Patent Publication Number: US-2010114057-A1

Title: System and method for delivery of biologic agents

Description:
FIELD 
     This disclosure relates to medical devices, systems and methods for delivering biologic agents to a patient. 
     BACKGROUND 
     Systems for delivering biologic agents in an operating room setting currently include the biologic agent and a delivery device. A mapping/navigation system, and a monitor for viewing the delivery process may also be used. The biologic agent is typically delivered to the operating room in an appropriate volume and concentration in a closed container, such as an Eppendorf tube. Once in the operating room and when the delivery device is ready to receive this biologic agent, the biologic agent is transferred from the container to a syringe which is in turn connected to the delivery device. The biologic agent is then carefully delivered from the syringe through the delivery device into target tissue. 
     The steps involved in such a process present several areas for improvement. For example, the transfer of the biologic agent from the container to the delivery system involves exposing the agent to the environment, risking contamination. Also, the transfer provides the potential for spilling and loss of the biologic agent, as well as potentially inaccurate amounts being delivered. Further, the number of different materials that the biologic agent contacts may be quite high. For example, the biologic agent contacts the container, such as the Eppendorf tube, the syringe, and the delivery device, allowing for possible compatibility issues and losses due to adhesion and adsorption to the container, syringe and delivery device. 
     Another source of potential concern with current methods for delivering biologic agents is excessive shear stress being placed on the biologic agent as it is delivered through the delivery system. The delivery system typically includes catheters having very small inner diameters; e.g., 29-27 G or about 0.007 inches to 0.009 inches. The inner diameters of the catheters are purposefully kept small to reduce dead space and thus to minimize the amount of deliverable biologic agent lost during the procedure. Exposure to shear stress may greatly reduce the efficacy of the biologic agent delivered, particularly cells. 
     BRIEF SUMMARY 
     This disclosure describes, inter alia, a system for delivering biologic agents that allows for delivery of biologic agents in a container via a catheter to a target tissue of a patient. As disclosed herein, an appropriate or predetermined amount of biologic agent may be transferred into the container in a sterile environment. In the operating room, the container is placed in a catheter having a distal end implanted at a target tissue site of a patient and is moved to the distal end of the catheter, where its contents are released into the target tissue. For purposes of brevity and clarity, containers are described herein in the context of biologic delivery systems. However, it will be understood that the containers may have utility outside of such systems; e.g., for general storage and housing. 
     In an embodiment, a container for housing a therapeutic agent is described. The container includes a body member, a sealing element, and a rupturable membrane. The body member has a proximal end and a distal end and a lumen that extends from the proximal end to the distal end. The sealing element is slidably disposable in the lumen. The sealing element is configured to sealingly engage the body member as the element is slid within the lumen. The rupturable membrane is disposed across the lumen in proximity to the distal end of the body member. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.1  is a schematic view of a partially implanted catheter in the environment of a patient. 
         FIG. 2  is a schematic perspective view of a representative delivery system. 
         FIG. 3  is a schematic side view of a catheter and tube with complementary connector fittings. 
         FIGS. 4A-D  are schematic longitudinal cross sections of representative catheters. 
         FIGS. 5A-B  and  6 A-B are schematic longitudinal cross sections of representative containers. 
         FIGS. 7-11  are schematic longitudinal cross sections of representative delivery systems. 
         FIG. 12-14  are block diagrams of representative components of control and drive systems of representative delivery systems 
         FIG. 15  is a schematic longitudinal cross section of a representative container. 
         FIGS. 16 and 17A  are schematic side views of representative two-part containers. 
         FIG. 17B  is a schematic longitudinal cross section of the container depicted in  FIG. 17A . 
         FIGS. 18-19  are schematic longitudinal cross sections of representative containers. 
         FIG. 20  is a block diagram of a container having two chambers. 
         FIGS. 21-22  are schematic longitudinal cross sections of representative multi-part containers capable of forming two chambers. 
     
    
    
     The drawings are not necessarily to scale. Like numbers used in the figures refer to like components, steps and the like. However, it will be understood that the use of a number to refer to a component in a given figure is not intended to limit the component in another figure labeled with the same number. In addition, the use of different numbers to refer to components is not intended to indicate that the different numbered components cannot be the same or similar. 
