Bronquitis plástica. Caso clínico interesante / Plastic Bronchitis. Interesting Case Report

La bronquitis plástica es una enfermedad infrecuente y poco estudiada. Se caracteriza por la obstrucción parcial o total de la vía aérea inferior por moldes o yesos gomosos y firmes, compuestos por múltiples sustancias como fibrina, mucina y otros, que se acumulan en la luz bronquial. En la actualidad, no hay un consenso de la fisiopatología real. Puede presentarse con síntomas leves como tos, sibilancias y disnea, hasta eventos fatales de insuficiencia respiratoria. Se clasifican en tipo I (inflamatorios) y tipo II (acelulares). La presencia de la bronquitis plástica es una complicación de varias enfermedades y está relacionada con procedimientos correctivos de cardiopatías congénitas (procedimiento de Fontan). El diagnóstico se hace a través de la identificación de los yesos bronquiales, ya sea cuando el paciente los expectora o por broncoscopía. Se han utilizado múltiples terapias que solo tienen evidencias anecdóticas. En los últimos años se han observado buenos resultados con el uso de heparinas, así como el alteplasa nebulizado e instilado por broncoscopia.

Plastic bronchitis is a rare and little-studied disease. It is characterized by partial or total obstruction of the lower airway by rubbery and firm molds or plasters, made up of multiple substances that accumulate in the bronchial lumen. Currently, there is no consensus on real pathophysiology. It can present itself with mild symptoms such as cough, wheezing and dyspnea, to fatal events of respiratory failure. They are classified into type I (inflammatory) and type II (acellular). The presence of plastic bronchitis is a complication of several diseases and in corrective procedures for congenital heart disease (Fontan procedure). Diagnosis is made by identifying bronchial casts, either by the patient expectorating them or by bronchoscopy. Multiple therapies have been used that only have anecdotal evidence. In recent years, good results have been observed with the use of heparins and tPA nebulized and instilled by bronchoscop.

Efficacy and safety of a new heterologous fibrin biopolymer on socket bone healing after tooth extraction: An experimental pre-clinical study.

AIM: To assess the efficacy of heterologous fibrin biopolymer (HFB) in promoting alveolar bone healing after tooth extraction in rats. MATERIALS AND METHODS: The upper right incisors of 48 Wistar rats were extracted. Toothless sockets were filled with HFB (HFBG, n = 24) or blood clot (BCG, n = 24). The tooth extraction sites were subjected to micro-computed tomography (micro-CT), histological, histomorphometric and immunohistochemical (for Runt-related transcription factor 2/Runx2 and tartrate-resistant acid phosphatase/TRAP) analyses on days 0, 7, 14 and 42 after extraction. RESULTS: Socket volume remained similar between days 0 and 14 (69 ± 5.4 mm3), except in the BCG on day 14, when it was 10% lower (p = .043). Although the number of Runx2+ osteoblasts was high and similar in both groups (34 × 102 cells/mm2), the HFBG showed lower inflammatory process and osteoclast activity than BCG at 7 days. On day 14, the number of Runx2+ osteoblasts remained high and similar to the previous period in both groups. However, osteoclast activity increased. This increase was 55% lower in the HFBG than BCG. In the BCG, the presence of an inflammatory process and larger and numerous osteoclasts on day 14 led to resorption of the alveolar bone ridge and newly formed bone. On day 42, numbers of Runx2+ osteoblast and TRAP+ osteoclasts decreased dramatically in both groups. Although the BCG exhibited a more mature cortical bone formation, it exhibited a higher socket reduction (28.3 ± 6.67%) and smaller bone volume (37 ± 5.8 mm3) compared with HFBG (socket reduction of 14.8 ± 7.14% and total bone volume of 46 ± 5.4 mm3). CONCLUSIONS: HFB effectively suppresses osteoclast activity and reduces alveolar bone resorption compared with blood clot, thus preventing three-dimensional bone loss, particularly during the early healing period. HFB emerges as a promising biopharmaceutical material for enhancing healing processes after tooth extraction.

Embryonic stem cells overexpressing high molecular weight FGF2 isoform enhance recovery of pre-ganglionic spinal root lesion in combination with fibrin biopolymer mediated root repair.

