WO2023037026A1 - Revêtement hybride à base d'un mélange de matériau composite adhésif, destiné à être utilisé sur des surfaces d'éléments implantables - Google Patents

Revêtement hybride à base d'un mélange de matériau composite adhésif, destiné à être utilisé sur des surfaces d'éléments implantables Download PDF

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Publication number
WO2023037026A1
WO2023037026A1 PCT/ES2022/070560 ES2022070560W WO2023037026A1 WO 2023037026 A1 WO2023037026 A1 WO 2023037026A1 ES 2022070560 W ES2022070560 W ES 2022070560W WO 2023037026 A1 WO2023037026 A1 WO 2023037026A1
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Prior art keywords
adhesive
sol
hybrid
doi
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PCT/ES2022/070560
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English (en)
Spanish (es)
Inventor
Miguel Suffo Pino
Manuel PIÑERO DE LOS RÍOS
Mercedes SALIDO PERACAULA
Nicolas DE LA ROSA FOX
María Virtudes REYES PECES
José Ignacio VILCHES PÉREZ
Rafael FERNÁNDEZ MONTESINOS
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Universidad De Cádiz
Servicio Andaluz De Salud
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Application filed by Universidad De Cádiz, Servicio Andaluz De Salud filed Critical Universidad De Cádiz
Publication of WO2023037026A1 publication Critical patent/WO2023037026A1/fr

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    • 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
    • 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

