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The development of effective biomaterials for tissue regeneration has led to the exploration of blood derivatives such as leucocyte- and platelet-rich fibrin (L-PRF). A novel variant, Albumin-Enriched Platelet-Rich Fibrin (Alb-PRF), has been introduced to improve structural stability and bioactivity, making it a promising candidate for bone regeneration. This study aimed to evaluate Alb-PRF's capacity for cytokine and growth factor release, along with its effects on the proliferation, differentiation, and mineralization of human osteoblasts in vitro. Alb-PRF membranes were analyzed using histological, scanning electron microscopy, and fluorescence microscopy techniques. Cytokine and growth factor release was quantified over seven days, and osteoinductive potential was evaluated with MG-63 osteoblast-like cells. Structural analysis showed Alb-PRF as a biphasic, highly cellularized material that releases lower levels of inflammatory cytokines and higher concentrations of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) compared to L-PRF. Alb-PRF exhibited higher early alkaline phosphatase activity and in vitro mineralization (p < 0.05) and significantly increased the OPG/RANKL mRNA ratio (p < 0.05). These results indicate that Alb-PRF has promising potential as a scaffold for bone repair, warranting further in vivo and clinical assessments to confirm its suitability for clinical applications. [ABSTRACT FROM AUTHOR]

The increasing demand for effective bone regeneration materials drives the exploration of biomaterials with enhanced bioactivity and biocompatibility, such as zinc-substituted compounds. This study investigates the in vitro cellular interactions with nanostructured spheres composed of alginate/carbonated hydroxyapatite (CHA), compared to zinc-substituted CHA (ZnCHA). This work aimed to compare the physicochemical properties and biological effects of ZnCHA and CHA on osteoblasts. ZnCHA was synthesized using a wet chemical method, followed by characterization through X-ray diffraction, Fourier transform infrared spectroscopy, total organic carbon analysis, Wavelength-dispersive X-ray spectroscopy, and BET surface area analysis to assess ion release and structural changes. Biological evaluation was conducted using cell viability, proliferation, and biomineralization assays on osteoblasts. Results showed successful incorporation of zinc and carbonate, leading to reduced crystallinity and increased surface area. Cell viability and proliferation assays indicated ZnCHA's cytocompatibility and enhanced osteoblastic activity, with increased mineralization nodules compared to CHA samples. The study concludes that ZnCHA composites are promising candidates for bone tissue engineering, demonstrating improved cytocompatibility and potential for further preclinical evaluations. [ABSTRACT FROM AUTHOR]

Zinc is known for its role in enhancing bone metabolism, cell proliferation, and tissue regeneration. Several studies proposed the incorporation of zinc into hydroxyapatite (HA) to produce biomaterials (ZnHA) that stimulate and accelerate bone healing. This systematic review aimed to understand the physicochemical characteristics of zinc-doped HA-based biomaterials and the evidence of their biological effects on osteoblastic cells. A comprehensive literature search was conducted from 2022 to 2024, covering all years of publications, in three databases (Web of Science, PUBMED, Scopus), retrieving 609 entries, with 36 articles included in the analysis according to the selection criteria. The selected studies provided data on the material's physicochemical properties, the methods of zinc incorporation, and the biological effects of ZnHA on bone cells. The production of ZnHA typically involves the wet chemical synthesis of HA and ZnHA precursors, followed by deposition on substrates using processes such as liquid precursor plasma spraying (LPPS). Characterization techniques confirmed the successful incorporation of zinc into the HA lattice. The findings indicated that zinc incorporation into HA at low concentrations is non-cytotoxic and beneficial for bone cells. ZnHA was found to stimulate cell proliferation, adhesion, and the production of osteogenic factors, thereby promoting in vitro mineralization. However, the optimal zinc concentration for the desired effects varied across studies, making it challenging to establish a standardized concentration. ZnHA materials are biocompatible and enhance osteoblast proliferation and differentiation. However, the mechanisms of zinc release and the ideal concentrations for optimal tissue regeneration require further investigation. Standardizing these parameters is essential for the effective clinical application of ZnHA. [ABSTRACT FROM AUTHOR]