BACKGROUND: Spinal ventral root avulsion results in massive motoneuron degeneration with poor prognosis and high costs. In this study, we compared different isoforms of basic fibroblast growth factor 2 (FGF2), overexpressed in stably transfected Human embryonic stem cells (hESCs), following motor root avulsion and repair with a heterologous fibrin biopolymer (HFB). METHODS: In the present work, hESCs bioengineered to overexpress 18, 23, and 31 kD isoforms of FGF2, were used in combination with reimplantation of the avulsed roots using HFB. Statistical analysis was conducted using GraphPad Prism software with one-way or two-way ANOVA, followed by Tukey's or Dunnett's multiple comparison tests. Significance was set at *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. RESULTS: For the first set of experiments, rats underwent avulsion of the ventral roots with local administration of HFB and engraftment of hESCs expressing the above-mentioned FGF2 isoforms. Analysis of motoneuron survival, glial reaction, and synaptic coverage, two weeks after the lesion, indicated that therapy with hESCs overexpressing 31 kD FGF2 was the most effective. Consequently, the second set of experiments was performed with that isoform, so that ventral root avulsion was followed by direct spinal cord reimplantation. Motoneuron survival, glial reaction, synaptic coverage, and gene expression were analyzed 2 weeks post-lesion; while the functional recovery was evaluated by the walking track test and von Frey test for 12 weeks. We showed that engraftment of hESCs led to significant neuroprotection, coupled with immunomodulation, attenuation of astrogliosis, and preservation of inputs to the rescued motoneurons. Behaviorally, the 31 kD FGF2 - hESC therapy enhanced both motor and sensory recovery. CONCLUSION: Transgenic hESCs were an effective delivery platform for neurotrophic factors, rescuing axotomized motoneurons and modulating glial response after proximal spinal cord root injury, while the 31 kD isoform of FGF2 showed superior regenerative properties over other isoforms in addition to the significant functional recovery.

Effects of permanent placental injury due to severe acute respiratory syndrome coronavirus 2 infection during pregnancy on the feto-placental circulation: a cross-sectional study.

OBJECTIVE: The aim of this study was to evaluate the effects of permanent placental injury due to a severe acute respiratory syndrome coronavirus 2 infection during pregnancy on feto-placental circulation. METHODS: In this cross-sectional study, 83 pregnant women with planned deliveries were divided into two groups according to their severe acute respiratory syndrome coronavirus 2 infection statuses during pregnancy. Their demographic parameters, obstetric histories, and prenatal risks were evaluated. A prenatal fetal Doppler ultrasound examination was performed for all participants, and umbilical artery and middle cerebral artery Doppler parameters were obtained. Postpartum placentas were examined for pathological findings under appropriate conditions. All placentas were evaluated according to the Amsterdam consensus criteria. Mann-Whitney U test, Student's t-test, and chi-square test were used for comparisons. RESULTS: Demographic parameters were statistically similar, except that they were borderline significant for gestational weeks at delivery (p=0.044). In the pathological examination of the placenta, regardless of the trimester of exposure to viral infection, perivillous fibrin deposition and villus dystrophic calcification were more common in group 2 (p=0.016 and p=0.048, respectively) than in group 1. In the prenatal Doppler examination between the groups, no statistically significant difference was found for all of the umbilical artery pulsatile index, middle cerebral artery pulsatile index, and cerebro-placental ratio values. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy causes an increase in perivillous fibrin deposition and villus dystrophic calcification in the placenta. Placental injury caused by the severe acute respiratory syndrome coronavirus 2 virus does not affect fetal Doppler parameters.

Megakaryocyte-induced contraction of plasma clots: cellular mechanisms and structural mechanobiology.

ABSTRACT: Nonmuscle cell contractility is an essential feature underlying diverse cellular processes such as motility, morphogenesis, division and genome replication, intracellular transport, and secretion. Blood clot contraction is a well-studied process driven by contracting platelets. Megakaryocytes (MKs), which are the precursors to platelets, can be found in bone marrow and lungs. Although they express many of the same proteins and structures found in platelets, little is known about their ability to engage with extracellular proteins such as fibrin and contract. Here, we have measured the ability of MKs to compress plasma clots. Megakaryocytes derived from human induced pluripotent stem cells (iPSCs) were suspended in human platelet-free blood plasma and stimulated with thrombin. Using real-time macroscale optical tracking, confocal microscopy, and biomechanical measurements, we found that activated iPSC-derived MKs (iMKs) caused macroscopic volumetric clot shrinkage, as well as densification and stiffening of the fibrin network via fibrin-attached plasma membrane protrusions undergoing extension-retraction cycles that cause shortening and bending of fibrin fibers. Contraction induced by iMKs involved 2 kinetic phases with distinct rates and durations. It was suppressed by inhibitors of nonmuscle myosin IIA, actin polymerization, and integrin αIIbß3-fibrin interactions, indicating that the molecular mechanisms of iMK contractility were similar or identical to those in activated platelets. Our findings provide new insights into MK biomechanics and suggest that iMKs can be used as a model system to study platelet contractility. Physiologically, the ability of MKs to contract plasma clots may play a role in the mechanical remodeling of intravascular blood clots and thrombi.

