Alternated activation with relaxation of periosteum stimulates bone modeling and remodeling.

Gradual elevation of the periosteum from the original bone surface, based on the principle of distraction osteogenesis, induces endogenous hard and soft tissue formation. This study aimed to assess the impact of alternating protocols of activation with relaxation (periosteal pumping) on bone modeling and remodeling. One hundred and sixty-two adult male Wistar rats were used in this study. Four test groups with different pumping protocols were created based on the relaxation applied. Two control groups underwent an activation period without relaxation or only a single activation. One group was sham-operated. Periosteal pumping without period of activation induced gene expression in bone and bone remodeling, and following activation period enhanced bone modeling. Four test groups and control group with activation period equaled the values of bone modeling at the end-consolidation period, showing significant downregulation of Sost in the bone and periosteum compared to that in the sham group (p < 0.001 and p < 0.001, respectively). When all test groups were pooled together, plate elevation from the bony surface increased bone remodeling on day 45 of the observation period (p = 0.003). Furthermore, bone modeling was significantly affected by plate elevation on days 17 and 45 (p = 0.047 and p = 0.005, respectively) and by pumping protocol on day 31 (p = 0.042). Periosteal pumping was beneficial for increasing bone repair when the periosteum remained in contact with the underlaying bony surface during the manipulation period. Following periosteal elevation, periosteal pumping accelerated bone formation from the bony surface by the modeling process.

The development of non-resorbable bone allografts: Biological background and clinical perspectives.

Bone grafts are typically categorized into four categories: autografts, allografts, xenografts, and synthetic alloplasts. While it was originally thought that all bone grafts should be slowly resorbed and replaced with native bone over time, accumulating evidence has in fact suggested that the use of nonresorbable xenografts is favored for certain clinical indications. Thus, many clinicians take advantage of the nonresorbable properties/features of xenografts for various clinical indications, such as contour augmentation, sinus grafting, and guided bone regeneration, which are often combined with allografts (e.g., human freeze-dried bone allografts [FDBAs] and human demineralized freeze-dried bone allografts [DFDBAs]). Thus, many clinicians have advocated different 50/50 or 70/30 ratios of allograft/xenograft combination approaches for various grafting procedures. Interestingly, many clinicians believe that one of the main reasons for the nonresorbability or low substitution rates of xenografts has to do with their foreign animal origin. Recent research has indicated that the sintering technique and heating conducted during their processing changes the dissolution rate of hydroxyapatite, leading to a state in which osteoclasts are no longer able to resorb (dissolve) the sintered bone. While many clinicians often combine nonresorbable xenografts with the bone-inducing properties of allografts for a variety of bone augmentation procedures, clinicians are forced to use two separate products owing to their origins (the FDA/CE does not allow the mixture of allografts with xenografts within the same dish/bottle). This has led to significant progress in understanding the dissolution rates of xenografts at various sintering temperature changes, which has since led to the breakthrough development of nonresorbable bone allografts sintered at similar temperatures to nonresorbable xenografts. The advantage of the nonresorbable bone allograft is that they can now be combined with standard allografts to create a single mixture combining the advantages of both allografts and xenografts while allowing the purchase and use of a single product. This review article presents the concept with evidence derived from a 52-week monkey study that demonstrated little to no resorption along with in vitro data supporting this novel technology as a "next-generation" biomaterial with optimized bone grafting material properties.

Optimization of platelet-rich fibrin.

The use of platelet-rich fibrin (PRF) has gained tremendous popularity in recent years owing to its ability to speed wound healing postsurgery. However, to date, many clinicians are unaware of methods designed to optimize the technology. This overview article will discuss the advancements and improvements made over the years aimed at maximizing cell and growth factor concentrations. First, a general understanding explaining the differences between RPM and RCF (g-force) is introduced. Then, the low-speed centrifugation concept, fixed angle versus horizontal centrifugation, and methods to maximize platelet concentrations using optimized protocols will be discussed in detail. Thereafter, the importance of chemically modified PRF tubes without the addition of chemical additives, as well as regulation of temperature to induce/delay clotting, will be thoroughly described. This article is a first of its kind summarizing all recent literature on PRF designed to optimize PRF production for clinical treatment.