Platelet-rich Fibrin (PRF), a second-generation blood concentrate, offers a versatile structure for bone regeneration due to its composition of fibrin, growth factors, and cytokines, with adaptations like denatured albumin-enriched with liquid PRF (Alb-PRF), showing potential for enhanced stability and growth factor dynamics. Researchers have also explored the combination of PRF with other biomaterials, aiming to create a three-dimensional framework for enhanced cell recruitment, proliferation, and differentiation in bone repair studies. This study aimed to evaluate a combination of Alb-PRF with nanostructured carbonated hydroxyapatite microspheres (Alb-ncHA-PRF), and how this association affects the release capacity of growth factors and immunomodulatory molecules, and its impact on the behavior of MG63 human osteoblast-like cells. Alb-PRF membranes were prepared and associated with nanocarboapatite (ncHA) microspheres during polymerization. MG63 cells were exposed to eluates of both membranes to assess cell viability, proliferation, mineralization, and alkaline phosphatase (ALP) activity. The ultrastructural analysis has shown that the spheres were shattered, and fragments were incorporated into both the fibrin mesh and the albumin gel of Alb-PRF. Alb-ncHA-PRF presented a reduced release of growth factors and cytokines when compared to Alb-PRF (p < 0.05). Alb-ncHA-PRF was able to stimulate osteoblast proliferation and ALP activity at lower levels than those observed by Alb-PRF and was unable to positively affect in vitro mineralization by MG63 cells. These findings indicate that the addition of ncHA spheres reduces the biological activity of Alb-PRF, impairing its initial effects on osteoblast behavior. [ABSTRACT FROM AUTHOR]

Bone tissue engineering seeks biomaterials that enable cell migration, angiogenesis, matrix deposition, and tissue regeneration. Blood concentrates like platelet-rich fibrin (L-PRF) offer a cost-effective source of cells and growth factors to enhance healing. The present study aimed to evaluate heated serum albumin with liquid PRF (Alb-PRF) and L-PRF clinically and biochemically after placement in dental sockets following mandibular third molar extraction. In a controlled, split-mouth study involving 10 volunteers, 20 extracted molars were treated with either Alb-PRF or L-PRF. Post-extraction, pain, trismus, infection presence, and swelling were measured. The concentrations of different analytes in the surgical sites were also examined. The data were statistically analyzed, with significance defined at p < 0.05 (t-test). No significant difference was noted between the groups for pain and trismus, but Alb-PRF showed a significant reduction in swelling on day seven. The Alb-PRF group showed lower levels of pro-inflammatory cytokines (GM-CSF, IL-1b, IL-6, IFNy, IL-8, IL-15, RANTES, and MIP-1a) after seven days, with only higher expressions of MIP-1b, IL-1b, and MCP-1 found in the L-PRF group. Differences were observed in the release of analytes between L-PRF and Alb-PRF, with Alb-PRF significantly reducing edema after seven days. Alb-PRF reduced edema, while L-PRF increased inflammatory cytokines. When compared to L-PRF, Alb-PRF reduced edema and the release of inflammatory cytokines, suggesting promising effects in socket healing while underscoring the role of growth factors and cytokines in potential applications of blood concentrates. [ABSTRACT FROM AUTHOR]

Platelet-rich fibrin (PRF) is a second-generation blood concentrate that serves as an autologous approach for both soft and hard tissue regeneration. It provides a scaffold for cell interaction and promotes the local release of growth factors. PRF has been investigated as an alternative to bone tissue therapy, with the potential to expedite wound healing and bone regeneration, though the mechanisms involved are not yet fully understood. This review aims to explore the in vitro evidence of PRF's effects on the behavior of mineralizing cells related to bone tissue regeneration. A systematic electronic search was conducted up to August 2023, utilizing three databases: PubMed, Web of Science, and Scopus. A total of 76 studies were selected, which presented in vitro evidence of PRF's usefulness, either alone or in conjunction with other biomaterials, for bone tissue treatment. PRF membranes' influence on the proliferation, differentiation, and mineralization of bone cells is linked to the constant release of growth factors, resulting in changes in crucial markers of bone cell metabolism and behavior. This further reinforces their therapeutic potential in wound healing and bone regeneration. While there are some notable differences among the studies, the overall results suggest a positive effect of PRF on cell proliferation, differentiation, mineralization, and a reduction in inflammation. This points to its therapeutic potential in the field of regenerative medicine. Collectively, these findings may help enhance our understanding of how PRF impacts basic physiological processes in bone and mineralized tissue. [ABSTRACT FROM AUTHOR]