Human venous blood derivatives as fetal bovine serum substitute for fibroblast culture cells in a fibrin construct

Aim: Venous blood derivatives (VBDs) have been suggested as substitutes for Fetal Bovine Serum (FBS) to improve the clinical transition of cell-based therapies. The literature is not clear about which is the best VBDs substitute. The present study aimed to evaluate the influence of VBDs on cell viability and describe a new method to seed these cells in a 3D Platelet-Rich Fibrin (PRF). Methods: Blood was processed to obtain Platelet-Poor Plasma from PRF (P-PRF), Human Serum (HS), Platelet-Poor Plasma from PRP (P-PRP), activated-PRP (a-PRP), and Platelet lysate (PL). Cells were supplemented with each VBD at 10% and FBS at 10% was the control. Cell viability (fibroblast 3T3/NIH) test was evaluated with MTT assay in two ways: i) cell-seeded and expanded with VBD; ii) cell-seed with FBS and expanded with VBD. To seed the Fibrin construct, cells were suspended in PBS and dropped into the blood sample before performing Choukroun's protocol for PRF. Constructs were cultured for 7 days in VBD supplements and FBS. Histological and Immunohistochemical analysis with vimentin was performed. Cell viability was analyzed by one-way ANOVA. Results: VBD's production time was very heterogeneous. Cells expanded in HS and a-PRP has grown faster. VBD-supplemented culture media provided cell culture highly sensible to trypsin/EDTA 0.25%. Cells seeded and expanded with VBD presented viability comparable to FBS in HS, a-PRP, and P-PRP (p>0.05) and lower in P-PRF and PL groups (p<0.05). The viability of cell seed with FBS and expanded with VBD was similar between P-PRF, a-PRP, PL, and FBS (p>0.05) and lower in HS and P-PRP (p<0.005). PRF-seeded cells showed a positive expression of vimentin and were able to maintain all cells supplemented with VBD. Conclusion: VBD supplements were able to maintain fibroblast cells in 2D and 3D cultures. The new method of the fibrin-cell construct was efficient to insert the cells into the fibrin network

[Colonic pseudotumoral involvement as an expression of severe plasminogen deficiency]. / Compromiso pseudotumoral colónico como expresión de déficit grave de plasminogéno.

Plasminogen deficiency is a very rare multisystem entity that affects different tissues of the economy through the deposition of fibrin-rich pseudomembrane and determines a heterogeneous and diverse clinical presentation. It is transmitted in an autosomal recessive manner by mutations of the PLG gene on chromosome 6 and can be divided into hypoplasminogenemia or type I and dysplasminogenemia or type II, the latter not related to clinical pathology. Severe plasminogen deficiency has a prevalence of 1.6 individuals per million inhabitants and although it can be diagnosed in adulthood, the most severe symptoms are observed in infants and children. The most common form of onset is the so-called woody conjunctivitis, characterized by fibrin membranes that are deposited on the eyelids since childhood, causing exophytic lesions that affect vision. It can also affect other mucous membranes such as the gingival, respiratory, oropharyngeal, digestive and genital mucosa, among others. We present a rare case of severe plasminogen deficiency with conjunctivitis and woody cervicitis who was admitted with clinical acute abdominal symptoms, associated with a tumor mass due to pseudomembranous deposition in the ascending colon that simulated inflammatory bowel disease and resolved spontaneously.

