scaffold (SC) (without nanohydroxyapatite) were synthesized using cryogelation. PRP (10 μL) (∼5 × 106 cells), rhBMP-2 (5 μg) and ZA (10 μg) were used to functionalize scaffolds. Bone formation was evaluated at ectopic sites in abdominal pouch and 4.0 mm critical defect in tibia metaphysis of rats. Tissue mineralization was evaluated by micro-CT and histological analysis 12 weeks postimplantation. In vitro cell based studies revealed, PRP functionalization enhances osteoblast proliferation and activity on scaffolds. In vivo BMP+ZA+PRP functionalized scaffolds had higher amount (28 mm3) of mineralized tissue formation as compared to empty defect (20 mm3), suggesting that PRP can augment the osteoinductive properties of functionalized scaffolds both in vitro and in vivo. Enhanced cell infiltration and mineralization can be achieved via CS in comparison to SC, implying their use as porous bone void fillers and substitutes for autografts.

Antibiotic Containing Bone Substitute in Major Hip Surgery: A Long Term Gentamicin Elution Study.

Objectives: The objective is to present the antibiotic elution from a locally implanted gentamicin containing hydroxyapatite and calcium sulphate bone substitute with an extended follow up of 30 days.We also compare the pharmacokinetics of the ceramic bone substitute with a published study on gentamicin containing poly (methyl methacrylate) (PMMA) bone cement used in primary total hip arthroplasty.Methods: Gentamicin release was measured in the urine for a month and the serum for 4 days in 10 patients operated for trochanteric hip fractures and 10 patients in uncemented hip revisions. 17 patients were followed up at one year and 3 patients at 6 months.Results and Discussion: The gentamicin concentrations measured in serum were low and approximately 100 times less than in urine during the first days, indicating high local concentrations at the implant site. The elution from the biphasic bone substitute showed a stronger burst and higher gentamicin concentrations for the first week compared to that reported for PMMA used in hip arthroplasty. Also, for the bone substitute a complete gentamicin elution was obtained after 30 days, while for the PMMA cement sub-inhibitory MIC levels of gentamicin were still present in urine 60 days past surgery. No infections were detected.Conclusions: A new biphasic bone substitute containing antibiotics could potentially be used to prevent infection in patients treated for trochanteric hip fractures or uncemented hip revisions. The gentamicin elution from the bone substitute is efficient with high initial local gentamicin concentrations and complete release at 30 days.

Natural Course of Local Bone Mineralization After Treatment of Benign or Borderline Bone Tumors and Cysts With a Composite Ceramic Bone Graft Substitute

After surgical bone tumor removal, filling of the bone defect is frequently performed using a bone graft or bone graft substitute. During follow-up, precise quantification of changes in bone mineral density, within the treated bone defect, is very difficult using conventional X-ray examinations. The objectives of this study were to characterize the pattern of resorption/biodegradation of a composite calcium sulfate/hydroxyapatite bone graft substitute and to quantify the bone defect healing with repeated dual-energy X-ray absorptiometry (DXA) measurements. Seventeen patients treated for 18 benign bone lesions, with subsequent defect filling using 2 variants of a composite ceramic bone graft substitute (CERAMENT™|BONE VOID FILLER or CERMAMENT™|G, BONESUPPORT AB, Lund, Sweden), were scanned postoperatively and after 2, 6, 12, 26, and 52 wk using DXA. After an initial increase in bone mineral density after implantation of the bone graft substitute, bone mineral density decreased in the bone defect region throughout the 52 wk: rapidly in the first 12 wk and slower in the remaining weeks. Despite this continuous decrease, bone mineral density remained, on average, 25% higher in the operated extremity, compared with the nonoperated extremity, after 52 wk. The observed pattern of reduction in bone mineral density is consistent with the anticipated resorption of calcium sulfate within the bone graft substitute during the first 12 wk after surgery. We believe the DXA technique provides a precise method for quantification of bone graft resorption, but for evaluation of new bone formation, 3-dimensional imaging is needed.

