Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/02—Inorganic materials
  • A61L27/10—Ceramics or glasses
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/28—Materials for coating prostheses
  • A61L27/30—Inorganic materials
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
  • A61L27/56—Porous materials, e.g. foams or sponges

Definitions

• the present invention refers to a biocompatible and bioactive material, in particular a bioactive glass to be used within the regenerative medicine in an orthopaedic, dentistry and surgical field, and a related use.
• Biomaterials those material for which an interface is provided with the biologic systems in order to evaluate, handle, improve or replace any tissue, organ or function of the human body have been defined as Biomaterials. Therefore, two concepts have been introduced: bio-functionality, namely the capability of reproducing a certain function, and bio-compatibility, namely the capability of a material to induce a favourable reaction of the host tissue in a specific application. Therefore, the so-called first-generation bio-materials, which can be defined as bio-inert, have been followed by the second-generation materials bio-active and bio-degradable - which are capable of establishing a real and actual link with the host tissue, and afterwards the third-generation materials, namely capable of inducing cellular and tissue responses.
• bio-functionality namely the capability of reproducing a certain function
• bio-compatibility namely the capability of a material to induce a favourable reaction of the host tissue in a specific application. Therefore, the so-called first-generation bio-materials, which can be defined as bio-inert
• the second-generation bio-materials are those bioactive materials capable of inducing a biologic response from the tissue with which they interact without producing harmful effects.
• the biomaterial which has these features as excellence is hydroxyapatite (HA) , similar from the composition and structural points of view to the biologic apatite, namely the natural mineral phase of the bone tissue.
• HA hydroxyapatite
• Hydroxyapatite is not suitable to build joint prostheses, since it has not a suitable mechanical strength, but it is anyway used as filler of bone recesses or as coating of metallic implants, in order to enable its bone-integration process.
• bio-glasses are also used, capable of inducing the formation of a new bone tissue, whose bioactivity and biologic performance features strongly depend on the specific chemical composition.
• the so-called third-generation bio-materials are materials which are typically both capable of being re-absorbed and bioactive, and the known prior art action mechanism consists in the stimulation and growth of tissues from totipotent bone-progenitor cells on three-dimensional supports called scaffolds.
• the production and quality of biomaterials have exponentially grown in the last years with strong clinical outcomes in all medical disciplines, a market which potentially has a global size: in fact, damages to tissues following traumas, neoplasms, congenital defects joined to wider problems, such as post-extraction bone gaps in dentistry and bacterial infections to bone tissues (above all in dentistry) account for big expenses for National Health Systems.
• Advanced regeneration approaches for the bone tissue are given by autologous or heterologous bone transplants, with the disadvantage that in the first case very widespread damages cannot always be solved, while with the heterologous, namely tissue taken from donors (even cadavers) a risk of transmitting pathogens cannot be excluded; the use of coated prostheses has partially solved such disadvantages .
• innovative materials which allow regenerating the bone tissue in a patient, but many of them, though being compatible with the bone tissue, have no such properties as to allow them to be colonized by mesenchymal cells (the progenitors of the bone tissue) and therefore they do not obtain a performing regeneration.
• bio-glass in fact, can be produced massively, with fine powders, such as fibers, coatings and, in particular, granules.
• each one of these products corresponds to specific biologic performances, to be calibrated depending on its particular clinical use.
• Bio-glasses are known, which contain silicon, sodium, calcium, phosphor, zinc, potassium, etc. , designed to enable bone metabolism and bone- integration processes, enabling the formation of bone tissue.
• the surfaces of such glasses after their implant in a body, encounter a complex sequence of chemical reactions which brings about the formation of a thin surface layer made of carbonated hydroxyapatite, similar as composition and structure to the mineral phase of a bone (the so-called biologic apatite) , making such materials suitable to be used as filling materials; on the other end, also bio-glasses have scarce mechanical properties and cannot therefore be used where the material is potentially subjected to loads or must perform a structural function.
• bio-glasses are clinically being used as granules and powders, known for their good performances in terms of bone-conductivity (the capability of providing support to bone growth) and bio- compatibility, which are mainly used for filling periodontal defects and post-extraction sites, for defects after removing cysts and after apicectomy interventions; among these materials, the most famous one is 45S5 Bio-glass®, developed by prof.
• bioactive materials have granules whose size is ⁇ 100 mm, namely relatively thin, or > 500 mm, namely coarse granules.
• bio-active glasses having a new composition and capable of improving the prior art results, namely capable of conjugating bioactivity, osteogenic action, suitable pH induced in the biologic environment, granulometry such as to be re-absorbed in useful times, in addition to a high crystallization temperature, which would make it feasible to produce a series of bio-glass-based products, from coatings to scaffolds to composites based on bio- glass and calcium phosphate .
• Object of the present invention is solving the above prior art problems, by providing a biocompatible and bioactive material composed of a bioactive glass, capable of enabling a bone regenerating process in the muscle-skeleton tissues and an action of osteogenic induction.
• Another object of the present invention is providing a biocompatible and bioactive material with a crystallization temperature greater than that of 45S5.
• a further object of the present invention is providing a biocompatible and bioactive material composed of a bioactive glass as granules with a specific granulometry designed to optimize the action of osteogenic induction.