Experimental research is critical for advancing medical knowledge and enhancing patient outcomes, including in vitro and in vivo preclinical assessments. Platelet-rich fibrin (PRF) is a blood by-product that has garnered attention in the medical and dental fields due to its potential for tissue regeneration and wound healing. Animal models, such as rabbits and rats, have been used to produce PRF and examine its properties and applications. PRF has demonstrated potential in the dental and medical fields for reducing inflammation, promoting tissue repair, and accelerating wound healing. This narrative review aims to compare existing evidence and provide guidelines for PRF animal research, emphasizing the importance of standardizing animal models, following ethical considerations, and maintaining transparency and accountability. The authors highlight the necessity to use the correct relative centrifugal force (RCF), standardize centrifugal calibration, and report detailed information about blood collection and centrifuge parameters for reproducible results. Standardizing animal models and techniques is crucial for narrowing the gap between laboratory research and clinical applications, ultimately enhancing the translation of findings from bench to bedside. [ABSTRACT FROM AUTHOR]

In vitro cell-based tests are an important preclinical step for the safety assessment of biomaterials and drugs. Three-dimensional cell culture models (3D) may improve the limitations of the usual 2D models, as they better simulate a physiological environment. This work describes the characterization of a 3D spheroid model of MC3T3-E1 murine preosteoblasts for the testing of bone-substitute materials and investigates its adequacy to some of the most employed cell viability tests. The spheroids presented structural stability for 28 days in culture, with a regular spheroidal aspect, compact surface, and dense inner structure, with high potential for mineralization, but a time-dependent reduction in size. The use of colorimetric tests (MTT, XTT, and NRU) did not achieve satisfactory optical densities and did not correlate with cell density in the 3D model, as the aggregates remain strongly stained even after dye extraction steps. On the other hand, the LDH test achieved appropriate optical density and a high correlation with cell density (r2 = 0.77) and identified a dose–response for a well-known cytotoxic polymer (latex), while no toxicity was identified for biocompatible PLA wires. These results indicate that material testing with 3D bone cell models requires a careful choice of test methods and parameters. [ABSTRACT FROM AUTHOR]

Optisol-GS is the most widely used pharmaceutical composition to preserve corneas for transplantation. This systematic review investigated the effects of different cold corneal storage media (CCSM) compared with Optisol-GS on the quality of stored corneas. The literature was searched throughout May 2022 on six databases and grey literature. Studies including corneas (population) exposed to distinct cold storage media (exposure) and Optisol-GS (comparison) that reported qualitative and/or quantitative parameters of cornea quality (outcome) were included. Methodological quality was assessed using ToxRTool. From 4520 identified studies, fourteen were included according to the eligibility criteria, comprising 769 evaluated cornea samples comparing Optisol-GS with commercial and noncommercial media. All studies showed good methodological quality. Experimental times ranged from 1–28 days, mainly using 4 °C as the preservation temperature. Viable endothelial cell density (ECD) and endothelial cell morphology (EC) were the most assessed parameters. ECD results for Cornisol were higher than Optisol-GS in 10 days (p = 0.049) and favored Cornea ColdTM up to 4 weeks (p < 0.05), which also showed better qualitative results. While the standardization of test protocols could improve comparisons, evidence indicates that most CCSM present similar performances on cornea preservation for transplantation at seven days, while some formulations may increase preservation at extended times. [ABSTRACT FROM AUTHOR]

