ITVI20130277A1 - METHOD FOR THE PERFUSION OF POROUS BIOMATERIALS WITH BIOLOGICAL LIQUIDS - Google Patents

Description

DESCRIPTION

Field of application

[0001] The present invention is generally applicable to the technical field of medical devices and particularly relates to a method for the perfusion of porous biomaterials with biological liquids.

State of the art

[0002] Methods are known for the perfusion of a biomaterial with a biological liquid particularly used in the medical sector in the context of therapeutic treatments.

[0003] In particular, such methods promote the perfusion of biomaterials intended to be grafted into the human body such as bone, cartilage, osteocartilaginous, tendon, ligament or meniscal substitutes and other connective tissues in general.

[0004] Peritisis biological materials are used in the surgical treatment of alterations and / or defects in the musculoskeletal tissue, caused for example by episodes of traumatic origin, neoplastic or degenerative pathologies, delays in consolidation, neonatal deformities or the like.

[0005] Furthermore, the perfusion liquid can be of various types and can include, for example, aqueous solutions, bone marrow or its derivatives, solutions containing antibiotics, peripheral blood, blood components or the like.

[0006] The perfusion methods allow to extract the air present in the porosities of the biomaterial by filling them with the biological liquid so as to increase the contact surface and improve the interaction between liquid and biomaterial.

[0007] The perfusion process must be carried out in a closed environment and for this reason devices have been developed for the perfusion of a biomaterial capable of maintaining the tissue and the fluid in sterile conditions.

[0008] From WO2009125282 a method for the perfusion of biomaterial is known which provides for a perfusion chamber intended to house the material to be perfused connected to a transfer chamber in which the biological liquid is contained.

[0009] The perfusion chamber and the transfer chamber are sealed coupled and isolated from the external environment and the latter consists of a syringe with an outlet for the liquid placed in fluid communication with the perfusion chamber.

[0010] A drawback of this method is represented by the difficulty of discharging the air contained in the biomaterial to the outside due to the complete isolation of the perfusion and transfer chambers.

[0011] In fact, while using the device, the operator must vertically position the perfusion and transfer chambers to allow the air extracted from the biomaterial to expand in the terminal portion of the transfer chamber left free by the liquid.

[0012] The presence of air inside the transfer chamber during the repetition of perfusion cycles also decreases the efficiency of the device and increases the risk of its reintroduction into the biomaterial to be perfused.

[0013] To overcome these drawbacks, methods are known for the perfusion of biomaterial with biological liquid which allow the air extracted from the material to be discharged outside during the perfusion cycle.

[0014] In US2008 / 0214998 a method is described for the perfusion of biomaterial with a biological liquid by means of a device that uses a single perfusion chamber capable of containing both the material to be treated and the biological liquid.

[0015] This device includes a piston housed in the chamber and can be operated by the user to decrease and / or increase the pressure in the chamber itself in order to facilitate the exit of air from the biological tissue and the entry of the liquid into the porosity of the same.

[0016] A hydrophobic seal is also provided associated with one end of the piston and designed to retain the liquid inside the perfusion chamber and to allow the air to escape through passages made in the piston itself.

[0017] A drawback of this solution is represented by the fact that between the hydrophobic seal and the end of the piston there is no high fluidic seal with the consequent risk of small quantities of liquid leaking out during use of the device.

[0018] A further drawback of this solution is represented by the fact that the leakage of the perfusion liquid through the piston often requires to be compensated with predetermined quantities of the liquid itself.

[0019] This compensation can be particularly difficult since many therapeutic treatments require perfusing the biomaterial with extremely small quantities of organic fluids taken from live patients through particularly complex and dangerous operations.

[0020] A further drawback of this solution is represented by the fact that the compensation of the fluid leaking from the device lengthens the total times of the perfusion process.

[0021] Not the least drawback of this solution is represented by the fact that the fluid and the biomaterial can be significantly contaminated due to the reduced fluidic seal present between the gasket and the piston.

Presentation of the invention

[0022] The purpose of the present invention is to overcome the drawbacks encountered above, by providing a method for the perfusion of porous biomaterials with biological liquids which has characteristics of high efficiency and relative cheapness.

[0023] A particular purpose of the present invention is to provide a method for the perfusion of porous biomaterials with biological liquids that allows to optimize the extraction of air from the porous biomaterial, and consequently saturate the biomaterial with liquid.

[0024] Another object of the present invention is to provide a method of perfusion of porous biomaterials with biological liquids which allows to maintain a high isolation of the liquid from the external environment so as to significantly reduce its losses during its use .

