From Coagulation to Oral Surgery Application: Platelets in Bone Regeneration

International audienceThe complexity of the treatment of tissue lesions, particularly bone lesions, in regenerative medicine depends on the origin of the substance loss (traumatic, tumoral, infectious, etc.), its size and mechanical requirements. In the field of dental surgery, the need to ensure rapid regeneration of injured bone tissue for periodontal, post-extractional or pre-implant corrective surgery leads dental surgeons to have a large number of biomaterials in their therapeutic arsenal. The mineral materials are most often used because of their chemical composition which is close to bone’s mineral phase. They also present a resorption time in agreement with the time of formation of new bone.However their benefits are inconstant and the need of new bioactive structures, well accepted by the host, and favoring tissue healing has grown. Here is the place for platelet concentrates such as Platelet Rich Plasma (PRP) and Platelet Rich Fibrin (PRF) which are rich in growth factors, cytokines and others proteins. PRF became the most commonly used in the last decade as it is easier to handle with its polymerized form which mimics an extracellular matrix favorable to cell proliferation and differentiation. A new option, called platelet lysate, has recently been highlighted in the general field of tissue regeneration and has the advantage of making platelet’s content directly available. Proteins concentrations are increased in these products even if their liquid form complicates their use in daily practice. This mini-review sums up the main clinical interests for the use of platelet concentrates and the new perspectives in the field of alveolar bone regeneration especially with platelet lysate

Oral care of a patient with a SAPHO syndrome and a nickel allergy

SAPHO is an acronym for Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis. The syndrome is difficult to diagnose because it may present many different manifestations in adults and children. Its origin is still unknown, although some infectious, genetic and immune hypotheses have been put forward. We report the case of a 49‐year‐old woman with SAPHO syndrome, who developed a serious cutaneous allergy following the insertion of a removable partial denture (RPD). The oral care and treatment of this patient are described

From Coagulation to Oral Surgery Application: Platelets in Bone Regeneration

The complexity of the treatment of tissue lesions, particularly bone lesions, in regenerative medicine depends on the origin of the substance loss (traumatic, tumoral, infectious, etc.), its size and mechanical requirements. In the field of dental surgery, the need to ensure rapid regeneration of injured bone tissue for periodontal, post-extractional or pre-implant corrective surgery leads dental surgeons to have a large number of biomaterials in their therapeutic arsenal. The mineral materials are most often used because of their chemical composition which is close to bone’s mineral phase. They also present a resorption time in agreement with the time of formation of new bone.However their benefits are inconstant and the need of new bioactive structures, well accepted by the host, and favoring tissue healing has grown. Here is the place for platelet concentrates such as Platelet Rich Plasma (PRP) and Platelet Rich Fibrin (PRF) which are rich in growth factors, cytokines and others proteins. PRF became the most commonly used in the last decade as it is easier to handle with its polymerized form which mimics an extracellular matrix favorable to cell proliferation and differentiation. A new option, called platelet lysate, has recently been highlighted in the general field of tissue regeneration and has the advantage of making platelet’s content directly available. Proteins concentrations are increased in these products even if their liquid form complicates their use in daily practice. This mini-review sums up the main clinical interests for the use of platelet concentrates and the new perspectives in the field of alveolar bone regeneration especially with platelet lysate

Thermogravimetric study of the behaviour of organic and inorganic polymers contained in four dental resin-based composites

The composition of dental resin-based composite (RBC) matrix is partly responsible for many clinical failures in restorations, which may come from dimensional variation or instability in a wet environment. The objective of this study is therefore to evaluate the thermal stability over time of four dental RBC with different matrices. Silicone cylinders were filled with four different materials and then photopolymerized. To simulate ageing in the buccal environment, half of the samples were placed in a dark place at 37°C for 45 days in sealed compartments containing 2 ml of water. All the RBC produced were subjected to thermogravimetric analysis to measure the loss of mass as a function of temperature. Bis-GMA-based resins and Ormocer materials have similar curves before and after soaking in humid atmosphere. The curves of the UDMA resin are different before and after water ageing, meaning that water imbibition has modified the structure of the composite and its degradation. Even if many curves are similar within the same RBC at different polymerization times or at different pre- and post-ageing times, it is rare to observe a common kinetics between two different composites. Our results show good wet stability of polymerized dental RBC according to the manufacturer’s instructions, although the UDMA-based materials show more variation. It therefore seems that Ormocer resin composite with mass placement have ageing properties that can compete with those of conventional composites whereas those incremented on 2 mm layers are more sensitive to the time necessary for polymerization

