Free Tissue Transfer in Head and Neck Reconstruction: A Multidisciplinary 15-Year Experience.

BACKGROUND: Free tissue transfer is considered the gold standard in reconstruction of extensive defects in head and neck surgery. The aim of this 15-year retrospective study is to analyze the outcomes of free tissue transfers in the head and neck area in a tertiary referral university hospital. MATERIALS AND METHODS: A retrospective, single-center study of all patients undergoing free tissue transfers for head and neck reconstruction between 2006 and 2020 was performed. Patient demographics, comorbidities, flap characteristics, outcomes and complications were assessed. RESULTS: A total of 353 free flaps were performed. The most common defect etiology was synchronous oncologic resection (74.2%). The majority of patients had at least one comorbidity (70.3%), with smoking recorded in 46.2% of the cases and alcohol consumption in 31.7%. The anterolateral thigh flap was the most commonly used flap (37.7%), followed by the osteoseptocutaneous fibula flap (26.9%). Our overall flap success rate was 97.7%, while the overall complication rate was 45.9%. CONCLUSIONS: Free tissue transfer in head and neck reconstruction is reliable. However, complication rates remain high due to the complexity of such cases and frequent presence of comorbidities. Nonetheless, when effectively managed within a multidisciplinary team, complications rarely jeopardize the overall reconstruction outcome.

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.

Risk of Osteonecrosis of the Jaw Under Denosumab Compared to Bisphosphonates in Patients With Osteoporosis.

Osteonecrosis of the jaw (ONJ) is a rare but serious adverse event associated with antiresorptive treatment. There is little evidence regarding the incidence of ONJ among patients with osteoporosis who are treated with denosumab versus bisphosphonates (BPs). The aim of this study was to determine the risk of ONJ in a real-world population. Subjects who underwent at least one dual-energy X-ray absorptiometry (DXA) examination were included in the osteoporosis register of the Swiss Society of Rheumatology between January 1, 2015, and September 30, 2019. Statistical analyses included incidence rates, rate ratios, and hazard ratios for ONJ, considering sequential therapies and drug holidays as covariates. Among 9956 registered patients, 3068 (89% female, median age 69 years [63 to 76]) were treated with BPs or denosumab for a cumulative duration of 11,101 and 4236 patient-years, respectively. Seventeen cases of ONJ were identified: 12 in patients receiving denosumab at the time of ONJ diagnosis and 5 in patients receiving oral or intravenous BP therapy. The diagnosis of ONJ was confirmed by independent and blinded maxillofacial surgeons, using the American Association of Oral and Maxillofacial Surgeons case definition of ONJ. The incidence of ONJ per 10,000 observed patient-years was 28.3 in patients receiving denosumab and 4.5 in patients with BP-associated ONJ, yielding a rate ratio of 6.3 (95% confidence interval [CI] 2.1 to 22.8), p < 0.001. Nine of 12 patients who developed ONJ during denosumab treatment had been pretreated with BPs, but none of the 5 patients with BP-related ONJ had previously received denosumab. The risk of ONJ was higher in patients receiving denosumab therapy compared with BPs (hazard ratio 3.49, 95% CI 1.16 to 10.47, p = 0.026). Previous BP therapy before switching to denosumab may be an additional risk factor for ONJ development. © 2021 American Society for Bone and Mineral Research (ASBMR).

Proposed Prediction Model and Nomogram for Systemic Complications in Patients Undergoing Free Flap Head and Neck Reconstruction.

Postoperative complications in head and neck surgery are well-known, but a predictive model to guide clinicians in free flap reconstructions has not been established. This retrospective single-center observational study assessed 131 patients who underwent ablative surgery and received free flap reconstruction. Primary endpoint was the occurrence of systemic complications (PSC). Secondary endpoint was the generation of a nomogram of complications according to the CDC classification. In the ordinal regression model, postoperative administration of furosemide [1.36 (0.63-2.11), p < 0.0001], blood loss [0.001 (0.0004-0.0020), p = 0.004], postoperative nadir hemoglobin [-0.03 (-0.07-0.01), p = 0.108], smoking [0.72 (0.02-1.44), p = 0.043], and type of flap reconstruction [1.01 (0.21-1.84), p = 0.014] as predictors. A nomogram with acceptable discrimination was proposed (Somer's delta: 0.52). Application of this nomogram in clinical practice could help identify potentially modifiable risk factors and thus reduce the incidence of postoperative complications in patients undergoing microvascular reconstruction of the head and neck.

