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WO2016008501A1 - Procédé et dispositif pour charger une ossature poreuse - Google Patents

Procédé et dispositif pour charger une ossature poreuse Download PDF

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Publication number
WO2016008501A1
WO2016008501A1 PCT/EP2014/001935 EP2014001935W WO2016008501A1 WO 2016008501 A1 WO2016008501 A1 WO 2016008501A1 EP 2014001935 W EP2014001935 W EP 2014001935W WO 2016008501 A1 WO2016008501 A1 WO 2016008501A1
Authority
WO
WIPO (PCT)
Prior art keywords
boundary surface
fluid
dimensional body
framework structure
porous framework
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2014/001935
Other languages
English (en)
Inventor
Michael SEIDENSTÜCKER
Hermann Mayr
Anke BERNSTEIN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Albert Ludwigs Universitaet Freiburg
Original Assignee
Albert Ludwigs Universitaet Freiburg
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Albert Ludwigs Universitaet Freiburg filed Critical Albert Ludwigs Universitaet Freiburg
Priority to PCT/EP2014/001935 priority Critical patent/WO2016008501A1/fr
Publication of WO2016008501A1 publication Critical patent/WO2016008501A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • 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
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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 invention relates to a method and a device for loading a porous framework structure including a bicontinuous morphology in at least partial areas or having non- interconnected side-by-side pores with a fluid containing at least one bioactive component.
  • Porous framework structures which consists of biodegradable materials
  • the volume of the pores allows the inclusion of a medium containing bioactive components, like antibiotics and/or growth factors which can be delivered after implantation to a locally defined intrakorporal region of tissue.
  • the porous framework structure loaded with at least one bioactive component serves as a matrix-like reservoir which exerts it's
  • the loading is very strong depending on the framework structure material as well on the material which is loaded into the porous framework structure.
  • the dynamic and temporal drug release from the matrix of the porous framework structure plays a very important role both in selecting materials and substances involved as well in regards of the loading technique. Concerning the dynamic and temporal drug release it is desired to reach release durations in periods of days, weeks or month.
  • hydrogel as a carrier substance for the at least one bioactive component is more appropriate as an aqueous solution for loading purpose of the porous framework structure, since the hydrogel have a much higher viscosity compared to the aqueous solutions. Due to the much higher viscosity of hydrogels loading techniques like dip and drip loading or adhesive loading procedure are not applicable.
  • the before mentioned article discloses a vacuum method, wherein the porous framework structure lying in the hydrogel is subjected to a vacuum by which the hydrogel enters the porous framework structure partially.
  • the known vacuum method does not lead to a complete filling of the whole pore volume, since the encapsulated air inside the porous framework structure escapes only partially, especially air contained near the core of the porous framework structure is subjected to an increase of volume only. As soon as normal pressure conditions are reached back the core area of the porous framework structure remains filled with air.
  • a fluid as the carrier of the at least one bioactive component which has the property that delivery of the bioactive component into the tissue environment after implantation occurs with a decelerated kinetics so that the time period in which drug delivery takes place can be extended up to several weeks or months starting with the event of implantation of the loaded porous framework structure.
  • a device for a loading a three dimensional body made of a porous framework structure is disclosed inventively in the independent claim 14.
  • the invention can be modified advantageously by the features disclosed in the sub claims as well in the following description especially referring to preferred embodiments.
  • the method for loading a porous framework structure including a bicontinuous morphology in at least partial areas or having non interconnected side-by-side pores with a fluid containing at least one bioactive component by using a pressure driven force for penetrating that fluid into that porous framework structure comprising the following steps inventively:
  • a three-dimensional body is prepared or provided consisting at least partially of said porous framework structure having along one spatial direction two opposing frontal boundary surfaces, a so called first and second frontal boundary surface, being a part from each other and both of which adjoin at least one lateral boundary surface encircling said three-dimensional body.
  • discontinuous morphology describes a porous framework structure in which each pores are interconnected with each other.
  • non-interconnected side-by-side pores expresses an alternative structure design of pores which are formed in the form of non-interconnected and largely parallel to each other extending channels being directed along the before mentioned one spatial direction.
  • the at least one lateral boundary surface of the three-dimensional body is sealed air tightly preferably by encapsulating said three-dimensional body with a silicon-encasement that is releasable fitted to the at least one lateral boundary surface of the three-dimensional body
  • the three-dimensional body is on both sides, i.e. on the first and second frontal boundary surface, freely accessible.
  • a reservoir of said fluid containing the at least one bioactive component is connected to the first frontal boundary surface of the three-dimensional body so that the first frontal boundary surface adjoins air tightly the before mentioned fluid.
  • a pressure different between the first frontal boundary surface adjoining air tightly to the reservoir and the second frontal boundary surface is applied such that the fluid penetrates through the porous framework structure along the spatial direction by pressure driven force only until the fluid exists over the entire second frontal boundary surface of the three-dimensional body.
  • the step of vacuum pressurized fluid penetration through the porous framework structure takes place under room temperature conditions, i.e. at