     DETAILED DESCRIPTION 
     In the following detailed description, reference is made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration several specific embodiments of devices, systems and methods. It is to be understood that other embodiments are contemplated and may be made without departing from the scope or spirit of the present disclosure. The following detailed description, therefore, is not to be taken in a limiting sense. 
     All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure. 
     As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” encompass embodiments having plural referents, unless the content clearly dictates otherwise. As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise. 
     As used herein, “have”, “having”, “include”, “including”, “comprise”, “comprising” or the like are used in their open ended sense, and generally mean “including, but not limited to”. 
     As used herein, the terms “treat”, “therapy”, and the like mean alleviating, slowing the progression, preventing, attenuating, or curing the treated disease. 
     As used herein, “disease”, “disorder”, “condition” and the like, as they relate to a subject&#39;s health, are used interchangeably and have meanings ascribed to each and all of such terms. 
     The present disclosure describes, inter alia, systems, devices and methods for delivering biologic agents to a target tissue of a patient. A container housing a therapeutic agent may be placed directly into a delivery system and delivered to the target tissue site where the therapeutic agent may be released. The therapeutic agent may be a biologic agent, such as a cell, a virus, a polypeptide, a polynucleotide or the like. Many of such biologic agents are susceptible to complications due to shear stress due to their large size or molecular weight. The therapeutic agent may be formulated in a solution, suspension, dispersion, or the like or may be in solid form. 
     Referring now to  FIG. 1 , a catheter  100  of a representative delivery system is schematically shown in the environment of a patient. The catheter  100  has a proximal end  110  and a distal end  120 . In the depicted embodiment, the proximal end  110  of the catheter  100  exterior to the patient, and the distal end  120  is implanted in the patient at a target tissue location, in this case in the pericardial sac  6  of the heart  8 . Biologic agents that are administered intravenously have a relatively short time for contacting cardiac tissue compared to agents delivered into the pericardium. Of course, in various embodiments, it may be desirable to deliver the agent intramyocardially, intracoronary or into the heart in any other suitable manner. While the catheter  100  in  FIG. 1  is depicted as being implanted for delivery of an agent to the heart  8 , it is contemplated that the delivery systems and methods described herein may be used to deliver agent to any suitable target tissue of a patient, including any suitable subcutaneous tissue, including brain parenchyma, spinal canal, perispinal tissue, cerebrospinal fluid, spleen, pancreas, stomach, intestine, kidney, liver, muscle, and the like. 
     Referring now to  FIGS. 2-3 , a schematic illustration of some representative components of a delivery system  1000  is shown. The depicted delivery system  1000  includes a catheter  100 , a capsule or container  200  for housing a biologic agent, and a bar  300 . The catheter  100  has a proximal end  110  and a distal end  120  and a body member defining a lumen that extends from the proximal end  110  to the distal end  120  of the catheter  100 . The container  200  is configured to house a biologic agent and is insertable into the lumen of the catheter  100  and slidably disposable in the lumen. The bar  300  is also slidably disposable in the lumen of the catheter  100 , as will be described in more detail below. In the embodiment depicted in  FIG. 2 , a pushing member  350  is coupled to the distal end  320  of the bar  300 . The pushing member  350  may be integrally formed with, connected, attached, bonded, or otherwise coupled to the bar  300 . 
     As shown in  FIG. 2 , an opening  130  is formed in the body of the catheter  100 . The opening  130  forms a bore in the catheter  100 . The bore intersects the lumen of the catheter  100  and is substantially perpendicular to the axis of the lumen. The opening  130  is configured to receive the container  200  such that the container  200  may be placed in the opening  130  to gain access to the catheter lumen. A cover (not shown) or other member may sealingly engage the opening  130 . The cover or other member may be removed or opened to insert the container  200  into the opening  130 , and replaced to sealingly engage the opening  130  after the container  200  is inserted in the opening. It will be understood, that when catheter  100  does not include such an opening  130  for receiving the container  200 , the container  200  may be inserted into the catheter lumen via an opening at the proximal end  110  of the catheter, through which the lumen extends. 
