US20050020899A1 - Post-biopsy cavity treatmetn implants and methods - Google Patents

Abstract

An embodiment of a post-biopsy cavity treatment implant includes a first portion including a first porous matrix defining a first controlled pore architecture or crosslinking density, and a second portion coupled to the first portion. The second portion includes a second porous matrix that defines a second controlled pore architecture or a second crosslinking density that is different from the first controlled pore architecture or the first crosslinking density, causing the second portion to swell in a different manner than the first portion when the implant is placed in an aqueous environment.

Description

BACKGROUND OF THE INVENTION
• 1. Field of the Invention
• The present invention relates to post-biopsy cavity treatment methods and implants. More particularly, the present inventions relates to post-biopsy cavity treatment implants inserted into cavities formed in soft tissue that may be created during a biopsy or therapeutic excisional procedure.
• 2. Description of the Related Art
• Breast biopsies are routinely performed in the United States following a detection of abnormalities discovered through mammographic visualization, manual palpation or ultrasound examination. There are a number of traditional methods to obtain breast biopsy tissue samples, including surgical excisional biopsies and stereotactic and ultrasound guided needle breast biopsies. Recently, methodologies have emerged that are based upon percutaneous minimally invasive large intact tissue sample collection. The use of these devices results in a unique cavity connected to the skin by a narrow neck. However, it is becoming apparent, therefore, that the post-biopsy biopsy cavities left by these procedures may both offer and require different post procedural treatments, as compared to the cavities left by needle, core biopsy procedures or open surgical procedures, due to the different nature, size and shape of the cavity created by conventional biopsy devices, as well as the narrow connection to the skin characterized by percutaneous approaches.
• In certain cases, locating a previously biopsied area is highly desirable. Therefore, to mark the biopsy site, a variety of biopsy site markers and identifiers have been developed, ranging from metal clips to pellets and sponges placed during or right after the biopsy procedure. Usually, these markers contain radiopaque and/or echogenic articles and include features such as metal clips and air or gas bubbles incorporated in a biodegradable matrix. From the foregoing, it is apparent that improved methods and devices are needed to treat the cavities left by biopsy devices that are configured to retrieve large intact specimens.
SUMMARY
• The present invention, according to an embodiment thereof, is a post-biopsy cavity treatment implant. The post-biopsy cavity treatment implant may include a first portion including a first porous matrix defining a first controlled pore architecture, and a second portion coupled to the first portion, the second portion including a second porous matrix defining a second controlled pore architecture that may be different from the first controlled pore architecture to cause the second portion to swell in a different manner than the first portion when the post-biopsy cavity treatment implant may be implanted in an aqueous environment.
• According to further embodiments, the second portion may swell faster than the first portion when the implant is implanted in the aqueous environment. The second portion may swell to a greater extent than the first portion when the implant is implanted in the aqueous environment. The first controlled pore architecture may differ from the second controlled pore architecture with respect to one or more of: pore density, pore shape, pore orientation and pore dimensions, for example. The first and/or second portions may include a radiopaque material disposed therein. The first and/or second portions may include a radioactive material disposed therein. The first and/or second portions may include a paramagnetic material disposed therein. The first and second portions may include a dye, a pigment, a contrast media and/or a therapeutic agent disposed therein, for example. The first and/or second portions may be biodegradable. The first and/or second portions may include collagen. The first and second portions include one or more of a polylactide (PLA), a polyglycolide (PGA), a poly(lactide-co-glycolide) (PLGA), a polyglyconate, a polyanhydride, PEG, cellulose, a gelatin, a lipids, a polysaccharide, a starches and a polyorthoesters, for example. The first and second portions may be configured so as to form a laminar structure. The first portion may define a first surface and the second portion may define a second surface that faces the first surface to define an interface between the first and second portions. The interface may be visualizable under ultrasound when the post-biopsy cavity treatment implant is implanted. At least the first portion may include a plurality of fibers and/or fibrils. The first portion may form an inner core and the second portion may form an outer shell disposed at least partially around the first portion. The first and/or second portions may include an internal reservoir configured to contain one or more of a dye, a pigment and a therapeutic agent, for example. The internal reservoir may be configured to deliver the dye, pigment and/or therapeutic agent through elution when the implant is implanted in the aqueous environment. The internal reservoir may be configured to deliver the dye, pigment and/or therapeutic agent (for example) at a first rate when the reservoir is breached and at a second rate that is lower than the first rate when the reservoir is not breached. The implant may include a third portion, the third portion being radiopaque. The third portion may include a metal. The third portion may include a third porous matrix defining a third controlled pore architecture, the first, second and third portions collectively defining a predetermined pore density gradient. The second portion may be configured to have a second crosslinking density and the first portion may be configured to have a first crosslinking density that is greater than the second crosslinking density. The second portion may be configured to swell to a greater degree than the first portion when the implant is implanted in the aqueous environment. The first and second portions may include collagen and a crosslinking density of the first and/or second portions may be controlled through adding a selected amount of a bifunctional reagent to the collagen. The bifunctional reagent may include a aldehyde and/or a cyanamide. The aldehyde may include a glutaraldehyde, for example. The first and second portions may include collagen and a crosslinking density of the first and second portions may be controlled by an application of energy to the collagen. The application of energy may include dehydrothermal processing and/or exposure to UV light or radiation, for example. The first and second portions may include collagen and a crosslinking density of the first and/or second portions may be controlled by a combination of dehydrothermal processing and exposure to cyanamide, for example.
• According to another embodiment thereof, the present invention is a method for mapping a lymphatic system following a cavity generating procedure. The method may include steps of providing a post-biopsy cavity treatment implant, the implant including a collagenous matrix having a non-uniform cross-linking density that is configured to cause the implant to swell non-uniformly when placed within an aqueous environment, the implant including a dye or a pigment contained therein; implanting the provided post-biopsy cavity treatment implant into the cavity; closing the cavity with the post-biopsy cavity treatment implant implanted therein; causing the dye/pigment to be released from the implant and to propagate through the lymphatic system, and visualizing the propagated dye/pigment in the lymphatic system using a selected visualization mode.
• The implant in the providing step may include a reservoir disposed within the collagenous matrix, the reservoir containing a volume of the dye/pigment and the causing step may include a step of breaching the reservoir to release the dye/pigment. The breaching step may include a step of squeezing the implanted post-biopsy cavity treatment implant. The causing step may include a step of waiting for a predetermined period of time during which the implant degrades within the cavity and releases the dye/pigment. The dye and/or pigment may be loaded within the collagenous matrix of the implant. The visualizing mode in the visualizing step may include ultrasound, X-ray, MRI, elastography, microwave and/or the unaided eye, for example.
• According to still another embodiment, a post-biopsy cavity treatment implant according to the present invention may include a first portion may include a first collagenous matrix, the first collagenous matrix being controlled to have a first crosslinking density, and a second portion in contact with the first portion, the second portion may include a second collagenous matrix, the second collagenous matrix being controlled to have a second crosslinking density, the first crosslinking density being controlled to be different than the second cross-linking density.
