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Biphasic Calcium Phosphate Biomaterials: Stem Cell-Derived Osteoinduction or In Vivo Osteoconduction? Novel Insights in Maxillary Sinus Augmentation by Advanced Imaging.

ABSTRACT: Maxillary sinus augmentation is often necessary prior to implantology procedure, in particular in cases of atrophic posterior maxilla. In this context, bone substitute biomaterials made of biphasic calcium phosphates, produced by three-dimensional additive manufacturing were shown to be highly biocompatible with an efficient osteoconductivity, especially when combined with cell-based tissue engineering. Thus, in the present research, osteoinduction and osteoconduction properties of biphasic calcium-phosphate constructs made by direct rapid prototyping and engineered with ovine-derived amniotic epithelial cells or amniotic fluid cells were evaluated. More in details, this preclinical study was performed using adult sheep targeted to receive scaffold alone (CTR), oAFSMC, or oAEC engineered constructs. The grafted sinuses were explanted at 90 days and a cross-linked experimental approach based on Synchrotron Radiation microCT and histology analysis was performed on the complete set of samples. The study, performed taking into account the distance from native surrounding bone, demonstrated that no significant differences occurred in bone regeneration between oAEC-, oAFMSC-cultured, and Ctr samples and that there was a predominant action of the osteoconduction versus the stem cells osteo-induction. Indeed, it was proven that the newly formed bone amount and distribution decreased from the side of contact scaffold/native bone toward the bulk of the scaffold itself, with almost constant values of morphometric descriptors in volumes more than 1 mm from the border.

SUBMITTER: Iezzi G

PROVIDER: S-EPMC8122985 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective: The objective of this study is to compare the bone induction of five kinds of calcium phosphate (Ca-P) biomaterials implanted in mice and explore the vascularization and particle-size-related osteoinductive mechanism. Methods: The following five kinds of Ca-P biomaterials including hydroxyapatite (HA) and/or tricalcium phosphate (TCP) were implanted in the muscle of 30 BALB/c mice (n = 6): 20 nm HA (20HA), 60 nm HA (60HA), 12 µm HA (12HA), 100 nm TCP (100TCP) and 12 µm HA + 100 nm TCP (HATCP). Then, all animals were put on a treadmill to run 30 min at a 6 m/h speed each day. Five and ten weeks later, three mice of each group were killed, and the samples were harvested to assess the osteoinductive effects by hematoxylin eosin (HE), Masson's trichrome and safranine-fast green stainings, and the immunohistochemistry of the angiogenesis and osteogenesis markers CD31 and type I collagen (ColI). Results: The numbers of blood vessels were 139 ±&nbsp;29,&nbsp;118&nbsp;±&nbsp;25,&nbsp;78&nbsp;±&nbsp;15,&nbsp;65&nbsp;±&nbsp;14 in groups HATCP, 100TCP, 60HA and 20HA, respectively, which were significantly higher than that of group 12HA (12 ± 5) in week 5 (p < 0.05). The area percentages of new bone tissue were (7.33 ± 1.26)% and (8.49 ±&nbsp;1.38)% in groups 100TCP and HATCP, respectively, which were significantly higher than those in groups 20HA (3.27 ±&nbsp;0.38)% and 60HA (3.43 ±&nbsp;0.27)% (p < 0.05); however, no bone tissue was found in group 12HA 10 weeks after transplantation. The expression of CD31 was positive in new blood vessels, and the expression of ColI was positive in new bone tissue. Conclusions: Nanoscale Ca-P biomaterials could induce osteogenesis in mice muscle, and the osteoinductive effects of TCP were about 124% higher than those of 20HA and 114% higher than those of 60HA. The particle size of the biomaterials affected angiogenesis and osteogenesis. There was a positive correlation between the number of blood vessels and the area percentage of new bone tissue; therefore, osteoinduction is closely related to vascularization. Our results provide an experimental basis for the synthesis of calcium-phosphorus matrix composites and for further exploration of the osteoinductive mechanism.

Project description:BACKGROUND:Sinus augmentation can be performed with or without grafting biomaterials, and to date, there is no quality evidence regarding the augmentation of the sinus floor using only platelet concentrates, which can improve the healing period and enhance bone regeneration by stimulating angiogenesis and bone formation. The main objective of this paper was to assess the effect of the sole use of platelet concentrates in sinus augmentation in terms of newly formed bone, augmented bone height, and clinical outcomes and to assess the additional beneficial effects of platelet-rich fibrin (PRF) in combination with other grafting biomaterials. METHODS:A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Pooled analyses were performed with the Review Manager software. RESULTS:For sinus elevation only using platelet concentrates, 11 studies met the inclusion criteria and were included for qualitative synthesis. Only one study was a clinical trial, which reported improved outcomes for the allograft group compared to the titanium-PRF (T-PRF) group. A total of 12 studies where PRF was used in addition to grafting biomaterials met eligibility criteria and were included in the review. Results from meta-analyses provided no additional beneficial effects of PRF in sinus augmentation in terms of bone height and percentage of soft tissue area. There was a statistically significant lower percentage of residual bone substitute material in the PRF (+) group compared to the PRF (-) group. The percentage of newly formed bone was slightly higher in the PRF (+) group, but this was not statistically significant. CONCLUSION:There is no robust evidence to make firm conclusions regarding the beneficial effects of the sole use of platelet concentrates in sinus augmentation. However, studies have shown favorable outcomes regarding implant survival, bone gain, and bone height. The use of PRF with other grafting biomaterials appears to provide no additional beneficial effects in sinus lift procedures, but they may improve the healing period and bone formation. Well-conducted randomized clinical trials (RCTs) are necessary to confirm the available results to provide recommendations for the clinical practice.