  • the first and second frontal boundary surfaces of the three-dimensional body should be of same size and shape preferably, in which the first and second frontal boundary surface overlap each other completely in projection of the spatial direction.
  • the fluid exists over the entire second boundary surface evidence is given that the whole pore volume is filled with the fluid, because it can be excluded that portions of the fluid can exist the three dimensional body elsewhere, for example at the at least one lateral boundary surface.
  • a three-dimensional body provided a second frontal boundary surface which is smaller or greater than the first frontal boundary surface for loading with the fluid inventively in which the second frontal boundary surface overlaps with the first frontal boundary surface completely or at least partially in projection of the spatial direction.
  • the three-dimensional body preferably has the shape of a wedge, a cube, a prism or a truncated cone but especially preferably in the shape of a straight cylinder. All the before mentioned three-dimensional geometries provide two frontal boundary surfaces facing each other along the one spatial direction. In case of a straight cylinder the first and second frontal boundary surfaces are of circular shape, in case of a wedge the first and second boundary surfaces are of triangle shape, in case of a cube the first and second frontal boundary surfaces are of square shape to name a view.
  • the porous framework structure is made of a biodegradable ceramic material preferably and contains pores having mean pore diameter ranging between 1 ⁇ to 10 ⁇ , preferably 2 ⁇ to 5 ⁇ .
  • the porous framework structure provides a porosity ranging between 30% and 50% preferably 40%.
  • the first and second frontal boundary surface of the three- dimensional body are separates along the spatial direction by a distance ranging between 10 mm and 100 mm preferably between 20 and 50 mm.
  • a preferred biodegradable ceramic material is a ⁇ - tricalciumphosphate ( ⁇ -TCP) which is known for example from an article of Bernstein, A., et al., "Histological and histomorphometric investigations on bone integration of rapidly resorbable calcium phosphate ceramics", J Biomed Mater Res B Appl
  • a hydrogel which is an alginate sole in which the at least one bioactive component is an antibiotics and/or growth factors contained therein.
  • the alginate sole bases on alginate mixed in distilled water.
  • the dynamical viscosity ⁇ of the hydrogel ranges between 1 ,5 mPa-s and 10 5 mPa s, preferably between 10 2 mPa-s and 2x10 4 mPa-s.
  • the pressure difference which is applied between the first and second frontal boundary surface, for sucking the fluid respectively hydrogel through the porous framework structure of the three-dimensional body measures between 800 mbar and 1500 mbar, preferably 1000 mbar ⁇ 100 mbar.
  • a vacuum source is connected to the second frontal boundary surface preferably, so that an underpressure of about 50 mbar can be produced at the second frontal boundary surface, whereas in the fluid reservoir which is connected to the first frontal boundary surface of the three-dimensional body normal atmospheric pressure prevails.
  • the inventive method allows the production of an inventive three-dimensional body consisting at least partially of a porous framework structure which is of biodegradable material including said bicontinuous morphology in at least partial areas or having non-interconnected side-by-side pores in which the whole enclosed pore volume is filled completely with a fluid containing at least one bioactive component which has a heat resistance of less than 100°C preferably less than 70°C.
  • an inventively designed device is used which provides a casing into which said three- dimensional body is insertable such that a contact wall of said casing or a contact wall of an insert into the casing encloses the at least one lateral boundary surface of said three-dimensional body air tightly but loose.
  • the casing provides along one spatial direction two opposing openings, a first and a second opening, in which the first opening is connected air tightly with a reservoir containing said fluid and said second opening is connected air tightly with a vacuum source.
  • the contact wall of the casing or of the insert is made of flexible material, preferably made of silicon, which enables a smooth and air tight contact to the at least one lateral boundary surface of the three-dimensional body.
  • a preferred shape of the three-dimensional body is of straight cylindrical form which cylinder surface corresponds to the lateral boundary surface which is enclosed air-tightly by the contact wall of the before described casing or insert.
  • the device for loading the three-dimensional body having the shape of a straight cylinder provides a hose which inner hose diameter corresponds to the diameter of the cylindrical three-dimensional body which is inserted into the hose so that the cylindrical surface matches the inner hose surface in a flush manner.
  • the reservoir filled with the fluid respectively hydrogel and at the other hose end a vacuum source are connected air tightly so that a directed pressure difference between both hose ends can be applied.
  • FIG. 4 illustration of an assembled realized streaming chamber.
  • Figure 1 shows a schematically longitudinal section view of a device for loading a three-dimensional body 1 consisting of a porous frame work structure having a bi- continual morphology, i.e. the pores of the frame work structure are interconnected to each other.
  • the three-dimensional body 1 has the shape of a straight cylinder providing two circular end surfaces, namely a first frontal boundary surface 2 and a second surface boundary surface 3.
  • the two circular end surfaces 2, 3 adjoin a lateral boundary surface 4 which completely adjoin air tightly the inner wall 5 of a casing 6.
  • the first and second frontal boundary surfaces 2, 3 of the three-dimensional body 1 are freely accessible.
  • the casing 6 For loading purposes the complete volume of the pores of the porous frame work structure of the three-dimensional body 1 the casing 6 is connected to a reservoir 7 in which a fluid 8 is stored under ambient atmospheric pressure. Said fluid is an alignate sol hydrogel containing at least one bioactive component. To the opposite end of the casing 6 a vacuum source 9 is connected so that low pressure can be generated at the second frontal boundary surface 4 of the three-dimensional body 1 , so that a pressure difference between the first frontal boundary surface 2 and the second frontal boundary surface 3 can be applied by which the fluid 8 will be sucked through the complete porous framework structure of the three-dimensional body 1.