Trivalent chromium incorporated in a crystalline calcium phosphate matrix accelerates materials degradation and bone formation in vivo

Remodeling of calcium phosphate bone cements is a crucial prerequisite for their application in the treatment of large bone defects. In the present study trivalent chromium ions were incorporated into a brushite forming calcium phosphate cement in two concentrations (10 and 50 mmol/mol β-tricalcium phosphate) and implanted into a femoral defect in rats for 3 and 6 month, non-modified brushite was used as reference. Based on our previous in vitro findings indicating both an enhanced osteoclastic activity and cytocompatibility towards osteoprogenitor cells we hypothesized a higher in vivo remodeling rate of the Cr3+ doped cements compared to the reference. A significantly enhanced degradation of the modified cements was evidenced by micro computed tomography, X-ray and histological examinations. Furthermore the formation of new bone tissue after 6 month of implantation was significantly increased from 29% to 46% during remodeling of cements, doped with the higher Cr3+ amount. Time of flight secondary ion mass spectrometry (ToF-SIMS) of histological sections was applied to investigate the release of Cr3+ ions from the cement after implantation and to image their distribution in the implant region and the surrounding bone tissue. The relatively weak incorporation of chromium into the newly formed bone tissue is in agreement to the low chromium concentrations which were released from the cements in vitro. The faster degradation of the Cr3+ doped cements was also verified by ToF-SIMS. The positive effect of Cr3+ doping on both degradation and new bone formation is discussed as a synergistic effect of Cr3+ bioactivity on osteoclastic resorption on one hand and improvement of cytocompatibility and solubility by structural changes in the calcium phosphate matrix on the other hand. Statement of SignificanceWhile biologically active metal ions like strontium, magnesium and zinc are increasingly applied for the modification of ceramic bone graft materials, the present study is the first report on the incorporation of low doses of trivalent chromium ions into a calcium phosphate based biomaterial and testing of its performance in bone defect regeneration in vivo. Chromium(III)-doped calcium phosphate bone cements show improved cytocompatibility and both degradation rate and new bone formation in vivo are significantly increased compared to the reference cement. This important discovery might be the starting point for the application of trivalent chromium salts for the modification of bone graft materials to increase their remodelling rate.

Coagulated concentrated anatase slurry leads to improved strength of ceramic TiO2 bone scaffolds

Slurry behaviour has an important influence on the properties of ceramic scaffolds produced by the polymer sponge method. By adding chloride salts to the TiO2 slurry, the viscosity was increased depending on the chloride concentration at low pH and high particle concentration. Slurries with higher viscosity led to closed and dense scaffold struts combined with high porosity, resulting in a compressive strength over 1.6MPa. Furthermore, scaffold prepared with 0.1M CaCl2 and SrCl2 showed the formation of Ca- and Sr-rich phases at the grain boundaries. These ions were also shown to reduce the activation energy for grain growth in the TiO2 scaffold as indicated by the significantly larger grain size. Ca2+-doped scaffolds had the highest compressive strength, while the strength of Sr2+-doped scaffolds was reduced by the formation of a solid solution phase below the sintering temperature.

Evaluation of calcination temperature and phase composition ratio for new hyroxyapatite

The demand of production of hydroxyapatite (HA) has been increasing for the purpose of medical and dental application. HA possesses the excellent properties leads to the priority choice for ceramic bone replacement. Synthesis route by wet chemical precipitation is commonly practised in industrial scale. Calcium hydroxide and Orthophosphoric acid are the precursors for production scale. The synthesis of HA is conducted by varying the synthetic condition: stirring rate, calcium-phosphate and calcination temperature. This paper is focused on the properties of HA produced by regulating the synthetic condition so that the qualities of HA can be well performed. Characterization studies were also carried out by Fourier Transform Infrared Spectroscopy (FT-IR) for functional group identification, Scanning Electron Microscope (SEM) for surface morphology analysis and X-Ray Diffraction (XRD) for phase composition and crystallinity respectively. Narrow particle size distribution contributed to better quality of hydroxyapatite for bone replacement. Both calcium-phosphate ratio and calcination temperature would affect the phase composition of calcium phosphate.