Guided bone regeneration (GBR) is a process that involves the regeneration of bone defects through the application of occlusive membranes that mechanically exclude the population of non-osteogenic cells from the surrounding soft tissue. Interestingly, platelet-rich fibrin (PRF) has previously been proposed as an autologous GBR membrane despite its short-term resorption period of 2–3 weeks. Recent clinical observations have demonstrated that, by heating a liquid platelet-poor plasma (PPP) layer and mixing the cell-rich buffy coat zone, the resorption properties of heated albumin gel with liquid-PRF (Alb-PRF) can be significantly improved. The aim of this study was to evaluate the inflammatory reaction, biocompatibility, and extended degradation properties of a new autologous Alb-PRF membrane in comparison to commonly utilized standard PRF after nude mice implantation, according to ISO 10993–6/2016. Two standard preparations of PRF (L-PRF and H-PRF) were compared to novel Alb-PRF following subcutaneous implantation at 7, 14, and 21 days. All groups demonstrated excellent biocompatibility owing to their autologous sources. However, it is worth noting that, while both L-PRF and H-PRF membranes demonstrated significant or complete resorption by 21 days, the Alb-PRF membrane remained volume-stable throughout the duration of the study. This study demonstrates—for the first time, to the best of our knowledge—a marked improvement in the membrane stability of Alb-PRF. This indicates its future potential for use as a biological barrier membrane for GBR procedures with a long-lasting half-life, or as a biological filler material in esthetic medicine applications. Thus, further studies are warranted to explore future clinical applications in various fields of medicine. [ABSTRACT FROM AUTHOR]

This study assessed the effects of leukocyte-platelet-rich fibrin (L–PRF) on soft tissue healing and the correlation with the local concentration of growth factors (GF) and cytokines in the dental socket of lower third molars. Forty lower-third molars (20 participants) were included in this randomized, double-blinded, split-mouth study. After extractions, randomized sides received alveolar filling with L–PRF on one side and a natural blood clot on the other side. The pain was assessed for up to seven days and soft tissue healing (Landry index) for 14 days post-extraction. Swabs were collected from the surgical sites for GF and cytokine assessment by flow luminometry. Participants reported lower postoperative pain on the sides grafted with L–PRF, which also presented increased tissue healing scores (p < 0.05). There were increased levels of all GFs and several cytokines at the L–PRF site at day one, while vascular endothelial growth factor (VEGF), IL–10, and IL1–RA remained higher throughout for seven days (p < 0.05). VEGF concentration at L–PRF sites correlated positively with the participants' blood platelet content (ρ = 0.769). PDGF correlated negatively with pain experience on days 2 and 3, and positively with soft tissue healing scores, while FGFb presented a weak correlation with a reduction of pain on day 3. The use of L–PRF improves the soft tissue healing process and decreases postoperative pain after the third molar extractions, which correlates with an increase in the local concentration of growth factors such as PDGF and FGFb. [ABSTRACT FROM AUTHOR]

This study evaluated the impact of rotor angle and time of storage after centrifugation on the in vitro biological properties of platelet‐rich fibrin (PRF) membranes. Blood samples (n = 9) were processed with a vertical fixed‐angle (V) or a swing‐out horizontal (H) centrifuge, with 20–60 min of sample storage after centrifugation. Leukocytes, platelets, and red blood cells were counted, and fibrin architecture was observed by scanning electron microscopy (SEM). The release of FGF2, PDGFbb, VEGF, IL‐6, and IL‐1β was measured after incubation on culture media for 7–21 days. Cell content was equivalent in all experimental groups (p >.05). The fibrin matrix was similar for fixed‐angle and horizontal centrifugation. Horizontal centrifugation induced a twofold increase in PDGF and 1.7× increase on FGF release as compared to V samples, while IL‐1β was significantly reduced (p <.05). No significant difference was observed on the release of growth factors and cytokines at different times after centrifugation (p <.05). These data suggest that both angles of centrifugation produce PRF membranes with similar structure and cellularity, but horizontal centrifugation induces a higher release of growth factors. Higher times of storage after centrifugation did not impact on cell content and the release of growth factors. [ABSTRACT FROM AUTHOR]