La deficiencia de plasminógeno es una entidad multisistémica, muy infrecuente, que afecta diferentes tejidos de la economía mediante el depósito de pseudo membranas ricas en fibrina y que determina una presentación clínica heterogénea y diversa. Se transmite en forma autosómica recesiva por mutaciones del gen PLG del cromosoma 6 y se puede dividir en hipoplasminogenemia o tipo I y displasminogenemia o tipo II, esta última no relacionada con patología clínica. El déficit grave de plasminógeno tiene una prevalencia de 1.6 individuos por millón de habitantes y si bien puede diagnosticarse en edad adulta, los síntomas más graves se observan en lactantes y niños. La forma de inicio más común es la denominada conjuntivitis leñosa, caracterizada por membranas de fibrina que se depositan en los parpados desde la infancia, provocando lesiones exofíticas que afectan la visión. También puede afectar otras mucosas como la gingival, respiratoria, orofaríngea, digestiva y genital entre otros. Presentamos un raro caso de deficiencia grave de plasminógeno con conjuntivitis y cervicitis leñosa que ingresó con un cuadro de abdomen agudo clínico, asociado a una masa tumoral por depósito de pseudomembranas en el colon ascendente que simuló una enfermedad inflamatoria intestinal y que se resolvió espontáneamente.

[Pembrolizumab-induced gastritis with PDL1 histological expression]. / Gastritis inducida por pembrolizumab con expresión histológica de PDL1.

Immune-mediated gastritis is a rare adverse effect in patients treated with immune checkpoint inhibitors. We present a patient with a diagnosis of cervical carcinoma under treatment with pembrolizumab who was admitted with nausea, vomiting and weight loss; an endoscopy revealed a ulcerated lesion covered by mucus in the antrum and gastric body. The biopsy revealed extensive denudation of the gastric mucosa with fibrin leukocyte reaction. Into the lamina propria, an increased lymphocytic and polymorphonuclear inflammatory infiltrate was observed. Immunohistochemistry confirmed positivity for PDL1 (clone SP2630) and combined positive score of 35%, with a relative contribution of epithelial cells of 25% and inflammatory cells of 10%. After three weeks with 30 mg meprednisone, a new endoscopy revealed a stomach with clear mucus content; fundus and body without lesions, and an antrum with congestive mucosa and multiple superficial ulcers covered by fibrin. Diagnostic and therapeutic aspects of immune-mediated gastritis are described.

La gastritis inmunomediada es un efecto adverso raro en pacientes bajo tratamiento con inhibidores del punto de control inmunitario; se presenta el caso de una paciente con carcinoma de cuello uterino bajo tratamiento con pembrolizumab que ingresa con náuseas, vómitos y pérdida de peso. La endoscopía demostró una lesión ulcerada cubierta por moco en antro y cuerpo gástrico. La biopsia reveló una extensa denudación de la mucosa gástrica con material fibrinoleucocitario. La lámina propia presentó incremento del infiltrado inflamatorio linfocitario y polimorfonuclear. La inmunohistoquímica confirmó positividad para PDL1 (clon SP2630) y un score positivo combinado (CPS) del 35%, con una contribución relativa de células epiteliales de 25% y de células inflamatorias de 10%. Luego de tres semanas de tratamiento con 30 mg de meprednisona, la endoscopía constató un estómago con contenido mucoso claro; fundus y cuerpo sin lesiones, antro con mucosa congestiva y múltiples úlceras extensas y superficiales cubiertas por fibrina. Se describen los aspectos diagnósticos y terapéuticos de la gastritis inmunomediada.

Cost-effective fibrinolytic enzyme production by microalga Dunaliella tertiolecta using medium supplemented with corn steep liquor.

A fibrinolytic enzyme from the microalga Dunaliella tertiolecta was produced under mixotrophic conditions using different corn steep liquor (CSL) concentrations ( 0 ≤ CLS ≤ 0.75%), purified using a combination of salting out and ion-exchange chromatography, and then biochemical characterized. Cultivation of this microalga using 0.5% CSL led to the highest maximum cell concentration (1.960±0.010 mg L-1) and cell productivity (0.140g L-1 day-1), besides a high fibrinolytic activity of the extract obtained by the homogenization method (102 ±1 U mL-1). The enzyme extracted from the microalgal biomass was 5-fold purified with a 20% yield and was found to have a specific activity of 670 U mg-1. The enzyme, whose molecular weight determined by fibrin zymography was 10 kDa, was shown to be stable at pH 3.0-9.0 and up to 70°C with optimal pH and temperature values of 8.0 and 50°C, respectively. When compared to other fibrinolytic enzymes, this protease stood out for its high fibrinolytic activity, which was enhanced by Fe2+, inhibited by Zn2+, Cu2+, Mg2+, and Ca2+, and strongly inhibited by phenylmethylsulfonyl fluoride, suggesting that it belongs to the serine metalloprotease family. Moreover, thanks to its thermal stability, the enzyme may be easily preserved and activated under high-temperature conditions.

