Biphasic Calcium Phosphate Group Research Articles

Stability of guided bone regeneration with two ratios of biphasic calcium phosphate at implant sites in the esthetic zone: A randomized controlled clinical trial.

The aim of this randomized, double-blind, clinical trial was to compare the stability of the horizontal dimensions (facial bone thickness) of augmented bone using biphasic calcium phosphate (BCP) with hydroxyapatite/β-tricalcium phosphate ratio of either 60/40 or 70/30. Sixty dental implants placed with contour augmentation in the esthetic zone were randomized to 60/40 BCP (n = 30) or 70/30 BCP (n = 30). Cone-beam computed tomographic was used to assess facial bone thickness post-implantation and 6 months later at implant platform and 2, 4, and 6 mm apical to it. The percentage of horizontal dimension reduction was 23.64%, 12.83%, 9.62%, and 8.21% in 70/30 BCP group, while 44.26%, 31.91%, 25.88%, and 21.49% in 60/40 BCP group at the level of the implant platform and 2, 4, and 6 mm apical, respectively. Statistically significant difference was found at 6 months at all levels of measurement (p-value < .05). BCP bone grafts with HA/β-TCP ratio of 60/40 and 70/30 showed comparable outcomes for contour augmentation simultaneously with implant placement. Interestingly, the 70/30 ratio was significantly superior in maintaining facial thickness and showed more stable horizontal dimensions of the augmented site.

Evaluation of the clinical and radiographic effectiveness of treating peri-implant bone defects with a new biphasic calcium phosphate bone graft: a prospective, multicenter randomized controlled trial.

Biphasic calcium phosphate (BCP), a widely used biomaterial for bone regeneration, contains synthetic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), the ratio of which can be adjusted to modulate the rate of degradation. The aim of this study was to evaluate the clinical and radiographic benefits of reconstructing peri-implant bone defects with a newly developed BCP consisting of 40% β-TCP and 60% HA compared to demineralized bovine bone mineral (DBBM). This prospective, multicenter, parallel, single-blind randomized controlled trial was conducted at the periodontology departments of 3 different dental hospitals. Changes in clinical (defect width and height) and radiographic (augmented horizontal bone thickness) parameters were measured between implant surgery with guided bone regeneration (GBR) and re-entry surgery. Postoperative discomfort (severity and duration of pain and swelling) and early soft-tissue wound healing (dehiscence and inflammation) were also assessed. Data were compared between the BCP (test) and DBBM (control) groups using the independent t-test and the χ² test. Of the 53 cases included, 27 were in the test group and 26 were in the control group. After a healing period of 18 weeks, the full and mean resolution of buccal dehiscence defects were 59.3% (n=16) and 71.3% in the test group and 42.3% (n=11) and 57.9% in the control group, respectively. There were no significant differences between the groups in terms of the change in mean horizontal bone augmentation (test group: -0.50±0.66 mm vs. control groups: -0.66±0.83 mm, P=0.133), postoperative discomfort, or early wound healing. No adverse or fatal complications occurred in either group. The GBR procedure with the newly developed BCP showed favorable clinical, radiographic, postoperative discomfort-related, and early wound healing outcomes for peri-implant dehiscence defects that were similar to those for DBBM. Clinical Research Information Service Identifier: KCT0006428.

Combined Application of Dentin Noncollagenous Proteins and Odontogenic Biphasic Calcium Phosphate in Rabbit Maxillary Sinus Lifting.