     As shown in  FIG. 3 , the proximal end  110  of the catheter  100  may include a connection fitting  140  for sealingly coupling to tube  500  having a complementary connection fitting  510 . The embodiment depicted in  FIG. 3  may be desirable when hydraulics are use to control movement of the bar within the lumen of the catheter  100 . 
     Referring now to  FIG. 4A , a schematic illustration of a cut away view of the catheter  100  shown in  FIG. 2  (along line  4 - 4 ) with bar  300  and container  200  disposed within the lumen  150  is shown. Again, catheter  100  has a proximal end  110  and a distal end  120  and a body member  140  defining a lumen  150  extending from the proximal end  100  to the distal end  120 . The container  200  and bar  300  are slidably disposable in the lumen  150 . In the depicted embodiment, a pushing member  350  is coupled to the bar  300 . The bar  300  and pushing member  350  are positioned in the lumen  150  of the catheter  200  such that the pushing member  350  is capable of engaging the container  200  and pushing the container  200  distally in the lumen  150  when the bar  300  is slid distally in the lumen  150 . 
     Referring now to  FIGS. 4B-D , longitudinal cross sections of representative embodiments of catheters  100  are shown. For purposes of illustration, the sections can be considered as being taken along line  4 - 4  of the catheter  100  depicted in  FIG. 2 . The catheters  100  depicted in  FIGS. 4B-D  have a proximal end  110 , a distal end  120 , and a body member  140  defining a lumen  150  extending from the proximal end  110  to the distal end  120 . A stop feature  400  is positioned in proximity to (e.g., at or near) the distal end  120  of the catheter  100 . The stop feature  400  extends into the catheter lumen  150  and is configured to engage the container  200  to inhibit or prevent the container from exiting the lumen  150  at the distal end  120  of the catheter  100 . It will be understood, as described below with regard to various embodiments, the stop feature  400  is intended to inhibit or prevent the entirety of the container  200  from exiting the lumen  150 , as a portion of the container  200  may exit the lumen  150 . The stop feature  400  may be integrally formed with, bonded to, adhered to, affixed to, or otherwise coupled to the body  140  of the catheter  100 . As shown in  FIG. 4D , a stop feature  400  may include a piercing element  410  positioned and configured to pierce the container, as described in more detail below with regard to various embodiments. 
     As shown in  FIG.4C , a filter  600  or screen may be disposed across the catheter lumen  150  in proximity to the distal end  120 . The filter  600  or screen may prevent unintended particulate matter from exiting the lumen  150  into target tissue of a patient when the catheter is put to use. In the embodiment depicted in  FIG. 4B , the stop feature  400  may serve as a filter or screen in addition to serving to inhibit or prevent the container from exiting the lumen. 
     A catheter as described herein may be made of any suitable material or combinations of material. For example, the body of the catheter may be formed from a suitable polymeric material, such as PTFE, ETFE, polyethylene, polypropylene, polycarbonate, or combinations of polymeric materials and may include reinforcing elements such as braids or meshes. In various embodiments, the catheter may be formed from silicone or polyurethane. 
     A catheter as described herein may have any suitable dimensions to carryout its intended therapeutic purpose. For example, the catheter is preferably long enough to allow its distal end to be implanted in a target tissue location and to allow its proximal end to be external to the patient. The diameter of the catheter lumen is sized to allow movement of a bar, pushing member if employed, and container within the lumen. 
     A bar as described herein may be made of any suitable material or combinations of material. When the catheter is flexible and follows a non-linear path through the body of a patient to the target tissue, the bar is preferably sufficiently flexible to follow the non-linear path within the catheter. However, for many therapies, the path that the catheter follows in the patient&#39;s body should be substantially linear. In such situations, the bar may be less flexible. In various embodiments, the bar is formed from silicone rubber, butyl rubber, fluorocarbon rubber, neoprene, polyurethane, polyethylene, polypropylene, polytetrafluoroethylene (PTFE), perfluoroalkoxy (PFA), fluorinated ethylene propylene (FEP), ethylene-propylene copolymers,polystyrene, polycarbonate, metals such as stainless steel or nitinol, glass or the like. 
