fibrin and Fractures--Bone

The therapeutic use of autologous platelet-rich plasma constitutes a relatively new biotechnology that has been a breakthrough in the stimulation and acceleration of soft-tissue and bone healing. The efficiency of this process lies in the local and continuous delivery of a wide range of growth factors and proteins, mimicking the needs of the physiological wound healing and reparative tissue processes. Consequently, the application of platelet-rich plasma has been extended to many different fields, including orthopedics, sports medicine, dentistry, cosmetic and periodontal medicine and cosmetic, plastic and maxillofacial surgery. This article highlights the use of this technology and discusses some of the obstacles and challenges that need to be addressed to maintain progress in this field.

Topics: Blood Platelets; Fibrin; Fractures, Bone; Humans; Musculoskeletal Diseases; Platelet Transfusion; Soft Tissue Injuries; Tissue Engineering

The use of clotting substances from blood for hemostasis dates back to 1909. In 1972, modern fibrin sealing (FS) was developed in Vienna. For application, the two components, i.e., a sealer protein solution (mainly fibrinogen) and a thrombin solution, are mixed to produce the fibrin clot. The sealant may be applied with a needle, as a spray, or by premixing (e.g., with antibiotics, bone chips) for subsequent sealant application in cavities. While the positive effect of FS in normal wound healing has been conclusively demonstrated, its influence on bone healing remains controversial. The positive experimental results mostly refer to the early phase of bone healing in rabbits (cortical drill hole, autologous and heterologous (Kiel) cancellous transplants, osteotomies, osteochondral fractures) and dogs (cortical bone and spongiosa defects). Some authors observed no effects (in dogs, osteotomy) or delayed healing in artificial bone growth chambers with the use of heterologous sealant. FS was also applied in combination with implantation material (tricalcium phosphate and bone gelatin) to facilitate application. Clinical results are especially convincing as to osteochondral fractures, repair of the Achilles tendon, and in hemophiliacs. Fibrin sealant facilitates hemostasis, permits tissue fixation, enhances plasticity of granular implant material, and stimulates fibroblast growth. Although its direct osteogenic effect remains questionable, fibrin sealant is known to be an excellent tool in orthopedic and trauma surgery.

Topics: Animals; Aprotinin; Bone and Bones; Cartilage; Dogs; Drug Combinations; Factor XIII; Fibrin; Fibrin Tissue Adhesive; Fibrinogen; Fractures, Bone; Hemophilia A; Hemorrhage; Hemostasis; Humans; Rabbits; Tendon Injuries; Thrombin; Tissue Adhesives; Wound Healing

Topics: Animals; Bone and Bones; Bone Cements; Cartilage, Articular; Cyanoacrylates; Fibrin; Fracture Fixation, Internal; Fractures, Bone; History, 20th Century; Humans; Thrombin; Wound Healing

Topics: Alpha-Globulins; Animals; Basal Metabolism; Blood Proteins; Burns; Carbon Isotopes; Dogs; Environmental Exposure; Fibrin; Fibrinogen; Fractures, Bone; gamma-Globulins; Humans; Iodine Isotopes; Nitrogen; Nitrogen Isotopes; Paralysis; Postoperative Complications; Proteins; Rats; Serum Albumin; Serum Albumin, Radio-Iodinated; Temperature; Wounds and Injuries

The hematoma that forms between broken fragments of bone serves as a natural fibrin scaffold, and its removal from the defect site delays bone healing. The hypothesis of this study is that the microarchitectural and mechanical properties of the initially formed hematoma has a significant effect on the regulation of the biological process, which ultimately determines the outcome of bone healing. To mimic three healing conditions in the rat femur (normal, delayed, and non-healing bone defects), three different defect sizes of 0.5, 1.5, and 5.0 mm, are respectively used. The analysis of 3-day-old hematomas demonstrates clear differences in fibrin clot micro-architecture in terms of fiber diameter, fiber density, and porosity of the formed fibrin network, which result in different mechanical properties (stiffness) of the hematoma in each model. Those differences directly affect the biological processes involved. Specifically, RNA-sequencing reveals almost 700 differentially expressed genes between normally healing and non-healing defects, including significantly up-regulated essential osteogenic genes in normally healing defects, also differences in immune cell populations, activated osteogenic transcriptional regulators as well as potential novel marker genes. Most importantly, this study demonstrates that the healing outcome has already been determined during the hematoma phase of bone healing, three days post-surgery.