Teeth can be used as a raw material for preparing bone substitutes due to their similar chemical composition to bone. The objective of our study was to evaluate the effect of odontogenic biphasic calcium phosphate (BCP) incorporating dentin noncollagenous proteins (DNCPs) on osteogenesis and stability in maxillary sinus augmentation. The composition, structure and morphology of the odontogenic BCP were tested by X-ray powder diffraction (XRD), Brunauer-Emmett-Teller, and scanning electron microscopy methods. The biocompatibility and osteoinduction of DNCPs and materials were examined in vitro and their bone regeneration capacity was verified in vivo. The results showed that the cells adhered and proliferated well on the DNCP-loaded BCP scaffold. The odontogenic BCP and DNCPs promoted osteogenic differentiation of cells, The new bone formation in the BCP groups and DNCP subgroups was significantly higher than the new bone formation in the control, and the new bone quality was better. The bone regeneration effect of odontogenic BCP was similar to the effect of deproteinized bovine bone mineral, but β-TCP did not maintain the height and volume of bone reconstruction. In conclusion, the combined application of DNCPs and odontogenic BCP is an effective strategy for tissue engineering osteogenesis in the maxillary sinus region. The biomimetic strategy could provide a new approach for patients requiring maxillary sinus lifting.

Use of biphasic calcium phosphate versus demineralized bone matrix: retrospective clinical and CT analysis of posterolateral fusion results.

Bone graft extenders have been developed to prevent donor site morbidity associated with iliac crest bone graft, but few studies compared the efficacy of various substitutes. Our purpose was to determine fusion rate and clinical outcome in patients undergoing lumbar arthrodesis using demineralized bone matrix (DBM) and biphasic calcium phosphate (BCP). Patients with degenerative spondylolisthesis undergoing one-level or two-level arthrodesis of lumbar spine were retrospectively reviewed. Two treatment groups placed either BCP or DBM, in addition to local autograft in lumbar posterolateral space. Three-dimensional CT exam and dynamic flexion-extension radiographs at postoperative 2-year were assessed for posterolateral fusion status and pain scale and Oswestry Disability Index (ODI) for clinical outcome. Of the 148 patients reviewed (including 23 in one- and 58 patients in two-level in BCP group, and 47 in one- and 20 patients in two-level in DBM group), no significant differences were found in terms of age, sex, BMI, smoking, diabetes, steroids, number of level fused, non-union rate or revision surgery between BCP and DBM groups. Significantly improved pain scale of back and leg and ODI were found in both groups postoperatively without group difference. We found a comparable fusion rate in one-level surgery (100% versus 93.6%) and a superior fusion rate of BCP group in two-level surgery (98.3% versus 80.0%, p = 0.01). Being a bone graft extender without osteoinductive property, with local autograft, BCP is comparable to DBM for one- and superior for two-level fusion. No significant difference was found in clinical outcomes.

Biological evaluation of polydopamine and chitosan composite coatings on the 3D printed porous biphasic calcium phosphate scaffold

A current, gradually growing trend is to use bioactive ceramics to develop new bone scaffolds to replace traditional bone implants. Biphasic calcium phosphate (BCP), a mixed material of hydroxyapatite and tricalcium phosphate, has limited osseointegration ability. Therefore, improving the bioactivity and osteoinductive ability of BCP scaffolds through various surface modification methods is an important issue. Polydopamine (PDA) coating, chitosan (CS) coating, and their composite coatings have been previously reported to individually possess a good ability to improve scaffold bioactivity, but few comparisons between them and the optimal coating sequence of PDA and CS have been reported. Herein, we fabricated a BCP scaffold by using a self-made 3D printer, sintered the scaffold, and then prepared PDA, CS, PDA/CS and CS/PDA coatings by solution immersion. Afterwards, the surface morphology, element composition and proportion, compressive strength and surface contact angle of the five groups of scaffolds were characterized. Finally, the adhesion, proliferation and osteogenesis-related gene expression levels of MC3T3-E1 on the five groups in vitro were evaluated in detail. The results showed that the five types of scaffolds were fabricated successfully and that the PDA/CS and CS/PDA coatings had different surface morphologies. The compressive strengths of the composite-coating groups were higher than those of the single-coating groups and the BCP group. The CCK-8 experiment revealed that the composite coatings can promote the initial adhesion and proliferation of cells. The detection results of three osteogenesis-related genes (OCN, COL-1 and Runx-2) proved that the composite coatings had a synergistic effect in promoting osteodifferentiation and that the CS/PDA coating had the greatest effect in improving cell viability and promoting osteogenic differentiation.