Bioceramic powders for bone regeneration modified by high-pressure CO2 process

Non-stoichiometric nanocrystalline apatites present enhanced bioactivity compared to stoichiometric hydroxyapatite. The purpose of this work was to modify the calcium phosphates (CaP) generally used to prepare bioactive ceramics in the aim of obtaining a biomimetic apatite powder. Hydroxyapatite (HA) powder, amorphous tricalcium phosphate (amTCP) powder and a blend of these two were modified by means of an innovative, simple, “green” carbonation process, involving water and high-pressure CO2 (80 bar). This process induced a modification of the CaP, which is sensitive to the environment in which it is located and, in particular, to the pH variations that occur during the treatment phase (decrease in the pH) and during the degassing phase (return to neutral pH). FTIR and Raman spectroscopy, XRD and SEM analyses showed that, depending on the type of initial CaP powder, high-pressure CO2 treatment led to the formation of different types of calcium phosphate phases. This process allowed partial dissolution of the initial powder, mainly of TCP when present, and precipitation of a new CaP phase. HA and HA/amTCP powders were transformed into a mixture of OCP and immature carbonated apatite (PCCA) phases, including OCP maturation/transformation into PCCA. In the case of amTCP powder, a DCPD phase was also present due to the high TCP solubility and an earlier precipitation during the degassing step. This work shows the great potential of such an innovative low-temperature and high-pressure process to transform HA, HA/TCP and TCP powder into bioactive biphasic ceramics composed of OCP and PCCA similar to bone mineral

Misdiagnosed Tooth Aspiration in a Young Handicapped Boy: Case Report and Recommendations

Tooth inhalation remains a rare incident but it may occur during dental care, especially in children. We report here the case of a four-year-old boy with Down syndrome who came to the hospital after a dental trauma. During the extraction procedure, he aspired his maxillary incisor without presenting any signs of respiratory distress and was discharged by the surgical team, who thought that he had swallowed the tooth. Three weeks later, he was admitted to the emergency service because of a pulmonary infection. Two endoscopy interventions under general anesthesia were necessary to recover the foreign body inside the left lung. Because of the multiple symptoms associated with the trisomy 21 syndrome (general hypotonia, impaired immunity, etc.), practitioners should be very mindful of aspiration risks and complications during dental care. The systematic prescription of lung radiography would prevent the onset of pulmonary infections and enable an earlier intervention

Development of a natural, bioactive, blood-derived biomaterial for tissue regeneration

Le Lysat Plaquettaire (LP) est un produit dérivé du sang naturellement riche en facteurs de croissance comme le VEGF, le PDGF ou encore le TGF-ß1. Cela lui confère la capacité de stimuler les cellules de l'hôte pour promouvoir la cicatrisation voire même la régénération des tissus lésés. Associé à du chlorure de calcium et de l'acide tranexamique, le LP peut former un hydrogel composé d'un réseau tridimensionnel de fibrine, mimant une matrice extracellulaire naturelle riche en facteurs de croissance dans laquelle les cellules trouvent tous les éléments nécessaires à leur développement. Les champs d'application de ces LP sont nombreux et leur utilisation en tant que matériaux bioactifs peuvent concerner toutes les disciplines médicales. L'objectif de cette thèse est de sécher l'hydrogel afin de développer un biomatériau d'origine biologique, à base de lysat plaquettaire, qui réponde au cahier des charges des structures optimisées pour la régénération tissulaire. Le manuscrit s'organise autour de cinq parties : 1) un état de l'art sur le sujet dans la littérature, 2) le protocole de conception du biomatériau, 3) sa caractérisation in vitro et in vivo, 4) les modifications qui peuvent lui être apportées pour optimiser ses performances et enfin 5) le cadre légal et règlementaire de son utilisation future. Le séchage de l'hydrogel de LP est réalisé grâce à l'utilisation du CO2 à l'état supercritique, un procédé permettant d'envisager l'obtention de matériaux secs, poreux et stériles. Ils pourront présenter une longue période de conservation, une manipulation plus aisée que celle des hydrogels, une capacité importante à se réhydrater et également un pouvoir hémostatique. Les observations réalisées au Microscope Electronique à Balayage, ainsi que les analyses au porosimètre à mercure montrent que les mousses sèches présentent une porosité totale de 83,42±4,85% avec des pores dont les diamètres varient entre 3nm et 360µm. Le suivi de la cinétique de relargage du VEGF démontre une libération prolongée de facteurs de croissance dans le temps sans qu'il n'y ait eu de perte au cours du procédé de séchage lorsque les quantités sont comparées à celles contenues dans les gels de départ. La résistance en compression des mousses se trouve supérieure à celle des hydrogels de LP. Les premières études menées in vitro sur des cellules stromales mesenchymateuses et in vivo sur un modèle murin sous-cutané confirment la biocompatibilité des biomatériaux conçus. L'ensemble de ces résultats offre des perspectives prometteuses dans le domaine de la régénération tissulaire et permet d'envisager également l'utilisation des mousses sèches de lysat plaquettaire comme support d'expansion cellulaire dans le cadre de la thérapie cellulaire.Platelet Lysate (PL) is a blood derivative product naturally rich in growth factors such as VEGF, PDGF or TGF-ß1. This gives it the ability to stimulate host cells to promote healing and even regeneration of damaged tissue. Combined with calcium chloride and tranexamic acid, the PL can form a hydrogel composed of a three-dimensional network of fibrin, mimicking a natural extracellular matrix rich in growth factors in which cells find all the elements necessary for their development. The fields of application of these PLs are numerous and their use as bioactive materials can concern all medical disciplines. The objective of this thesis is to dry the hydrogel in order to develop a biomaterial of biological origin, based on platelet lysate, which meets the specifications of structures optimized for tissue regeneration. The manuscript is organized around five parts: 1) a state of the art on the topic in the literature, 2) the protocol designed to obtain the biomaterial, 3) its in vitro and in vivo characterizations, 4) the modifications that can be made to optimize its performances and finally 5) the legal and regulatory framework for its future use. PL hydrogel is dried using CO2 in a supercritical state, a process that makes it possible to obtain dry, porous and sterile materials. They may have a long shelf life, easier handling than hydrogels, and also a high capacity to rehydrate. The observations made by Scanning Electron Microscopy, as well as the analyses with the mercury porosimeter show that the dry foams have a total porosity rate of 83.42±4.85% with pores whose diameters vary between 3nm and 360µm. Monitoring of the VEGF release kinetics shows a prolonged release of growth factors over time without any loss during the drying process when the quantities are compared to those contained in the starting gels. The compressive strength of the foams is higher than that of PL hydrogels. Initial studies conducted in vitro on mesenchymal stromal cells and in vivo in a subcutaneous mouse model confirm the biocompatibility of the designed biomaterials. All these results offer promising prospects in the field of tissue regeneration and also make it possible to envisage the use of dry platelet lysate foams as a support for cell expansion in the context of cell therapy