  • the three-dimensional body 1 advantageously consists of a micro-porous ceramic preferably a beta-tricalcium-phosphat ( ⁇ -TCP) having a total porosity of around 40% interconnected micro pores that having an average pore diameter of 5 microns.
  • the length of the cylindrical shape of the three-dimensional body can range between 10 mm and 100 mm, preferably between 20 mm and 50 mm. In a realized setting the length of the ceramic cylinder measures 26 mm and the cylinder diameter 7 mm.
  • the fluid 8 provides preferably a dynamical viscosity ⁇ greater than said of water, i.e. the dynamical viscosity ⁇ ranges between 1 ,5 and 10 5 , preferably between 10 2 and 2 x 10 4 .
  • the fluid 8 is a hydrogel, preferable an alginate sole, having self-curing properties.
  • the hydrogel contains an antibiotics and/or growth factors additionally.
  • the porous framework network of the three-dimensional body 1 can have a non-interconnected side-by-side pore structure which means that each of the pores are not-interconnected to each other but provides the nature of channels which completely penetrate the three-dimensional body and empty open at the first and second frontal boundary surface 2, 3.
  • FIGS 2a to f longitudinal cross-sections of three-dimensional bodies are illustrated. In each case it is assumed that the direction of penetration of the fluid through the three-dimensional body 1 is from the right to the left which is indicated by the arrow.
  • Figures 2a and b shows a three-dimensional body of truncated conical shape
  • figures 2c and d illustrates the longitudinal section of a wedge-shaped three- dimensional body
  • figure 2e shows a prismatic three-dimensional body
  • figure 2f a cubic shaped three-dimensional body.
  • the list of illustrated examples is not limited so that other geometries are conceivable.
  • Figure 3 shows a realized device in a dissembled arrangement for loading a three- dimensional body (not shown), whereas figure 4 shows the device in an assembled state.
  • Figure 3 shows the device consisting of at least four separate components 10, 11 , 12, 13 which can be assembled to a so called fluid type streaming chamber.
  • the components 10 and 11 each provides a channel like recess 14 into which the three-dimensional body (not shown) can be inserted.
  • the recesses 14 are coated with a flexible material, preferably made of silicon, which join the lateral boundary surface of the three-dimensional body, not shown in figure 3, air tightly.
  • the components 10 and 11 can be fitted together by screws which are insertable into the holes 15 shown in figure 3.
  • components 12 and 13 each provides a connecting flank in which an O-ring 16 is integrated for a fluid and air tight connection with the flow chamber which results from the mated recesses 14 inside of the assembled components 10, 11.
  • Component 12 further provides a connection pipe 17 for connection to the reservoir not shown.
  • the component 13 also provides a connection pipe 18 for connection to the vacuum source 9, also not shown.
  • Figure 4 shows a partially sliced device for loading a three-dimensional body 1 containing the components shown in figure 3 in an assembled status. Further in figure 4 the three-dimensional body 1 which is of straight cylindrical shape is inserted inside the flow chamber enclosed by the mated recesses 14 inside the components 10 and 1 1.
  • a low vacuum of about 50 mbar at the left hand side of the flow chamber, i.e. by connecting a vacuum source to the connection pipe 18 the fluid which is a hydrogel, preferably an alginate sol, enters the flow chamber from the right to the left and penetrates the porous framework network of the ⁇ -TCP-three- dimensional body 1 .
  • the cylindrical shaped three-dimensional body 1 is radially surrounded by a silicon seal 19 which ensures that the loading can take place only through the end surfaces of the micro-porous ceramic cylinder.
  • the silicon seal 19 further ensures that the ceramic body 1 does not move during the loading process.
  • the components 10 and 11 can provide a recess into which a modular insert can be inserted which is individually adapted to the size and shape of the three-dimensional body to be loaded with the fluid.
  • the inner walls of the insert which contacts the three- dimensional body provides a silicon wall to ensure a gas/fluid tight enclosure of the lateral boundary layer of the respective three-dimensional body.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention porte sur un procédé et sur un dispositif pour charger une structure d'ossature poreuse comprenant une morphologie bicontinue dans au moins des zones partielles, ou ayant des pores côte à côte non interconnectés avec un fluide contenant au moins un composant bioactif, à l'aide d'une force provoquée par une pression pour faire pénétrer ledit fluide dans ladite structure d'ossature poreuse, lequel procédé comprend les étapes suivantes : – la préparation ou la délivrance d'un corps en trois dimensions constitué au moins partiellement par ladite structure d'ossature poreuse, ayant, le long d'une direction spatiale, deux surfaces de limite frontales opposées, une première et une seconde surfaces de limite frontales, qui sont mutuellement espacées l'une de l'autre et qui sont toutes deux jointives à au moins une surface de limite latérale encerclant ledit corps en trois dimensions, scellant hermétiquement vis-à-vis de l'air ladite au moins une surface de limite latérale, – la réunion de façon hermétique vis-à-vis de l'air d'un réservoir dudit fluide au niveau de ladite première surface de limite frontale, et – l'application d'une différence de pression entre la première surface de limite frontale et la seconde surface de limite frontale, de telle sorte que le fluide pénètre à travers la structure d'ossature poreuse le long de la direction spatiale du fait d'une force provoquée par une pression jusqu'à ce que le fluide sorte sur la totalité de la seconde surface de limite frontale.
PCT/EP2014/001935 2014-07-15 2014-07-15 Procédé et dispositif pour charger une ossature poreuse Ceased WO2016008501A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/EP2014/001935 WO2016008501A1 (fr) 2014-07-15 2014-07-15 Procédé et dispositif pour charger une ossature poreuse