Evaluate the cytocompatibility of Calen®/ZO, Calcicur®, Vitapex®, Endoflas®, and zinc oxide/eugenol-based (ZOE) root canal pastes (RCP) to human primary osteoblasts (HPO) through a simplified model for primary teeth. The model employed pipette tips filled with 0.037 g of paste, exposed to 185 µL of culture medium for 24 h (n = 6). Release of components was analysed by Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR). HPO were exposed to conditioned media for 24 h. Cell viability was assessed by cell density and metabolic activity, and release of interleukin 6 (IL-6), vascular endothelial growth factor (VEGF) and fibroblast growth factor (bFGF) by immunological assay. Physicochemical properties and antimicrobial efficacy were also evaluated. 1H-NMR spectra analysis showed similarity between ZOE, Endoflas®, Calcicur®, and Vitapex® compared to Calen®/ZO and positive control, which showed distinct released components. Calen®/ZO and Calcicur® exhibited high alkaline pH in all periods and showed similar solubility. Calen®/ZO, ZOE, and Vitapex® showed similar flow rate. Calen®/ZO, Calcicur®, and Vitapex® did not exhibit antimicrobial efficacy. Calen®/ZO presented cytotoxicity (p < 0.05). Pastes did not increase IL-6 release compared to control. Apart from Vitapex®, all pastes significantly induced VEGF/bFGF release. Interactive effects among released products may affect biological response to filling pastes. Calcicur®, ZOE, Endoflas® and Calen®/ZO presented good to moderate cytocompatibility, with low impact on pro-inflammatory cytokine release and induction of growth factors of interest to tissue repair. This simplified model, specific for the evaluation of the cytocompatibility of RCPs on primary teeth, suggests how these pastes might contribute to bone repair in clinical situations of apical periodontitis in children. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical outcomes of platelet-rich fibrin (PRF) application for hemostasis after dental extraction in patients receiving anticoagulant therapy with factor Xa inhibitors. Methods: In total, 25 patients receiving anticoagulant therapy with rivaroxaban or apixaban who required routine dental extraction were evaluated. In all patients, PRF was used for hemostasis in addition to adapting sutures. Bleeding was subjectively assessed using a sterilize gauze pad at 24, 48, and 72 h after the procedure. Results: All invited participants (n = 25) consented to participate. The PRF clots successfully arrested bleeding after extraction in all patients, with no complications at any time point after the procedure. Favorable soft tissue healing was observed during suture removal at 10 days after the procedure in all patients, with no signs of infection or late healing. Conclusions: The results of this case series indicate that PRF is a promising natural hemostatic agent for the management of bleeding after dental extraction in patients receiving factor Xa inhibitor therapy. Further controlled clinical studies with larger patient samples are necessary to clarify the findings of this case series. [ABSTRACT FROM AUTHOR]

Objective: The combination of calcium phosphate with blood-derived growth factors (BDGF) has been widely used in bone regeneration procedures although its benefits are still unclear. The purpose of this study was to evaluate whether or not BDGF improves the efficacy of a modified carbonated calcium phosphate biomaterial in sinus floor augmentation.Material and methods: Ten patients underwent 20 sinus floor augmentation procedures using nanostructured carbonated hydroxyapatite (cHA) microspheres alone or associated with BDGF in a randomized controlled clinical trial. The in vitro release of growth factors was assessed by an elution assay. Bone grafts were randomly implanted in the right and left maxillary sinuses of each participant, associated either with a 0.9% saline solution or BDGF. Bone gain was evaluated through cone beam tomography after 180 days.Results: Nine women and one man composed the sample. The blood-derived concentrates were able to release high levels of growth factors and cytokines. A significant clinical advantage was observed in the use of the BDGF after fibrin polymerization around the biomaterial microspheres, optimizing the surgical procedures, thereby reducing the time and displacement, and improving the adaptation of the biomaterial in the maxillary sinus. No synergistic effect was observed in bone formation when cHA was associated with BDGF (p > 0.05).Conclusion: Equivalent new bone formation was observed for cHA in the presence or absence of the BDGF concentrate in bilateral sinus floor elevation after 6 months. Blood-derived growth factors did not improve bone repair when associated with calcium phosphate in sinus lift procedures. [ABSTRACT FROM AUTHOR]

The control of postoperative bleeding represents one of the main intercurrent events associated with soft tissue surgical procedures in the oral cavity. In this context, platelet-rich fibrin (PRF) membranes are materials with great potential for optimizing soft tissue healing and induction of hemostasis. This interventional case series describes the treatment of 10 patients with excisional biopsy of benign oral cavity lesions, following a screening sequence at the surgery clinic of a Brazilian dental school between the years of 2015 and 2017. After treatment with PRF, patients presented mean time for postoperative hemostasis of 10.3 ± 2.5 s, requiring the average use of three membranes to cover the surgical area. The results suggest that the use of platelet-rich fibrin membranes may represent a feasible alternative hemostatic material for the treatment of oral lesions. [ABSTRACT FROM AUTHOR]