Topics: Animals; Fibrin; Fracture Healing; Fractures, Bone; Hematoma; Osteogenesis; Rats

Forensic imaging technology has rapidly advanced over the past several decades and is gaining increasing significance in medico-legal death investigations. Medical-grade computed tomography (CT) is now routinely used in post-mortem examinations at numerous institutions across the globe. However, the resolution of medical-grade CT is limited and unsuitable when used to depict some smaller anatomical structures or micro-trauma. High-resolution micro-CT offers up to 100× the resolution to overcome this problem but is a very recent addition to the field of forensic radiology. Few studies so far have attempted to validate the results which is an essential prerequisite for it to be used in the criminal justice process as demanded by regulatory bodies. This study directly compares micro-CT images with histology, the current gold standard. Three cases were examined: two larynges from suspected strangulations and one ribcage of a case of fatal child abuse. A strong correlation was observed between histology and micro-CT as the majority of skeletal injuries were identified correctly. This paper discusses the forensic implications of the results and how micro-CT is complementary to histology.

Topics: Adult; Female; Fibrin; Forensic Medicine; Fractures, Bone; Fractures, Cartilage; Hematoma; Humans; Hyoid Bone; Imaging, Three-Dimensional; Infant; Larynx; Necrosis; Osteoblasts; Osteoclasts; Osteocytes; Rib Fractures; Thyroid Cartilage; X-Ray Microtomography

Regeneration of load-bearing segmental bone defects is a major challenge in trauma and orthopaedic surgery. The ideal bone graft substitute is a biomaterial that provides immediate mechanical stability, while stimulating bone regeneration to completely bridge defects over a short period. Therefore, selective laser melted porous titanium, designed and fine-tuned to tolerate full load-bearing, was filled with a physiologically concentrated fibrin gel loaded with bone morphogenetic protein-2 (BMP-2). This biomaterial was used to graft critical-sized segmental femoral bone defects in rats. As a control, porous titanium implants were either left empty or filled with a fibrin gels without BMP-2. We evaluated bone regeneration, bone quality and mechanical strength of grafted femora using in vivo and ex vivo µCT scanning, histology, and torsion testing. This biomaterial completely regenerated and bridged the critical-sized bone defects within eight weeks. After twelve weeks, femora were anatomically re-shaped and revealed open medullary cavities. More importantly, new bone was formed throughout the entire porous titanium implants and grafted femora regained more than their innate mechanical stability: torsional strength exceeded twice their original strength. In conclusion, combining porous titanium implants with a physiologically concentrated fibrin gels loaded with BMP-2 improved bone regeneration in load-bearing segmental defects. This material combination now awaits its evaluation in larger animal models to show its suitability for grafting load-bearing defects in trauma and orthopaedic surgery.

Topics: Animals; Biomechanical Phenomena; Bone Morphogenetic Protein 2; Bone Regeneration; Bone Substitutes; Femur; Fibrin; Fractures, Bone; Gels; Male; Microscopy, Electron, Scanning; Porosity; Prostheses and Implants; Rats, Wistar; Titanium; Weight-Bearing; X-Ray Microtomography

The changes of hemostasis in the injured persons, in the lower extremities long bones fracture were analyzed. Complex dynamic investigation of the hemostasis system was conducted preoperatively in 76 injured persons, in whom long bones of the lower extremities fracture have occurred, and in 31--with injury of meniscus. Instrumental diagnostic method--a low-frequency piezoelectric thromboelastography--was applied for investigation of the blood coagulation system. The shift in a system of hemostasis towards hypercoagulation, fibrinolytic and the thrombine activity inhibition, the thrombocytes spontaneous aggregation intensity, duration of formation of a clot fibrinthrombocytic structure; the blood fibrinthrombocytic constanta enhancement, a summary index of the clot retraction and spontaneous lysis reduction were revealed in a hemostasis system before start of the treatment. The hemostasis system disorders in the injured persons may cause thrombohemorrhagic complications, what trusts a necessity for rational choice of preoperative methods of prophylaxis and intensive therapy in a system of hemostasis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Coagulation; Female; Fibrin; Fractures, Bone; Humans; Lower Extremity; Male; Middle Aged; Platelet Aggregation; Preoperative Care; Thrombelastography; Thrombin; Thrombosis