Neuroregeneration and immune response after neurorrhaphy are improved with the use of heterologous fibrin biopolymer in addition to suture repair alone.

INTRODUCTION/AIMS: Peripheral nerve injuries result in impaired neuromuscular interactions, leading to morphological and functional alterations. Adjuvant suture repair methods have been used to improve nerve regeneration and modulate the immune response. Heterologous fibrin biopolymer (HFB), a scaffold with adhesive properties, plays a critical role in tissue repair. The aim of this study is to evaluate neuroregeneration and immune response focusing on neuromuscular recovery, using suture-associated HFB for sciatic nerve repair. METHODS: Forty adult male Wistar rats were distributed into four groups (n = 10): C (control), only sciatic nerve location; D (denervated), neurotmesis and 6-mm gap removal and fixation stumps in subcutaneous tissue; S (suture), neurotmesis followed by suture; and SB (suture + HFB), neurotmesis followed by suture and HFB. Analysis of M2 macrophages (CD206+ ), as well as the morphology and morphometry of nerves, soleus muscle, and neuromuscular junctions (NMJs), were performed at 7 and 30 days after surgery. RESULTS: The SB group had the highest M2 macrophage area in both periods. After 7 days, SB was the only group similar to the C group regarding the number of axons; furthermore, after 30 days, the SB group was closer to the C group concerning blood vessel and central myonuclear numbers, NMJ angle, and connective tissue volume. After 7 days, increases in nerve area, as well as the number and area of blood vessels, were also observed in SB. DISCUSSION: HFB potentiates the immune response, increases axonal regeneration, induces angiogenesis, prevents severe muscle degeneration, and assists in NMJ recovery. In conclusion, suture-associated HFB has major implications for improved peripheral nerve repair.

Cicatrization of oncological wounds by autologous fibrin biopolymer dressing treatment: a case series.

INTRODUCTION: Traditional therapies used to treat chronic wounds are often expensive and, in general, are not adequate to support healing. A promising alternative to conventional dressings is the autologous biopolymer FM, full of cytokines and growth factors that accelerate the healing process of wounds of various etiologies. MATERIALS AND METHODS: The authors report 3 cases in which FM was used to treat chronic oncological wounds that had been conventionally treated for more than 6 months with no sign of healing. RESULTS: Among the 3 reported cases, there was complete healing of 2 wounds. The other lesion did not heal, mainly due to the location (at the base of the skull). However, it significantly reduced its area, extension, and depth. No adverse effects or hypertrophic scar formation were recorded, and the patients reported an absence of pain from the second week of FM application. CONCLUSIONS: The proposed FM dressing approach was effective in healing and speeding up tissue regeneration. It can also be considered one of the most versatile delivery systems to the wound bed, as it is an excellent carrier of growth factors and leukocytes.

Histological, Immunohistochemical, Biomechanical, and Wettability Evaluations of the Leukocyte- and Platelet-Rich Fibrin Membranes Derived from Canine Blood.

This study aimed to perform histological, immunohistochemical, biomechanical, and wettability assessments of leukocyte- and platelet-rich fibrin (L-PRF) membranes obtained from the blood of healthy dogs. Ten client-owned Labrador Retriever dogs were enrolled. Blood samples were obtained from the external jugular vein using a vacuum tube without anticoagulant, which was immediately centrifuged at 400g for 12 min in a dedicated centrifuge. The L-PRF clot was removed from the tube, and the red clot was released from the buffy coat using a spatula. The membrane was produced using a PRF box. Histological examination identified the three portions of the L-PRF membranes. The first portion was composed mainly of red blood cells with the presence of a low number of leukocytes among them. The second portion was composed of white blood cells, mainly neutrophils. The third portion was composed of the fibrin network which was characterized by acidophilic staining. The immunohistochemical analysis showed that vascular endothelial growth factor and platelet-derived growth factor were expressed in all samples at different intensities, both in cellular components and fibrin mesh. The tensile test and wettability assessments were measured in membranes 30 min and 3 h after production. The 30 min L-PRF membranes supported twice the ultimate tensile strength compared to 3 h L-PRF membranes. The wettability of the 30 min sample membranes was statistically higher than the 3 h sample membranes. In conclusion, the centrifugation protocol allowed production of the L-PRF membrane using canine blood and this was confirmed by histological and immunohistochemical analysis. The mechanical resistance and wettability of the L-PRF membrane were significantly reduced over time.