In Vivo Efficacy of Neutrophil-Mediated Bone Regeneration Using a Rabbit Calvarial Defect Model.

Reconstruction of bone due to surgical removal or disease-related bony defects is a clinical challenge. It is known that the immune system exerts positive immunomodulatory effects on tissue repair and regeneration. In this study, we evaluated the in vivo efficacy of autologous neutrophils on bone regeneration using a rabbit calvarial defect model. Methods: Twelve rabbits, each with two surgically created calvarial bone defects (10 mm diameter), were randomly divided into two groups; (i) single application of neutrophils (SA-NP) vs. SA-NP control, and (ii) repetitive application of neutrophils (RA-NP) vs. RA-NP control. The animals were euthanized at 4 and 8 weeks post-operatively and the treatment outcomes were evaluated by micro-computed tomography, histology, and histomorphometric analyses. Results: The micro-CT analysis showed a significantly higher bone volume fraction (bone volume/total volume) in the neutrophil-treated groups, i.e., median interquartile range (IQR) SA-NP (18) and RA-NP (24), compared with the untreated controls, i.e., SA-NP (7) and RA-NP (14) at 4 weeks (p < 0.05). Similarly, new bone area fraction (bone area/total area) was significantly higher in neutrophil-treated groups at 4 weeks (p < 0.05). Both SA-NP and RA-NP had a considerably higher bone volume and bone area at 8 weeks, although the difference was not statistically significant. In addition, immunohistochemical analysis at 8 weeks revealed a higher expression of osteocalcin in both SA-NP and RA-NP groups. Conclusions: The present study provides first hand evidence that autologous neutrophils may have a positive effect on promoting new bone formation. Future studies should be performed with a larger sample size in non-human primate models. If proven feasible, this new promising strategy could bring clinical benefits for bone defects to the field of oral and maxillofacial surgery.

[Pentoxifylline and tocopherol - The importance in the treatment of osteoradionecrosis - Literature review and case report]. / Pentoxifyllin und Tocopherol. Die Bedeutung in der Behandlung der Osteoradionekrose ­ Literaturreview und Fallbericht.

Osteoradionecrosis (ORN) is a serious complication after radiotherapy for head and neck cancer and is a challenging condition for both the therapist and the patient because of its difficult treatment. Different non-invasive approaches have been published for the treatment of low-grade ORN cases without establishing a standard regimen for treatment. Based on the approach of ORN pathogenesis, the so-called radiatio-induced fibroathrophic process (RIF), a new treatment concept with pentoxifylline and tocopherol (PENTO) has been published. The results of PENTO therapy seem promising as a conservative treatment approach for mild ORN or as an alternative when surgical intervention is not possible or desired. The present study summarizes the current state of the literature and shows the effectiveness of PENTO therapy based on a case report.

Survival of dental implants and occurrence of osteoradionecrosis in irradiated head and neck cancer patients: a systematic review and meta-analysis.

OBJECTIVES: This systematic review assesses dental implant survival, calculates the incidence rate of osteoradionecrosis, and evaluates risk factors in irradiated head and neck cancer patients. MATERIALS AND METHODS: Various databases (e.g., Medline/Embase using Ovid) and gray literature platforms were searched using a combination of keywords and subject headings. When appropriate, meta-analysis was carried out using a random effects model. Otherwise, pooled analysis was applied. RESULTS: A total of 425 of the 660 included patients received radiotherapy. In total, 2602 dental implants were placed, and 1637 were placed in irradiated patients. Implant survival after an average follow-up of 37.7 months was 97% (5% confidence interval, CI 95.2%, 95% CI 98.3%) in nonirradiated patients and 91.9% (5% CI 87.7%, 95% CI: 95.3%) after an average follow-up of 39.8 months in irradiated patients. Osteoradionecrosis occurred in 11 cases, leading to an incidence of 3% (5% CI 1.6%, 95% CI 4.9%). The main factors impacting implant survival were radiation and grafting status, while factors influencing osteoradionecrosis could not be determined using meta-analysis. CONCLUSION: Our data show that implant survival in irradiated patients is lower than in nonirradiated patients, and osteoradionecrosis is-while rare-a serious complication that any OMF surgeon should be prepared for. The key to success could be a standardized patient selection and therapy to improve the standard of care, reduce risks and shorten treatment time. CLINICAL RELEVANCE: Our analysis provides further evidence that implant placement is a feasible treatment option in irradiated head and neck cancer patients with diminished oral function and good long-term cancer prognosis.