This study assessed the clinical results and second-look arthroscopy after fibrin matrix-mixed gel-type autologous chondrocyte implantation to treat osteochondral lesions of the talus.. Chondrocytes were harvested from the cuboid surface of the calcaneus in 38 patients and cultured, and gel-type autologous chondrocyte implantation was performed with or without medial malleolar osteotomy. Preoperative American orthopedic foot and ankle society ankle-hind foot scores, visual analogue score, Hannover scoring system and subjective satisfaction were investigated, and the comparison of arthroscopic results (36/38, 94.7 %) and MRI investigation of chondral recovery was performed. Direct tenderness and relationship to the active daily life of the donor site was evaluated.. The preoperative mean ankle-hind foot scores (71 ± 14) and Hannover scoring system (65 ± 10) had increased to 91 ± 12 and 93 ± 14, respectively, at 24-month follow-up (p < 0.0001), and the preoperative visual analogue score of 58 mm had decreased to 21 mm (p < 0.0001). Regarding subjective satisfaction, 34 cases (89.5 %) reported excellent, good or fair. Chondral regeneration was analysed by second-look arthroscopy and MRI. Complications included one non-union and two delayed-unions of the osteotomy sites, and 9 ankles (9/31, 29.0 %) sustained damaged medial malleolar cartilage due to osteotomy. Marked symptoms at the biopsy site did not adversely affect the patient's active daily life.. Fibrin matrix-mixed gel-type autologous chondrocyte implantation using the cuboid surface of the calcaneus as a donor can be used for treating osteochondral lesions of the talus.

Topics: Adult; Arthroscopy; Calcaneus; Cartilage, Articular; Chondrocytes; Debridement; Female; Fibrin; Fractures, Bone; Gels; Humans; Male; Middle Aged; Osteotomy; Talus; Thrombin; Transplantation, Autologous; Young Adult

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair.

Topics: Animals; Biomarkers; Bone and Bones; Bone Resorption; Bony Callus; Early Growth Response Protein 1; Fibrin; Fracture Healing; Fractures, Bone; Mice; Muscle, Skeletal; Osteogenesis; Osteotomy; Ribs

An example of the barriers and conceptual differences between forensic anthropology and pathology can be seen in determining the vitality of a wound. Pathology can make use of skin color and microscopic techniques; anthropology (as concerns the study of dry bone) needs different criteria. The diagnosis of the vitality of a wound (whether it is produced antemortem or postmortem) as well as determination of the time elapsed between the production of the wound and death is a crucial issue in forensic pathology. In fresh skin, the red-purplish coloration of a cut or bruise will reveal its vitality, whereas the change in coloration, from a macroscopic perspective, will reveal the time of survival. In more difficult cases, microscopic analyses can be performed. Bone follows similar "laws" as concerns the evolution of the histologic picture, but even if the beginning of healing processes (periosteal bone production and callus formation) can be detected macroscopically and radiologically, these processes require a long time.The scope of this pilot study was therefore to collect bone fractures from cadavers with a known time of survival, have them undergo a simulated putrefaction procedure until they became "dry or macerated bone" and perform macroscopic and microscopic analysis to verify the potential of histology in identifying "vital" processes in putrefied soft-tissue-free bone.A total of 6 samples of fractured bone (cranium, rib, and tibia) were taken from cadavers with known time of survival between trauma and death. Time intervals ranged from a few seconds after the bone fracture had been inflicted, to several hours, days, and weeks. A negative control was included (postmortem fracture). The bone was decalcified and stained with hematoxylin and eosin, Perls' (for the demonstration of hemosiderin deposits), Periodic Acid Schiff, phosphotungstic acid-hematoxylin, and Weigert (for the demonstration of fibrin). Immunohistochemistry was performed using a monoclonal antibody antihuman Glycophorin A.Results show the presence of clots and red blood cell residues on the fractured margins, strongly indicative of vital reaction.This study, though certainly not conclusive, shows that it may be worth pursuing the study of bone fractures from a histopathological point of view even on "dry bone" to verify whether the fracture is vital or not, and, if so, if its time of production can be verified.