Evaluation of a modified subchondroplasty technique in an equine full-thickness cartilage defect model: a pilot study.

OBJECTIVE: To perform a pilot study with the intent of assessing the feasibility of a modified subchondroplasty (mSCP) technique in a validated preclinical equine model of full-thickness articular cartilage loss and evaluate the short-term patient response to the injected materials. ANIMALS: 3 adult horses. PROCEDURES: Two 15-mm-diameter full-thickness cartilage defects were created on the medial trochlear ridge of each femur. Defects were treated with microfracture and then filled by 1 of 4 techniques: (1) autologous fibrin graft (FG) via subchondral injection of fibrin glue (FG), (2) autologous fibrin graft via direct injection of FG, (3) subchondral injection of a calcium phosphate bone substitute material (BSM) with direct injection of FG, and (4) untreated control. Horses were euthanized after 2 weeks. Patient response was evaluated via serial lameness examination, radiography, magnetic resonance imaging, computed tomography, gross evaluation, microcomputed tomography, and histopathology. RESULTS: All treatments were successfully administered. The injected material perfused through the underlying bone into the respective defects without adversely affecting the surrounding bone and articular cartilage. Increased new bone formation was seen at the margins of the trabecular spaces containing BSM. There was no treatment effect on the amount or composition of tissue within defects. CLINICAL RELEVANCE: The mSCP technique was a simple, well-tolerated technique in this equine articular cartilage defect model without significant adverse effects to host tissues after 2 weeks. Larger studies with long-term follow-ups are warranted.

Bilayer scaffold from PLGA/fibrin electrospun membrane and fibrin hydrogel layer supports wound healingin vivo.

Hybrid scaffolds from natural and synthetic polymers have been widely used due to the complementary nature of their physical and biological properties. The aim of the present study, therefore, has been to analyzein vivoa bilayer scaffold of poly(lactide-co-glycolide)/fibrin electrospun membrane and fibrin hydrogel layer on a rat skin model. Fibroblasts were cultivated in the fibrin hydrogel layer and keratinocytes on the electrospun membrane to generate a skin substitute. The scaffolds without and with cells were tested in a full-thickness wound model in Wistar Kyoto rats. The histological results demonstrated that the scaffolds induced granulation tissue growth, collagen deposition and epithelial tissue remodeling. The wound-healing markers showed no difference in scaffolds when compared with the positive control. Activities of antioxidant enzymes were decreased concerning the positive and negative control. The findings suggest that the scaffolds contributed to the granulation tissue formation and the early collagen deposition, maintaining an anti-inflammatory microenvironment.

Tissue Bioengineering with Fibrin Scaffolds and Deproteinized Bone Matrix Associated or Not with the Transoperative Laser Photobiomodulation Protocol.

Extending the range of use of the heterologous fibrin biopolymer, this pre-clinical study showed a new proportionality of its components directed to the formation of scaffold with a lower density of the resulting mesh to facilitate the infiltration of bone cells, and combined with therapy by laser photobiomodulation, in order to accelerate the repair process and decrease the morphofunctional recovery time. Thus, a transoperative protocol of laser photobiomodulation (L) was evaluated in critical bone defects filled with deproteinized bovine bone particles (P) associated with heterologous fibrin biopolymer (HF). The groups were: BCL (blood clot + laser); HF; HFL; PHF (P+HF); PHFL (P+HF+L). Microtomographically, bone volume (BV) at 14 days, was higher in the PHF and PHFL groups (10.45 ± 3.31 mm3 and 9.94 ± 1.51 mm3), significantly increasing in the BCL, HFL and PHFL groups. Histologically, in all experimental groups, the defects were not reestablished either in the external cortical bone or in the epidural, occurring only in partial bone repair. At 42 days, the bone area (BA) increased in all groups, being significantly higher in the laser-treated groups. The quantification of bone collagen fibers showed that the percentage of collagen fibers in the bone tissue was similar between the groups for each experimental period, but significantly higher at 42 days (35.71 ± 6.89%) compared to 14 days (18.94 ± 6.86%). It can be concluded that the results of the present study denote potential effects of laser radiation capable of inducing functional bone regeneration, through the synergistic combination of biomaterials and the new ratio of heterologous fibrin biopolymer components (1:1:1) was able to make the resulting fibrin mesh less dense and susceptible to cellular permeability. Thus, the best fibrinogen concentration should be evaluated to find the ideal heterologous fibrin scaffold.