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.

Perioperative predictors of early surgical revision and flap-related complications after microvascular free tissue transfer in head and neck reconstructions: a retrospective observational series.

OBJECTIVES: The aim of this study was to determine the influence of perioperative fluid management and administration of vasopressors on early surgical revision and flap-related complications in free tissue transfer. MATERIALS AND METHODS: Intraoperative amount of fluid and of vasopressors, relevant perioperative parameters, and comorbidities were recorded in 131 patients undergoing head and neck microvascular reconstruction and compared with early surgical complications, defined as interventions requiring surgery after a flap-related complication, and/or other surgical problems in the operating room within 30 days after initial surgery. The relationship between perioperative variables for each revision category was determined using an optimized multiple logistic regression. RESULTS: The administration of diuretics (p=0.001) as a treatment for perioperative fluid overload and the type of flap (p=0.019) was associated with a higher risk of early surgical revisions. Perioperative fluid overload (p=0.039) is significantly related to flap-related complications. We found no effect of intraoperative administration of vasopressors on early surgical revisions (p=0.8) or on flap-related complications (norepinephrine p=0.6, dobutamine p=0.5). CONCLUSION: Perioperative fluid overload is associated with higher risks of early surgical revision and flap-related complications. In contrast, the administration of vasopressors seemed to have no effect on either surgical revision rate or flap-related complications. CLINICAL RELEVANCE: In patients receiving microvascular reconstructions, a balanced fluid administration perioperatively and a targeted use of vasopressors should be the necessary strategy to reduce the complication rates in head and neck surgery.

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.

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.

Histological comparison of Platelet rich fibrin clots prepared by fixed-angle versus horizontal centrifugation.

Platelet-rich fibrin (PRF) is prepared from whole blood without any exogenous coagulation factors. Several preparation methods have now been introduced, particularly with differences in centrifugation parameters including g-force and time to improve their regenerative potential. Nevertheless, the centrifugation systems have not yet been clearly investigated for their influences on the PRF clot properties. The aim of the present study was to visually and histologically characterize the cell separation manner and blood cell localization on the whole PRF clots prepared by two different centrifugation system, fixed-angle and horizontal centrifugation. Leukocyte- and platelet-rich fibrin (L-PRF) was prepared on a fixed-angle centrifuge machine (IntraSpin, Intra-Lock, FL, USA) at 2700 rpm (~400 g at the RCF-clot; ~700 g at the RCF-max) for 12 min. The PRF prepared by horizontal centrifugation was prepared on a horizontal centrifugation (H-PRF) (Eppendorf 5702, Eppendorf, Germany) at 700 g at the RCF-max for 8 min. The cell morphology and localization were observed on the surface of PRF clots by scanning electron microscopy (SEM) and histologically by transaxial frozen sections by means of a film method. L-PRF clots demonstrated a sloped separation between the upper plasma and the bottom red blood cell (RBC) layers according to the angle of the rotor. Red dots were often observed on the distal walls of the tubes in the upper layers, consisting of aggregations of RBCs, leukocytes and platelets by SEM and histology. Clots produced on the horizontal centrifuge showed much smoother cell layer distribution/separation along the tube surfaces when compared to L-PRF. Horizontal centrifugation also demonstrated more evenly distributed platelets throughout the PRF clots when compared to L-PRF that gathered the majority of cells along the distal tube surface or within the buffy-coat region. In summary, it was found that horizontal centrifugation resulted in a more uniform blood cell separation of PRF clots when compared to the accumulation of cells gathered along the distal tube surfaces produced prepared by fixed-angle centrifugation. Future research is needed to evaluate the benefit of horizontal centrifugation in clinical practice.

