Fibrin scaffold
Encyclopedia
A fibrin scaffold is a network of protein that holds together and supports a variety of living tissues. It is produced naturally by the body after injury, but also can be engineered as a tissue substitute to speed healing. The scaffold consists of naturally occurring biomaterial
s composed of a cross-linked fibrin
network and has a broad use in biomedical applications.
Fibrin consists of the blood proteins fibrinogen and thrombin
which participate in blood clotting. Fibrin glue
or fibrin sealant is also referred to as a fibrin
based scaffold and used to control surgical bleeding, speed wound healing
, seal off hollow body organs or cover holes made by standard sutures, and provide slow-release delivery of medications like antibiotics to tissues exposed.
Fibrin scaffold use is helpful in repairing injuries to the urinary tract, liver lung, spleen, kidney, and heart. In biomedical research, fibrin scaffolds have been used to fill bone cavities, repair neurons, heart valves, vascular grafts and the surface of the eye.
The complexity of biological systems requires customized care to sustain their function. When they are no longer able to perform their purpose, interference of new cells and biological cues is provided by a scaffold material. Fibrin scaffold has many aspects like being biocompatible, biodegradable and easily processable. Furthermore, it has an autologous nature and it can be manipulated in various size and shape. Inherent role in wound healing is helpful in surgical applications. Many factors can be bound to fibrin scaffold and those can be released in a cell-controlled manner. Its stiffness can be managed by changing the concentration according to needs of surrounding or encapsulated cells. Additional mechanical properties can be obtained by combining fibrin with other suitable scaffolds. Each biomedical application has its own characteristic requirement for different kinds of tissues and recent studies with fibrin scaffold are promising towards faster recovery, less complications and long-lasting solutions.
approaches as a scaffold material. It is advantageous opposed to synthetic polymers and collagen
gels when cost, inflammation
, immune response, toxicity
and cell adhesion
are concerned. When there is a trauma
in body, cells at site start the cascade of blood clotting and fibrin is the first scaffold formed normally. To achieve in clinical use of a scaffold, fast and entire incorporation into host tissue is very essential. Regeneration
of the tissue and the degradation of the scaffold should be balanced in terms of rate, surface area and interaction so that ideal templating can be achieved. Fibrin satisfies many requirements of scaffold functions. Biomaterials made up of fibrin
can attach many biological surfaces with high adhesion. Its biocompatibility
comes from being not toxic, allergenic or inflammatory. By the help of fibrinolysis
inhibitors or fiber cross-linkers, biodegradation can be managed. Fibrin can be provided from individuals to be treated many times so that gels from autologous fibrin have no undesired immunogenic reactions in addition to be reproducible. Inherently, structure and biochemistry of fibrin has an important role in wound healing. Although there are limitations due to diffusion, exceptional cellular growth and tissue development can be achieved. According to the application, fibrin scaffold characteristics can be adjustable by manipulating concentrations of components. Long-lasting durable fibrin hydrogels are enviable in many applications.
time of fibrinogen
and thrombin
is affected primarily by concentration of thrombin and temperature, while fibrinogen concentration has a minor effect. Fibrin gel characterization by scanning electron microscopy reveals that thick fibers make up a dense structure at lower fibrinogen concentrations (5 mg/ml) and thinner fibers and looser gel can be obtained as fibrinogen concentration (20 mg/ml) increases whereas increase in thrombin concentration (from 0.5 U/ml to 5 U/ml) has no such significant result although the fibers steadily get thinner.
Fibrin gels can be enriched by addition of other extracellular matrix
(ECM) components such as fibronectin
, vitronectin
, laminin
and collagen
. These can be linked covalently to fibrin scaffold by reactions catalyzed by transglutaminase
. Laminin originated substrate amino acid
sequences for transglutaminase can be IKVAV, YIGSR or RNIAEIIKDI. Collagen originated sequence is DGEA and many other ECM protein originated RGD
sequence can be given as other examples. Heparin
binding sequences KβAFAKLAARLYRKA, RβAFARLAARLYRRA, KHKGRDVILKKDVR, YKKIIKKL are from antithrombin III, modified antithrombin III, neural cell adhesion molecule
and platelet factor 4
, respectively. Heparin-binding growth factors can be attached to heparin binding domains via heparin. As a result, a reservoir can be provided instead of passive diffusion by liberation of growth factors in extended time. Acidic and basic fibroblast growth factor
, neurotrophin 3, transforming growth factor beta 1, transforming growth factor beta 2, nerve growth factor
, brain derived neurotrophic factor can be given as examples for such growth factors.