The effect of hard-type crosslinked hyaluronic acid with particulate bone substitute on bone regeneration: positive or negative?

PurposeThe role of hard-type crosslinked hyaluronic acid (HA) with particulate bone substitutes in bone regeneration for combined inlay-onlay grafts has not been fully investigated. We aimed to evaluate the effect of hard-type crosslinked HA used with bone substitute in terms of new bone formation and space maintenance.MethodsA 15-mm-diameter round defect was formed in the calvaria of 30 New Zealand White rabbits. All animals were randomly assigned to 1 of 3 groups: the control group (spontaneous healing without material, n=10), the biphasic calcium phosphate (BCP) graft group (BCP, n=10), and the BCP graft with HA group (BCP/HA, n=10). The animals were evaluated 4 and 12 weeks after surgery. Half of the animals from each group were sacrificed at 4 and 12 weeks after surgery. Samples were evaluated using micro-computed tomography, histology, and histomorphometry.ResultsThe BCP group showed higher bone volume/tissue volume (BV/TV) values than the control and BCP/HA groups at both 4 and 12 weeks. The BCP and BCP/HA groups showed higher bone surface/tissue volume (BS/TV) values than the control group at both 4 and 12 weeks. The BCP group showed higher BS/TV values than the control and BCP/HA groups at both 4 and 12 weeks. No statistically significant difference in newly formed bone was found among the 3 groups at 4 weeks. The BCP group showed significantly higher new bone formation than the BCP/HA group at 12 weeks.ConclusionsHard-type crosslinked HA did not show a positive effect on new bone formation and space maintenance. The negative effect of hard-type crosslinked HA may be due to the physical properties of HA that impede osteogenic potential.

IN VIVO EVALUATION OF THE ABILITY OF BIPHASIC CALCIUM PHOSPHATE IN ALVEOLAR BONE REGENERATION

Background: The alveolar bone can be damaged by a variety of causes such as trauma, bone tumors and cysts, infection and tooth loss, affecting function, aesthetics, comfort and confidence of the patient. In order to reconstruct the alveolar bone defect, besides autologous bone, cellular and inorganic biological materials are being developed and widely applied including Biphasic Calcium Phosphate (BCP). Therefore, it is very essential to establish an animal model of alveolar bone defect to evaluate the progress of bone formation and the potential of materials before clinical application. Materials and Methods: The study was performed on 18 white, male, healthy rabbits weighing 2.5 ± 0.2 kg, 8-to-10-week aged, divided into 2 groups: group 1 (control), group 2 (BCP). The alveolar bone defect formation was performed in 2 groups, then reconstructed with BCP (group 2). Evaluation of soft tissue healing characteristics in 2 groups after 1, 3, 5, 7, 14 days after surgery and assessment of alveolar bone regeneration by X-ray and histological analysis after 2, 4, 6 weeks. Results: Healing score in each group increased gradually from day 1 to day 14, having statistical significance from day 5. Healing score of 2 groups tended to increase gradually in order: control group &lt; BCP group (p &gt; 0.05). X-ray scores in each group increased from week 2 to week 6, with statistical significance at week 6 (p &lt; 0.05). X-ray scores of 2 groups tended to increase in order: the control group &lt; BCP group (p &gt; 0.05). New connective tissue formed in the control group reached the highest at week 4 and decreased after week 6 (p &lt; 0.05). New bone formation in each group increased statistically from week 2 to week 6. The amount of newly formed bone in BCP group was significantly higher than in control group (p &lt; 0.05). Conclusions: The above established model allows us to evaluate the capability of the bone regeneration of various materials. In addition, BCP is a potential material which can be used to reconstruct alveolar bone defects in patients

Ex Vivo and In Vivo Analyses of Novel 3D-Printed Bone Substitute Scaffolds Incorporating Biphasic Calcium Phosphate Granules for Bone Regeneration.