A Custom-Made Surgical Guide for Accurate Enucleation of Nasopalatine Duct Cysts: A Technical Note and Case Report.

Nasopalatine cysts are common nonodontogenic cysts that occur in the maxilla. During the nucleation of large cysts extending to the floor of the nasal cavity, care must be taken to avoid damage to the nasal mucosa. In the present report, an innovative custom-made surgical guide made by a Three-dimensional printer is introduced for accurate enucleation surgery. The patient's cone-beam computerized tomography and dental model scan data were obtained, and a tooth-supported type of surgical guide was designed containing a circular plate structure showing the size of the cystic region, an indicator that showed the position of the bottom of the cyst, and a sliding stopper that was used to accurately indicate the position of the deepest cyst wall. The surgical tool enabled us to indicate the accurate size, location of the cysts, and approach direction. Although effective and accurate navigation systems have become increasingly available, the cost-effective and accurate computer-aided design/computer-aided manufacturing surgical guide system introduced in the present report could support the safe enucleation of large nasopalatine duct cysts.

Skin and Bone Regeneration of Solid Bone Marrow Aspirate Concentrate Versus Platelet-Rich Fibrin.

Solid bone marrow aspirate concentrate (sBMAC) is harvested from bone marrow aspirate without anticoagulants by a centrifugation protocol similar to that for platelet-rich fibrin (PRF) prepared from peripheral blood. It was hypothesized that sBMAC could accelerate not only wound healing but also bone regeneration because of the abundant growth factor (GF) releases from enriched bone marrow cells. The purpose of the present study was to investigate skin wound healing and bone regenerative potential of sBMAC compared with arterial blood-derived PRF (Ar-PRF) and venous blood-derived PRF (Ve-PRF) in a skin defect and calvarial bone defect model in rabbits. GF release assays revealed significantly higher release of transforming growth factor-ß (TGF-ß), alkaline phosphatase (ALP), and osteocalcin (OCN) from sBMAC compared with PRFs for 24 h. In the skin defect animal model, sBMAC and PRFs promoted wound bed angiogenesis and re-epithelization in skin defect sites with higher collagen 1 synthesis, cytokeratin AE1/AE3, vascular endothelial growth factor (VEGF) expressions on week 1. Furthermore, a calvarial defect assay revealed that sBMAC promoted new bone formation with a sufficient bone marrow structure similar to that of intact bone in the bone defects. Ar-PRF achieved the second highest bone closure and new bone volume but yielded new bone that was thinner than the intact bone. In conclusion, sBMAC treatment might be a good option instead of PRF as an adjuvant therapy for both skin and bone tissue regeneration therapies in certain clinical situations. Impact statement Solid bone marrow aspirate concentrate (sBMAC) is new type of clot material prepared from bone marrow aspirate. The present study for the first time showed that sBMAC significantly accelerated both skin wound healing and bone formation in the defects, compared with conventional platelet-rich fibrin in rabbit experiment models.

In vitro and in vivo evaluation of surface functionalization of titanium with H2 O2 hydrothermal treatment and FGF-2.

The goals of the study were to investigate the effects on bone bioactivity of a titanium dioxide layer formed by hydrothermal oxidation of a titanium surface with hydrogen peroxide (H2 O2 ) and loading with fibroblast growth factor-2 (FGF-2) in vitro and in vivo. Ti-6Al-4V discs were hydrothermally oxidized with H2 O2 and then loaded with FGF-2. After cytotoxicity testing, Ti-6Al-4V mini-implants were subjected to the same treatment, and their osteogenic potential was evaluated histologically in a rat model. H2 O2 hydrothermal oxidation resulted in a dense porous network structure and hydrophilic changes, which improved retention of FGF-2. Morphologically, the cell density was higher, cell elongation was more pronounced, and the cell adhesion area was significantly higher in FGF-2-loaded cells than in those without FGF-2. In a cell proliferation assay using mouse osteoblast-like cells, absorbance tended to increase over time, especially in the FGF-2 group after 7 and 14 days, and in a bone differentiation assay based on ALP activity, there was a significant increase in the FGF-2 group after 14 days. In the rat model, H2 O2 hydrothermal oxidation and FGF-2 loading both resulted in more laminar bone tissue in the bone marrow around the mini-implant. These results suggest that titanium surface functionalization by H2 O2 hydrothermal oxidation and FGF-2 may promote initial cell adhesion, proliferation, and osteodifferentiation, and enhance bone bioactivity. These effects all contribute to early bonding of an implant with the surrounding bone.