• a still further object of the present invention is providing a use for such biocompatible and bioactive material.
• a bioactive material is designed to develop a link with the organic structures composing the connective tissue and the bone tissue, the collagen fibers, and to induce the mineralization of these latter ones with the activation of the progenitor cells of bones and the supply of a mineral substance; it is also known that the entity of the link with a natural bone, the efficiency, the speed and the time length of such link are strongly affected by the chemical composition of the used bioactive material.
• the present invention deals with a biocompatible and bioactive material designed to enable a bone regenerating process in the muscle- skeleton tissues, in particular in the dentistry, orthopedic, and surgical fields, and to enable an action of osteogenic induction of mesenchymal cells optimally isolated from human bone marrow.
• the biocompatible and bioactive material according to the present invention is composed of a bioactive glass composed of Sodium oxide (Na 2 O) , with a molar concentration in percentage included between 3.0 mol% and 7.0 mol%; Calcium oxide (CaO) , with a molar concentration in percentage included between 26.3 mol% and 36.3 mol%; Magnesium oxide (MgO) , with a molar concentration in percentage included between
• the bioactive glass according to the present invention is essentially composed of
• the bioactive glass according to the present invention contains Magnesium oxide
• Bio-glass ® is aimed to raise the crystallization temperature of the bioactive glass in view of possible uses which require a heat treatment.
• the bioactive glass is obtained as granules through a melting and casting process, which is followed by a suitable dry milling and a final sieving, till granules are obtained whose sizes are included in a range from 100mm to 500mm; such granulometry, located in a laboratory, guarantees optimum reactivity and ionic release in physiologic pH, capable of promoting as first instance the adhesion of mesenchymal cells from human bone marrow, which afterwards are capable of growing and completely colonizing the material.
• Adhesion and proliferation are major and preparatory features to obtain a tissue which has been demonstrate capable of being differentiated from the osteogenic point of view after an addition of suitable reagents to the culture medium, as will be described below in more detail, and guaranteeing the optimum exploitation of all biologic potentialities of the bioactive glass.
• the bioactive glass composed of Sodium oxide (Na 2 O) , of Calcium oxide (CaO) , of
• Magnesium oxide (MgO) of Strontium oxide (SrO) , of
• Phosphorus oxide of Silica oxide (SiO 2 ) as granules whose sizes are included between 100mm and 500 ⁇ m, is designed to optimize the bone regenerative process and the action of osteogenic induction.
• said bioactive and biocompatible material is characterized by a high crystallization temperature which makes it particularly advantageous with respect to marketed bio-glasses, allowing sintering processes starting from powders , or deposition processes of coatings which provide for heat treatments, or production processes for dense and porous manufactured goods, even shaped as composite material with the addition of other bioactive and biocompatible materials, avoiding or anyway limiting the crystallization of the material during the heat treatment, thereby preserving the amorphous nature typical of the starting material and its biologic and osteogenic potentialities.
• a process for actuating the bioactive glass as granules comprises the steps of:
• a damaged host tissue such as for example a bone tissue, or a muscle-skeleton tissue, or other similar one, next to a tissue damage or defect
• increasing the local pH and forming a layer of silica-gel on the surface of the bioactive glass releasing and depositing specific ions, such as, for example, strontium or magnesium ions, on the surface of the layer of gel;
• the size of the granules of bioactive glass included between 100mm and 500mm prevents that said granules of bioactive glass are absorbed, or are partially embedded in the newly- formed tissue, or are absorbed too quickly, inducing cytotoxic effects without optimally performing the bone-stimulating effect.
• the bioactive glass provides a biocompatible and bioactive interface suitable to the bone migration, developing a bioactive surface which is colonized by the osteogenic stem cells, stimulating the re-growth of natural bones which replaced in short times (from some weeks to some months, according to the width of the defect) the bioactive glass in granules, where said granules compose the "scaffold" from which the natural bone grows again.
• the bioactive glass with such composition can be added to other biomaterials, such as for example calcium phosphates and, more specifically, hydroxyapatite or tri-calcium phosphate, polymers (for example poly-caprolactone, poly-lactic acid, poly-glycol acid, etc. ) , collagen, etc • 9 for therapeutic applications of bone regeneration in dentistry and orthopaedics.
• biomaterials such as for example calcium phosphates and, more specifically, hydroxyapatite or tri-calcium phosphate, polymers (for example poly-caprolactone, poly-lactic acid, poly-glycol acid, etc. ) , collagen, etc • 9 for therapeutic applications of bone regeneration in dentistry and orthopaedics.
• bioactive glass of the present invention in further forms, for example as coating on metallic or polymeric or ceramic or composite substrates, porous or of a scaffold, or of a product in a dense or porous shape obtained from sintering, starting from fine powders of the material, even shaped as composite with the addition of other bioactive and biocompatible materials, or of very fine powders to be used within regenerative medicine and/or tissue engineering for the regeneration of damaged tissues, or as very fine powders to be used in the production of products for personal hygiene, such as, for example, mouthwashes, or dentifrices, with anti-demineralizing and re-mineralizing action of the dental enamel.
• CSM human mesenchymal stem cells
• CSM mesenchymal stem cells

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Citations (4)

• 2019
  • 2019-02-15 IT IT102019000002229A patent/IT201900002229A1/it unknown
• 2020
  • 2020-02-12 WO PCT/IT2020/000015 patent/WO2020165926A1/en unknown
  • 2020-02-12 EP EP20724235.5A patent/EP3924006A1/en not_active Withdrawn

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