Clinical results of two different three-dimensional titanium plates in the treatment of condylar neck and base fractures: A retrospective study.

PURPOSE: The aim of this study was to examine two different types of three-dimensional plate for their suitability for the treatment of condylar neck and base fractures, and to evaluate the most frequent complications, while considering three different surgical approaches. MATERIALS AND METHODS: This retrospective study was conducted in patients who received two different types of three-dimensional plate for the treatment of condylar neck and base fractures, using three different surgical approaches, from January 2016 to December 2018. Medical records were obtained during an average follow-up period of 9 months after the traumatic event, with data collected on factors affecting success and failure of miniplates, clinical outcome parameters, and complications. RESULTS: A total of 43 fractures (38 patients) were examined. No differences were found between the two plate designs (mean = 0.093, SD = 0.294, p = 0.562). All fractures achieved complete bone healing, but in four cases, a revision operation had to be performed. No significant complications were found regardless of the surgical approaches chosen. There was no correlation between plate system (mean = 0.419, SD = 0.492, p = 0.497) or surgical access (mean = 0.163, SD = 0.432, p = 0.247) and the occurrence of facial nerve palsy found. Due to the extraoral approach used, permanent facial nerve palsy was reported in one case. With the intraoral approach, one case of transient facial paresis was observed. No facial palsy was observed in patients treated via a preauricular approach. CONCLUSION: Deltoid and trapezoid plates seem to perform equally in the treatment of condylar neck and base fractures.

Violence as the Most Frequent Cause of Oral and Maxillofacial Injuries among the Patients from Low- and Middle-Income Countries-A Retrospective Study at a Level I Trauma University Emergency Department in Switzerland.

Preventive strategies can be developed by gathering more information about oral and maxillofacial injuries and oral pathologies in immigrants from low- to middle-income countries (LMIC). Additional information on the quality of care can also improve the allocation of clinical resources for the management of these patients. We studied immigrants from LMIC who presented in the emergency department (ED) at Berne University Hospital with dental problems or oral or maxillofacial injuries. The patient data included age, gender, nationality, the etiology and type of trauma and infection in the oral-maxillofacial area, and overall costs. The greatest incidence of maxillofacial injuries was observed in the age group of 16-35 years (n = 128, 63.6%, p = 0.009), with males outnumbering females in all age groups. Trauma cases were most frequent in the late evening and were mostly associated with violence (n = 82, 55.4%, p = 0.001). The most common fracture was fracture of the nose (n = 31). The mean costs were approximately the same for men (mean = 2466.02 Swiss francs) and women (mean = 2117.95 Swiss francs) with maxillofacial injuries but were greater than for isolated dental problems. In conclusion, the etiology of dental and maxillofacial injuries in immigrants in Switzerland requires better support in the prevention of violence and continued promotion of oral health education.

Cytotoxicity and Gene Expression Changes of a Novel Homeopathic Antiseptic Oral Rinse in Comparison to Chlorhexidine in Gingival Fibroblasts.

Most available antiseptic solutions available today have strong antibacterial effects, however most also possess major cytotoxic effects on human gingival tissues. The VEGA Oral Care Recovery Kit (StellaLife), previously evaluated in clinical studies, consists of 16 active ingredients that are monographed in the Homeopathic Pharmacopeia of United States (HPUS) and recognized for their accelerated healing properties (reduction in post-op pain). The aim of this study was to compare VEGA to chlorhexidine (CHX) in vitro on gingival fibroblast viability, survival at various concentrations, migration assay, proliferation activity, expression of both regenerative growth factors as well as inflammatory markers, and collagen synthesis. A 10-fold dilution of standard CHX (0.02%) led to cell death, whereas cell viability was significantly better in the VEGA group for all tested parameters. Furthermore, VEGA also induced significantly greater fibroblast migration and proliferation. CHX negatively impacted the cellular inflammatory response of gingival fibroblasts, and also led to a reduction in collagen synthesis (50% decrease). Findings from the present study provide support from basic laboratory experiments that validate the previous clinical studies supporting the use of the VEGA oral rinse on its superior biocompatibility and wound healing properties when compared to CHX.