Abstract: Platelet‐rich fibrin membranes are biomaterials widely used for therapeutic purposes, and canonically produced through the processing of peripheral blood with fixed‐angle rotor centrifuges. In this work, we evaluate the in vitro stability and release of cytokines and growth factors when these biomaterials are produced with a horizontal swing‐out clinical centrifuge. Membranes produced from the blood of 14 donors were morphologically evaluated by scanning electron microscopy and fluorescence microscopy, and their stability was assessed by photographic recording after incubation in culture medium for up to 28 days. The release of 27 cytokines and growth factors was monitored for three weeks through a multiparametric immunoassay. The fibrin membranes presented complex three‐dimensional structure with a high density of nucleated cells. A large release of growth factors [platelet derived growth factor, fibroblastic growth factor (bFGF), and vascular endothelial growth factor] was detected in the first 24 h, followed by time‐dependent decay, maintaining significant concentrations after three weeks. Both anti‐inflammatory and pro‐inflammatory cytokines presented different release peaks, maintaining high rates of elution for up to 21 days. Chemokines of relevance in tissue repair [RANTES, granulocyte colony‐stimulating factor (G‐CSF)] were also produced in large quantities throughout the experimental period. The present results demonstrate that blood‐derived fibrin membranes with high structural stability and cell content can be generated by horizontal centrifugation, being able of a prolonged production/release of growth factors and pro‐ and anti‐inflammatory cytokines. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1373–1380, 2018. [ABSTRACT FROM AUTHOR]

The antimicrobial peptides human β-defensins (hBDs) are encoded by β-defensin genes (DEFBs) and are possibly involved in caries susceptibility. In this study we aimed (1) to investigate the relationship between salivary hBDs and caries and (2) to evaluate the association of genetic polymorphisms in DEFB1 and microRNA202 (miRNA202) with salivary levels of hBDs and caries experience. Two data sets were available for this study, totalizing 678 Brazilian children. Dental examination and saliva collection were performed in all included children. The salivary level for hDB1, hBD2, and hBD4 was assessed by ELISA sandwich technique in 168 children. The DNA was extracted from saliva, and polymorphisms in DEFB1 and miRNA202 were analyzed by real-time PCR. Statistical analysis was performed to investigate the associations between caries experience, hBD salivary level, genotype, and allele distribution, with an alpha of 0.05. The hBD1 level was significantly higher in caries-free children (p < 0.0001). The miRNA202 was associated with a lower level of salivary hBD1 (p < 0.05). Also, the polymorphic distribution of miRNA202 was associated with caries (p = 0.006). The polymorphisms in DEFB1 were not associated with hBD salivary level and caries experience (p > 0.05). In conclusion, our results indicate that genetic polymorphism in miRNA202 is involved in hBD1 salivary level as well as caries experience in children. [ABSTRACT FROM AUTHOR]