Développement d'un biomatériau naturel, bioactif, dérivé du sang pour la régénération tissulaire

Platelet Lysate (PL) is a blood derivative product naturally rich in growth factors such as VEGF, PDGF or TGF-ß1. This gives it the ability to stimulate host cells to promote healing and even regeneration of damaged tissue. Combined with calcium chloride and tranexamic acid, the PL can form a hydrogel composed of a three-dimensional network of fibrin, mimicking a natural extracellular matrix rich in growth factors in which cells find all the elements necessary for their development. The fields of application of these PLs are numerous and their use as bioactive materials can concern all medical disciplines. The objective of this thesis is to dry the hydrogel in order to develop a biomaterial of biological origin, based on platelet lysate, which meets the specifications of structures optimized for tissue regeneration. The manuscript is organized around five parts: 1) a state of the art on the topic in the literature, 2) the protocol designed to obtain the biomaterial, 3) its in vitro and in vivo characterizations, 4) the modifications that can be made to optimize its performances and finally 5) the legal and regulatory framework for its future use. PL hydrogel is dried using CO2 in a supercritical state, a process that makes it possible to obtain dry, porous and sterile materials. They may have a long shelf life, easier handling than hydrogels, and also a high capacity to rehydrate. The observations made by Scanning Electron Microscopy, as well as the analyses with the mercury porosimeter show that the dry foams have a total porosity rate of 83.42±4.85% with pores whose diameters vary between 3nm and 360µm. Monitoring of the VEGF release kinetics shows a prolonged release of growth factors over time without any loss during the drying process when the quantities are compared to those contained in the starting gels. The compressive strength of the foams is higher than that of PL hydrogels. Initial studies conducted in vitro on mesenchymal stromal cells and in vivo in a subcutaneous mouse model confirm the biocompatibility of the designed biomaterials. All these results offer promising prospects in the field of tissue regeneration and also make it possible to envisage the use of dry platelet lysate foams as a support for cell expansion in the context of cell therapy.Le Lysat Plaquettaire (LP) est un produit dérivé du sang naturellement riche en facteurs de croissance comme le VEGF, le PDGF ou encore le TGF-ß1. Cela lui confère la capacité de stimuler les cellules de l'hôte pour promouvoir la cicatrisation voire même la régénération des tissus lésés. Associé à du chlorure de calcium et de l'acide tranexamique, le LP peut former un hydrogel composé d'un réseau tridimensionnel de fibrine, mimant une matrice extracellulaire naturelle riche en facteurs de croissance dans laquelle les cellules trouvent tous les éléments nécessaires à leur développement. Les champs d'application de ces LP sont nombreux et leur utilisation en tant que matériaux bioactifs peuvent concerner toutes les disciplines médicales. L'objectif de cette thèse est de sécher l'hydrogel afin de développer un biomatériau d'origine biologique, à base de lysat plaquettaire, qui réponde au cahier des charges des structures optimisées pour la régénération tissulaire. Le manuscrit s'organise autour de cinq parties : 1) un état de l'art sur le sujet dans la littérature, 2) le protocole de conception du biomatériau, 3) sa caractérisation in vitro et in vivo, 4) les modifications qui peuvent lui être apportées pour optimiser ses performances et enfin 5) le cadre légal et règlementaire de son utilisation future. Le séchage de l'hydrogel de LP est réalisé grâce à l'utilisation du CO2 à l'état supercritique, un procédé permettant d'envisager l'obtention de matériaux secs, poreux et stériles. Ils pourront présenter une longue période de conservation, une manipulation plus aisée que celle des hydrogels, une capacité importante à se réhydrater et également un pouvoir hémostatique. Les observations réalisées au Microscope Electronique à Balayage, ainsi que les analyses au porosimètre à mercure montrent que les mousses sèches présentent une porosité totale de 83,42±4,85% avec des pores dont les diamètres varient entre 3nm et 360µm. Le suivi de la cinétique de relargage du VEGF démontre une libération prolongée de facteurs de croissance dans le temps sans qu'il n'y ait eu de perte au cours du procédé de séchage lorsque les quantités sont comparées à celles contenues dans les gels de départ. La résistance en compression des mousses se trouve supérieure à celle des hydrogels de LP. Les premières études menées in vitro sur des cellules stromales mesenchymateuses et in vivo sur un modèle murin sous-cutané confirment la biocompatibilité des biomatériaux conçus. L'ensemble de ces résultats offre des perspectives prometteuses dans le domaine de la régénération tissulaire et permet d'envisager également l'utilisation des mousses sèches de lysat plaquettaire comme support d'expansion cellulaire dans le cadre de la thérapie cellulaire