     A pushing element as described herein may be made of any suitable material or combinations of material. For example, a pushing element may be formed from materials similar to those enumerated above with regard to the bar. 
     A piercing element as described herein may be made of any suitable material or combinations of material. In various embodiments, the piercing element is formed from a rigid polymeric material, such as polystyrene, high density polyethylene, polycarbonate, or the like. 
     A filter as described herein may be made of any suitable material or combinations of material. For example, a pushing element may be formed from materials similar to those enumerated above with regard to pushing member. 
     Referring now to  FIGS. 5-6 , schematic illustrations of cross sections of representative containers  200  are shown. In the embodiment depicted in  FIG. 5A , the container  200  includes a housing  210  defining a reservoir  220  for containing a biologic agent. In various embodiments, the wall is formed from an elastomeric material and the volume of the reservoir  220  is variable. In numerous embodiments, the housing  210  is sufficiently stiff to maintain its shape to ensure proper slidability within a lumen of a catheter of a delivery system. Regardless of the degree of stiffness of housing  210 , the container  200  is configured such that force applied to one face (e.g., in the direction of line F), or a portion thereof, of the container  200 , while the opposing face is substantially stationary, causes the face on which force is exerted to move towards the opposing stationary face to force contents out of the reservoir. In various embodiments, the housing  210  is configured to be piercable by a piercable element, to allow contents of the reservoir  220  to escape, and in some embodiments, to reduce internal reservoir pressure so that such pressure does not overcome force F. 
     In the embodiment depicted in  FIG. 5B , a rupturable membrane  250  sealingly engages the interior perimeter of a wall  212  of the housing  210  such that the rupturable membrane  250  and the housing together define the reservoir  220  for containing a biologic agent. While not shown, it will be understood that rupturable membrane  250  may sealingly engage an exterior perimeter of the wall  212 . The membrane  250  may be bonded, adhered, affixed or otherwise attached or sealingly engaged to the wall  212 . The rupturable membrane  250  may be piercable by a piercable element of a catheter of a delivery system, may rupture upon increased pressure (e.g., when force F is applied), may include a line of weakening along which the rupture may occur, or the like. In various embodiments, the rupturable membrane  250  is a self sealing septum that allows introduction of the biologic agent into the reservoir  220  via a needle (not shown) and sealingly contains the biologic agent upon withdrawal of the needle. 
     Referring now to  FIGS. 6A-B , container  200  includes a body member  210  having a proximal end  202  and a distal end  204 . The body member  210  defines a lumen extending from the proximal end  202  to the distal end  204 . The container further includes a sealing element  230  slidably disposable within the lumen of the container  200 . The sealing element  230  is configured to sealingly engage the body member  210  as the element  230  is slid within the lumen. In the depicted embodiment, the sealing element  230  includes an O-ring  235  for sealingly engaging the body member  210  within the lumen. Of course, sealing element  230  may form a seal in any suitable manner. For example, sealing member may include wiper seals or the like. A rupturable membrane  250  is disposed across the lumen in proximity to the distal end  204  of the body member  200 . A reservoir  220  for containing a biologic agent is formed between the rupturable membrane  250 , the sealing element  230  and the body member  210 . 
     The housing of the container may be made of any suitable material. For example, the housing, or portions thereof, may be formed from, glass, silicanized stainless steel, silicanized titanium, nitinol, polystyrene, polyethylene, polycarbonate, ethylene vinyl acetate, polypropylene, polysulfone, polymethylpentene, polytetrafluoroethylene (PTFE) or compatible fluoropolymer, a silicone rubber or copolymer, poly(styrene-butadiene-styrene), polyurethane or the like, or a combination thereof. In various embodiments, the housing is made of polyurethane. It will be appreciated that the material of choice and thickness of the housing may be varied depending on the whether an elastic or rigid housing is desired. 
     Body (as shown in  FIGS. 6A-B ) may be formed of any suitable material. For example, body member may be formed of the same or similar materials as those described above with regard to a rigid housing. 
     Surfaces of the housing or other portions of a container that may come into contact with the biologic agent may be treated or coated to improve compatability with the biologic, reduce adherence of the biologic agent, or the like. 