Addition of Synthetic Biomaterials to Deproteinized Bovine Bone Mineral (DBBM) for Bone Augmentation-A Preclinical In Vivo Study.

(1) Aim: To investigate the effect of synthetic bone substitutes, α-tricalcium phosphate (α-TCP) or bi-layered biphasic calcium-phosphate (BBCP) combined with deproteinized bovine bone mineral (DBBM), on bone formation. (2) Methods: Thirty critical size defects were randomly treated with the following five different treatment modalities: (1) negative control (NC, empty), (2) DBBM, (3) α-TCP + DBBM (1:1), (4) BBCP 3%HA/97%α-TCP + DBBM (1:1), and (5) BBCP 6%HA/94%α-TCP + DBBM (1:1). The samples, at four weeks post-surgery, were investigated by micro-CT and histological analysis. (3) Results: A similar level of new bone formation was demonstrated in the DBBM with α-TCP bone substitute groups when compared to the negative control by histomorphometry. DBBM alone showed significantly lower new bone area than the negative control (p = 0.0252). In contrast to DBBM, the micro-CT analysis revealed resorption of the α-TCP + DBBM, BBCP 3%HA/97%α-TCP + DBBM and BBCP 6%HA/94%α-TCP + DBBM, as evidenced by a decrease of material density (p = 0.0083, p = 0.0050 and p = 0.0191, respectively), without changing their volume. (4) Conclusions: New bone formation was evident in all defects augmented with biomaterials, proving the osteoconductive properties of the tested material combinations. There was little impact of the HA coating degree on α-TCP in bone augmentation potential and material resorption for four weeks when mixed with DBBM.

Osteoclast behaviors on the surface of deproteinized bovine bone mineral and carbonate apatite substitutes in vitro.

The present study investigated the osteoclast differentiation potential and paracrine effects of osteoclasts on osteoblast differentiation when the cells were cultured directly on two bone substitutes (BSs): deproteinized bovine bone mineral (DBBM) and carbonate apatite (CO3 Ap). Human primary osteoclasts cultured on the BSs were assessed by tartrate-resistant acid phosphatase (TRAP) and actin ring staining. Thereafter, the mRNA levels of osteoclastic differentiation markers were quantified by real-time PCR. Osteoblast behaviors in response to conditioned media collected from osteoclast cultures were investigated. Interestingly, mature osteoclasts were occasionally observed on the surface of the CO3 Ap granules, whereas very few and small osteoclasts were observed on DBBM. Similarly, real-time PCR analysis showed higher mRNA levels of osteoclast markers, including cathepsin K and TRAP, in the cells cultured on CO3 Ap than in those cultured on DBBM. Furthermore, compared to DBBM, CO3 Ap promoted osteoblast differentiation in human primary osteoblasts, whereas few paracrine effects of osteoclasts cultured with either BS were observed on the osteoblast differentiation potential. These limited results showed that CO3 Ap provided a favorable surface for osteoclast differentiation, as well as osteoblasts, compared to DBBM in vitro.

Regenerative Potential of Solid Bone Marrow Aspirate Concentrate Compared with Platelet-Rich Fibrin.