For some tissues like cartilage
, highly dense polymeric scaffolds such as polyethylene glycol
(PEG) are essential due to mechanical stress and that can be achieved by combining them with natural biodegradable cell-adhesive scaffolds since cells can not attach to synthetic polymers and take proper signals for normal cell function. Various scaffold combinations with PEG-based hydrogels are studied to assess the chondrogenic response to dynamic strain stimulation in a recent study. PEG-Proteoglycan
, PEG-Fibrinogen
, PEG-Albumin
conjugates and only PEG including hydrogels are used to evaluate the mechanical effect on bovine chondrocytes by using a pneumatic reactor system. The most substantial increase in stiffness is observed in PEG-Fibrinogen conjugated hydrogel after 28 days of mechanical stimulation.
, methods with minimum invasion are desired and improving injectable systems is a leading aim. Bone cavities can be filled by polymerizing materials when injected and adaptation to the shape of the cavity can be provided. Shorter surgical operation time, minimum large muscle retaraction harm, smaller scar size, less pain after operation and consequently faster recovery can be obtained by using such systems. In a study to evaluate if injectable fibrin scaffold is helpful for transplantation of bone marrow stromal cell (BMSC) when central nervous system
(CNS) tissue is damaged, Yasuda et al. found that BMSC has extended survival, migration and differentiation after transplantation to rat cortical lesion although there is complete degradation of fibrin matrix after four weeks. Another study to assess if fibrin glue
enriched with platelet
is better than just platelet rich plasma (PRP) on bone formation was conducted. Each combined with bone marrow mesenchymal stem cells and bone morphogenetic protein 2
(BMP-2) are injected into the subcutaneous space. Results shows that fibrin glue enriched with platelet has better osteogenic properties when compared to PRP. To initiate and speed up tissue repair and regeneration, platelet-rich fibrin gels are ideal since they have a high concentration of platelet releasing growth factors and bioactive proteins. Addition of fibrin glue to calcium phosphate
granules has promising results leading to faster bone repair by inducing mineralization and possible effects of fibrin on angiogenesis, cell attachment and proliferation.
is a major cause of death globally. Both mechanical valves and fixed biological xenograft or homografts used clinically have many drawbacks. One study focused on fibrin-based heart valves to assess structure and mechanical durability on sheep revealed promising potential for patient originated valve replacements. From autologous arterial-derived cells and fibrin scaffold, tissue engineered heart valves are formed, then mechanically conditioned and transplanted into the pulmonary trunk of the same animals. The preliminary result are potentially hopeful towards autologous heart valve production.
, a severe disease in modern society, coronary blood vessels occlude. These vessels have to be freed and held open i.e. by stents. Unfortunately after certain time these vessels close again and have to be bypassed to allow for upkeep of circulation. Usually autologous vessels from the patient or synthetic polymer grafts are used for this purpose. Both options have disadvantages. Firstly there are only few autologous vessels available in a human body that might be of low quality, considering the health status of the patient. The synthetic polymer based grafts on the other hand often have insufficient haemocompatibility and thus rapidly occlude - a problem that is especially prone in small calibre grafts. In this context the fibrin gel based tissue engineering of autologous vessel substitutes is a very promising approach to overcome the current problems. Cells and fibrin are isolated by low invasive procedure from the patient and shaped in individual moulds to meet the required dimensions. Additional pre-cultivation in a specialized bioreactor is inevitable to ensure appropriate properties of the graft.
, can show various responses to differences in matrix stiffness. Neuronal development of precursor cells is maintained by gels with low elastic modulus
. When stiffness of the matrix is more than that of a normal brain, extension of spinal cord
and cortical brain neurons is inhibited since neurite extension and branch forming take place on soft materials (<1000Pa). In a study, fibrins from different species are used to compare the effects on neurite growth of mouse spinal cord neurons. Among salmon, bovine and human fibrin in addition to Matrigel
(R), salmon fibrin promotes the neurite
growth best and it is more proteolysis
resistant than mammalian fibrins. Because down to 0 °C, salmon
fibrinogen can clot whereas polymerization of human fibrinogen occurs slowly below 37 °C, this can be taken as an advantage in surgical settings that are cooler. Therefore, for treatment of central nervous system damages, salmon fibrin can be a useful biomaterial.