(1) Background: The aim of this study was examining the ex vivo and in vivo properties of a composite made from polycaprolactone (PCL) and biphasic calcium phosphate (BCP) (synprint, ScientiFY GmbH) fabricated via fused deposition modelling (FDM); (2) Methods: Scaffolds were tested ex vivo for their mechanical properties using porous and solid designs. Subcutaneous implantation model analyzed the biocompatibility of PCL + BCP and PCL scaffolds. Calvaria implantation model analyzed the osteoconductive properties of PCL and PCL + BCP scaffolds compared to BCP as control group. Established histological, histopathological and histomorphometrical methods were performed to evaluate new bone formation.; (3) Results Mechanical testing demonstrated no significant differences between PCL and PCL + BCP for both designs. Similar biocompatibility was observed subcutaneously for PCL and PCL + BCP scaffolds. In the calvaria model, new bone formation was observed for all groups with largest new bone formation in the BCP group, followed by the PCL + BCP group, and the PCL group. This finding was influenced by the initial volume of biomaterial implanted and remaining volume after 90 days. All materials showed osteoconductive properties and PCL + BCP tailored the tissue responses towards higher cellular biodegradability. Moreover, this material combination led to a reduced swelling in PCL + BCP; (4) Conclusions: Altogether, the results show that the newly developed composite is biocompatible and leads to successful osteoconductive bone regeneration. The new biomaterial combines the structural stability provided by PCL with bioactive characteristics of BCP-based BSM. 3D-printed BSM provides an integration behavior in accordance with the concept of guided bone regeneration (GBR) by directing new bone growth for proper function and restoration.

Scanning Electron Microscopic Evaluation of the Internal Fit Accuracy of 3D-Printed Biphasic Calcium Phosphate Block: An Ex Vivo Pilot Study.

The aim of this study was to assess the internal fit accuracy of a three-dimensional (3D)-printed biphasic calcium phosphate (BCP) block compared with a 3D-milled poly methyl methacrylate (PMMA) block by scanning electron microscope (SEM) analysis. In a total of 20 porcine rib bones, two different types of defects having two adjacent walls and a floor were produced: a defect with a flat floor (flat defect; N = 10) and a defect with a concave floor (curved defect; N = 10). Each defect was grafted with either the 3D-printed BCP block or the 3D-milled PMMA block fabricated following the computer aided design. The defects were then cut cross-sectionally and evaluated under the SEM. The extents of internal contact and gap were measured and statistically analyzed (p < 0.05). All blocks in both BCP and PMMA groups were successfully fit to the flat and curved defects. The internal contact ratio was significantly higher in the BCP group (flat defect: 0.47 ± 0.10; curved defect: 0.29 ± 0.05) compared with the PMMA group (flat defect: 0.21 ± 0.13; curved defect: 0.17 ± 0.04; p < 0.05). The internal gap area was similar between the two groups regardless of the defect types (p > 0.05). The internal fit accuracy of the 3D-printed BCP block was reliable in both the flat and curved defects when compared with the accuracy of the 3D-milled PMMA block.

Tissue response to biphasic calcium phosphate covalently modified with either heparin or hyaluronic acid in a mouse subcutaneous implantation model.

Biphasic calcium phosphate (BCP) materials are widely employed as bone substitute materials due to their resorption/degradation properties. Inflammation after implantation of such materials represents a prerequisite for bone tissue repair and regeneration but can be also problematic if it is not only transient and if it is followed by fibrosis and scarring. Here, we modified BCP covalently with hyaluronan (HA) and heparin (Hep), glycosaminoglycans that possess anti-inflammatory properties. Beside the characterization of particle surface properties, the focus was on in vivo tissue response after subcutaneous implantation in mice. Histological analysis revealed a decrease in signs of inflammatory response to BCP when modified with either HA or Hep. Reduced vascularization after 30 days was noticed when BCP was modified with either HA or Hep with greater cellularity in all examined time points. Compared to plain BCP, expression of endothelial-related genes Flt1 and Vcam1 was higher in BCP-HA and BCP-Hep group at day 30. Expression of osteogenesis-related genes Sp7 and Bglap after 30 days was the highest in BCP group, followed by BCP-Hep, while the lowest expression was in BCP-HA group which correlates with collagen amount. Hence, coating of BCP particles with HA seems to suppress inflammatory response together with formation of new bone-like tissue, while the presence of Hep delays the onset of inflammatory response but permits osteogenesis in this subcutaneous bone-forming model. Transferring the results of this study to other coated materials intended for biomedical application may also pave the way to reduction of inflammation after their implantation.