[0025] A further object of the present invention is to provide a method for the perfusion of porous biomaterials with biological liquids which allows the perfusion of the tissue with reduced quantities of biological liquid.

[0026] Another object of the present invention is to provide a method of perfusion of porous biomaterials with biological liquids which allows to reduce the perfusion times.

[0027] A further object of the present invention is to provide a method of perfusion of porous biomaterials with biological liquids which maintains the biomaterial and the liquid in aseptic conditions.

[0028] These objects, as well as others which will appear more clearly later, are achieved by a method for perfusion of porous biomaterials with biological liquids in accordance with claim 1.

[0029] Thanks to this method, it is possible to optimize the extraction of the ana from the biomaterial, while maintaining a high isolation of the liquid from the external environment in order to significantly reduce the losses of the same during its use and reducing the amount of biological liquid required for perfusion.

[0030] Advantageous embodiments of the invention are obtained in accordance with the dependent claims.

Brief description of the drawings

[0031] Further characteristics and advantages of the invention will become more evident in the light of the detailed description of a preferred but not exclusive embodiment of a method for the perfusion of a porous biomaterial with biological liquids or the like, illustrated by way of non-limiting example with the help of the joined drawing tables in which:

FIG. 1 is a block diagram of the perfusion method according to the invention;

FIG. 2 is an exploded perspective view of a perfusion device used to carry out the perfusion method of Fig.1;

FIG. 3 is a sectional side view of the device of Fig. 2.

Detailed description of a preferred embodiment [0032] With reference to the block diagram of FIG. 1, a method is described for the perfusion of porous biomaterials with biological liquids that allows to optimize the extraction of air from the porosity of the biomaterial while ensuring a reduction in the loss of biological liquid necessary for perfusion.

[0033] The biomaterial can be of various shapes and nature to make an implantable graft in the human body as a substitute for bone, cartilage, osteocartilage, tendon, ligament, meniscal or connective tissue in general.

[0034] The perfusion liquids normally used may be of biological origin, such as for example peripheral blood and its derivatives, bone marrow, marrow concentrate, cellular concentrates from adipose tissue, physiological solutions containing antibiotics or other similar drugs.

[0035] The method according to the invention can be carried out by means of a device 1 for the perfusion of a porous biomaterial P with biological liquids L, illustrated in FIG. 2.

[0036] The method essentially comprises a step a) of preparing a tubular body 2 having an internal cavity 3 defining a perfusion chamber 4.

[0037] Preferably, at the distal end 5 of the tubular body 2 a closing cover 6 can be arranged.

[0038] After removing the cover 6 and allowing access to the chamber 4 of the tubular body 2, a step b) of positioning a porous biomaterial P inside the chamber 4 will follow.

[0039] Eventually, the volume of the perfusion chamber 4 can be varied and adapted to the volume of the porous biomaterial P to be perfused by positioning a transverse septum 7 that can be moved longitudinally inside the cavity 3.

[0040] In this way it will be possible to optimize the volume of the chamber 4 and to minimize the volume and quantity of liquid L necessary for its filling.

[0041] Once the porous biomaterial P has been introduced into the perfusion chamber 4, the lid 6 can be reassembled on the distal end 5 of the tubular body 2 and it is possible to proceed with step c) of filling the chamber 4 with the perfusion liquid L.

[0042] For this purpose, a fitting 8 can be provided on the lid 6 for the fluidic connection, by means of a small tube, to an external tank containing the biological liquid L, not shown in the figures.

[0043] The chamber 4 containing the biomaterial P to be perfused can be filled by gravity. Alternatively, the perfusion chamber 4 can be filled through the use of suitable pumping means.

[0044] The step c) of filling the perfusion chamber 4 with the biological liquid L can be carried out in conditions of complete sterility, in order to maintain stable the isolation of the liquid L from the external environment.

[0045] Following the filling of the chamber 4 and the removal of the external tube, the fitting 8 can be closed again by means of a Luer-Lock cap 9 of a per se known type, in order to avoid the leakage of the liquid L from the chamber 4 towards the 'external.

[0046] Subsequently, there will be a step d) of insertion, inside the cavity 3 of the tubular body 2, of an axially movable piston 10 with an axial through hole 11.

[0047] Conveniently, the piston 10 will be chosen with an external diameter just lower than the internal diameter of the tubular body 2 and will be provided with O-ring seals 12 towards its distal end 13 so as to slide tightly into the internal cavity 3 .

[0048] The method also provides for a step e) of housing a rigid stem 14 inside the axial hole 11.