     Rupturable membrane may be made of any suitable material, such as those enumerated above with regard to housing. In some embodiments, where rupturable membrane is a sealable septum, the membrane is made from a suitable elastomeric material, such as silicone rubber, butyl rubber, flurorcarbon rubber, polyethylene, polypropylene, polytetrafluoroethylene (PTFE) or the like. In many embodiments, the membrane is permeable to atmospheric gasses but is impermeable to aqueous liquids. In such embodiments, the membrane may be formed from polystyrene, polycarbonate, ethylene vinyl acetate, polysulfone, polymethylpentene, polytetrafluoroethylene (PTFE) or compatible fluoropolymer, a silicone rubber or copolymer, poly(styrene-butadiene-styrene), or polyolefin, such as polyethylene or polypropylene, or combinations of these materials. It will be understood that desired thickness may vary depending on the material from which the membrane is formed. By way of example, the membrane may be between about 0.02 millimeters and 0.8 millimeters thick. 
     Sealing member (moveable wall) may be formed from any suitable material. If the sealing member is a one-piece element formed from a single material, sealing member may be formed from a suitable elastomeric material, such as silicone rubber, butyl rubber, flurorcarbon rubber, neoprene, polyurethane, polyethylene, polypropylene, polytetrafluoroethylene (PTFE), perfluoroalkoxy (PFA), fluorinated ethylene propylene (FEP), ethylene-propylene copolymers, or the like If sealing element includes a separate sealing feature, such as an O-ring, wiper seal, or the like, the non sealing feature of the sealing element may be formed, for example, materials as enumerated above with regard to housing. 
     In various embodiments, the housing, sealing member, and rupturable membrane are all made of the same material to reduce the number of materials that the therapeutic agent contacts. For example, the housing, sealing member, and rupturable membrane may all be formed from polyurethane. 
     Referring now to  FIGS. 7-11 , longitudinal cross sections of some components of representative delivery systems  1000  are shown. In the various embodiments depicted in  FIGS. 7-11 , a container  200  is slidably disposed in a lumen  150  of a catheter  100 . A bar  300  including a distally located pushing element  350  is slidably disposed in the lumen  150 . 
     The container  200  is positioned in the lumen  150  distally relative to the bar  300  and pushing element  350 . As the bar  300 ,  500  is slid distally in the lumen  150 , the pushing element  350 ,  550  engages the container  200  and causes the container  200  to slide distally in the lumen  150 . Stopping feature(s)  400  located in proximity to (i.e., generally at or near) the distal end  120  of body member  140  inhibit or prevent container  200 , or a portion thereof, from exiting the lumen  150  of the catheter  100 . When the stop feature(s)  400  engage the container  200 , further distal movement of bar  300 ,  500  in lumen forces the contents (not shown) of the container  200  out of the container  200  and out of the distal end of the lumen  150 . 
     In the embodiment depicted in  FIGS. 7A-D , piercing element  410  pierces a portion of the face of the container housing  210 ′ facing the distal end  120  of the catheter body  140  as the container moves distally in the catheter lumen  150 . Further distal movement of bar  300  in lumen  150  forces contents (not shown) out of the container  200  and out of the distal end of the lumen  150  through the pierced region. In addition, the side walls  210 ″,  210 ′″ of the container housing collapse as the bar is moved distally when the container  200  engages the stop feature  400  (see  FIG. 7D ). The side walls  210 ″,  210 ′″ may be in the form of a bellows, may be sufficiently deformable to collapse, or the like. In various embodiments (not shown), the piercing element  410  may be a needle advanced distally through the lumen  150  of the catheter  100  and through the container  200 . For example, the needle (not shown) may be inserted through a lumen (not shown) of the bar  300 . The needle may have an etched surface for piercing the container  200  or may have a surface that is covered with an array of microneedles to allow for more spreadout distribution of the agent. 