Sinus Floor Elevation with Biphasic Calcium Phosphate or Deproteinized Bovine Bone Mineral: Clinical and Histomorphometric Outcomes of a Randomized Controlled Clinical Trial.

To clinically and histomorphometrically compare a biphasic calcium phosphate (BCP) and deproteinized bovine bone mineral (DBBM) for sinus floor elevation. Sinus floor elevation procedures (lateral window) were performed randomly applying either BCP (test) or DBBM (control). At 6 months, bone biopsy specimens were harvested and dental implants were placed. The proportions of new bone, residual grafting material, and nonmineralized soft tissue were calculated. Four months after implant placement, the prosthetic reconstructions were inserted and the implant survival was assessed. Fifty-one patients were treated; 25 were randomly allocated to the BCP group and 26 to the DBBM group. After 6 months in 50 patients, bone biopsy specimens could be harvested, and a total of 121 implants could be placed subsequently. The histomorphometric analysis revealed a comparable percentage of new bone in both groups (BCP 35.9%, DBBM 35.4%; P > .05). The remaining grafting material was significantly lower with BCP (25.3%) compared with DBBM (45.9%; P < .001). Nonmineralized tissue was significantly higher for the BCP group (38.1%) compared with the DBBM group (18.2%; P < .001). The implant survival rate at loading was assessed at the level of the patients (96.0% for BCP and 88.8% for DBBM; P > .05) and at the level of the implants (96.9% for BCP and 94.7% for DBBM; P > .05). Grafting with DBBM or BCP showed similar percentages of new bone 6 months after sinus floor elevation. Implant survival presented no significant difference until loading.

Complexation of Injectable Biphasic Calcium Phosphate with Phosphoserine-Presenting Dendrons with Enhanced Osteoregenerative Properties.

Injectable biphasic calcium phosphates have been proposed as a solution in the treatment of a range of clinical applications including as fillers in the augmentation of osteoporotic bone. To date, various biodegradable natural or synthetic organics have been used as a polymer component of bone materials to increase their cohesiveness. Herein, a novel bone material was developed combining osteoconductive biphasic calcium phosphate (BCP) nanoparticles with phosphoserine-tethered generation 3 poly(epsilon-lysine) dendron (G3-K PS), a class of hyperbranched peptides previously shown to induce biomineralization and stem cell osteogenic differentiation. Strontium was also incorporated into the BCP nanocrystals (SrBCP) to prevent bone resorption. Within 24 h, an antiwashout behavior was observed in G3-K PS-integrated pure BCP group (BCPG3). Moreover, both in vitro tests by relevant cell phenotypes and an in vivo tissue regeneration study by an osteoporotic animal bone implantation showed that the integration of G3-K PS would downregulate Cxcl9 gene and protein expressions, thus enhancing bone regeneration measured as bone mineral density, new bone volume ratio, and trabecular microarchitectural parameters. However, no synergistic effect was found when Sr was incorporated into the BCPG3 bone pastes. Notably, results indicated a concomitant reduction of bone regeneration potential assessed as reduced Runx2 and PINP expression when bone resorptive RANKL and CTX-I levels were reduced by Sr supplementation. Altogether, the results suggest the potential of injectable BCPG3 bone materials in the treatment of osteoporotic bone defects.

Nano-Hydroxyapatite Coating Promotes Porous Calcium Phosphate Ceramic-Induced Osteogenesis Via BMP/Smad Signaling Pathway.