[0049] The stem 14 will be positioned inside the axial hole 11 with predetermined clearance, so as to define an air collection gap 15 in fluidic connection towards the distal end 13 with the perfusion chamber 4 and towards the proximal end 16 of the piston 10 with the outside.

[0050] Furthermore, the stem 14 inside the axial hole 11 may have control means 17 of the fluidic communication with the outside.

[0051] The control means 17 will promote the discharge to the outside of the air extracted during the perfusion process.

[0052] The method also includes a step f) of positioning the rod 14 with respect to the piston 10 in an advanced locking position to prevent the passage of air from the interspace 15 to the outside and facilitate their simultaneous sliding.

[0053] The removable locking of the rod 14 with respect to the piston 10 can be achieved by means of separable constraint means 18 positioned near the proximal end 16 of the piston 10 and accessible by a user.

[0054] Preferably, the locking step f) can be carried out by helical coupling between a thread obtained on the proximal portion 16 of the internal surface 19 of the axial hole 11 of the piston 10 and a counter-thread obtained on the external surface 20 of the proximal portion 21 of the stem 14.

[0055] Following the locking step f), the method includes a step g) of alternating movement of the rod-piston assembly in a locked condition to create 4 repeated depressions and compressions inside the perfusion chamber.

[0056] The alternating movement of the assembly will allow the pressure of the biological liquid L inside the perfusion chamber 4 and its effective penetration into the porosities of the biomaterial P.

[0057] Furthermore, following the extraction of the air from the porous biomaterial P, the repetition of the alternate movement of the rod-piston assembly will favor the separation of the air bubbles from the liquid L and their conveyance inside the cavity collection 15.

[0058] Advantageously, this solution will allow the air to be collected in the interspace 15, avoiding the communication of the internal portions of the tubular body 2 with the outside.

[0059] Preferably, the repetition of the alternating movement of the assembly can be performed a number of times sufficient to obtain a complete removal of the air from the porosities of the biomaterial P and from the biological liquid L and consequently saturate the biomaterial P with liquid.

[0060] Furthermore, during the repetition of the alternating compression and depression phases, the user will exert an energetic tapping on the tubular body 2 with the palm of the hand to favor the separation of the air bubbles still present in the porosities of the biomaterial P due to the effect cavitation.

[0061] The method provides, at the end of the perfusion process, a step h) for positioning the stem 14 in a retracted unlocking position with respect to the piston 10 to allow communication of the interspace 15 with the outside and discharge the air contained therein.

[0062] The movement of the stem 14 can be carried out by means of the provision and longitudinal movement of a maneuvering ring 22 constrained to the proximal end 21 of the stem 14. Advantageously, the ring nut 22 of the stem 14 can define the control means 17 suitable for promoting selectively the communication of the collection interspace 15 with the outside.

[0063] Conveniently, the communication between the collection interspace 15 and the outside can be enabled by a passage 23 arranged at the proximal end 21 of the piston 10, where a seat 24 for the control ring 22 can also be suitably arranged .

[0064] Advantageously, the closing and opening of the passage 23 can be carried out by advancing the stem 14 and the complete insertion of the ring nut 22 in its seat 24 and respectively by the retraction of the stem 14 and the removal of the ring nut 22 from seat 24 to allow the passage and discharge to the outside of the air contained in the interspace 15.

[0065] The controlled retraction of the stem 14 can be repeatedly performed by the user until the air contained in the collection gap 15 has been completely expelled into the external environment.

[0066] The method also comprises a step i) of repeating steps e) to g) for a number of times sufficient to expel almost completely the air from the pores of the biomaterial P and its elimination to the outside .

[0067] Subsequently to the repetition step i) there are provided a step j) for draining the liquid L from the perfusion chamber 4 and a step k) for opening the perfusion chamber 4 and removing the completely treated porous biomaterial P.

[0068] Preferably, the method may include, at the inlet and outlet of the interspace 15, the execution of the respective filtering phases I) designed to separate the air extracted from the porous biomaterial P from the biological liquid L.

[0069] The filtering steps I) can be carried out by means of a plurality of longitudinal micrometric grooves 25 which define microchannels formed in correspondence with the end areas of the axial hole 11 and one or more annular gaskets 26 mounted on the corresponding areas of the stem 14.

[0070] In particular, these filtering steps I) can be carried out through the interaction between the grooves 25 and the annular gaskets 26 in order to create micrometric lights designed to prevent the leakage of liquids and allow the selective passage of air.