In Vitro Comparison of Macrophage Polarization and Osteoblast Differentiation Potentials between Granules and Block Forms of Deproteinized Bovine Bone Mineral.

Deproteinized bovine bone mineral (DBBM) bone grafts are commonly utilized for guided bone regeneration (GBR) techniques in regenerative dentistry. It has been hypothesized that different forms (blocks versus particulates) might demonstrate the varying properties of cell behavior during the regenerative process. Therefore, the aim of the present study was to investigate DBBM granules and blocks for their effects on osteoblasts and macrophages (Mφs). DBBM granules and blocks were filled to the same size (φ6.4 mm in diameter × 2.0 mm in height) in cell culture wells and assessed for cell viability and cell differentiation of human osteoblast-like Saos-2 cells, and Mφs derived from human monocyte THP-1 cells. The two groups were first characterized by micro-CT analysis, which demonstrated that DBBM granules had a two-fold greater material volume and a four-fold larger surface area than the blocks. DBBM blocks showed superior viability for both osteoblasts and Mφs. Osteoblast experiments were then utilized to better characterize the influence of DBBM shapes/forms on osteoblast differentiation. Alkaline phosphatase (ALP) staining on the undecalcified frozen sections was observed throughout the DBBM granule surface, yet this staining was only observed on the upper portion of the DBBM blocks. Furthermore, DBBM blocks showed M1-Mφ polarization trends with higher IL-1 and IL-6 mRNA expression in Mφs, while the conditioned media from Mφs cultured on DBBM granules promoted osteoblast differentiation with higher mRNA levels of Runx 2, ALP and osteocalcin. In conclusion, the DBBM granules showed more regenerative effects, lower M1 marker expression, and higher osteoblast differentiation potential when compared with the blocks, which might be related to the larger material volume, higher surface area and greater ability for the cells to penetrate through the scaffold.

Use of platelet-rich fibrin for the treatment of gingival recessions: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis was to compare the use of platelet-rich fibrin (PRF) with other commonly utilized treatment modalities for root coverage procedures. MATERIALS AND METHODS: The eligibility criteria comprised randomized controlled trials (RCTs) comparing the performance of PRF with that of other modalities in the treatment of Miller class I or II (Cairo RT I) gingival recessions. Studies were classified into 5 categories as follows: (1) coronally advanced flap (CAF) alone vs CAF/PRF, (2) CAF/connective tissue graft (CAF/CTG) vs CAF/PRF, (3) CAF/enamel matrix derivative (CAF/EMD) vs CAF/PRF, (4) CAF/amnion membrane (CAF/AM) vs CAF/PRF, and (5) CAF/CTG vs CAF/CTG/PRF. Studies were evaluated for percentage of relative root coverage (rRC; primary outcome), clinical attachment level (CAL), keratinized mucosa width (KMW), and probing depth (PD) (secondary outcomes). RESULTS: From 976 articles identified, 17 RCTs were included. The use of PRF statistically significantly increased rRC and CAL compared with CAF alone. No change in KMW or reduction in PD was reported. Compared with PRF, CTG resulted in statistically significantly better KMW and RC. No statistically significant differences were reported between the CAF/PRF and CAF/EMD groups or between the CAF/PRF and CAF/AM groups for any of the investigated parameters. CONCLUSIONS: The use of CAF/PRF improved rRC and CAL compared with the use of CAF alone. While similar outcomes were observed between CAF/PRF and CAF/CTG for CAL and PD change, the latter group led to statistically significantly better outcomes in terms of rRC and KTW. In summary, the use of PRF in conjunction with CAF may represent a valid treatment modality for gingival recessions exhibiting adequate baseline KMW. CLINICAL RELEVANCE: The data indicate that the use of PRF in conjunction with CAF statistically significantly improves rRC when compared with CAF alone but did not improve KMW. Therefore, in cases with limited baseline KMW, the use of CTG may be preferred over PRF.