Computational design of curvilinear bone scaffolds fabricated via direct ink writing

Bone scaffold porosity and stiffness play a critical role in the success of critical-size bone defect rehabilitation. In this work, we present a computational procedure to design ceramic bone scaffolds to provide adequate mechanical support and foster bone healing. The scaffolds considered in our study consist of a lattice of curved rods fabricated via direct ink writing. We develop cellular solids models of the scaffold’s effective elastic constants as functions of its geometric parameters, up to some unknown coefficients. To determine numeric values for these coefficients, we execute a computational design of experiments whereby effective elastic properties are obtained using numerical homogenization with the finite element method. In order to automate these experiments and circumvent re-meshing for every scaffold geometry, we project a representative volume element of the scaffold onto a fixed uniform mesh and assign an ersatz material for the analysis. We use these calibrated models in conjunction with finite element analysis and efficient gradient-based optimization methods to design patient-specific scaffolds (i.e., shape, location, and loading) by varying geometric parameters that can be controlled in the fabrication, namely the separation between rods in the lattice, and the printing path of the rods. At present, our methodology is restricted to 2-d idealizations of flat bones subject to in-plane loading. The optimization procedure renders element-wise values of these parameters. As this representation is not amenable to fabrication, lastly, we generate the final scaffold geometry by posing a differential equation whose solution is a function such that its level set lines at specified values correspond to the directrices of the rods in the scaffold. We present examples where we perform the maximization of stiffness of a scaffold implant with a constraint on porosity.

Sinus augmentation using a mini-pig model: Effect of ceramic and allogeneic bone biomaterials.

Present clinical practice broadly relies on off-the-shelf allogeneic, xenogeneic or synthetic bone biomaterials in support of sinus augmentation. Also, recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support clinically relevant bone formation when used to augment the maxillary sinus. To evaluate local bone formation/dental implant osseointegration following implantation of two particulate bone biomaterials using the mini-pig sinus augmentation model. Nine adult Göttingen mini-pigs were used for evaluation of a biphasic ceramic (15%/85% HA/ß-TCP) and an allogeneic mineralized bone biomaterial. Treatments randomized to contralateral sinus sites included sham-surgery (control) and biomaterials. Two threaded dental implants (ø4.0×11.5mm) were placed at each sinus site. The animals were euthanized at 8weeks for histologic analysis. Execution of the surgical protocol and healing was unremarkable. Limited infraorbital swelling was observed until suture removal. The biphasic ceramic and allogeneic bone biomaterials produced significantly increased bone formation (5.2±1.9mm and 4.9±1.6mm vs. 2.6±0.5mm, p<0.05) and osseointegration (18.0±6.0% and 25.1±18.2% vs. 10.1±8.0%, p<0.05) over the sham-surgery control. No significant differences were observed between biomaterials. Implantation of biphasic ceramic or allogeneic bone biomaterials enhances bone formation in the mini-pig maxillary sinus, however, dental implant bone support is incomplete resulting in overall limited osseointegration.

The kinetics of remodeling of a calcium sulfate/calcium phosphate bioceramic.

In the last years considerable research and development activity have been expended to find new ceramic bone substitutes for the treatment of bone defects. However in many cases the drawback of synthethic bone substitutes are the slow graft incorporation and remodelling into the host bone. The purpose of this study was to analyze the kinetics of resorption and new bone formation of new calcium sulfate (CaSO4)/calcium phosphate (CaPO4) bioceramic engineered to enhance its bone forming properties. We prospectively evaluated the results of a series of 15 hips with osteonecrosis of the femoral head (ONFH) treated at with core decompression and injection of the CaSO4/CaPO4 composite. In all hips, a quantitative computed tomography (QTC) scan was taken within one week after the surgery, at 12 months, 2 years and finally with a minimum of 4 years follow-up. The mean HU in the immediate post-operative period was 1445 (Range 1388-1602); At one year the mean HU strongly decrease at 556.6 HU (P < 0.01); The mean HU at 2 years follow-up further decreased to 475.1. The mean HU at 4 years was unchanged. The quantitative and qualitative CT scan data of this series indicates that the CaSO4-CaPO4 ceramic composite resorbs over a narrow timeframe and the gradual resorption of the graft within the defect provides an ideal environment for the direct new bone growth that propagates across the defect.