[0071] The annular gaskets 26 will be able to interact directly with the internal wall of the axial hole 11 to ensure the hermetic seal against the leakage of the biological liquid L towards the interspace 15 and the simultaneous formation of micrometric ports for the air extracted from the porous material P.

[0072] The method of perfusion of a porous biomaterial with biological liquids according to the invention is susceptible of modifications and variations falling within the inventive concept expressed in the attached claims.

[0073] All the procedures may be replaced by other technically equivalent methods and the processes may be different according to requirements, without departing from the scope of the invention.

[0074] Although the method according to the invention has been described with particular reference to the attached figures, the reference numbers used in the description and in the claims are used to improve the intelligence of the invention and do not constitute any limitation to the scope of protection claimed .

Industrial applicability

[0075] The present invention finds industrial application in the technical sector of medical devices and in particular in the production of porous biomaterials perfused with biological liquids.

Claims (10)

R I V E N D I C A Z I O N I 1. A method for the perfusion of porous biomaterials with biological liquids, comprising the following steps: a) provision of a tubular body (2) with an internal cavity (3) defining a perfusion chamber (4); b) positioning inside said chamber (4) of a porous biomaterial (P); c) filling said chamber (4) with a perfusion liquid (L); d) insertion inside said cavity (3) of an axially movable piston (10) having an axial through hole (11); e) housing inside said hole (11) of a stem (14) having a predetermined clearance to define an air gap (15) communicating with said chamber (4) and with the outside and having means control (17) of communication with the outside; f) positioning of said rod (14) with respect to said piston (10) in an advanced locking position to prevent the passage of air from the interspace (15) to the outside; g) alternating movement of the rod-piston assembly in a blocked condition to create repeated depressions and compressions inside said chamber (4) and promote the separation of the air bubbles from the liquid and their conveyance towards said collection interspace (15 ); h) positioning of said rod (14) with respect to said piston (10) in a rearward unlocking position to allow the communication of said cavity (15) with the outside and discharge the air collected there; i) repetition of steps e) to g) for a number of times sufficient to almost completely expel the air from the pores of the porous material (P) and fill them with the perfusion liquid (L); j) drainage of the liquid (L) from the perfusion chamber (4); k) opening of the perfusion chamber (4) and removal of the porous material (P) completely treated. 2. Method according to claim 1, in which at the inlet and outlet of said interspace (15) filtering steps I) are provided by means of a plurality of longitudinal micrometric grooves (25) formed in correspondence with the end areas of said hole axial (11) and one or more annular gaskets (26) on the corresponding areas of said stem (14). 3. Method according to claim 2, in which said filtering steps I) take place through interaction between said grooves (25) and said annular gaskets (26) so as to create micrometric openings suitable for preventing the leakage of liquids and allowing the selective passage of the air. 4. Method as per claim 1, in which the volume of said perfusion chamber (4) is adapted to the volume of the biomaterial to be perfused (P) by means of a transverse septum (7) that can be moved longitudinally in said cavity (3) so as to minimize the volume and quantity of liquid (L) intended to fill it. 5. Method according to claim 1, wherein said rod (14) is locked with respect to said piston (10) by means of separable constraint means (18) positioned in proximity to the proximal end (16) of the piston (10) and accessible from part of a user. 6. Method according to claim 1, in which the retraction and the advancement of said stem (14) inside the axial hole (11) are carried out by means of the provision of an operating ring nut (22) constrained to the proximal end ( 21) of said stem (14) and its longitudinal displacement by the user. 7. Method according to claim 6, wherein near the proximal end (16) of said piston (10) there is a passage (23) between said interspace (15) and the outside and a seat (24) for said ring nut (22) placed at the outlet of said passage (23), the closure of said passage (23) being carried out by advancing said stem (14), complete insertion of said ring nut (22) in said seat (24) and occlusion of said passage (23). 8. Method according to claim 6, in which the discharge to the outside of the air collected in said interspace (15) is carried out by retracting said stem (14), moving away said ring nut (22) from said seat (24) and opening of said passage (23). 9. Method according to claim 1, in which the positioning of the biomaterial to be perfused (P) inside said chamber (4) is carried out by providing a closure cover (6) of the distal end (5) of said body tubular (2) and removal of the same to make said chamber (4) accessible before inserting the biomaterial (P). 10. Method according to claim 9, wherein the filling of said chamber (4) with the perfusion liquid (L) takes place by providing a fitting (8) in said closing lid (6) and connecting said fitting (8). ) to an external liquid reservoir by means of a tube for filling by gravity or by pumping means.