Platelet-rich fibrin (PRF) prepared from venous blood is used in the clinic to improve soft tissue wound healing. Nevertheless, arterial blood or bone marrow aspirate might also be a candidate for the source of PRF-like concentrates. The purpose of the present study was to investigate blood/bone marrow aspirate concentrates obtained from arterial blood, venous blood, and bone marrow aspirate to determine its respective regenerative potential in vitro. Arterial blood-derived PRF (Ar-PRF), venous blood-derived PRF (Ve-PRF), and solid-type bone marrow aspirate concentrate (sBMAC) were prepared from New Zealand white rabbits. Each clot was evaluated for its cytocompatibility and regenerative potential on primary rabbit gingival fibroblasts and osteoblasts. Both gingival fibroblasts and osteoblasts treated with each concentrate showed excellent viability. Interestingly, the sBMAC-treated cells demonstrated a significantly greater migratory potential than the other treatment groups. Furthermore, higher mRNA levels of transforming growth factor-beta, vascular endothelial growth factor, and collagen 1 (COL1) in gingival fibroblasts were observed in the sBMAC group compared with the Ar-PRF and Ve-PRF groups. Greater osteoblast differentiation potential, including higher osteocalcin (OCN) expression and mineralization potential, was found in osteoblasts treated with sBMAC. However, minor differences between the behaviors of cells treated with Ar-PRF and Ve-PRF were observed. In conclusion, sBMAC might be a new candidate for promoting wound healing and bone regeneration. Further preclinical and clinical experiments are necessary to prove the regenerative potential of sBMAC in the body. Impact Statement Blood concentrate material such as platelet-rich plasma or platelet-rich fibrin (PRF) is used in clinical practice to promote tissue regeneration in the field of dentistry, orthopedic surgery, and plastic surgery. The present study introduces a new type of solid bone marrow aspirate concentrate material and, for the first time, shows its excellent regenerative potential in both gingival fibroblasts and osteoblasts in vitro compared with that of conventional PRF.

Cross-linked hyaluronic acid slows down collagen membrane resorption in diabetic rats through reducing the number of macrophages.

OBJECTIVES: We previously showed that accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated here its effect on the number of macrophages and endothelial cells (ECs) within the CM as a possible mechanism for inhibition of CM resorption. MATERIALS AND METHODS: Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS, and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and transglutaminase II, respectively. RESULTS: Diabetes increased the number of macrophages and ECs within the CMs (∼2.5-fold and fourfold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p < 0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. CONCLUSIONS: Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals. CLINICAL RELEVANCE: The combination of CLHA and CM may represent a valuable approach when guided tissue regeneration or guided bone regeneration procedures are performed in diabetic patients.

Efficacy of platelet-rich fibrin on bone formation, part 2: Guided bone regeneration, sinus elevation and implant therapy.

PURPOSE: To investigate the effect of platelet-rich fibrin on bone formation by investigating its use in guided bone regeneration, sinus elevation and implant therapy. MATERIALS AND METHODS: This systematic review and meta-analysis were conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The eligibility criteria comprised human controlled clinical trials comparing the clinical outcomes of platelet-rich fibrin with those of other treatment modalities. The outcomes measured included percentage of new bone formation, percentage of residual bone graft, implant survival rate, change in bone dimension (horizontal and vertical), and implant stability quotient values. RESULTS: From 320 articles identified, 18 studies were included. Owing to the heterogeneity of the investigated parameters, a meta-analysis was only possible for sinus elevation. There is a general lack of data from comparative randomised clinical trials evaluating platelet-rich fibrin for guided bone regeneration procedures (only two studies), with no quantifiable advantages in terms of new bone formation or dimensional bone gain found in the platelet-rich fibrin group. For sinus elevation, the meta-analysis demonstrated no advantage in terms of histological new bone formation in the control group (bone graft alone) compared with the test group (bone graft and platelet-rich fibrin). Two studies demonstrated that platelet-rich fibrin may shorten healing periods prior to implant placement. Platelet-rich fibrin was also shown to slightly enhance primary implant stability (implant stability quotient value < 5) as assessed using implant stability quotients and resonance frequency analysis parameters, with no histological data evaluating bone-implant contact yet available on this topic. In one study, platelet-rich fibrin was shown to improve the clinical parameters when utilised as an adjunct for the treatment of peri-implantitis. CONCLUSIONS: In the majority of studies, platelet-rich fibrin offered little or no clear advantage in terms of new bone formation as evaluated in various studies on guided bone regeneration and sinus elevation, nor in implant stability and treatment of peri-implantitis. Various authors and systematic reviews on the topic have now expressed criticism of the various study designs and protocols, and the lack of appropriate controls and available information regarding patient selection. Well-controlled human studies on these specific topics are required.