For sciatic nerve
regeneration, fibrin scaffold is used with glial derived neurotrophic factor (GDNF) in a recent study. Survival of both sensory and motor neurons is promoted by glial-derived neurotrophic factor and its delivery to peripheral nervous system improves regeneration after an injury. GDNF and nerve growth factor
(NGF) is sequestered in the gel via a bi-domain peptide. This peptide is composed of heparin binding domain and transglutaminase substrate domain which can be cross-linked into the fibrin matrix by polymerization via transglutaminase activity of factor XIIIa. Many neurotrophic factors can bind to heparin through its sulfated domains. This is the affinity-based delivery system in which growth factors are released by cell-based degradation control. After a 13 mm rat sciatic nerve defect is made, the fibrin matrix delivery system is applied to the gap as a nerve guiding channel. Results show that such a delivery system is efficient to enhance maturity and promote organized architecture of nerve regenerating in presence of GDNF, in addition to expressing the promising treatment variations for peripheral nerve injuries.
(transfection
) is studied to address essential factors controlling the delivery process such as fibrinogen and pDNA concentration in addition to significance of cell-mediated fibrin degradation for pursuing the potential of cell-transfection microarray
engineering or in vivo gene transfer. Gene transfer is more successful in-gel than on-gel probably because of proximity of lipoplexes and target cells. Less cytotoxicity is observed due to less use of transfection agents like lipofectamine
and steady degradation of fibrin. Consequently, each cell type requires optimization of fibrinogen and pDNA concentrations for higher transfection yields and studies towards high-throughput transfection microarray experiments are promising.
Biomaterial
A biomaterial is any matter, surface, or construct that interacts with biological systems. The development of biomaterials, as a science, is about fifty years old. The study of biomaterials is called biomaterials science. It has experienced steady and strong growth over its history, with many...
s composed of a cross-linked fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
network and has a broad use in biomedical applications.
Fibrin consists of the blood proteins fibrinogen and thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
which participate in blood clotting. Fibrin glue
Fibrin glue
Fibrin glue is a formulation used to create a fibrin clot. It is made up of fibrinogen and thrombin that are injected through one head into the site of a fibrin tear. Thrombin is an enzyme and converts the fibrinogen into fibrin between 10 and 60 seconds and acts as a tissue adhesive. It may also...
or fibrin sealant is also referred to as a fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
based scaffold and used to control surgical bleeding, speed wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
, seal off hollow body organs or cover holes made by standard sutures, and provide slow-release delivery of medications like antibiotics to tissues exposed.
Fibrin scaffold use is helpful in repairing injuries to the urinary tract, liver lung, spleen, kidney, and heart. In biomedical research, fibrin scaffolds have been used to fill bone cavities, repair neurons, heart valves, vascular grafts and the surface of the eye.
The complexity of biological systems requires customized care to sustain their function. When they are no longer able to perform their purpose, interference of new cells and biological cues is provided by a scaffold material. Fibrin scaffold has many aspects like being biocompatible, biodegradable and easily processable. Furthermore, it has an autologous nature and it can be manipulated in various size and shape. Inherent role in wound healing is helpful in surgical applications. Many factors can be bound to fibrin scaffold and those can be released in a cell-controlled manner. Its stiffness can be managed by changing the concentration according to needs of surrounding or encapsulated cells. Additional mechanical properties can be obtained by combining fibrin with other suitable scaffolds. Each biomedical application has its own characteristic requirement for different kinds of tissues and recent studies with fibrin scaffold are promising towards faster recovery, less complications and long-lasting solutions.
Advantages of fibrin scaffold
Fibrin scaffold is an important element in tissue engineeringTissue engineering
Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to improve or replace biological functions...
approaches as a scaffold material. It is advantageous opposed to synthetic polymers and collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
gels when cost, inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, immune response, toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
and cell adhesion
Cell adhesion
Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
are concerned. When there is a trauma
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
in body, cells at site start the cascade of blood clotting and fibrin is the first scaffold formed normally. To achieve in clinical use of a scaffold, fast and entire incorporation into host tissue is very essential. Regeneration
Regeneration (biology)
In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organs, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans. At its most...
of the tissue and the degradation of the scaffold should be balanced in terms of rate, surface area and interaction so that ideal templating can be achieved. Fibrin satisfies many requirements of scaffold functions. Biomaterials made up of fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
can attach many biological surfaces with high adhesion. Its biocompatibility
Biocompatibility
Biocompatibility is related to the behavior of biomaterials in various contexts. The term may refer to specific properties of a material without specifying where or how the material is used , or to more empirical clinical success of a whole device in...