• Another embodiment of the present invention is a post-biopsy cavity treatment implant that includes a first portion including a first collagenous matrix defining a first controlled pore architecture, and a second portion coupled to the first portion, the second portion may include a second collagenous matrix, the second collagenous matrix being controlled to have a first controlled crosslinking density to cause the second portion to swell in a different manner than the first portion when the post-biopsy cavity treatment implant is implanted in an aqueous environment.
• Yet another embodiment of the present invention includes a method of filling a cavity created by an excisional procedure. The cavity may have a predetermined shape and the method may include the steps of providing an implant, the implant including at least a first portion and a second portion, the first portion may include a first collagenous matrix that defines a first selected crosslinking density, the second portion may include a second collagenous matrix that defines a second selected crosslinking density that may be different than the second cross-linking density, the first and second cross-linking densities being selected so as to cause the first and second portions to swell into a size and a shape that may be similar to the predetermined shape of the cavity when the implant is implanted; implanting the implant within the cavity through an incision; adding an aqueous solution to the cavity if the cavity may be not sufficiently aqueous to cause the implant to swell, and closing the incision with the implant implanted in the cavity.
• The first portion may include a plurality of first collagenous fibers (or fibrils), each of the plurality of first collagenous fibers having the first selected crosslinking density. The second portion may include a plurality of second collagenous fibers (or fibrils), each of the plurality of second collagenous fibers having the second selected crosslinking density.
BRIEF DESCRIPTION OF THE DRAWINGS
• For a further understanding of the objects and advantages of the present invention, reference should be made to the following detailed description, taken in conjunction with the accompanying figures, in which:
• FIG. 1 shows an exemplary large intact specimen percutaneous biopsy device in operation.
• FIG. 2 shows further aspects of the exemplary large intact specimen percutaneous biopsy device ofFIG. 1 in operation.
• FIG. 3 shows further aspects of the exemplary large intact specimen percutaneous biopsy device ofFIG. 1 in operation.
• FIG. 4 shows still further aspects of the exemplary large intact specimen percutaneous biopsy device ofFIG. 1 in operation.
• FIG. 5 shows further aspects of the exemplary large intact specimen percutaneous biopsy device ofFIG. 1 in operation.
• FIG. 6A shows further aspects of the exemplary large intact specimen percutaneous biopsy device ofFIG. 1 in operation, and illustrates the creation of a cavity within the soft tissue from which the excised specimen was taken.
• 6B is a cross sectional view of the post treatment cavity ofFIG. 6A, taken along cross-sectional line II′.
• FIG. 7 shows further aspects of the exemplary large intact specimen percutaneous biopsy device ofFIG. 1 in operation, and further illustrates the creation of a cavity within the soft tissue from which the specimen was taken, with the aforementioned narrow neck or access path connecting the cavity to the skin.
• FIG. 8 shows an exemplary delivery device for a post-biopsy cavity treatment implant, according to an embodiment of the present invention.
• FIG. 9 shows the delivery device ofFIG. 8 in operation, delivering a post-biopsy cavity treatment implant according to an embodiment of the present invention within the cavity ofFIG. 7.
• FIG. 10A shows the cavity ofFIG. 7, after the implantation of the post-biopsy cavity treatment implant shown inFIGS. 8 and 9, with the percutaneous incision closed.
• FIG. 10B shows the cavity ofFIG. 7, after the implantation of the post-biopsy cavity treatment implant shown inFIGS. 8 and 9 in another orientation, with the percutaneous incision closed.
• FIG. 10C shows the cavity ofFIG. 7, after the implantation of a post-biopsy cavity treatment implant according to another embodiment of the present invention, with the percutaneous incision closed.
• FIG. 11 shows a post-biopsy cavity treatment implant having a predetermined pore architecture, according to an embodiment of the present invention.
• FIG. 12 shows another post-biopsy cavity treatment implant having another predetermined pore architecture, according to another embodiment of the present invention.
• FIG. 13A shows a post-biopsy cavity treatment implant that includes a plurality of fibers, according to another embodiment of the present invention.
• FIG. 13B shows a cross-section of a post-biopsy cavity treatment implant, according to another embodiment of the present invention.
• FIG. 13C shows a portion of another post-biopsy cavity treatment implant, according to a further embodiment of the present invention.
• FIG. 13D shows another post-biopsy cavity treatment implant, according to still another embodiment of the present invention.
• FIG. 13E shows another post-biopsy cavity treatment implant, according to still another embodiment of the present invention.
• FIG. 14A shows a post-biopsy cavity treatment implant that includes a plurality of fibers having predetermined pore architectures, according to another embodiment of the present invention.
• FIG. 14B shows a front view of a post-biopsy cavity treatment implant, according to another embodiment of the present invention.
• FIG. 14C shows a portion of another post-biopsy cavity treatment implant, according to a further embodiment of the present invention.
• FIG. 14D illustrates the stacked structure of a post-biopsy cavity treatment implant, according to a further embodiment of the present invention.
• FIG. 14E illustrates the stacked structure of another post-biopsy cavity treatment implant, according to a further embodiment of the present invention.
• FIG. 14F illustrates the stacked structure of a post-biopsy cavity treatment implant, according to a further embodiment of the present invention.
• FIG. 14G illustrates the stacked structure of another post-biopsy cavity treatment implant, according to a further embodiment of the present invention.
• FIG. 15A shows a post-biopsy cavity treatment implant that includes a radiopaque and/or echogenic member around which one or more fibers are wound, according to another embodiment of the present invention.
• FIG. 15B shows a post-biopsy cavity treatment implant that includes a core portion surrounded by an outer shell portion, each of the core and shell portions having a predetermine core architecture, according to another embodiment of the present invention.
• FIG. 15C is a cross-sectional representation of the implant ofFIG. 15B, taken along cross-sectional line II-II′.
• FIG. 15D shows a post-biopsy cavity treatment implant that includes a core portion having a first predetermine core architecture surrounded by an outer shell portion formed by a plurality of wound collagenous fibers having a second predetermined pore architecture, according to another embodiment of the present invention.
• FIG. 15E shows a post-biopsy cavity treatment implant that includes a core portion having a first predetermine core architecture surrounded by an outer shell portion formed by a plurality of collagenous fibers having a second predetermined pore architecture, according to another embodiment of the present invention.
• FIG. 15F is a cross-sectional view of the embodiment ofFIG. 15D, taken along cross-sectional line I-I′.
• FIG. 16 is a photomicrograph of a collagen matrix having a predetermined pore architecture with post-biopsy cavity treatment implants according to embodiments of the present invention may be constructed.
• FIG. 16 is a photomicrograph of a collagen matrix having a predetermined pore architecture with post-biopsy cavity treatment implants according to embodiments of the present invention may be constructed.
• FIG. 17 is a photomicrograph of a collagen matrix having another predetermined pore architecture with post-biopsy cavity treatment implants according to embodiments of the present invention may be constructed.
• FIG. 18 is a photomicrograph of a collagen matrix having still another predetermined pore architecture with post-biopsy cavity treatment implants according to embodiments of the present invention may be constructed.
• FIG. 19 is a photomicrograph of a collagen matrix having a still further predetermined pore architecture with post-biopsy cavity treatment implants according to embodiments of the present invention may be constructed.
• FIG. 20 is a photomicrograph of a collagen matrix having yet another predetermined pore architecture with post-biopsy cavity treatment implants according to embodiments of the present invention may be constructed.