Impact of Cross-Linking of Collagen Matrices on Tissue Regeneration in a Rabbit Calvarial Bone Defect.

The cross-linking of collagen matrices (Cl_CM) may provide volume-stable enhanced defect regeneration when compared to non-cross-linked matrices (Ncl_CM). The aim of the present study was to investigate the bone forming potential of collagen matrices (CMs) and the effects of cross-linking CMs in a rabbit calvaria defect model. (1) Empty controls (n = 6), (2) Ncl_CM (n = 8), and (3) Cl_CM (n = 8) were selected to be observed for the healing in 10 mm critical-sized calvarial bone defects. The potential for the bone as well as the connective tissue formation were evaluated by micro-CT and histomorphometry at three months post-surgery. There were no statistically significant differences in terms of new bone volume in the defects between the groups. However, the Cl_CM induced significantly greater fibrous tissue regeneration (5.29 ± 1.57 mm2) when compared to the controls (3.51 ± 0.93 mm2) by histomorphometry. The remnants of collagen fibers with immune cells, including macrophages and giant cells, were occasionally observed in the Cl_CM group but not in the Ncl_CM group. In conclusion, the cross-linking of collagen did not influence the potential for bone formation. Nevertheless, Cl_CM might be advantageous for the maintenance of fibrous tissue volume without disturbing bone formation in the defects.

Efficacy of platelet-rich fibrin on bone formation, part 1: Alveolar ridge preservation.

PURPOSE: To investigate the use of platelet-rich fibrin for alveolar ridge preservation compared to natural healing, bone graft material and platelet-rich fibrin in combination with bone graft material. MATERIALS AND METHODS: The present systematic review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The review examined randomised controlled trials comparing the clinical outcomes of platelet-rich fibrin with those of other modalities for alveolar ridge preservation. Studies of third molar extraction site healing were excluded. The studies were classified into three categories: natural wound healing vs platelet-rich fibrin; bone graft material vs platelet-rich fibrin; and bone graft material vs bone graft material and platelet-rich fibrin. RESULTS: From 179 articles identified, 16 randomised controlled trials were included. Owing to the heterogeneity of the investigated parameters, it was not possible to perform a meta-analysis. In total, 10 randomised controlled trials compared platelet-rich fibrin to natural wound healing, with seven of these demonstrating favourable outcomes to either limit postextraction dimensional changes or improve new bone formation in the platelet-rich fibrin group. Three of four studies comparing healing with bone graft material to platelet-rich fibrin found that the latter led to significantly greater horizontal or vertical bone resorption, and the bone graft material was more able to maintain the ridge dimensions. Two out of three randomised controlled trials investigating healing with both bone graft material and platelet-rich fibrin reported better outcomes using this combined approach than with bone graft material alone. All studies investigating soft tissue healing with platelet-rich fibrin demonstrated better outcomes in the platelet-rich fibrin group. CONCLUSIONS: The majority of studies comparing healing with platelet-rich fibrin to natural healing concluded that the former more successfully limits postextraction dimensional changes than the latter. However, 75% of studies investigating platelet-rich fibrin vs bone graft material reported better results in the bone graft group with respect to its ability to maintain postextraction dimensional changes. The addition of platelet-rich fibrin to bone graft material may improve clinical outcomes, although data are limited.

A technical note on contamination from PRF tubes containing silica and silicone.