BackgroundThe hierarchical porous structure and surface topography of calcium phosphate (CaP) bioceramics have a crucial impact on their osteoinductivity.PurposeTo fabricate a biomimetic bone graft with an interconnected porous structure analogous to that of trabecular bone and a bioactive nanostructured surface with excellent osteoinductive potential.Materials and methodsA biphasic CaP (BCP) substrate with highly porous structure was fabricated by an improved sponge replication method. Surface modification was performed by uniformly depositing a hydroxyapatite (HA) nanoparticle layer to create nHA-coated BCP scaffolds. The effects of these scaffolds on osteogenic differentiation of murine bone marrow-derived stem cells (BMSCs) were investigated in vitro, and their osteoinductivity was further assessed in vivo.ResultsThe BCP and nHA-coated BCP scaffolds had similar trabecular bone-like architectures but different surface structures, with mean grain sizes of ~55 nm and ~1 μm, respectively. Compared with the BCP substrate, the nHA-coated BCP scaffolds favored cell adhesion and promoted osteogenic differentiation of BMSCs, as evidenced by upregulated expression of osteogenic genes, enhanced alkaline phosphatase activity, and increased osteocalcin production. This could be attributed to activation of the BMP/Smad signaling pathway, as significantly higher expression levels of BMPRI, Smad1, Smad4, and Smad5 were observed in the nHA-coated BCP group. The nHA-coated BCP scaffold not only maintained scaffold integrity but also induced ectopic bone formation when implanted into rabbit dorsal muscle in vivo for 90 days, whereas the BCP substrate underwent marked biodegradation that led to severe inflammation with no sign of osteogenesis.ConclusionThe present study demonstrates the potential of this biomimetic bone graft with a trabecular framework and nanotopography for use in orthopedic applications.

Guided Bone Regeneration Using BioGlue As a Barrier Material With and Without Biphasic Calcium Phosphate.

The aim of this study was to investigate the effects of Bioglue as a mechanical barrier with or without biphasic calcium phosphate (BCP) in a rat tibia model. Sixty Sprague Dawley male rats weighing 250 ± 20 g and 10 to 12 weeks of age were studied. Unicortical defects were created on the right tibia of all rats. Subjects were randomly divided into 3 groups. BioGlue group (24 rats); BioGlue alone, Graft group (24 rats); BioGlue + BCP and Control group; unfilled and uncovered (12 rats). Animals were euthanized at 7th, 21st, and 45th days postoperatively for histological and histomorphometric analyses. BioGlue material exhibited no adverse effects until the end of observation period. Bone-healing scores did not differ statistically between Control and BioGlue group, but found to be lower in Graft group on 21st and 45th days, (P < 0.001 and P < 0.01 on the 21st day and P < 0.01 and P < 0.05 on the 45th day, respectively). New bone formation in Graft group was found to be statistically different from Control group on the 7th and 21st days (P < 0.01 and P < 0.05 respectively), whereas no statistical difference was observed between BioGlue and Control group at all times. The present analysis indicates that BioGlue functioned well as a mechanical barrier allowing new bone formation. No additional benefit of combination treatment was detected in this study design and BCP did not offer any advantage for bone regeneration, thus it can serve as only a space maintainer.

Osseointegration of dental implants in ectopic engineered bone in three different scaffold materials