The Use of Potassium Iodide in Pediatric Dentistry Does Not Change the Retention of Glass Ionomer Cement on a Dentin Treated with Silver Fluoride: In Vitro Results

In pediatric and operative dentistry, caries treatment benefits from a therapeutic option based on the use of silver fluoride (AgF) associated with potassium iodide (KI) to avoid dark colorations on dental tissues. The objective of this in vitro study is to evaluate the retention of glass ionomer cement (GIC) on a dentin when treated with AgF and KI. Twenty-two healthy human permanent molars and eight human primary teeth, all free of any decay, were cut to obtain occlusal flat dentinal surfaces and were then treated with AgF for a duration of 60 s. For half of the teeth, a drop of KI was applied for a duration of 30 s. All samples were covered with a plot of GIC and their resistance to shear bond strength was measured. The fracture resistance in both permanent and primary teeth does not show any statistically significant differences whether KI was applied or not. For permanent teeth, the resistance is slightly higher in the group treated with KI than in the group treated with AgF alone. To our knowledge, these data are the first to describe the possible application of KI both on primary and permanent teeth. In any case, further studies are needed to investigate the bond strength between dentin and GIC on a wider range of samples

From Coagulation to Oral Surgery Application: Platelets in Bone Regeneration

International audienceThe complexity of the treatment of tissue lesions, particularly bone lesions, in regenerative medicine depends on the origin of the substance loss (traumatic, tumoral, infectious, etc.), its size and mechanical requirements. In the field of dental surgery, the need to ensure rapid regeneration of injured bone tissue for periodontal, post-extractional or pre-implant corrective surgery leads dental surgeons to have a large number of biomaterials in their therapeutic arsenal. The mineral materials are most often used because of their chemical composition which is close to bone’s mineral phase. They also present a resorption time in agreement with the time of formation of new bone.However their benefits are inconstant and the need of new bioactive structures, well accepted by the host, and favoring tissue healing has grown. Here is the place for platelet concentrates such as Platelet Rich Plasma (PRP) and Platelet Rich Fibrin (PRF) which are rich in growth factors, cytokines and others proteins. PRF became the most commonly used in the last decade as it is easier to handle with its polymerized form which mimics an extracellular matrix favorable to cell proliferation and differentiation. A new option, called platelet lysate, has recently been highlighted in the general field of tissue regeneration and has the advantage of making platelet’s content directly available. Proteins concentrations are increased in these products even if their liquid form complicates their use in daily practice. This mini-review sums up the main clinical interests for the use of platelet concentrates and the new perspectives in the field of alveolar bone regeneration especially with platelet lysate