BACKGROUND: Platelet-rich fibrin (PRF) has been widely utilized in modern medicine and dentistry owing to its ability to rapidly stimulate neoangiogenesis, leading to faster tissue regeneration. While improvements over traditional platelet rich plasma therapies (which use chemical additives such as bovine thrombin and calcium chloride) have been observed, most clinicians are unaware that many tubes utilized for the production of 'natural' and '100% autologous' PRF may in fact contain chemical additives without appropriate or transparent knowledge provided to the treating clinician. The aim of this overview article is therefore to provide a technical note on recent discoveries related to PRF tubes and describe recent trends related to research on the topic from the authors laboratories. METHODS: Recommendations are provided to clinicians with the aim of further optimizing PRF clots/membranes by appropriate understanding of PRF tubes. The most common additives to PRF tubes reported in the literature are silica and/or silicone. A variety of studies have been performed on their topic described in this narrative review article. RESULTS: Typically, PRF production is best achieved with plain, chemical-free glass tubes. Unfortunately, a variety of other centrifugation tubes commonly used for lab testing/diagnostics and not necessarily manufactured for human use have been utilized in clinical practice for the production of PRF with unpredictable clinical outcomes. Many clinicians have noted an increased variability in PRF clot sizes, a decreased rate of clot formation (PRF remains liquid even after an adequate protocol is followed), or even an increased rate in the clinical signs of inflammation following the use of PRF. CONCLUSION: This technical note addresses these issues in detail and provides scientific background of recent research articles on the topic. Furthermore, the need to adequately select appropriate centrifugation tubes for the production of PRF is highlighted with quantitative data provided from in vitro and animal investigations emphasizing the negative impact of the addition of silica/silicone on clot formation, cell behavior and in vivo inflammation.

Collagen-Based Matrices for Osteoconduction: A Preclinical In Vivo Study.

The aim of this study was to evaluate the influence of additional hydroxyapatite (HA) in collagen-based matrices (CM) and membrane placement on bone formation in calvarial defects. Critical size defects in the calvaria of 16 New Zealand White Rabbits were randomly treated with CM or mineralized collagen-based matrices (mCM). Half of the sites were covered with a collagen membrane. Animals were euthanized after 12 weeks of healing. The samples were studied by micro-CT and histology. Newly formed lamellar bone was observed in all samples at the periphery of the defect. In the central areas, however, new bone composed of both woven and lamellar bone was embedded in the soft tissue. Samples treated with mCM showed more residual biomaterial and induced more small bony islands in the central areas of the defects than samples with CM. Nevertheless, a complete defect closure was not observed in any of the samples at 12 weeks. Membrane placement resulted in a decrease in bone density and height. Significant differences between the groups were revealed only between CM groups with and without membrane coverage for bone height in the central area of the defect. Neither mineralization of CM nor membrane placement improved the osteogenic capacity in this particular defect. Nevertheless, mineralisation influenced bone density without a membrane placement and bone volume underneath a membrane. CM may be used as a scaffold in bone regeneration procedures, without the need of a membrane coverage. Further preclinical studies are warrant to optimise the potential of mCM.

The impact of the size of bone substitute granules on macrophage and osteoblast behaviors in vitro.

OBJECTIVE: Bone substitute (BS) size might influence the clinical outcomes of guided bone regeneration (GBR) procedures. The aim of the present study was to investigate the influence of BS size on macrophage (Mφ) and osteoblast behaviors in vitro. MATERIALS AND METHODS: Two different granule sizes (S and M/L) were assessed for four different commercial BSs: deproteinized bovine bone mineral (DBBM), biphasic calcium phosphate type 1 (BCP1), BCP type 2 (BCP2), and carbonate apatite (CO3Ap). The BSs were compared for their impacts on the cell viability and differentiation potential of THP-1-derived Mφs and human osteoblast-like Saos-2 cells. RESULTS: The smaller granules showed higher material volumes and surface areas than the larger granules. Significantly higher viability of Mφs and Saos-2 cells was observed with the DBBM_L-size granules than with the DBBM_S-size granules. Gene expression experiments in Mφs revealed few differences between the two sizes of each BS, although higher CD206 mRNA levels were observed in the BCP1_L group and the CO3Ap_M group than in the respective S-size groups on day 1. Only DBBM showed significantly higher mRNA levels of osteogenic markers, including Runx2 and osteocalcin, in Saos-2 cells in the S-size group than in the L-size group. CONCLUSIONS: The S-size and L-size DBBM granules exhibited clear differences in cell outcomes: cells cultured on the S-size granules exhibited lower cell viability, higher osteopromotive ability, and no noticeable Mφ polarization changes. CLINICAL RELEVANCE: A smaller granule size might be advantageous due to greater bone regeneration potential in the use of DBBM granules to treat defects.