The in vivo regeneration of bone flaps might be an alternative to autogenous bone grafting. The first human case of mandibular reconstruction using the greater omentum as a bioreactor was reported in 2016. However, whether engineered bone will support the osseointegration of dental implants has not yet been investigated. In this study, bone tissue engineering was performed in the greater omentum of nine miniature pigs using bone morphogenetic protein 2, bone marrow aspirate, and three different scaffolds: hydroxyapatite, biphasic calcium phosphate (BCP), and titanium. After 8 weeks, two implants were placed in each scaffold; after another 8 weeks, the bone blocks were harvested for radiographic, histological, and histomorphometric analysis. All implants exhibited sufficient primary stability, and the success rate was 100%. The bone-to-implant contact ratios (BICs) were 38.2%, 68.5%, and 42.9%; the inter-thread bone densities were 29.4%, 64.9%, and 33.5%; and the peri-implant bone-scaffold densities were 56.4%, 87.6%, and 68.6% in the hydroxyapatite, BCP, and titanium groups, respectively. The BIC showed a strong correlation (r = 0.76) with the peri-implant bone-scaffold density. This study shows that de novo engineered bone leads to successful osseointegration and therefore may allow implant-based prosthodontic rehabilitation.

Bone regeneration using three-dimensional hexahedron channel structured BCP block in rabbit calvarial defects.

The purpose of this study is to evaluate the efficacy of bone regeneration and volume maintenance of the three-dimensional (3D) structured biphasic calcium phosphate (BCP) block with porous hexahedron channels in a rabbit calvarial model. In this work, four circular defects (diameter: 8 mm) in calvarium of rabbits were randomly assigned to (1) negative control (control), (2) 3D hexahedron channel structured BCP block, (3) deproteinized bovine bone mineral particle, and (4) deproteinized porcine bone mineral particle. Animals were euthanized at 2 (n = 5) and 8 weeks (n = 5). Outcome measures included micro-computed tomography (CT) and histomorphometrical analysis. Results indicated that in micro-CT, BCP group showed the highest new bone volume with significant difference compared to control (p = 0.008) at 8 weeks. Histomorphometrically, total augmented area of BCP group was the highest with significant difference compared to control (p = 0.008) at 8 weeks. BCP group also maintained total volume of the original defect without collapsing. BCP block with 3D hexahedron channel structure seems to have favorable osteogenic and volume maintaining ability and highly porous structure might attribute to new bone formation. Further studies regarding the optimal internal structure and porosity of the BCP block bone substitute are needed. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2254-2262, 2019.

Reconstruction of mandibular bone defects using biphasic calcium phosphate bone substitutes with simultaneous implant placement in mini-swine: A pilot in vivo study.

This study aimed to investigate implant osseointegration using a new strategy of biphasic calcium phosphate (BCP) bone substitutes with simultaneous implant placement in mandibular reconstruction. Additionally, the temporal transcriptional profile associated with the early biological processes during osseointegration was determined. BCP and hydroxyapatite (HA) bone substitutes with simultaneous implant placement were grafted into mandibular defects created in mini-swine. Radiographic, histological, and biochemical analyses were applied for evaluation of osseointegration effects at 4 months after the grafting procedure. Bone formation around the implant was assessed by the bone area percentage (BA%) and the bone-implant-contact percentage (BIC%). The biomechanical evaluation was performed by the implant pullout test and the removal torque test. Microarray technology was utilized for gene expression comparison analysis at day 14 postoperatively. Radiographic and histological observation indicated enhanced bone formation in the BCP group compared to the HA group. Histomorphometric analyses of BA% and BIC% as well as biochemical analyses of the maximal pull-out force and the ultimate shear strength were all significantly greater in the BCP group (p < 0.05). Transcriptional analysis at an early stage of osseointegration revealed that genes belonging to biological processes associated with cell proliferation, development, osteogenesis, angiogenesis, and neurogenesis as well as the osteogenesis-related TGF-β/BMP and WNT signaling pathways were upregulated in the BCP group. In conclusion, the reconstruction of mandibular defects using BCP with simultaneous implant placement resulted in superior osseointegration effects. A number of candidate genes that were differentially expressed may contribute to the superior osseointegration effects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2071-2079, 2019.