comes from being not toxic, allergenic or inflammatory. By the help of fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
inhibitors or fiber cross-linkers, biodegradation can be managed. Fibrin can be provided from individuals to be treated many times so that gels from autologous fibrin have no undesired immunogenic reactions in addition to be reproducible. Inherently, structure and biochemistry of fibrin has an important role in wound healing. Although there are limitations due to diffusion, exceptional cellular growth and tissue development can be achieved. According to the application, fibrin scaffold characteristics can be adjustable by manipulating concentrations of components. Long-lasting durable fibrin hydrogels are enviable in many applications.
Fibrin gel formation and enrichment
PolymerizationPolymerization
In polymer chemistry, polymerization is a process of reacting monomer molecules together in a chemical reaction to form three-dimensional networks or polymer chains...
time of fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
and thrombin
Thrombin
Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...
is affected primarily by concentration of thrombin and temperature, while fibrinogen concentration has a minor effect. Fibrin gel characterization by scanning electron microscopy reveals that thick fibers make up a dense structure at lower fibrinogen concentrations (5 mg/ml) and thinner fibers and looser gel can be obtained as fibrinogen concentration (20 mg/ml) increases whereas increase in thrombin concentration (from 0.5 U/ml to 5 U/ml) has no such significant result although the fibers steadily get thinner.
Fibrin gels can be enriched by addition of other extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
(ECM) components such as fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
, vitronectin
Vitronectin
Vitronectin also known as VTN is a protein that in humans is encoded by the VTN gene.The protein encoded by this gene is a member of the pexin family...
, laminin
Laminin
Laminins are major proteins in the basal lamina , a protein network foundation for most cells and organs...
and collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
. These can be linked covalently to fibrin scaffold by reactions catalyzed by transglutaminase
Transglutaminase
Transglutaminases are a family of enzymes that catalyze the formation of a covalent bond between a free amine group and the gamma-carboxamid group of protein- or peptide-bound glutamine. Bonds formed by transglutaminase exhibit high resistance to proteolytic degradation.Transglutaminases were...
. Laminin originated substrate amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequences for transglutaminase can be IKVAV, YIGSR or RNIAEIIKDI. Collagen originated sequence is DGEA and many other ECM protein originated RGD
RGD
RGD may refer to:*The Association of Registered Graphic Designers of Ontario *Rat genome database, a collection of genetic and genomic information about the rat*The Reacting Gas Dynamics Laboratory at the Massachusetts Institute of Technology...
sequence can be given as other examples. Heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
binding sequences KβAFAKLAARLYRKA, RβAFARLAARLYRRA, KHKGRDVILKKDVR, YKKIIKKL are from antithrombin III, modified antithrombin III, neural cell adhesion molecule
Neural Cell Adhesion Molecule
Neural Cell Adhesion Molecule is a homophilic binding glycoprotein expressed on the surface of neurons, glia, skeletal muscle and natural killer cells...
and platelet factor 4
Platelet factor 4
Platelet factor 4 is a small cytokine belonging to the CXC chemokine family that is also known as chemokine ligand 4 . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like...
, respectively. Heparin-binding growth factors can be attached to heparin binding domains via heparin. As a result, a reservoir can be provided instead of passive diffusion by liberation of growth factors in extended time. Acidic and basic fibroblast growth factor
Fibroblast growth factor
Fibroblast growth factors, or FGFs, are a family of growth factors involved in angiogenesis, wound healing, and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal...
, neurotrophin 3, transforming growth factor beta 1, transforming growth factor beta 2, nerve growth factor
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
, brain derived neurotrophic factor can be given as examples for such growth factors.
For some tissues like cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
, highly dense polymeric scaffolds such as polyethylene glycol
Polyethylene glycol
Polyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...
(PEG) are essential due to mechanical stress and that can be achieved by combining them with natural biodegradable cell-adhesive scaffolds since cells can not attach to synthetic polymers and take proper signals for normal cell function. Various scaffold combinations with PEG-based hydrogels are studied to assess the chondrogenic response to dynamic strain stimulation in a recent study. PEG-Proteoglycan
Proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
, PEG-Fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
, PEG-Albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
conjugates and only PEG including hydrogels are used to evaluate the mechanical effect on bovine chondrocytes by using a pneumatic reactor system. The most substantial increase in stiffness is observed in PEG-Fibrinogen conjugated hydrogel after 28 days of mechanical stimulation.