Efficacy of fibrin-rich platelets and leukocytes (L-PRF) in tissue repair in surgical oral procedures in patients using zoledronic acid-case-control study.

INTRODUCTION: Medication-related osteonecrosis of the jaws (MRONJ) is a complication that develops in patients who use or have used antiresorptive or antiangiogenic medications for the treatment of bone metabolic disease and bone metastases. Clinically, MRONJ is characterized by the appearance of an inflammation in soft tissues and exposure of necrotic bone tissue in mandible or maxilla, for a period of 8 weeks, in patients with no history of head and neck radiotherapy that were being or are being treated with antiresorptive and/or antiangiogenic agents. The fibrin-rich platelets and leukocytes (L-PRF) membrane has been used as an alternative for MRONJ prevention. The aim of this study was to evaluate the use of L-PRF in prevention and treatment of bone necrosis. MATERIAL AND METHODS: The patients included had MRONJ diagnosis confirmed after clinical and radiographic examination and patients whose only therapeutic option was dental extraction. RESULTS: Twenty patients were included in the study and were divided in three groups. Two patients were removed from the study due to previous history of pentoxifylline and tocopherol use. The result of surgical treatment was successful in 57% in group 1 (control/MRONJ prevention), 100% in group 2 (MRONJ prevention), and 80% in group 3 (MRONJ treatment). CONCLUSION: L-PRF is an autologous biomaterial that allows the release of growth factors for a prolonged time, resulting in a better healing, reducing the risk contamination, edema, and postoperative pain, being a great ally in the prevention and treatment of MRONJ because it returns to these patients, mainly quality of life, reducing pain, and recurrent infections commonly seen in the processes of bone necrosis of the jaws.

Biological and Cellular Properties of Advanced Platelet-Rich Fibrin (A-PRF) Compared to Other Platelet Concentrates: Systematic Review and Meta-Analysis.

Platelet concentrates are used for cell induction and stimulation in tissue repair processes. The aim of the present systematic review and meta-analysis was to compare the biological and cellular properties of advanced platelet-rich fibrin (A-PRF) to those of other platelet concentrates. Searches were conducted on the PubMed/Medline, Scopus, Web of Science, Embase and LILACS databases using a search strategy oriented by the guiding question. A total of 589 records were retrieved. Seven articles of in vitro experimental studies were selected for qualitative data analysis and four were selected for meta-analysis. The release of growth factors, distribution of cells in the fibrin membrane, and cell viability, the fibrin network, and fibroblast migration were investigated. In the final analysis, statistically significant differences were found for the A-PRF group with regard to platelet-derived growth factor, transforming growth factor, epidermal growth factor and vascular endothelial growth factor at all assessment times. A difference was found with regard to bone morphogenetic protein only in the later assessment, and no differences among groups were found with regard to platelet-derived growth factor or insulin-like growth factor. The results of this systematic review and meta-analysis suggest that A-PRF has superior cellular properties and better release of growth factors compared to other platelet concentrates.

Platelet-rich fibrin improves the osteoneogenesis in non-critical defects in calvaria: a histological and histometric study

Purpose: The aim of this study was to evaluate the effect of platelet-rich fibrin (PRF) and autograft on non-critical bone repair. Methods: Four bone defects (8.3 × 2 mm) were produced on the calvarium of 15 rabbits. The surgical defects were treated with either autograft, autograft associated to PRF, PRF alone, and sham. Animals were euthanized on the second, fourth or sixth posteoperative week. Histological analyses for presence of bone development on deffect was evaluated comparing the groups treated with autograft and without the autograft separately within the same period. Mann-Whitney's tests were used to compare the percentage of bone repair in each post-operative period for autograft × autograft + PRF groups and also for control × PRF groups (α = 5%). Results: No differences were observed between the groups that received autograft and autograft associated to PRF on the second and fourth postoperative week, but areas treated with PRF demonstrated significant osteogenesis when compared to sham group on the fourth and sixth weeks. The groups that received PRF (with autograft or alone) demonstrated an enlarged bone deposition when compared to their control group. Conclusions: The use of PRF may influence bone repair and improve the bone deposition in late period of repair demonstrating osteoconductive and osteogenic properties.