• FIG. 21 combination of photomicrographs of collagen matrices illustrating the formation of a stacked laminate structure including a first layer having a first predetermined pore architecture and a second layer having a second predetermined pore structure, according to an embodiment of the present invention.
• FIG. 22 is a combination of photomicrographs of collagen matrices that collectively illustrate a post-biopsy cavity treatment implant having a predetermined pore density gradient and/or predetermined graduated crosslinking gradient, according to a further embodiment of the present invention.
• FIG. 23 is a combination of photomicrographs of collagen matrices that collectively illustrate a post-biopsy cavity treatment implant according to another embodiment of the present invention.
DESCRIPTION OF EMBODIMENTS OF THE INVENTION
• FIGS. 1-7 show aspects of a percutaneous method for cutting, collecting and isolating a tissue specimen and the subsequent creation of a cavity within which embodiments of the present inventions may be implanted. The excisional device shown inFIGS. 1-7 is described in commonly assigned U.S. Pat. No. 6,022,362 and in copending and commonly assigned patent application Ser. No. 10/189,277 filed on Jul. 3, 2002, the disclosure of each being incorporated herein in its entirety. Although embodiments of the present invention are described relative to a cavity created by the excisional device shown inFIGS. 1-7, it is to be understood that the present inventions are not to be limited thereby. Indeed, embodiments of the present invention may be advantageously utilized to treat cavities of various shapes and sizes created by other devices, including devices that obtain tissue specimen through coring or ablation techniques, for example.
• As shown inFIG. 1, theexcisional device100 is introduced into a mass oftissue110 through theskin102, with the integrated cut and collectassembly112 thereof in a retracted position. Thedevice100 is then advanced such that theassembly112 is adjacent to thetarget lesion108. Theassembly112 may then be energized and expanded as shown inFIG. 2 by acting upon theactuator118. As theassembly112 is RF energized and expanded, it cuts the tissue through which it travels. As shown atFIG. 3, theexcisional device100 may then be rotated, while theassembly112 remains energized, causing the leading edge thereof to cut through the tissue, preferably with clean margins. The expanded integrated cut and collectassembly112 deploys themembrane114 and thecut specimen108 is collected in the open bag formed by the close-ended deployedflexible membrane114. As shown inFIGS. 4 and 5, the rotation of thedevice100 may then be continued as needed, preferably under ultrasonic guidance. To fully sever thespecimen108 from the surroundingtissue110, theassembly112, while still energized, is retracted to capture, encapsulate and isolate thespecimen108 within theflexible membrane114. As shown inFIG. 6A, thespecimen108 may then be recovered by retracting thedevice100 through theretraction path127, stretching it as necessary.FIG. 7 shows a fully retracteddevice100, containing a collected andisolated specimen108.
• As shown inFIGS. 6A-7, after the procedure described above or after any procedure in which a substantial volume of tissue specimen is taken, a void orcavity126 is created where thetissue specimen108 used to be. Cavities as shown at126 may require different post procedural treatments, as compared to procedures such as needle biopsies due to the different nature, size and shape created by the biopsy device. As shown inFIGS. 6A and 6B, theexemplary cavity126 is characterized by a relativelynarrow access path127 that emerges into alarger cavity chamber128 formed by the extension and rotation of the cut and collectassembly112 during the above-described procedure. After thedevice100 is withdrawn from the patient as shown inFIG. 7, portions of thecavity126 and/oraccess path127 may settle and collapse somewhat, as the interior tissue walls defining thecavity126 are no longer supported by the tissue previously occupying that space.
• Treating thepost-biopsy cavity126 is desirable for a variety of reasons. One such reason is to accommodate the unique size and shape of thecavity126 created by thedevice100. It is desirable to influence and/or promote the healing process of the cavity, and to do so in a predictable manner. One aspect of influencing the healing process of thecavity126 is promoting the growth of new connective tissue within thecavity126 in a predictable manner. Indeed, it is desirable to influence and promote both tissue ingrowth within the cavity and to influence the formation of hematomas and seromas. Another reason for treating thepost-biopsy cavity126 is to modify it in such a manner as to render it recognizable immediately and preferably long after the procedure that created thecavity126. Thecavity126, left untreated, may be visible under ultrasound. However, that may not be the case and it is believed to be desirable to at least partially fill thecavity126 with a cavity treatment implant that will render thecavity126 clearly visible under various imaging modalities, including modalities such as ultrasound, X-ray, MRI, elastography, microwave and the unaided eye, for example. Such visibility may be due to the structure of a cavity treatment implant or devices implanted within the cavity and/or a recognizable pattern of tissue ingrowth caused or influenced by the continuing or past presence of post-biopsy cavity treatment implants disclosed herein. Other desirable attributes of embodiments of the implantable post-biopsy cavity treatment implant of the present invention include hemostasis, and the ability to deliver one or more therapeutic agents to the patient at the post-biopsy cavity treatment implant site such as, for example, lido/epi, Non-Steroidal Anti-Inflammatory Drugs (NSAIDS), tissue growth factors, anti-neoplastic medications (to name a few) or combinations of the above and/or others. Filling thecavity126 may have other benefits, including cosmetic. Indeed, filling the cavity and promoting a smooth, gradual, recognizable and orderly tissue ingrowth pattern may prevent dimpling, skin depressions and the like sometimes associated with the removal of a large intact specimen during the biopsy procedure. Embodiments of the present invention may also find utility in augmentation or reconstructive procedures for the breast or other soft tissue.
• According to an embodiment of the present invention, the post-biopsy cavity treatment implant may have a size and a shape that at least partially fills the cavity. Advantageously, the present post-biopsy cavity treatment implant, after insertion, may have a characteristic shape that is readily perceptible and recognizable through various modalities, including, for example, ultrasound, X-ray or MRI. The shape of the present post-biopsy cavity treatment implant may also influence the manner in which tissue growths therein. Preferably, embodiments of the present post-biopsy cavity treatment implant should be shaped and dimensioned so as to uniquely accommodate the size and shape of thecavity126 created by thedevice100 ofFIGS. 1-7. However, embodiments of the present invention may be readily sized and shaped to specifically accommodate cavities of any shape and size created by other devices and/or biopsy or therapeutic surgical procedures.
• According to an embodiment thereof, the present invention may include an implantable post-biopsy cavity treatment implant having one or more of the structures, characteristic and properties described herein. As shown inFIG. 8, the implantable post-biopsycavity treatment implant802, in a pre-implanted state, may be loaded into an introducer, an illustrative example of which is shown atreference numeral804. Theintroducer804 may then be inserted into thetissue110 through theaccess path127 and at least partially into thecavity chamber128 of thecavity126. The post-biopsycavity treatment implant802 may then be delivered to thecavity126 and thereafter be left in place and theintroducer804 withdrawn. The pre-implanted state of the post-biopsycavity treatment implant802 is preferably in a state in which the post-biopsy cavity treatment implant occupies its minimum volume. According to an embodiment of the present invention, the pre-implanted state of the post-biopsycavity treatment implant802 is a lyophilized (e.g., dehydrated) state and the post-biopsy cavity treatment implant may be configured to swell when placed within aqueous environment such as thecavity126. The post-biopsycavity treatment implant802 may define aproximal portion806 that is closest to theaccess path127 and adistal portion808 that is relatively further away from theaccess path127 than is theproximal portion806.