Project description:ObjectivesTo evaluate the performances of six different bone substitute materials used as graft in maxillary sinus augmentation by means of histological and histomorphometric analysis of bone biopsies retrieved from human subjects after a 6-month healing period.Materials and methodsSix consecutive patients (3 males, 3 females, aged 50-72 years), healthy, nonsmokers, and with good oral hygiene, presenting edentulous posterior maxilla with a residual bone crest measuring ≤ 4 mm in vertical height and 3 to 5 mm in horizontal thickness at radiographic examination, were selected to receive sinus augmentation and delayed implant placement. Under randomized conditions, sinus augmentation procedures were carried out using mineralized solvent-dehydrated bone allograft (MCBA), freeze-dried mineralized bone allograft (FDBA), anorganic bovine bone (ABB), equine-derived bone (EB), synthetic micro-macroporous biphasic calcium-phosphate block consisting of 70% beta-tricalcium phosphate and 30% hydroxyapatite (HA-β-TCP 30/70), or bioapatite-collagen (BC). After 6 months, bone core biopsies were retrieved and 13 implants were placed. Bone samples were processed for histological and histomorphometric analysis. CT scans were taken before and after surgery. After 4 months of healing, patients were restored with a provisional fixed acrylic resin prosthesis, as well as after further 2-4 months with a definitive cemented zirconia or porcelain-fused-to-metal crowns.ResultsThere were no postoperative complications or implant failures. The histological examination showed that all biomaterials were in close contact with newly formed bone, surrounding the graft granules with a bridge-like network. No signs of acute inflammation were observed. The histomorphometry revealed 20.1% newly formed bone for MCBA, 32.1% for FDBA, 16.1% for ABB, 22.8% for EB, 20.3% for HA-β-TCP 30/70, and 21.4% for BC.ConclusionsWithin the limitations of the present investigation, all the six tested biomaterials showed good biocompatibility and osteoconductive properties when used in sinus augmentation procedures, although the FDBA seemed to have a better histomorphometric result in terms of newly formed bone and residual graft material. This trial is registered with ClinicalTrials.gov Identifier (Registration Number): NCT03496688.

Project description:BackgroundEvidence has been provided that a cell-based therapy combined with the use of bioactive materials may significantly improve bone regeneration prior to dental implant, although the identification of an ideal source of progenitor/stem cells remains to be determined.AimIn the present research, the bone regenerative property of an emerging source of progenitor cells, the amniotic epithelial cells (AEC), loaded on a calcium-phosphate synthetic bone substitute, made by direct rapid prototyping (rPT) technique, was evaluated in an animal study.Material and methodsTwo blocks of synthetic bone substitute (?0.14 cm(3)), alone or engineered with 1×10(6) ovine AEC (oAEC), were grafted bilaterally into maxillary sinuses of six adult sheep, an animal model chosen for its high translational value in dentistry. The sheep were then randomly divided into two groups and sacrificed at 45 and 90 days post implantation (p.i.). Tissue regeneration was evaluated in the sinus explants by micro-computer tomography (micro-CT), morphological, morphometric and biochemical analyses.Results and conclusionsThe obtained data suggest that scaffold integration and bone deposition are positively influenced by allotransplantated oAEC. Sinus explants derived from sheep grafted with oAEC engineered scaffolds displayed a reduced fibrotic reaction, a limited inflammatory response and an accelerated process of angiogenesis. In addition, the presence of oAEC significantly stimulated osteogenesis either by enhancing bone deposition or making more extent the foci of bone nucleation. Besides the modulatory role played by oAEC in the crucial events successfully guiding tissue regeneration (angiogenesis, vascular endothelial growth factor expression and inflammation), data provided herein show that oAEC were also able to directly participate in the process of bone deposition, as suggested by the presence of oAEC entrapped within the newly deposited osteoid matrix and by their ability to switch-on the expression of a specific bone-related protein (osteocalcin, OCN) when transplanted into host tissues.

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Biphasic Calcium Phosphate Biomaterials: Stem Cell-Derived Osteoinduction or In Vivo Osteoconduction? Novel Insights in Maxillary Sinus Augmentation by Advanced Imaging.

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