Biomedical materials for bone therapy are usually assessed for their biocompatibility and safety employing animal models or in vitro monolayer cell culture assays. However, alternative in vitro models may offer controlled conditions closer to physiological responses and reduce animal testing. In this work, we developed a 3D spheroidal cell culture with potential to evaluate simultaneously material-cell and cell-cell interactions. Different cell densities of murine MC3T3-E1 preosteoblasts or human primary osteoblasts (HOb) were used to determine the ideal procedure of spheroidal cultures and their adequacy to material testing. Cells were seeded on 96-well plates coated with agar and incubated in agitation from 1 to 7 days. Aggregate morphology was qualitatively evaluated considering the shape, size, repeatability, handling, and stability of spheroids. Higher cell densities induced more stable spheroids, and handling was considered appropriate starting from 2 × 104 cells. Confocal microscopy and Scanning Electron Microscopy indicate that most cells within the aggregate core are viable. Exposure to positive controls has shown a dose dependent cell death as measured by XTT assay. Aggregates were stable and presented good viability when employed on standardized testing of metallic and polymer-based biomaterials. Therefore, osteoblast spheroids may provide a promising tool for material screening and biocompatibility testing. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA), a stable and biocompatible material for bone tissue therapy, may present a variable stoichiometry and accept a large number of cationic substitutions. Such substitutions may modify the chemical activity of HA surface, with possible impact on biocompatibility. In this work, we assessed the effects of calcium substitution with diverse divalent cations (Pb2+, Sr2+, Co2+, Zn2+, Fe2+, Cu2+, or Mg2+) on the biological behavior of HA. Physicochemical analyses revealed that apatite characteristics related to crystallinity and calcium dissolution/uptake rates are very sensitive to the nature of cationic substitution. Cytocompatibility was evaluated by mitochondrial activity, membrane integrity, cell density, proapoptotic potential, and adhesion tests. With the exception of Zn-HA, all the substituted HAs induced some level of apoptosis. The highest apoptosis levels were observed for Mg-HA and Co-HA. Cu-HA was the only material to impair simultaneously mitochondrial activity, membrane integrity, and cell density. The highest relative cell densities after exposure to the modified HAs were observed for Mg-HA and Zn-HA, while Co-HA significantly improved cell adhesion onto HA surface. These results show that changes on surface dissolution caused by cationic substitution, as well as the increase of metal species released to biological media, were the main responsible factors related to alterations on HA biocompatibility. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011. [ABSTRACT FROM AUTHOR]

Sticky bone, a growth factor-enriched bone graft matrix, is a promising autologous material for bone tissue regeneration. However, its production is strongly dependent on manual handling steps. In this sense, a new device was developed to simplify the confection of the sticky bone, named Sticky Bone Preparation Device (SBPD®). The purpose of this pilot study was to investigate the suitability of the SBPD® to prepare biomaterials for bone regeneration with autologous platelet concentrates. The SBPD® allows the blending of particulate samples from synthetic, xenograft, or autogenous bone with autologous platelet concentrates, making it easy to use and avoiding the need of further manipulations for the combination of the materials. The protocol for the preparation of sticky bone samples using the SBPD® is described, and the resulting product is compared with hand-mixed SB preparations regarding in vitro parameters such as cell content and the ability to release growth factors and cytokines relevant to tissue regeneration. The entrapped cell content was estimated, and the ability to release biological mediators was assessed after 7 days of incubation in culture medium. Both preparations increased the leukocyte and platelet concentrations compared to whole-blood samples (p < 0.05), without significant differences between SB and SBPD®. SBPD® samples released several growth factors, including VEGF, FGFb, and PDGF, at concentrations physiologically equivalent to those released by SB preparations. Therefore, the use of SBPD® results in a similar product to the standard protocol, but with more straightforward and shorter preparation times and less manipulation. These preliminary results suggest this device as a suitable alternative for combining bone substitute materials with platelet concentrates for bone tissue regeneration. [ABSTRACT FROM AUTHOR]

Successful biomaterials for bone tissue therapy must present different biocompatible properties, such as the ability to stimulate the migration and proliferation of osteogenic cells on the implantable surface, to increase attachment and avoid the risks of implant movement after surgery. The present work investigates the applicability of a three-dimensional (3D) model of bone cells (osteospheres) in the evaluation of osteoconductive properties of different implant surfaces. Three different titanium surface treatments were tested: machined (MA), sandblasting and acid etching (BE), and Hydroxyapatite coating by plasma spray (PSHA). The surfaces were characterized by Scanning Electron Microscopy (SEM) and atomic force microscopy (AFM), confirming that they present very distinct roughness. After seeding the osteospheres, cell–surface interactions were studied in relation to cell proliferation, migration, and spreading. The results show that BE surfaces present higher densities of cells, leaving the aggregates towards than titanium surfaces, providing more evidence of migration. The PSHA surface presented the lowest performance in all analyses. The results indicate that the 3D model allows the focal analysis of an in vitro cell/surfaces interaction of cells and surfaces. Moreover, by demonstrating the agreement with the clinical data observed in the literature, they suggest a potential use as a predictive preclinical tool for investigating osteoconductive properties of novel biomaterials for bone therapy. [ABSTRACT FROM AUTHOR]