• WhereasFIG. 9 shows the present post-biopsycavity treatment implant802 immediately after implantation in tissue (i.e., still in a state in which it occupies its minimum volume),FIG. 10A shows the state of the present post-biopsy cavity treatment implant802 a short period of time after implantation. As shown, the post-biopsycavity treatment implant802 is no longer in its pre-implanted state. Indeed, the post-biopsycavity treatment implant802, having been placed in an aqueous environment (such as the patient's tissue), begins to swell. According to an embodiment of the present invention, thepost-cavity treatment implant802 may be configured to swell in a uniform manner. In another example, the surgeon may inject fluids after placing the device with the intent to “wet” the present post-cavity treatment implant. Substances such as saline, fibrin solution or other catalyst or activator may be used for that purpose. The activator or swelling fluid could be injected preferentially at theproximal portion806 or selectively at points in the post-cavity treatment implant to cause it to secure itself in position inside thecavity126. Alternatively, as part of the insertion device (such as, for example, the introducer804), an integral vial may be crushed by the surgeon to release the activating fluid (for example, an aqueous solution, dye/pigment) in the area of theproximal portion806 for example, thus causing rapid swelling of that region. Alternately, theintroducer804 may define aninternal lumen811 over its length and may include afluid injection port812 at the proximal end of the device. Fluids such as the aforementioned saline or fibrin may then be introduced into thecavity126 through thefluid injection port812 and theinternal lumen811 to cause the rapid swelling of the implant or for any other reason. Delivering such fluids can be especially useful if the field within the cavity is relatively dry as can occur in the ideal case. According to another embodiment of the present invention, the post-biopsycavity treatment implant802 may be configured to swell non-uniformly. Such non-uniform swelling rates may be advantageous in insuring that the post-biopsycavity treatment implant802 stays where it is placed during the implantation procedure. In the embodiment shown inFIG. 10A, the post-biopsycavity treatment implant802 is structured such that the rate at which theproximal portion806 swells faster than the rate at which thedistal portion808 swells. When implanted in acavity126 such as shown inFIGS. 6A, 6B,7,9 and10, theproximal portion806 swells faster than thedistal portion808, thereby serving to maintain the post-biopsycavity treatment implant802 within thecavity chamber128 of thecavity126. This may be achieved by, for example, controlling the crosslinking densities or creating a gradient of crosslinking densities within the post-biopsycavity treatment implant802, where certain regions of the post-biopsycavity treatment implant802 are controlled to have a greater crosslinking density than other regions, resulting in a non-uniform swelling pattern over the extent of thedevice802. For example, thedistal portion808 may be configured to be relatively more crosslinked than theproximal portion806 thereof, resulting in theproximal portion806 swelling more and/or faster than thedistal portion808. As theproximal portion806 of the post-biopsycavity treatment implant802 swells, it preferably swells from a shape in which it is easily implantable through theaccess path127 to a shape and size wherein at least theproximal portion806 thereof no longer fits through theaccess path127. As this swelling occurs rapidly after the post-biopsycavity treatment implant802 comes into contact with the fluids present within thecavity126, the surgeon may retract theintroducer804 from thecavity126, close the initial incision and be confident that the post-biopsycavity treatment implant802 has remain in its intended position, squarely within thecavity chamber128 of thecavity126, and has not migrated back into theaccess path127.
• The post-biopsycavity treatment implant802 may alternatively be structured such that its distal808 portion swells faster than itsproximal portion806 such as shown inFIG. 10B, such that both the proximal and distal portions8fthe post-biopsy cavity treatment implant swell relatively faster than the portion thereof between the proximal and distal portions or such that the proximal anddistal portions852,856 of theimplant850 swell relatively slower than amiddle portion854, as shown inFIG. 10C. Alternatively still, the post-biopsycavity treatment implant802 may not have well defined proximal and distal portions and the post-biopsycavity treatment implant802 may be structured such that one portion thereof swells at a different rate than another portion thereof, for the purpose outlined above or for different purposes altogether—such as cavity shaping, for example. As suggested inFIGS. 9 and 10A,10B, the post-biopsycavity treatment implant802 may be formed from a tightly rolled up sheet of swellable material. Alternatively, the post-biopsycavity treatment implant802 may be formed of stacked layers of swellable material as shown inFIG. 1C. Alternatively still, the post-biopsycavity treatment implant802 may be formed as a single unitary and homogeneous mass of swellable material and molded or cut (stamped) into the desired shape. Other embodiments include post-biopsy cavity treatment implants formed of or including fibers, fibrils and/or bundles of fibers and/or fibrils.
• According to embodiments of the present invention, the present post-biopsy cavity treatment implant may include or be formed of biocompatible and water swellable material, such as collagen, for example. The collagen molecule is rod-shaped triple helix and consists of a three polypeptide chains coiled about each other. Besides the central triple helical region of the collagen molecule, there are terminal peptides regions known as telopeptides. These telopeptides are non-helical and are subdivided into two groups; namely, amino terminals and carboxyl terminals. Intermolecular crosslinking between triple helical molecules of collagen occurs in the telopeptides regions. Crosslinking may also occur within the central triple helical region of the collagen molecule, and is known as intramolecular crosslinking. It is the control of the formation and density of such crosslinks that is responsible for some of the mechanical, physicochemical and biological properties of the embodiments of the present post-biopsy cavity treatment implant disclosed herein.
• The embodiments of the present post-biopsy cavity treatment implant may be selectively biodegradable and/or bio-absorbable such that it degrades and/or is absorbed after its predetermined useful lifetime is over. An effective way of controlling rate of biodegradation of embodiments of the present post-biopsy cavity treatment implant is to control and selectively vary the number and nature (e.g., intermolecular and/or intramolecular) of crosslinks in the implant material. Control of the number and nature of such collagen crosslinks may be achieved by chemical and/or physical means. Chemical means include the use of such bifunctional reagents such as aldehyde or cyanamide, for example. Physical means include the application of energy through dehydrothermal processing, exposure to UV light and/or limited radiation, for example. Also, a combination of both the chemical and the physical means of controlling and manipulating crosslinks may be carried out. Aldehydes such as glutaraldehydes, for example, are effective reagents of collagenous biomaterials. The control and manipulation of crosslinks within the collagenous matrix of the present post-surgery cavity treatment implant may also be achieved, for example, through a combination of dehydrothermal crosslinking and exposure to cyanamide. For example, the present post-surgery cavity treatment implant may, through proper control of the crosslinking density within the collagen matrix thereof, be designed and implemented to remain long term in situ at the implant site within thecavity126. Crosslinking density may be indirectly measured, for example, via measurement of the swelling ratio where identical dry and wetted samples are weighted and weight is compared.