Bone tissue
In orthopedicsOrthopedics
Orthopedics is the study of the musculoskeletal system. The Greek word 'ortho' means straight or correct and 'pedics' comes from the Greek 'pais' meaning children. For many centuries, orthopedists have been involved in the treatment of crippled children...
, methods with minimum invasion are desired and improving injectable systems is a leading aim. Bone cavities can be filled by polymerizing materials when injected and adaptation to the shape of the cavity can be provided. Shorter surgical operation time, minimum large muscle retaraction harm, smaller scar size, less pain after operation and consequently faster recovery can be obtained by using such systems. In a study to evaluate if injectable fibrin scaffold is helpful for transplantation of bone marrow stromal cell (BMSC) when central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) tissue is damaged, Yasuda et al. found that BMSC has extended survival, migration and differentiation after transplantation to rat cortical lesion although there is complete degradation of fibrin matrix after four weeks. Another study to assess if fibrin glue
Fibrin glue
Fibrin glue is a formulation used to create a fibrin clot. It is made up of fibrinogen and thrombin that are injected through one head into the site of a fibrin tear. Thrombin is an enzyme and converts the fibrinogen into fibrin between 10 and 60 seconds and acts as a tissue adhesive. It may also...
enriched with platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
is better than just platelet rich plasma (PRP) on bone formation was conducted. Each combined with bone marrow mesenchymal stem cells and bone morphogenetic protein 2
Bone morphogenetic protein 2
Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins.-Function:BMP-2 like other bone morphogenetic proteins, plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine...
(BMP-2) are injected into the subcutaneous space. Results shows that fibrin glue enriched with platelet has better osteogenic properties when compared to PRP. To initiate and speed up tissue repair and regeneration, platelet-rich fibrin gels are ideal since they have a high concentration of platelet releasing growth factors and bioactive proteins. Addition of fibrin glue to calcium phosphate
Calcium phosphate
Calcium phosphate is the name given to a family of minerals containing calcium ions together with orthophosphates , metaphosphates or pyrophosphates and occasionally hydrogen or hydroxide ions ....
granules has promising results leading to faster bone repair by inducing mineralization and possible effects of fibrin on angiogenesis, cell attachment and proliferation.
Cardiac tissue
Valvular heart diseaseValvular heart disease
Valvular heart disease is any disease process involving one or more of the valves of the heart . Valve problems may be congenital or acquired...
is a major cause of death globally. Both mechanical valves and fixed biological xenograft or homografts used clinically have many drawbacks. One study focused on fibrin-based heart valves to assess structure and mechanical durability on sheep revealed promising potential for patient originated valve replacements. From autologous arterial-derived cells and fibrin scaffold, tissue engineered heart valves are formed, then mechanically conditioned and transplanted into the pulmonary trunk of the same animals. The preliminary result are potentially hopeful towards autologous heart valve production.
Vascular graft
In atherosclerosisAtherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
, a severe disease in modern society, coronary blood vessels occlude. These vessels have to be freed and held open i.e. by stents. Unfortunately after certain time these vessels close again and have to be bypassed to allow for upkeep of circulation. Usually autologous vessels from the patient or synthetic polymer grafts are used for this purpose. Both options have disadvantages. Firstly there are only few autologous vessels available in a human body that might be of low quality, considering the health status of the patient. The synthetic polymer based grafts on the other hand often have insufficient haemocompatibility and thus rapidly occlude - a problem that is especially prone in small calibre grafts. In this context the fibrin gel based tissue engineering of autologous vessel substitutes is a very promising approach to overcome the current problems. Cells and fibrin are isolated by low invasive procedure from the patient and shaped in individual moulds to meet the required dimensions. Additional pre-cultivation in a specialized bioreactor is inevitable to ensure appropriate properties of the graft.