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2014/001935 WO2016008501A1 (fr) 2014-07-15 2014-07-15 Procédé et dispositif pour charger une ossature poreuse

Publications (1)

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WO2016008501A1 true WO2016008501A1 (fr) 2016-01-21

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5769897A (en) * 1991-12-13 1998-06-23 Haerle; Anton Synthetic bone
US20060135938A1 (en) * 2004-12-17 2006-06-22 Mckay William F Device and method for the vacuum infusion of a porous medical implant
US20100185299A1 (en) * 2006-11-27 2010-07-22 Berthold Nies Bone Implant, and Set for the Production of Bone Implants

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5769897A (en) * 1991-12-13 1998-06-23 Haerle; Anton Synthetic bone
US20060135938A1 (en) * 2004-12-17 2006-06-22 Mckay William F Device and method for the vacuum infusion of a porous medical implant
US20100185299A1 (en) * 2006-11-27 2010-07-22 Berthold Nies Bone Implant, and Set for the Production of Bone Implants

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
STEPHEN J. FLORCZYK ET AL: "Enhanced bone tissue formation by alginate gel-assisted cell seeding in porous ceramic scaffolds and sustained release of growth factor", JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, vol. 100A, no. 12, 6 July 2012 (2012-07-06), pages 3408 - 3415, XP055176143, ISSN: 1549-3296, DOI: 10.1002/jbm.a.34288 *

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