• According to further embodiments of the present invention, the post-biopsy cavity treatment implant may be formed of or include other biomaterials such as, for example, bioresorbable poly(ester)s such as polylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolides) (PLGA), polyglyconate, polyanhydrides and their co-polymers, PEG, cellulose, gelatins, lipids, polysaccharides, starches and/or polyorthoesters and the like. According to an embodiment of the present invention, the present post-biopsy cavity treatment implant may be formed of or include collagen having a predetermined structure. Such predetermined structure refers not only to the overall shape of the implant, but also to the structure of its internal collagen matrix. Indeed, embodiments of the present invention include a macroporous cross-linked polymer matrix having a predetermined pore architecture. A “pore”, as the term is used herein, includes a localized volume of the present post-biopsy cavity treatment implant that is free of the material from which the post-biopsy cavity treatment implant is formed. Pores may define a closed and bounded volume free of the material from which the post-biopsy cavity treatment implant is formed. Alternatively, pores may not be bounded and many pores may communicate with one another throughout the internal matrix of the present post-biopsy cavity treatment implant. The pore architecture, therefore, may include closed and bounded voids as well as unbounded and interconnecting pores and channels. The internal structure of the post-biopsy cavity treatment implant according to embodiment of the present invention defines pores whose dimensions, shape, orientation and density (and ranges and distributions thereof), among other possible characteristics are tailored so as to maximize the visibility of the resultant post-biopsycavity treatment implant802 under various modalities, notably ultrasound and X-ray, for example. Unlike polymeric matrices that contain bubbles of gas through a process in which gas is forced through a dispersion in a hydrated state, embodiments of the present post-biopsy cavity treatment implant have an internal structure that defines internal voids without requiring such gas to be forced therethrough. There are numerous methods and technologies available for the formation collagenous matrices of different pore architectures and porosities. By tailoring the dimensions, shape, orientation and density of the pores of the present implant, a recognizable pattern of post-biopsy cavity treatment implant material may be formed that may be readily visualized under, for example, ultrasound, X-ray, elastography or microwave radiation. This recognizable pattern may then influence the pattern of tissue ingrowth within thecavity126, forming a porous scaffold on and within which tissue may infiltrate and grow. In turn, this pattern of tissue ingrowth may be readily recognizable under ultrasound and/or other imaging modalities discussed above long after the post-biopsy cavity treatment implant has been absorbed by the body or has degraded.
• According to an embodiment of the present invention, the post-biopsy cavity treatment implant may be formed of or include a collagen matrix having a predetermined pore architecture. For example, the post-biopsy cavity treatment implant may include one or more sponges of lyophilized collagen having a predetermined pore architecture. Suitable collagen material for the post-biopsy cavity treatment implant may be available from, for example, DEVRO, Integra Life Sciences, Collagen Matrix and Kensey Nash, among others. The present post-biopsy cavity treatment implant, after implantation in thecavity126, swells on contact with various body fluids therein and substantially fills a predetermined portion or the entire biopsied cavity, and does so in predictable manner.
• Such a post-biopsy cavity treatment implant may be configured to have a hemostatic functionality to stop bleeding within thecavity126 through a biochemical interaction with blood (such as coagulation) and/or other bodily fluids. The post-biopsy cavity treatment implant may, according to further embodiments, also be used to medically treat the patient. That is, the porous matrix of the present post-biopsy cavity treatment implant may be imbibed or loaded with a therapeutic agent to deliver the agent through elution at thecavity126. Such a therapeutic agent may include, for example, an antibiotic agent, an analgesic agent, a chemotherapy agent, an anti-angiogenesis agent or a steroidal agent, to name but a few of the possibilities.
• The post-biopsycavity treatment implant802 shown inFIGS. 9 and 10 may be formed of one or more thin sheets of collagen material having a predetermined (and controlled) pore architecture that has been rolled up into a cylinder shape. As the post-biopsycavity treatment implant802 swells with water from thecavity126, it may unroll partially or entirely, and at least partially fill thecavity126, including at least a portion of thecavity chamber128. Some of theaccess path127 may also be filled as the post-biopsycavity treatment implant802 swells. The post-biopsycavity treatment implant802, according to embodiments of the present invention, has a predetermined pore architecture or a combination of predetermined pore architectures, as will be described hereunder with reference to the drawings. The description of the figures below assumes that the post-biopsy cavity treatment implant is formed of or contains collagen, it being understood that the embodiments of the present invention disclosed herein are not limited to collagen and that aspects of the present inventions may readily be applied to such non-collagen containing post-biopsy cavity treatment implants.
• FIG. 11 shows a post-biopsycavity treatment implant1100 having predetermined pore architectures, according to an embodiment of the present invention. As shown therein, the post-biopsycavity treatment implant1100 may include afirst portion1102 and asecond portion1104. The collagen matrix of thefirst portion1102 of thedevice1100 defines a plurality ofpores1106 having a first predetermined pore architecture and the collagen matrix of thesecond portion1104 of thedevice1100 defines a plurality ofpores1108 having a second predetermined pore architecture. The dimensions of the layers or portions may be selected at will, preferably accounting for the dimensions of the cavity into which the device is to be inserted. As shown, the first pore architecture featurespores1106 that are relatively small, have a narrow pore size distribution and are substantially randomly oriented. In contrast, the second pore architecture featurespores1108 that have a relatively larger size, have a wider pore size distribution, are predominantly oriented along the axis indicated by double-headedarrow1110 and are less densely distributed than thepores1106 of thefirst portion1102 of the post-biopsycavity treatment implant1100. Between the first andsecond portions1102 and1104 lies theinterface1103. As shown, the post-biopsycavity treatment implant1100 may be formed of a first collagen matrix having a first predetermined pore architecture and a second collagen matrix having a second pore architecture. The two collagen matrices may each be formed from separate collagen dispersions, each of which may be caused to form pores having predetermined characteristics and may each be lyophilized and formed (e.g., molded, cut or stamped) into the desired shape (in the illustrative case ofFIG. 11, a substantially cylindrical shape). The two collagen plugs formed thereby may then be stacked one on the other, re-wetted and again lyophilized through a lyophilization process in a specifically shaped mold (for example) to form the stacked laminate structure shown inFIG. 11. Other methods of making the post-biopsycavity treatment implant1100 may occur to those of skill in this art. Not only may the predetermined pore architectures of thefirst portion1102 and of thesecond portion1104 cause these portions to be visible under, for example, ultrasound, but theinterface1103 therebetween may also be visualizable and recognizable under, for example, ultrasound as the boundary between two regions having a pronounced density differential. As can be seen, the post-biopsycavity treatment implant1100 is not formed of a rolled up sheet of material, as is the post-biopsycavity treatment implant802 inFIGS. 9 and 10. Instead, the post-biopsycavity treatment implant1100 is formed of solid matrices of collagenous material. It is to be understood that the pore architecture of the first andsecond portions1102,1104 may be varied at will by, for example, changing the porosity and/or crosslinking of the collagen chains, the pore density, the distribution of pore size, the orientation of the pores and the shape of the pores, to mention a few of the possible pore parameters. By judiciously choosing the pore architectures of the first andsecond portions1102,1104, one end of the post-biopsycavity treatment implant1100 may be caused to swell at a faster rate than the other end thereof. This is the case illustrated inFIG. 10.