Use of platelet-rich fibrin for the treatment of periodontal intrabony defects: a systematic review and meta-analysis.

OBJECTIVES: This study aims to compare the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities. MATERIALS AND METHODS: The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 10 categories as follows: (1) open flap debridement (OFD) alone versus OFD/PRF; (2) OFD/bone graft (OFD/BG) versus OFD/PRF; (3) OFD/BG versus OFD/BG/PRF; (4-6) OFD/barrier membrane (BM), OFD/PRP, or OFD/enamel matrix derivative (EMD) versus OFD/PRF; (7) OFD/EMD versus OFD/EMD/PRF; (8-10) OFD/PRF versus OFD/PRF/metformin, OFD/PRF/bisphosphonates, or OFD/PRF/statins. Weighted means and forest plots were calculated for probing depth (PD), clinical attachment level (CAL), and radiographic bone fill (RBF). RESULTS: From 551 articles identified, 27 RCTs were included. The use of OFD/PRF statistically significantly reduced PD and improved CAL and RBF when compared to OFD. No clinically significant differences were reported when OFD/BG was compared to OFD/PRF. The addition of PRF to OFD/BG led to significant improvements in CAL and RBF. No differences were reported between any of the following groups (OFD/BM, OFD/PRP, and OFD/EMD) when compared to OFD/PRF. No improvements were also reported when PRF was added to OFD/EMD. The addition of all three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements of PD, CAL, and RBF. CONCLUSIONS: The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone with similar levels being observed between OFD/BG and OFD/PRF. Future research geared toward better understanding potential ways to enhance the regenerative properties of PRF with various small biomolecules may prove valuable for future clinical applications. Future research investigating PRF at histological level is also needed. CLINICAL RELEVANCE: The use of PRF in conjunction with OFD statistically significantly improved PD, CAL, and RBF values, yielding to comparable outcomes to OFD/BG. The combination of PRF with bone grafts or small biomolecules may offer certain clinical advantages, thus warranting further investigations.

The effect of synthetic bone graft substitutes on bone formation in rabbit calvarial defects.

The aim of this study was to evaluate the influence of the intensity of the biomimetic hydroxyapatite (HA) coating of α-tricalcium phosphate (α-TCP) on biomaterial degradation and bone formation. Twenty-four female NZW rabbits of approximately 12 weeks of age were used. Critical size defects were randomly treated with 3%:97% HA:α-TCP (BBCP1), 12%:88% HA:α-TCP (BBCP2), and 23%:77% HA:α-TCP (BBCP3), respectively or sham. All defects were covered with a resorbable collagen membrane. Animals were euthanized after 3 and 12 weeks of healing and samples were investigated by micro-CT and histologic analysis. Ingrowth of newly formed woven bone from the original bone at 3-week healing period was observed in all samples. At the 12-week healing period, the new bone in the peripheral area was mainly lamellar and in the central region composed of both woven and lamellar bone. New bony tissue was found on the surface of all three types of granules and at the interior of the BBCP1 granules. Samples with 3% HA showed significantly less residual biomaterial in comparison to the other two groups. Furthermore, BBCP1 significantly promoted new bone area as compared to other three groups and more bone volume as compared to the control. Within its limitations, this study indicated the highest degradation rate in case of BBCP1 concomitant with the highest rate of bone formation. Hence, formation of new bone can be affected by the level of biomimetic HA coating of α-TCP.

Correlation of the mechanical and biological response in light-cured RBCs to receiving a range of radiant exposures: Effect of violet light.