     As further shown in  FIG. 7D , a screen  600  or filter may be disposed in the catheter lumen  150  in proximity to the distal end  120  to inhibit or prevent unintended particulate matter, such as parts of the container housing  210 , from exiting the lumen  150 . As further shown in the embodiment depicted in  FIGS. 7A-D , pushing element  350  includes a sealing element  355 , such as an O-ring, so that pushing element  355  sealingly engages body  140  in lumen  150 . By sealingly engaging body  140  in lumen  150 , pushing element  350  can inhibit or prevent contents that leave container  200  from moving proximally in the lumen  150 . In various embodiments, pushing element  350  does not sealingly engage body  140  of catheter  100 . 
     Referring now to  FIGS. 8A-C , a container  200  similar to that depicted in and discussed with regard to  FIGS. 6A-B  is shown disposed in catheter lumen  200  distally to bar  300 . The bar  300  is slidably disposed in lumen  510  a second bar  500 , which is slidably disposed in the lumen  150  of the catheter  100 . The second bar  500  includes a body member  520  that defines the lumen  510 . The second bar  500  includes a pushing member  550  at the distal end of the bar  500 . The second pushing member  550  includes an opening  530  axially aligned with the lumen  512 . The first bar  300  is axially slidable in the lumen  510  of the second bar  500  and extendable beyond the opening  530 . The second pushing member  550  is configured to engage the container  200  and move the container  200  distally in the catheter lumen  150  as the second bar  500  slides distally in the catheter lumen  150 . The second bar  500  pushes the container  200  distally in the catheter lumen  150  until the container  200  engages stop feature  400 . If the second bar  500  is moved manually within the catheter lumen  150 , tactile feedback that the container  200  has engaged the stop feature  400  may indicate to the user that no further distal pushing of the bar  500  is desirable. If the bar  500  is moved via an automated mechanism, feedback, such as increased resistance to movement, increased pressure on stop feature, increased power consumption without further movement or the like may be used to indicate that further distal movement of the bar  500  should be ceased. 
     In the embodiment depicted in  FIGS. 8A-C , distal movement of the second bar  500  causes distal movement of the first bar  300 , as the second pushing element  550  engages the first pushing element  350  and pushes the first pushing element  350  distally as the second bar  500  is slid distally in catheter lumen  150 . At a point where the second bar  500  is pushed distally such that the container  200  engages stop feature  400 , the first bar  300  may be moved distally to force contents (not shown) out of the container  200  and out of the catheter  100 . In the embodiment shown, the pushing element  350  of the first bar  300  is configured to engage the moveable sealing member  230  of the container  200 . As the first bar  300  is moved distally when the container  200  is engaged with stop feature  400 , the pushing element  350  moves the sealing member  230  distally forcing contents out of container  200  via rupturable membrane  250 . While not shown, it will be understood that a filter or screen may be disposed across the catheter lumen  150  (e.g., as shown in  FIGS. 7-D ). 
     Referring now to  FIGS. 9A-B , an embodiment similar to that shown in  FIGS. 8A-C  is shown, with like numbers referring to like parts. In the embodiment shown in  FIGS. 9A-B , the stop feature  400  includes piercing elements  410 . When the container  200  is pushed distally in catheter lumen  150  such that the container  200  engages the stop feature  400 , piercing element  410  pierces rupturable membrane  250 . As the sealing member  230  is moved distally, contents of the container  200  can exit via the pierced portion of the membrane  250 . 
     Referring now to  FIGS. 10A-C , an embodiment similar to that shown in  FIGS. 8A-C  is shown, with like numbers referring to like parts. In  FIG. 10 , container  200  includes a tapered distal region configured to extend beyond the distal end  120  of the catheter  100  when the stop feature  400  engages the container  200 . In various embodiments, the distal tapered region of the container  200  has a sufficiently large inner diameter to avoid subjecting the contents of the container  200  to shear stress as the contents are forced through the distal tapered region. As shown in  FIG. 10 , the sealing member  230  of the container  200  may be sized and shaped in a similar manner to the distal tapered region to increase the amount of contents that may be forced out of the container  200 . 
     Referring now to  FIG. 11 , a bar  300  or pushing member  350  of the bar may serve as a sealing member of a container. In the depicted embodiment, pushing member  350  sealingly engages the body of the container as the pushing member  350  is moved distally within the container to force contents out of the container. 