• Moreover, the cross-sectional characteristics of the post-biopsycavity treatment implant1100 may be changed. For example, thefirst portion1102 may form a cylindrical inner core of collagenous material having a first predetermined pore architecture and thesecond portion1104 may form a cylindrical outer shell around the inner core and may define a second pore architecture. In this manner, the outer surface of the post-biopsycavity treatment implant1100 may swell at a different rate (e.g., faster) than the rate at which the inner core swells. Moreover, the pore architectures may be chosen to maximize not only water absorption, but also to promote tissue ingrowth, to facilitate imaging and/or may be tailored to contain and release a pharmaceutical agent at a controllable rate and/or under predetermined conditions. Alternatively, the inner core may be formed of or include a non-collagenous material (such as a polylactic or polyglycolic material, for example) and the outer shell may include a collagenous material, for example. The outer shell may include a solid matrix of collagenous material having a predetermined pore architecture and/or may include wound fibers of collagenous material having a predetermined pore architecture, for example.
• FIG. 12 shows a post-biopsycavity treatment implant1200 having predetermined pore architectures, according to another embodiment of the present invention. As shown, the post-biopsycavity treatment implant1200 includes afirst portion1202 and asecond portion1204, each of which has a predetermined pore architecture. It is to be noted that the present post-biopsy cavity treatment implants may have more than the two portions shown in bothFIGS. 11 and 12 (or may define only a single portion). As shown, the post-biopsycavity treatment implant1200 is shaped as a substantially rectangular sponge. Thefirst portion1202 is stacked on thesecond portion1204. As with the embodiment shown inFIG. 11, the first and second portions may have pore architectures that facilitates tissue ingrowth, wound healing and are readily visualizable and/or recognizable under one or more imaging modalities. The different pore architectures of post-biopsy cavity treatment implants according to embodiments of the present invention may also be chosen so as to maximize the visibility of the interface (such asreference numeral1203 inFIG. 12) therebetween under the desired imaging modality such as, for example, ultrasound.
• Post-biopsy cavity treatment implants according to embodiments of the present invention need not be formed as a solid mass of collagen (FIGS. 11, 12) or as a rolled up sheet of collagen (FIGS. 9, 10).FIGS. 13A, 13B and13C show various other configurations for the present implant. As shown therein, embodiments of the present invention may include or be formed of a bundle of fibers orfibrils1302 of (for example) collagenous material having one or more predetermined pore architectures. The pores defined within the collagen matrix of all or some of the fibers are not shown inFIGS. 13A-13C, but are nevertheless present. Thebundle1300 of fibers shown inFIG. 13A may be used to form post-biopsy cavity treatment implants by, for example, forming them into a rope-like structure as shown inFIG. 13B. In the cross-sectional representation ofFIG. 13B, the longitudinal axis of the individual constituent fibers is perpendicular to the plane of the page on which they are printed. Post-biopsy cavity treatment implants may also be formed from thebundle1300 ofFIG. 13A by cutting (at1304, for example) thebundle1300 into a plurality of sections at an angle that is (for example) perpendicular to the longitudinal axis of thefibers1302, so as to form a post-biopsy cavity treatment implant whose constituent fibers run from one end of the post-biopsy cavity treatment implant to the other end thereof, as shown in the detail representation ofFIG. 13C. According to an embodiment of the present invention, a post-biopsy cavity treatment implant may be formed of a volume of collagenous material having a predetermined pore architecture or a combination of several bounded volumes of collagenous materials, each with a predetermined pore architecture. For example, several sponges having the structure shown inFIG. 13C may be stacked onto each other to define a laminate structure having a layered, composite pore architecture.
• FIG. 13D shows another embodiment of the present post-biopsy cavity treatment implant. As shown, theimplant1306 includes afirst portion1308 and asecond portion1310. According to an embodiment of the present invention, thefirst portion1308 may include a solid matrix ofcollagenous material1312 having a first predetermined pore architecture. Thesecond portion1310 may include a plurality of fibers orfibrils1314. The plurality of fibers may also be formed of or include collagenous material, and this collagenous material may have the same pore architecture as thefirst portion1308 or a different pore architecture. The plurality of fibers may be formed or include non-collagenous material, such as polylactic or polyglycolic acid, for example. In the case wherein the plurality offibers1314 are formed of a collagenous material, after implantation in an aqueous environment such as a cavity within a patient, thesecond portion1310 may swell at a faster rate than thefirst portion1310, as theconstituent fibers1314 thereof may be exposed to the aqueous environment of the cavity over their entire surface. This swelling rate differential between the first andsecond portions1308,1310 may serve to further secure theimplant1306 within the cavity. In the case wherein the cavity is relatively dry, the physician may choose to introduce a volume of an aqueous solution, such as saline, into the cavity to speed the swelling of theimplant1306. Theimplant1306 may be formed from a collagen dispersion in a mold configured to form thefirst portion1308 and thesecond portion1310 and lyophilized. Alternatively, thefibers1314 may be formed after lyophilization by cutting theimplant1306 so as to form the plurality offibers1314. Alternatively still, the first andsecond portions1308,1310 may be formed by superimposition of the first andsecond portions1310,1310, as discussed above. Other means of forming the first andsecond portions1310,1312 may occur to those of skill in this art.
• FIG. 13E shows another embodiment of the present post-biopsy cavity treatment implant. As shown therein, theimplant1316 is similar to the embodiment ofFIG. 13D, but for the addition of athird portion1318 on another surface of thefirst portion1308. Thethird portion1318 may be formed as detailed above relative tosecond portion1310. The pore architecture of thethird portion1318 may be the same as that of thefirst portion1308 and thesecond portion1310, or may be different therefrom. It should be noted that various modifications to the embodiments ofFIGS. 13D and 13E may be envisaged. For example, the embodiment of theimplant1316 ofFIGS. 13E may be modified to include additional fibers or fibrils projecting from other surfaces of thefirst portion1308. Other modifications may occur to those of skill in this art, and all such modifications are deemed to fall within the scope of the present invention.
• FIG. 14A through 14E show other illustrative embodiments of the post-biopsy cavity treatment implants according to the present invention. As shown inFIG. 14A, two or more bundles of fibers of collagenous material (for example—the fibers may be made of or include other materials) may be used in the formation of post-biopsy cavity treatment implants according to embodiments of the present invention. As shown, the pores within the fibers of thefirst bundle1402 may collectively define a first pore architecture, whereas the pores within the fibers of asecond bundle1404 may collectively define a second pore architecture that is different from the first pore architecture. The twobundles1402,1404 may then be joined together, for example, by re-wetting the bundles, stacking them and lyophilizing the composite structure. The length and diameter of the fibers may be selected and varied at will. The fibers or bundles thereof may even be woven together. From this composite structure, post-biopsy cavity treatment implants may be formed. As shown inFIG. 14B, the bundles of fibers may be arranged in a cylindrical shape, for example. Such a cylindrical shape may include aninner core1406 of fibers having a first pore architecture and anouter shell1408 surrounding theinner core1406. The outer shell may include fibers having a second pore architecture that is different from the pore architecture of theinner core1406.FIG. 14C shows a detail of a post-biopsy cavity treatment implant having afirst portion1402 of fibers having a first pore architecture and asecond portion1404 having a second pore architecture, formed, for example, by cutting the composite structure ofFIG. 14A at1410. Alternatively still, the fibers may be arranged such that the constituent fibers thereof closer to the center of the post-biopsy cavity treatment implant conform to a first pore architecture whereas the outside constituent fibers thereof conform to a second pore architecture that is different from the first pore architecture. As shown in the exploded views ofFIGS. 14D and 14E, the post-biopsy cavity treatment implant may be have a layered laminate structure in which sheets formed of fibers (or woven fibers) having a first pore architecture are stacked onto sheets formed of fibers having a second pore architecture. As shown inFIG. 14E, many variations on this theme are possible. As shown therein, the orientation of the fibers (and thus of the pores defined by the collagenous matrix thereof) may be varied. For instance, whereas the fibers of the first (top or outer, for example) portion of the post-biopsy cavity treatment implant may be oriented in a first direction, whereas the fibers of the second (bottom or inner, for example) portion of the post-biopsy cavity treatment implant may be oriented along a direction that is different from the first direction (perpendicular thereto, for example). Imaging such post-biopsy cavity treatment implants within a cavity (such as shown at126 inFIGS. 9 and 10, for example) using sonography may yield an image in which any fluids contained in thecavity126 may appear substantially black, because the sound waves travel directly through such anechoic media, and a gradation of visible structures defined by comparatively hypoechoic layers or portions of the post-biopsy cavity treatment implant whose echogenicity is lower than the surrounding area and defined by hyperechoic layers or portions of the post-biopsy cavity treatment implant whose echogenicity is higher than the surrounding area.