Definitions

  • the present invention belongs to the field of adhesive technology, tissue engineering and biomechanics.
  • the technical object consists of a composite material made up of a mixture of an epoxy-type adhesive and a certain sol-gel material, which is applied as a coating on implantable elements in the biomedical, trauma, orthopedics, and oral industries.
  • prostheses in traumatology for example: in ATR total knee arthroplasty, or ATC hip
  • materials used have been based on stainless steels, titanium alloys, Cr-Co-N ⁇ alloys and other dangerous metals for humans (Keegan, Learmonth, & Case, 2007).
  • the problem arises from a lack of proven biocompatibility in the medium or long term.
  • an increase in their useful life is sought, facilitating their integration into the bone by incorporating a cemented material to the implantable surfaces, which serves as a real osteoinductive barrier and protects against infections.
  • the surface of the implant is considered to be that which will be in direct contact with the oral tissues, either the soft tissues (gum and connective tissue), or the hard tissues (bone).
  • the biology of both is totally different, so the part of the implant that has to come into contact with them has been modified to allow a greater interrelation between them.
  • the surface of the implants can be classified as smooth or treated.
  • the smooth one is one that has not undergone more processing than that of the manufacture since the turning of the bar. It is almost flat, with only the roughness typical of the passage of the drill and has a lower incidence in bone formation. It is used to be the one that is in contact with the soft tissues, in order to obtain a possible union with them and an area that is easier to clean.
  • the treated one is irregular and seeks union with the bone tissue.
  • the pattern obtained will depend on the way in which the smooth surface is modified to reach it, which may be with addition methods (plasma, material coating, anodization,%), subtraction (shot blasting, acid etching, laser , ...), oxidation or mixed (combination of several). Implants obtained by synthesizing always give a rough finish on their surface and must be reworked to smooth it out. In the case of coatings, these are usually porous, based on hydroxyapatite (HA), made by diffusion and by plasma spraying (Heimann, 2016).
  • HA hydroxyapatite
  • the reference [RU2684617C1] describes a method for applying a bioactive coating on titanium implants, the coating is a electrolyte composed of orthophosphoric acid, hydroxyapatite (HA, Cas(PO4)3(OH)), germanium and distilled water.
  • the reference refers to a hybrid coating material made up of a silicon xerogel and chitosan to coat surfaces of titanium implants.
  • the consulted bibliography does not report cases of obtaining a hybrid coating material made up of a mixture of an epoxy resin-based adhesive with an airgel or a TEOS xerogel and chitosan, such as the one described in this invention.
  • This material potentially plays an active role in the biomineralization of HA, being capable of inducing its nucleation and growth on the surface of the material.
  • the adhesive hybrid biomatenals and biocomposites resulting from the processing described in this Report avoid the main problems that arise with implants based on metallic materials such as stainless steel, titanium or chrome alloys - cobalt-nickel, which do not guarantee bone formation and cause problems in the vicinity of surgery and, above all, corrosion phenomena.
  • the invention demonstrates the possibility of coating non-bioactive and non-biodegradable metal surfaces in implantable elements with these characteristics, but with the guarantee of not suffering detachments.
  • the invention develops a method for obtaining a hybrid biomaterial composed of a synthesized aerogel/xerogel based on tetraethylorthosilicate (TEOS) and chitosan, with a solid bond mediated by an epoxy adhesive.
  • TEOS tetraethylorthosilicate
  • chitosan a solid bond mediated by an epoxy adhesive.
  • the hybrid adhesive biomaterial can be applied to any metallic or non-metallic implant or prosthesis of the hip, knee, shoulder, etc.
  • the proposed hybrid coating is the result of mixing a sol-gel material (airgel or xerogel) and a commercial medical grade epoxy resin, beginning with the manufacture of airgel or xerogel.
  • the sol-gel technique has been selected, which is quite versatile since it allows obtaining hybrid materials by combining organic and inorganic compounds until the desired physicochemical and biological properties are achieved.
  • the components of the material will be tetraethylorthosilicate (TEOS) and chitosan.
  • TEOS through the acid catalysis of hydrochloric acid (HCI), will react and form a silica network.
  • Silica is known to be a bioactive material, that is, if it is introduced into simulated biological fluid, it is capable of growing hydroxyapatite (HA) on its surface (Gótz, Tobiasch, Witzleben, & Schulze, 2019).
  • HA is the mineral component of bone, so if by simulating the physiological conditions of the human body it is able to grow on the material, it will also grow once it is introduced into the body.
  • chitosan is a biopolymer found in the shell of crustaceans. This compound is biocompatible, biodegradable and favors cell adhesion (Preethi Soundarya, Haritha Menon, Viji Chandran, & Selvamurugan, 2018) (Turnbull et al., 2018).
  • the adhesive used is a medical grade epoxy called LOCTITE® M31 CLTM from the manufacturer HENKEL IBÉRICA, SA.
  • the sol-gel material is obtained, it is manually ground in an agate mortar.
  • the aerogel/xerogel is mixed manually with the biocompatible epoxy adhesive until a hybrid material with a homogeneous texture is obtained.
  • the adhesive affects the properties of aerogels and xerogels, one of the compositions described in the reference given above has been selected, in this case, 4% chitosan, to carry out the different tests. The results obtained can be extrapolated to the rest of the compositions as they are all bioactive and non-cytotoxic.
  • the mixture with the adhesive was carried out following different proportions for aerogel and xerogel, since they have different densities and specific surfaces, as shown in Table 1, which affects their behavior.
  • a n R and X m R where A refers to aerogel and X to xerogel, where n and m are the ratio by weight of airgel: resin and xerogel resin, respectively.
  • the proportions prepared appear in Table 2. These mixtures cure in 90 minutes at 50°C and have withstood the autoclaving process without deformation or phase changes.
  • cell cultures with COPH are carried out in the presence of the different biomaterials to determine if the material affects cell viability.
  • COPH were cultured in osteogenic media and viability/cytotoxicity assays were performed at 7 days.
  • LIVE/DEAD dead cells are labeled with EthD-1 and live cells with Calcein AM.
  • Calcein AM live cells with Calcein AM.
  • COPH cultures were incubated with 70% methanol for 30 minutes. Cultures of COPH without any treatment were used as a positive control.
  • the culture medium was removed, then they were washed with PBS and finally the labeling solution was added. After a 30 minute incubation at room temperature, they were observed under fluorescence microscopy.
  • the material is synthesized from a 2% by weight chitosan solution in 0.5M acetic acid to which GPTMS is added in a 2:1 GPTMS/chitosan molar ratio and a solution of hydrolyzed TEOS under the catalytic effect of ultrasonic high power with 0.1 M hydrochloric acid. Subsequently, both solutions are mixed until obtaining 4% by weight of chitosan with respect to silica. This mixture is allowed to stir for 30 minutes and then it is poured into cylindrical plastic cans and left in an oven for 10 days at 50°C where they will gel. After this time, the samples are introduced into ethanol. Then drying takes place. In this case, it is dried with CO2 under supercritical conditions. In this way, an airgel with 4% chitosan with respect to silica and a GPTMS: chitosan 2:1 molar ratio is obtained.
  • This material is hand-ground to a powder and mixed with the adhesive at an airgel:adhesive weight ratio of 0.25:1. Once a homogeneous mixture is obtained, it is applied to the surface of a titanium sample and allowed to dry for 24 hours. Subsequently, it is introduced into SBF and it is observed that it grows after 7 days immersed, HA appears on its surface, as observed by microscopy. scanning electron (see Figure 1 j) k) ), demonstrating that the A0.25R material is bioactive.
  • cell cultures are performed with COPH in the presence of the different biomaterials.
  • COPH were cultured in osteogenic media and viability/cytotoxicity assays were performed at 7 days.
  • this assay called LIVE/DEAD, dead cells are labeled with EthD-1 and live cells with Calcein AM.
  • EthD-1 live cells with Calcein AM.
  • Calcein AM Calcein AM
  • the culture medium was removed, then they were washed with PBS and finally the labeling solution was added. After a 30 minute incubation at room temperature, they were observed under fluorescence microscopy.
  • the other materials have a similar cell compatibility to the COPH in a state of normal growth (positive control), and therefore, in these tests we can rule out that these materials have any effect cytotoxic in human osteoblastic cells, as we observed in the negative control (70% Methanol). Mode in which the invention is capable of industrial application