Ocular tissue
Bullous keratopathy that is characterized by corneal stromal edema related to cell loss and endothelial decompensation as well as subepithelial fibrosis and corneal vascularization in further cases, results vision problems due to loss of corneal transparency. Fibrin glue is used as a sutureless method onto the corneal surface to fix amniotic membrane that is cryopreserved. Complete re-epithelialization on the ocular surface with no symptom is achieved in 3 weeks. Results show that fibrin glue fixation is easy, reliable and efficient with the corneal surface.Nervous tissue
Because fibrin fulfills the mechanical aspects of neuronal growth without initiation of glial proliferation, it can be potentially used in neuronal wound healing even with no need of growth factors or such constituents. Neurons and astrocytes, two major cell type of central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, can show various responses to differences in matrix stiffness. Neuronal development of precursor cells is maintained by gels with low elastic modulus
Elastic modulus
An elastic modulus, or modulus of elasticity, is the mathematical description of an object or substance's tendency to be deformed elastically when a force is applied to it...
. When stiffness of the matrix is more than that of a normal brain, extension of spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
and cortical brain neurons is inhibited since neurite extension and branch forming take place on soft materials (<1000Pa). In a study, fibrins from different species are used to compare the effects on neurite growth of mouse spinal cord neurons. Among salmon, bovine and human fibrin in addition to Matrigel
Matrigel
Matrigel is the trade name for a gelatinous protein mixture secreted by Engelbreth-Holm-Swarm mouse sarcoma cells and marketed by BD Biosciences and by Trevigen Inc under the name Cultrex BME...
(R), salmon fibrin promotes the neurite
Neurite
A neurite refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before...
growth best and it is more proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
resistant than mammalian fibrins. Because down to 0 °C, salmon
Salmon
Salmon is the common name for several species of fish in the family Salmonidae. Several other fish in the same family are called trout; the difference is often said to be that salmon migrate and trout are resident, but this distinction does not strictly hold true...
fibrinogen can clot whereas polymerization of human fibrinogen occurs slowly below 37 °C, this can be taken as an advantage in surgical settings that are cooler. Therefore, for treatment of central nervous system damages, salmon fibrin can be a useful biomaterial.
For sciatic nerve
Sciatic nerve
The sciatic nerve is a large nerve fiber in humans and other animals. It begins in the lower back and runs through the buttock and down the lower limb...
regeneration, fibrin scaffold is used with glial derived neurotrophic factor (GDNF) in a recent study. Survival of both sensory and motor neurons is promoted by glial-derived neurotrophic factor and its delivery to peripheral nervous system improves regeneration after an injury. GDNF and nerve growth factor
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
(NGF) is sequestered in the gel via a bi-domain peptide. This peptide is composed of heparin binding domain and transglutaminase substrate domain which can be cross-linked into the fibrin matrix by polymerization via transglutaminase activity of factor XIIIa. Many neurotrophic factors can bind to heparin through its sulfated domains. This is the affinity-based delivery system in which growth factors are released by cell-based degradation control. After a 13 mm rat sciatic nerve defect is made, the fibrin matrix delivery system is applied to the gap as a nerve guiding channel. Results show that such a delivery system is efficient to enhance maturity and promote organized architecture of nerve regenerating in presence of GDNF, in addition to expressing the promising treatment variations for peripheral nerve injuries.
Use in gene delivery
The use of fibrin hydrogel in gene deliveryGene delivery
Gene delivery is the process of introducing foreign DNA into host cells. Gene delivery is, for example, one of the steps necessary for gene therapy and the genetic modification of crops. There are many different methods of gene delivery developed for a various types of cells and tissues, from...
(transfection
Transfection
Transfection is the process of deliberately introducing nucleic acids into cells. The term is used notably for non-viral methods in eukaryotic cells...
) is studied to address essential factors controlling the delivery process such as fibrinogen and pDNA concentration in addition to significance of cell-mediated fibrin degradation for pursuing the potential of cell-transfection microarray
Microarray
A microarray is a multiplex lab-on-a-chip. It is a 2D array on a solid substrate that assays large amounts of biological material using high-throughput screening methods.Types of microarrays include:...
engineering or in vivo gene transfer. Gene transfer is more successful in-gel than on-gel probably because of proximity of lipoplexes and target cells. Less cytotoxicity is observed due to less use of transfection agents like lipofectamine
Lipofectamine
Lipofectamine or Lipofectamine 2000 is a common transfection reagent, produced and sold by Invitrogen, used in molecular and cellular biology. It is used to introduce, that is transfect, siRNA or plasmid DNA into in vitro cell cultures by lipofection...
and steady degradation of fibrin. Consequently, each cell type requires optimization of fibrinogen and pDNA concentrations for higher transfection yields and studies towards high-throughput transfection microarray experiments are promising.