• FIGS. 14F and 14G illustrate the stacked structure of a post-biopsy cavity treatment implant, according to further embodiments of the present invention. The embodiments ofFIGS. 14F and 14G are similar to the embodiments shown inFIGS. 14D and 14E, but for the structure of the stacked sheets of collagenous material. InFIGS. 14F and 14G, the stacked sheets of collagenous material are not formed of fibers or fibrils, but instead are each formed of a solid mass of collagenous material. The sheets may have the same or different pore architectures. Moreover, the sheets of collagenous material may define pore architectures in which the predominant orientation of the pores is varied. For example, some of the sheets may have a pore architecture in which the pores are predominantly oriented along the y-axis (FIG. 14F) or along the x-axis (FIG. 14G), for example. Alternatively, the constituent sheets of collagenous materials may define pore architectures in which other pore characteristics (size, shape, density, for example) are varied according to a predetermined pattern to influence tissue growth, visualization, etc. The resulting laminate structure may be formed (e.g., molded or cut) in the desired shape of the implant. For example, the resulting laminate structure may then be rolled into a cylindrical shape, as suggested inFIGS. 8 and 9, for example.
• FIG. 15A shows a post-biopsy cavity treatment implant according to another embodiment of the present invention. As shown, the post-biopsycavity treatment implant1500 includes aninner portion1502 and anouter portion1504. Theinner portion1502 may be radiopaque. For example, theinner portion1502 may be or include a metallic element. The metallic element may have a simple bar shape as shown, or may have a more complex shape such as, for example, a ring. Theinner portion1502 may have other structures to, for example, adhere or hook onto the walls of thecavity126. Wound around theinner portion1502 is one ormore fibers1504 of swellable (collagenous, for example) material having one or more predetermined pore architectures and/or one or more controlled crosslinking densities. The inner portion may be completely encased within the wound bundles of fibers orfibrils1504 or may be only partially encased, as shown inFIG. 15A. Theinner element1502, rather than being radiopaque, may have a predetermined echogenicity so as to be immediately recognizable under ultrasound. Theinner element1502, moreover, may include an inner reservoir configured to contain a volume of therapeutic agent. For example, theinner element1502 may be bioabsorbable and may be configured to release the contained pharmaceutical agent at a controlled rate. A plurality of fibers1504 (having the same or different pore architectures) may be wound about theinner element1502, the windings thereof being oriented at a given inclination or mutually different inclinations. Moreover, the embodiments ofFIGS. 11 through 14E may advantageously be provided with an inner element as shown at1502 and/or as described immediately above.
• FIG. 15B and the cross-sectional representation ofFIG. 15C show another embodiment of the present post-biopsy cavity treatment implant. As shown therein, theimplant1506 may include a firstinner portion1508 forming an inner core and a secondouter portion1510 forming an outer shell around the firstinner portion1508. Both the first and second portions may be formed of or include a collagenous material. Thefirst portion1508 may have a first predetermined pore architecture and thesecond portion1510 may have a second predetermined pore architecture that is different from pore architecture of thefirst portion1508. For example, thefirst portion1508 may have a greater pore density (number of pores per unit volume) than thesecond portion1510. In theexemplary implant1506 shown inFIGS. 15B and 15C, the pore architecture of thefirst portion1508 is such that the collagenous material thereof defines pores that are both smaller and more densely packed than those defined by the collagenous material of thesecond portion1510. AlthoughFIGS. 15B and 15C show theimplant1506 as shaped as a right cylinder, theimplant1506 may be molded into most any shape, to accommodate most any cavity shape. In this manner, the implant may be configured such that its ultimate size and shape after implantation and swelling, substantially matches the size and shape of the cavity in which it is implanted. As shown in the cross-sectional representation ofFIG. 15C, thefirst portion1508 of theimplant1506 may define an inner reservoir1512 (created as a void within thefirst portion1508 or as a discrete biocompatible reservoir or pouch having a predetermined biodegradability rate). Theinner reservoir1512 may be pre-loaded with a dye/pigment and/or a pharmaceutical agent, as indicated at1514 inFIG. 15C. The pharmaceutical agent may be configured to slowly release into thecavity126 as soon as the implant is inserted therein and/or may be configured to require a physician or a RN to pinch or squeeze (or otherwise breach) theimplant1506 to rupture thereservoir1512 to release the dye/pigment and/orpharmaceutical agent1514 contained therein.
• FIG. 15D shows another embodiment of the implant according to the present invention. Theimplant1516 includes afirst portion1508 defining a first pore architecture, such as described above relative toFIGS. 15B and 15C. Theimplant1516 may include areservoir1512, and thereservoir1512 may contain a volume of dye/pigment and/or one or more therapeutic agents. Wound around thefirst portion1508 is one or more fibers or fibrils of collagenous material defining a second pore architecture that may be different from the first pore architecture. The fibers orfibrils1520 may completely encase thefirst portion1508 or may do so only partially, as shown inFIG. 15D.FIGS. 15E and 15F show another embodiment of the present invention. In this embodiment, theimplant1518 also includes afirst portion1508 defining a first pore architecture, as described relative toFIGS. 15B-15D above. At least partially surrounding thefirst portion1508 are a plurality of fibers orfibrils1508 that define a second pore architecture that may be different from the first pore architecture. Several layers of such fibers orfibrils1508 may be disposed around thefirst portion1508, as suggested by the cross-sectional view ofFIG. 15F.
• Most any of the portions or layers of the embodiments disclosed herein may be configured to contain one or more dyes/pigments and/or pharmaceutical agents. The post-biopsy cavity treatment implants discussed herein may be rendered selectively radiopaque by the selective mechanical, chemical or physical incorporation of a radiopaque articles or particles into the collagenous matrix of embodiments of the present post-biopsy cavity treatment implant. For example, the post-biopsy cavity treatment implant may define pores having a predetermined and recognizable architecture and may incorporate some radiopaque compound or particles such as, for example barium sulfate or other commonly used radiopaque or radioactive materials.