     While not shown, it will be understood that mechanisms other than bars  300 ,  500  may be used to move container  200  distally in lumen  150  and force contents out of the container  200 . For example, air pressure or hydraulic fluid pressure (e.g., saline) may be used to move the container  200  and provide force to release contents. In such embodiments, it may be desirable for the container  200  to sealingly engage the body  140  of the catheter  100 . It will be further understood that a bar  300 ,  500  may be moved in the lumen  150  by any suitable mechanism, such as hydraulic fluid pressure, air pressure, motor, manually, or the like. 
     Referring now to  FIGS. 12-14 , block diagrams of some representative components of automated systems for moving bars as discussed above within lumens of catheters are shown. In the simple form shown in  FIG. 12 , such a system may include a controller  2100 , a driving mechanism  2200 , and a bar  300 . Any suitable controller  2100 , such as a microprocessor, may be employed to control the driving mechanism  2200 . Any suitable driving mechanism  2200  may be employed to move bar  300 . In various embodiments, the driving mechanism  2200  is a motor, such as a stepper motor. In some embodiments, the driving mechanism  2200  is a hydraulic or air pressure driving mechanism. In such embodiments, the bar  300  preferably sealingly engages the body of the catheter to prevent hydraulic fluid from leaking in the lumen distal to the bar  300 . As shown in  FIGS. 13-14 , in embodiments where first  300  and second  500  bars are employed, a single drive mechanism  2200  may be used to drive both bars  300 ,  500  or a first drive mechanism  2210  may be used to move the first bar  300  and a second drive mechanism  2220  may be used to move the second bar  500 . 
     Referring now to  FIGS. 15-22 , schematic illustrations of various configurations of containers  200  useful in delivery systems as described above are shown. In  FIG. 15 , a schematic longitudinal cross section of a container  200  is shown. The container  200  includes a sealing element  230  and a rupturable membrane  250 . The rupturable membrane  250  may be a self sealing septum to allow contents to be added to the container  200 . The sealing element  230  includes a piercing element  290  configured to pierce rupturable membrane  250  to allow contents to exit the container  200  when the sealing member  230  is moved distally. As shown in the schematic side view of  FIG. 16 , a container  200  may include first  260  and second  270  connectable portions. The second portion  270  may serve as a removable and resealable cap. The cap may be removed so that contents may be added to the first portion  260  and resealed to prevent the contents of the container  200  from leaking or spilling. The first  260  and second  270  portions include complementary mating features  261 ,  271  to allow disconnecting and reconnecting of the first and second parts. In the depicted embodiment, the first portion  260  includes external threads  261 . The second portion  270  includes complementary internal threads  271  (represented by internal dashed lines). Of course, any other suitable form of connection may be employed. As shown in  FIGS. 17A-B , which is similar to the embodiment depicted in  FIG. 16  with like numbers referring to like parts, the second portion  270  of the container  200  may include a rupturable membrane  250 . In the embodiment depicted in  FIG. 18 , the first part  260  includes a sealing element  230  and the second part  270  includes a rupturable membrane  250 . 
     Referring now to  FIG. 19 , container  200  may include an outer sheath  280  that surrounds the housing  210  of the container. In various embodiments, the outer sheath  280  may be removed in the operating room prior to insertion of the container  200  into the lumen of a catheter of a delivery system. The sheath  280  may thus prevent excessive exposure (and thus contamination) of the housing  210  prior to delivery of its contents. In some embodiments, the outer sheath  280  may be removable following insertion into the catheter so that physician contact with the inner housing  210  is prevented. Of course, the outer sheath  280  and housing  210  may be ruptured in proximity to the distal end of the catheter as the agent disposed in the housing is released. In various embodiments, the outer sheath  280  is permeable to atmospheric gases, but impermeable to aqueous liquids. Such breathable outer sheaths  280  may be desirable when the container  200  houses cells and it is desirable to preserve the viability of the cells prior to delivery. 