OBJECTIVE: This study correlates the mechanical and biological response of commercially available resin-based composites (RBCs) to clinically relevant light-curing conditions. METHODS: Two RBCs (Venus and Venus Pearl; Kulzer) that use different monomer and photo-initiator systems, but have a similar filler volume and shade, were exposed to either just blue light, or violet and blue light from two different LCUs (Translux Wave and Translux 2Wave; Kulzer). Distance and exposure times were adjusted so that both LCUs delivered 5 similar levels of radiant exposures (RE) between 1.5 J/cm²-25 J/cm² in the blue wavelength range. Thus, the violet light was additional light. The top and bottom of 2-mm thick specimens were subjected to a depth-sensing indentation test (Martens hardness/HM, Vickers hardness/HV, indentation modulus/YHU, mechanical work/Wtotal, plastic deformation work/Wplas, creep/Cr). The viability of human gingival fibroblasts was assessed after three days of exposure to RBC eluates. One and multiple-way analysis of variance (ANOVA), the Tukey honestly significant difference (HSD) post-hoc tests (α = 0.05), t-test and a Spearman correlation analysis were used. RESULTS: As the RE increased, the mechanical properties increased at a greater rate at the top compared to the bottom of the RBCs. Values measured at the bottom of 2-mm increments approached the values measured at the top only when RE > 25 J/cm² of blue light was delivered. Toxicity decreased with RE and elution cycles and was lower for Venus Pearl. Within one RE level, addition of violet light resulted in significantly improved properties (in 131 out of 150 comparisons, p < 0.05). This effect was stronger for Venus Pearl. There was a good correlation between mechanical and biological parameters. This correlation decreased as the number of eluates increased. CLINICAL SIGNIFICANCE: The mechanical and biological response to variation in RE is interrelated. The addition of violet light has a positive effect, particularly at low RE.

Biological characterization of an injectable platelet-rich fibrin mixture consisting of autologous albumin gel and liquid platelet-rich fibrin (Alb-PRF).

Platelet-rich fibrin (PRF) has been proposed as an autologous membrane with the advantages of host accumulation of platelets and leukocytes with entrapment of growth factors. However, limitations include its faster resorption properties (~2 weeks). Interestingly, recent studies have demonstrated that by heating a liquid platelet-poor plasma (PPP) layer, the resorption properties of heated albumin (albumin gel) can be extended from 2 weeks to greater than 4 months (e-PRF). The aim of the present study was to characterize the biological properties of this novel regenerative modality. Whole blood collected from peripheral blood in 9-mL plastic tubes was centrifuged at 700 g for 8 minutes. Thereafter, the platelet-poor plasma layer was heated at 75°C for 10 minutes to create denatured albumin (albumin gel). The remaining cells and growth factor found within the buffy coat layer (liquid PRF) were thereafter mixed back together with the cooled albumin gel to form Alb-PRF. Histological analysis, including the distribution of cells within Alb-PRF, was then performed. Seven different growth factor release kinetics from Alb-PRF were characterized up to 10 days, including PDGF-AA, PDGF-AB, PDGF-BB, TGF-ß1, VEGF, IGF and EGF. Thereafter, gingival fibroblast cell responses to Alb-PRF were investigated by means of a live/dead assay at 24 hours; migration assay at 24 hours; proliferation assay at 1, 3 and 5 days; real-time PCR for the expression of TGF-ß and collagen 1a2 at 3 and 7 days; and collagen 1 immunostaining at 14 days. It was first observed histologically that viable cells were evenly distributed throughout the Alb-PRF formulation. Growth factor release demonstrated a slow and gradual release, particularly for TGF-ß1 and PDGF-AA/AB, during the entire 10-day period. Alb-PRF also exhibited statistically significantly higher cell biocompatibility at 24 hours and statistically significantly induced greater fibroblast proliferation at 5 days when compared to those of control TCP. Alb-PRF further induced statistically significantly greater mRNA levels of TGF-ß at 3 and 7 days, as well as collagen 1 at 7 days. The present results indicate that Alb-PRF possesses regenerative properties induced by the slow and gradual release of growth factors found in liquid PRF via albumin gel degradation. Future studies are thus warranted to fully characterize the degradation properties of Alb-PRF in vivo and explore future clinical applications in various fields of medicine.