Radiographic and Clinical Outcome of Silicate-substituted Calcium Phosphate (Si-CaP) Ceramic Bone Graft in Spinal Fusion Procedures.

Retrospective cohort study. To evaluate the radiographic and clinical outcome of silicate-substituted calcium phosphate (Si-CaP), utilized as a graft substance in spinal fusion procedures. Specific properties of Si-CaP provide the graft with negative surface charge that can result in a positive effect on the osteoblast activity and neovascularization of the bone. This study included those patients who underwent spinal fusion procedures between 2007 and 2011 in which Si-CaP was used as the only bone graft substance. Fusion was evaluated on follow-up CT scans. Clinical outcome was assessed using Oswestry Disability Index, Neck Disability Index, and the visual analogue scale (VAS) for back, leg, neck, and arm pain. A total of 234 patients (516 spinal fusion levels) were studied. Surgical procedures consisted of 57 transforaminal lumbar interbody fusion, 49 anterior cervical discectomy and fusion, 44 extreme lateral interbody fusion, 30 posterior cervical fusions, 19 thoracic fusion surgeries, 17 axial lumbar interbody fusions, 16 combined anterior and posterior cervical fusions, and 2 anterior lumbar interbody fusion. At a mean radiographic follow-up of 14.2±4.3 months, fusion was found to be present in 82.9% of patients and 86.8% of levels. The highest fusion rate was observed in the cervical region. At the latest clinical follow-up of 21.7±14.2 months, all clinical outcome parameters showed significant improvement. The Oswestry Disability Index improved from 45.6 to 13.3 points, Neck Disability Index from 40.6 to 29.3, VAS back from 6.1 to 3.5, VAS leg from 5.6 to 2.4, VAS neck from 4.7 to 2.7, and VAS arm from 4.1 to 1.7. Of 7 cases with secondary surgical procedure at the index level, the indication for surgery was nonunion in 3 patients. Si-CaP is an effective bone graft substitute. At the latest follow-up, favorable radiographic and clinical outcome was observed in the majority of patients. Level-III.

The biocompatibility of bone cements: progress in methodological approach.

The ideal bone graft substitute should have certain properties and there are many studies dealing with mixture of polymethylmetacrilate (PMMA) and ß-tricalciumphospate (ß-TCP) presenting the best characteristics of both. Scanning Electron Microscopy (SEM), for ultra-structural data, resulted a very reliable in vivo model to better understand the bioactivity of a cement and to properly evaluate its suitability for a particular purpose. The present study aims to further improve the knowledge on osteointegration development, using both parameters obtained with the Environmental Scanning Electron Microscopy (ESEM) and focused histological examination. Two hybrid bone graft substitute were designed among ceramic and polymer-based bone graft substitutes. Based on ß-TCP granules sizes, they were created with theoretical different osteoconductive properties. An acrylic standard cement was chosen as control. Cements were implanted in twelve New Zealand White (NZW) rabbits, which were sacrificed at 1, 2, 3, 6, 9 and 12 months after cement implantation. Histological samples were prepared with an infiltration process of LR white resin and then specimens were studied by X-rays, histology and Environmental Scanning Electron Microscopy (ESEM). Comparing the resulting data, it was possible to follow osteointegration’s various developments resulting from different sizes of ß-TCP granules. In this paper, we show that this evaluation process, together with ESEM, provides further important information that allows to follow any osteointegration at every stage of develop.