Topics: Bone and Bones; Erythrocytes; Feasibility Studies; Fibrin; Forensic Anthropology; Forensic Pathology; Fractures, Bone; Humans; Immunohistochemistry; Microscopy; Pilot Projects; Staining and Labeling; Thrombosis

Topics: Bicycling; Bone Marrow Transplantation; Bone Nails; Clavicle; Fibrin; Fracture Fixation, Internal; Fracture Healing; Fractures, Bone; Humans; Male; Middle Aged; Pain Measurement; Radiography; Thoracic Outlet Syndrome

Old calcified fibrin coagula are frequently found in simple bone cysts. They provide a scaffold on which new bone is laid down, in a process analogous to endochondral ossification. It is suggested that these coagula are derived in substantial part from the plasma-like contents of the cyst, after the release of plasma-clotting factors as the result of injury. Major haemorrhage is not involved and in many cases there is no antecedent fracture. The phenomenon is not seen in other common cystic conditions of bone and its recognition is thus helpful in the histological diagnosis of simple bone cyst. Cystic bone infarcts and their possible confusion with simple bone cysts are also briefly discussed.

Topics: Blood Coagulation; Bone Cysts; Fibrin; Fractures, Bone; Hemorrhage; Humans; Osteogenesis; Radiography

A fibrinolysis inhibitor was purified in serum from post-traumatic patients by the use of flat bed electrofocusing of serum desalted by gel chromatography followed by affinity chromatography on a column of matrix-linked plasminogen. Disc gel electrophoresis yielded one protein band. The inhibitor protein was also found in normal serum, but in a lower concentration.

Topics: Antifibrinolytic Agents; Chromatography, Affinity; Fibrin; Fractures, Bone; Humans; Isoelectric Focusing; Lung

Topics: Adolescent; Adult; Aged; alpha 1-Antitrypsin; Blood Platelets; Embolism, Fat; Fibrin; Fibrinogen; Fibrinolysis; Fractures, Bone; Hematocrit; Humans; Macroglobulins; Middle Aged; Plasminogen

Topics: Animals; Burns; Fibrin; Fractures, Bone; Humans; Hypoxia; Lung; Microcirculation; Pulmonary Edema; Pulmonary Embolism; Wounds and Injuries

Topics: Animals; Biopsy; Blood Coagulation Tests; Bone and Bones; Collagen; Disease Models, Animal; Disseminated Intravascular Coagulation; Dogs; Embolism, Fat; Exudates and Transudates; Fibrin; Fractures, Bone; Hindlimb; Hypoxia; Leukocytes; Lung; Microscopy; Microscopy, Electron; Muscles; Musculoskeletal System; Pulmonary Edema; Pulmonary Embolism; Triolein

Topics: Accidents, Traffic; Aged; Autopsy; Blood Coagulation Disorders; Embolism, Fat; Female; Femoral Fractures; Fibrin; Fracture Fixation, Intramedullary; Fractures, Bone; Humans; Intracranial Embolism and Thrombosis; Lipids; Lung; Male; Middle Aged; Pelvic Bones; Pulmonary Artery; Pulmonary Embolism; Pulmonary Veins; Tibial Fractures; Time Factors; Wounds and Injuries

Topics: Adipose Tissue; Animals; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Embolism, Fat; Factor V; Female; Fibrin; Fibrinogen; Fractures, Bone; Heparin; Hindlimb; Injections, Intravenous; Iodine Isotopes; Lipids; Lung; Pulmonary Embolism; Rabbits; Rats; Thrombosis

Topics: Animals; Blood Coagulation; Dogs; Drainage; Fibrin; Fracture Healing; Fractures, Bone; Hematoma; Inflammation; Osteotomy; Pathology; Physiology; Research; Suction; Ulna; Wound Healing

Topics: Embolism; Fibrin; Forensic Medicine; Fractures, Bone; Humans; Pulmonary Embolism; Wounds and Injuries

Topics: Adolescent; Adult; Animals; Anticoagulants; Blood Coagulation Disorders; Bone Development; Child; Child, Preschool; Female; Fibrin; Fractures, Bone; Fractures, Ununited; Hematoma; Hemophilia A; Heparin; Humans; Infant; Male; Periosteum; Pseudarthrosis; Rabbits; Radiography; Radius Fractures; Warfarin; Wound Healing