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Materials For Medical Uses (AREA)
  • Adhesives Or Adhesive Processes (AREA)

Abstract

Le revêtement hybride adhésif/sol-gel est un matériau composite ayant des caractéristiques biocompatibles et ostéo-conductrices depuis les premières 24 heures de son application sur des surfaces implantables ou comme remplissage osseux indépendant, ce dernier se comportant comme un matériau qui se solidifie en moins de 3 heures et, du fait qu'il présente des mésopores sur tout son volume, accepte l'infiltration de sang du patient qui subit une intervention chirurgicale.
PCT/ES2022/070560 2021-09-09 2022-09-05 Revêtement hybride à base d'un mélange de matériau composite adhésif, destiné à être utilisé sur des surfaces d'éléments implantables WO2023037026A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES202130841A ES2935742B2 (es) 2021-09-09 2021-09-09 Recubrimiento hibrido basado en una mezcla de material compuesto adhesivo, para aplicacion en superficies de elementos implantables
ESP202130841 2021-09-09

Publications (1)

Publication Number Publication Date
WO2023037026A1 true WO2023037026A1 (fr) 2023-03-16

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PCT/ES2022/070560 WO2023037026A1 (fr) 2021-09-09 2022-09-05 Revêtement hybride à base d'un mélange de matériau composite adhésif, destiné à être utilisé sur des surfaces d'éléments implantables

Country Status (2)

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ES (1) ES2935742B2 (fr)
WO (1) WO2023037026A1 (fr)

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
GUZEL KAYA GULCIHAN, YILMAZ ELIF, DEVECI HUSEYIN: "Sustainable nanocomposites of epoxy and silica xerogel synthesized from corn stalk ash: Enhanced thermal and acoustic insulation performance", COMPOSITES PART B, ELSEVIER, AMSTERDAM, NL, vol. 150, 1 October 2018 (2018-10-01), AMSTERDAM, NL, pages 1 - 6, XP093047398, ISSN: 1359-8368, DOI: 10.1016/j.compositesb.2018.05.039 *
HYUNG MIN KIM, KIM HYUN SU, KIM SEONG YUN, YOUN JAE RYOUN: "Silica aerogel/epoxy composites with preserved aerogel pores and low thermal conductivity", E-POLYMERS, WALTER DE GRUYTER GMBH, DE, vol. 15, no. 2, 14 February 2015 (2015-02-14), DE , XP055434495, ISSN: 2197-4586, DOI: 10.1515/epoly-2014-0165 *
JUN, S.H. ; LEE, E.J. ; YOOK, S.W. ; KIM, H.E. ; KIM, H.W. ; KOH, Y.H.: "A bioactive coating of a silica xerogel/chitosan hybrid on titanium by a room temperature solgel process", ACTA BIOMATERIALIA, ELSEVIER, AMSTERDAM, NL, vol. 6, no. 1, 1 January 2010 (2010-01-01), AMSTERDAM, NL, pages 302 - 307, XP026781991, ISSN: 1742-7061, DOI: 10.1016/j.actbio.2009.06.024 *
PALLA-RUBIO B., ARAÚJO-GOMES N., FERNÁNDEZ-GUTIÉRREZ M., ROJO L., SUAY J., GURRUCHAGA M., GOÑI I.: "Synthesis and characterization of silica-chitosan hybrid materials as antibacterial coatings for titanium implants", CARBOHYDRATE POLYMERS, APPLIED SCIENCE PUBLISHERS , LTD BARKING, GB, vol. 203, 1 January 2019 (2019-01-01), GB , pages 331 - 341, XP093047402, ISSN: 0144-8617, DOI: 10.1016/j.carbpol.2018.09.064 *
REYES-PECES MARÍA V., PÉREZ-MORENO A., DE-LOS-SANTOS DESEADA MARÍA, MESA-DÍAZ MARÍA DEL MAR, PINAGLIA-TOBARUELA GONZALO, VILCHES-P: "Chitosan-GPTMS-Silica Hybrid Mesoporous Aerogels for Bone Tissue Engineering", POLYMERS, MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL (M DP I) AG., CH, vol. 12, no. 11, 1 November 2020 (2020-11-01), CH , pages 2723 - 24, XP093047393, ISSN: 2073-4360, DOI: 10.3390/polym12112723 *

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ES2935742A1 (es) 2023-03-09

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