     Referring now to  FIG. 20 , a container  200  may be sealingly subdivided into first  298  and second chambers  299 . The first  298  and second  299  chambers may house different agents that may not be compatible if stored together. In various embodiments, the first chamber  298  houses a fluoroscopic medium to enable visualization via imaging techniques and the second chamber  299  houses a biologic agent. Just prior to introduction into a patient through the use of a delivery system as described above, the contents of the first  298  and second  299  chambers may be mixed.  FIGS. 21-22  depict schematic longitudinal cross sections of two embodiments of such two-compartment containers. 
     In the embodiment depicted in  FIG. 21 , the container  200  includes first  260 , second  270 , third  260 ′ and fourth  270 ′ parts. The first  260  and second  270  parts include complementary mating features  261 ,  271  to allow for disconnection and sealing reconnection. The first  260  and second  270  parts together form the first chamber  298  of the container  200 . A first material may be disposed in the first part  260  and the second part  270  may be connected to the first part  260  to seal the material in the first chamber  298 . A rupturable membrane  250  prevents the material from exiting the sealed first chamber  298 . The third part  260 ′ includes a complementary mating feature  261 ′ to a mating feature  271 ′ of the second part  270  to allow for disconnection and sealing reconnection. The second  270 , third  260 ′, and fourth  270 ′ parts together form the second chamber  299 . The third part  260 ′ includes a complementary mating feature  261 ″ to a mating feature  271 ″ of the fourth part  270 ′ to allow for disconnection and sealing reconnection. When the second  270  and third  260 ′ parts are connected, a second material may be introduced in the third part  260 ′. The fourth part  270 ′ may then be sealingly connected to the third part  260 ′. The fourth part  270 ′ includes a rupturable membrane  250 ′ to prevent the contents of the second chamber  299  from leaking or spilling. The rupturable membrane  250  prevents interaction between the contents of the first  298  and second  299  chambers during storage. Upon rupture of the membrane  250  in use, the contents of the first  298  and second chambers  299  can mix. 
     In the embodiment depicted in  FIG. 22 , the container  200  includes first  260 , second  260 ′, and third  270 ′ parts. The first  260  and second  260 ′ parts include complementary mating features  261 ,  271  to allow for disconnection and sealing reconnection. The first  260  and second  270  parts together form the first chamber  298  of the container  200 . A first material may be disposed in the first part  260  and the second part  270  may be connected to the first part  260  to seal the material in the first chamber  298 . A rupturable membrane  250  prevents the material from exiting the sealed first chamber  298 . The third part  270 ′ includes a complementary mating feature  271 ′ to a mating feature  261 ′ of the second part  260 ′ to allow for disconnection and sealing reconnection. The second  260 ′ and third  270 ′ parts together form the second chamber  299 . A second material may be introduced in the second part  260 ′. The third part  270 ′ may then be sealingly connected to the second part  260 ′. The third part  270 ′ includes a rupturable membrane  250 ′ to prevent the contents of the second chamber  299  from leaking or spilling. The rupturable membrane  250  prevents interaction between the contents of the first  298  and second  299  chambers during storage. Upon rupture of the membrane  250  in use, the contents of the first  298  and second chambers  299  can mix. 
     In the embodiments depicted in  FIGS. 21-22 , the moveable sealing member includes a tapered distal region that may serve as a piercing element to facilitate rupturing membranes  250 ,  250 ′. 
     While not described at length herein, it will be understood that the biologic agent to be delivered may be delivered in any form, e.g. liquid or solid. By using a system as described herein, solid forms and liquid forms of the biologic agent should be readily interchangeable without the need to design and develop new catheters or components of the system. Examples of suitable solid forms of biologics that may be delivered in accordance with the teachings provided herein include lyophilized particles or solid scaffolds. In many circumstances, solid scaffolds are considered more effective for delivering therapy to a highly vascularized region such as the myocardium. 
     The various embodiments shown and described herein include various components. One of skill in the art will readily understand that components of a given described embodiment may be readily substituted for, or used in addition to, components of a different described embodiment. 
     Thus, embodiments of the SYSTEM AND METHOD FOR DELIVERY OF BIOLOGIC AGENTS are disclosed. One skilled in the art will appreciate that the present invention can be practiced with embodiments other than those disclosed. The disclosed embodiments are presented for purposes of illustration and not limitation, and the present invention is limited only by the claims that follow.