Biomimetic porous silk fibroin/biphasic calcium phosphate scaffold for bone tissue regeneration

The purpose of our study is to prepare a biomimetic porous silk fibroin (SF)/biphasic calcium phosphate (BCP) scaffold, and evaluate its performance in bone tissue regeneration. The differences in pore size, porosity, mechanical strength and biocompatibility of four different fibroin-containing scaffolds (0, 20, 40, and 60% SF) were studied in vitro. After inoculation with MC3T3-E1 cells, the ectopic bone formation ability of the SF/BCP bionic scaffold was evaluated in a rat model. The SEM and CT demonstrated that compared with pure BCP group (0% SF), the pore size and porosity of SF/BCP scaffolds were proportional to SF content, of which 40% of SF and 60% of SF groups were more suitable for cell growth. The compressive strength of SF/BCP scaffold was greater than that of the pure BCP scaffold, and showed a trend of first increasing and then decreasing with the increase of SF content, among which 40% of SF group had the maximum compressive strength (40.80 + 0.68) MPa. The SF/BCP scaffold had good biocompatibility, under the electron microscope, the cells can be smoothly attached to and propagated on the scaffold. After loading the osteoblasts, it showed excellent osteogenic capacity in the rat model. The SF/BCP scaffold can highly simulate the micro-environment of natural bone formation and can meet the requirements of tissue engineering. The SF/BCP biomimetic porous scaffold has excellent physical properties and biocompatibility. It can highly simulate the natural bone matrix composition and microenvironment, and can promote the adhesion and proliferation of osteoblasts. The SF/BCP scaffold has good ectopic osteogenesis after loading with osteoblasts, which can meet the requirements of scaffold materials in tissue engineering, and has broad application prospects in clinical application.

In vivo biocompatibility and degradation of novel Polycaprolactone-Biphasic Calcium phosphate scaffolds used as a bone substitute.

Biocompatibility and degradation of poly ε-caprolactone (PCL)-Biphasic Calcium Phosphate (BCP) scaffolds fabricated by the "Melt Stretching and Compression Molding (MSCM)" technique were evaluated in rat models. Degradation behaviors and histological biocompatibility of the PCL-20% BCP MSCM scaffolds and compare with those of PCL-20% β-tricalcium phosphate (TCP) scaffolds commercially fabricated by Fused Deposition Modeling (FDM) were evaluated. The study groups included Group A: PCL-20% BCP MSCM scaffolds and Group B: PCL-20% TCP FDM scaffolds, which were implanted subcutaneously in twelve male Wistar rats. On day 14, 30, 60 and 90, dimensional changes of the scaffolds and their surrounding histological features were assessed using Micro-Computed Tomography (μ-CT) and histological analysis. Changes of their molecular weight were assessed using Gel Permeation Chromatography (GPC). Formation of collagen and new blood vessels throughout the scaffolds of both groups increased with time with low degrees of inflammation. The μ-CT and GPC analysis demonstrated that the scaffolds of both groups degraded with time, but, their molecular weight slightly changed over the observation periods. All results of both groups were not significantly different. The PCL-20% BCP MSCM scaffolds were biocompatible and biodegradable in vivo. Their properties were comparable to those of the commercial PCL-20% TCP scaffolds.

Effects of BMP-2 Delivery in Calcium Phosphate Bone Graft Materials with Different Compositions on Bone Regeneration.

This study was undertaken to investigate the effect of loading rhBMP-2 onto biphasic calcium phosphate (BCP) and calcium pyrophosphate (CPP) on bone regeneration, and to examine the efficacies of BCP and CPP as rhBMP-2 carriers. Specimens were divided into the BCP, CPP, BCP/BMP, and CPP/BMP groups; BCP and CPP were in granules and not coated with rhBMP-2. BCP/BMP and CPP/BMP were prepared as discs, which were treated with rhBMP-2 and collagen. Physical and biological features were investigated using in-vitro and in-vivo tests. New bone area percentages (%) in the BCP/BMP and CPP/BMP groups were significantly greater than in the BCP and CPP groups. At weeks 4 and 8 post-implantation, CPP/BMP showed the most new bone growth. Within the limitations of this study, treatment of BCP and CPP with rhBMP-2 significantly enhanced bone regeneration. CPP was found to be a suitable carrier for rhBMP-2.