Calcium phosphates and silicon: exploring methods of incorporation

BackgroundBioinorganics have been explored as additives to ceramic bone graft substitutes with the aim to improve their performance in repair and regeneration of large bone defects. Silicon (Si), an essential trace element involved in the processes related to bone formation and remodeling, was shown not only to enhance osteoblasts proliferation but also to stimulate the differentiation of mesenchymal stem cells (MSCs) and preosteoblasts into the osteogenic lineage. In this study, the added value of Si to calcium phosphate (CaP) coatings was evaluated.MethodsTissue culture plastic well plates were coated with a thin CaP layer to which traces amounts of Si were added, either by adsorption or by incorporation through coprecipitation. The physicochemical and structural properties of the coatings were characterized and the dissolution behavior was evaluated. The adsorption/incorporation of Si was successfully achieved and incorporated ions were released from the CaP coatings. Human MSCs were cultured on the coatings to examine the effects of Si on cell proliferation and osteogenic differentiation. For the statistical analysis, a one-way ANOVA with Bonferroni post-hoc test was performed.ResultsThe results showed that human MSCs (hMSCs) responded to the presence of Si in the CaP coatings, in a dose-dependent manner. An increase in the expression of markers of osteogenic differentiation by human MSCs was observed as a result of the increase in Si concentration.ConclusionsThe incorporation/adsorption of Si into CaP coatings was successfully achieved and hMSCs responded with an increase in osteogenic genes expression with the increase of Si concentration. Furthermore, hMSCs cultured on CaP-I coatings expressed higher levels of ALP and OP, indicating that this may be the preferred method of incorporation of bioinorganics into CaPs.

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

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.

Doped Calcium Silicate Ceramics: A New Class of Candidates for Synthetic Bone Substitutes.

Doped calcium silicate ceramics (DCSCs) have recently gained immense interest as a new class of candidates for the treatment of bone defects. Although calcium phosphates and bioactive glasses have remained the mainstream of ceramic bone substitutes, their clinical use is limited by suboptimal mechanical properties. DCSCs are a class of calcium silicate ceramics which are developed through the ionic substitution of calcium ions, the incorporation of metal oxides into the base binary xCaO–ySiO2 system, or a combination of both. Due to their unique compositions and ability to release bioactive ions, DCSCs exhibit enhanced mechanical and biological properties. Such characteristics offer significant advantages over existing ceramic bone substitutes, and underline the future potential of adopting DCSCs for clinical use in bone reconstruction to produce improved outcomes. This review will discuss the effects of different dopant elements and oxides on the characteristics of DCSCs for applications in bone repair, including mechanical properties, degradation and ion release characteristics, radiopacity, and biological activity (in vitro and in vivo). Recent advances in the development of DCSCs for broader clinical applications will also be discussed, including DCSC composites, coated DCSC scaffolds and DCSC-coated metal implants.

Calcium-phosphate ceramics and polysaccharide-based hydrogel scaffolds combined with mesenchymal stem cell differently support bone repair in rats

Research in bone tissue engineering is focused on the development of alternatives to autologous bone grafts for bone reconstruction. Although multiple stem cell-based products and biomaterials are currently being investigated, comparative studies are rarely achieved to evaluate the most appropriate approach in this context. Here, we aimed to compare different clinically relevant bone tissue engineering methods and evaluated the kinetic repair and the bone healing efficiency supported by mesenchymal stem cells and two different biomaterials, a new hydrogel scaffold and a commercial hydroxyapatite/tricalcium phosphate ceramic, alone or in combination.Syngeneic mesenchymal stem cells (5 × 105) and macroporous biphasic calcium phosphate ceramic granules (Calciresorb C35®, Ceraver) or porous pullulan/dextran-based hydrogel scaffold were implanted alone or combined in a drilled-hole bone defect in rats. Using quantitative microtomography measurements and qualitative histological examinations, their osteogenic properties were evaluated 7, 30, and 90 days after implantation. Three months after surgery, only minimal repair was evidenced in control rats while newly mineralized bone was massively observed in animals treated with either hydrogels (bone volume/tissue volume = 20%) or ceramics (bone volume/tissue volume = 26%). Repair mechanism and resorption kinetics were strikingly different: rapidly-resorbed hydrogels induced a dense bone mineralization from the edges of the defect while ceramics triggered newly woven bone formation in close contact with the ceramic surface that remained unresorbed. Delivery of mesenchymal stem cells in combination with these biomaterials enhanced both bone healing (>20%) and neovascularization after 1 month, mainly in hydrogel.Osteogenic and angiogenic properties combined with rapid resorption make hydrogels a promising alternative to ceramics for bone repair by cell therapy.