• Embodiments of the present invention may also include recognizable articles or substances within the collagenous matrix such as, for example, dyes and/or pigments (i.e., including both synthetic dyes and natural pigments). The dyes/pigments may be incorporated within the collagenous dispersion that forms the constituent layers or portions of the embodiments of the post-biopsy cavity treatment implants disclosed herein. Such dyes/pigments may form mapping compounds that may be gradually released into the body upon implantation of the present post-surgery cavity treatment implant and may form the basis of lymphatic mapping in the future. In this manner, lymphatic mapping may be carried out immediately after a biopsy procedure via elution of the mapping compound (e.g., dyes/pigments and/or radioactive agent) deposited into the collagenous matrix of the implant. In the case wherein a cancer is detected or suspected in the tissue specimen retrieved by the biopsy procedure, this elution of mapping compound from the post-biopsy cavity treatment implant may enable the physician to skip the conventional step of injecting dyes/pigments into the patient, which dye/pigment injection step is conventionally carried out prior to a (sentinel) lymph node status evaluation procedure. Embodiments of the post-biopsy cavity treatment implant according to present invention may include metal-less dyes/pigments as well radiopaque, radioactive or paramagnetic metal-containing dyes/pigments such as, for example, porphyrins and/or porphyrin derivatives (such as chlorophyll and/or chlorophyll derivatives, for example) that are bound to the collagenous matrix. The porphyrins and/or porphyrin derivatives may be tailored, for example, to enhance crosslinking and enhance wound healing and/or to control biodegradation, among other reasons. A metal with paramagnetic properties (such as Mn, for example) may be placed within the porphyrins or porphyrin derivatives so that another mode of recognition may be achieved. Impregnation of the present post-biopsy cavity treatment implant with porphyrins or porphyrin derivatives (for example, copper chlorophyllin) gives the post-biopsy cavity treatment implant a lymphatic mapping functionality due to the elution of the porphyrins or porphyrin derivatives into the surrounding tissue lymphatic drainage system.
• According to other embodiments of the present invention, the present post-biopsy cavity treatment implants may define or include an internal reservoir configured to contain a volume of a mapping compound and/or a beneficial therapeutic agent. Following the biopsy procedure and the subsequent implantation of the present post-biopsy cavity treatment implant having a predetermined pore architecture into the biopsy cavity and following a histopathology report on the excised biopsy specimen, the physician or RN may pinch or squeeze the post-biopsy cavity treatment implant to express the mapping compound(s) and/or agent(s) into the surrounding tissue via lymphatic system to the sentinel node and other lymphatics. In the absence of such squeezing or pinching, the mapping compound and/or therapeutic agent may much more gradually find its way into the surrounding tissue through elution following a gradual biodegradation of the reservoir.
• FIGS. 16-20 are photomicrographs of collagenous matrices having various pore architectures. As shown, the porosity of the collagenous material is not formed by bubbles forced through the collagen dispersion prior to lyophilization thereof. Indeed, it is the structure of the collagen material itself that creates and defines the voids or pores (anechoic regions that appear black in the photomicrographs) within the material.FIGS. 17 and 19 show relatively round pores having a wide size distribution, whereasFIGS. 16 and 18 show a relatively denser collagen matrix having a smaller pore size distribution.FIG. 20 shows an example of a collagenous matrix that is relatively less dense than, for example, the matrix shown inFIG. 18.
• FIGS. 21-23 are combinations of photomicrographs to illustrate further embodiments of the post-biopsy cavity treatment implants according to the present invention.FIG. 21 shows a post-biopsycavity treatment implant2100 that includes afirst portion2102 having a first pore architecture and, stacked thereon, asecond portion2104 having a second pore architecture. As shown, the pore architecture of thefirst portion2102 may be characterized as being relatively denser than the pore architecture of thesecond portion2104. Alternatively, the post-biopsycavity treatment implant2100 may be structured such that the first portion has a higher porosity (is less dense) than that of thesecond portion2104. The thicknesses of the first andsecond portions2102,2104 may be varied at will. More than two layers of collagenous material may be provided.
• FIG. 22 shows a post-biopsycavity treatment implant2200 having a graduated porosity profile. Such a post-biopsycavity treatment implant2200 may be formed by lining up a plurality of collagen matrices having of progressively lower densities. That is, matrix2002 has the highest density (amount of collagen per unit volume),matrix2204 has the next highest density,matrix2206 has the next to lowest porosity andmatrix2208 has the lowest porosity of the entire post-biopsycavity treatment implant2200. Alternatively, the degree to which each matrix is crosslinked may be varied and controlled. For example, each matrix may be crosslinked to a different degree through the use of, for example, gluteraldehyde. For example,matrix2202 may be configured to have about 0.0085% gluteraldehyde,matrix2204 may be configured with about 0.0075% gluteraldehyde,matrix2206 may be configured with about 0.0065% gluteraldehyde andmatrix2208 may be configured with about 0.0055% gluteraldehyde, for example. Other concentrations are possible, as are different reagents. After superimposing all foursuch matrices2202,2204,2206 and2208, a (in this case, piece-wise linear) cross-linking and/or porosity gradient may be achieved across the embodiment of the present post-biopsy cavity treatment implant shown at2200.
• FIG. 23 shows a composite post-biopsycavity treatment implant2300 having a more complex structure, according to another embodiment of the present invention. The post-biopsycavity treatment implant2300 includes three distinct collagen matrices, as shown at2302,2306 and2308. As shown, each of thematrices2302,2306 and2308 has a unique pore architecture. Indeed, the portion of the post-biopsy cavity treatment implant referenced at numeral2302 has a dense appearance, in which the pores have a high aspect ration and are aligned substantially parallel to the length of thedevice2300. The post-biopsycavity treatment implant2300 also includes asecond portion2304 that includes two unique collagenous matrices referenced at2306 and2308, each having different pore architectures. Whereasmatrix2306 features a wide distribution of pore shapes and sizes,matrix2308 features comparatively larger, generally rounder pores than those ofmatrix2306. Each of thesematrices2302,2306 and2308 may have a unique ultrasonic or X-ray signature and/or contain dyes/pigments or radiopaque materials or compounds. Moreover, not only may the various matrices be visible under selected modalities, the interfaces therebetween may also provide the physician with position and orientation information of the post-biopsy cavity treatment implant within the cavity. Indeed, there are distinct interfaces between dissimilar materials betweenmatrices2302 and2306, betweenmatrices2302 and2308 as well as a distinct interface between adjoiningmatrices2306 and2308, each of which may be readily visible under, for example, ultrasound. It is to be noted that the interfaces between the external surfaces of all threematrices2302,2306 and2308 with the surrounding tissue may also provide the physician with additional visual clues are to the position and orientation of the post-biopsycavity treatment implant2300 within the cavity in which it is implanted. The interfaces described herein, as well as the different rates of swelling may be achieved through control of the porosity and/or as through the control of crosslinking. A single post-biopsy cavity treatment implant may include constituent portions controlled to have a predetermined pore architecture and/or predetermined portions having controlled crosslinking. Although the irregular closed features within the drawings are intended to suggest pores of various configurations and densities, they are alternatively intended to indicate crosslinking. Therefore, illustrated differences in these irregular closed features between adjacent portions of an implant may also be interpreted as being differences in crosslinking densities between adjacent portions in the implant.
• Use of the post-biopsy cavity treatment implants disclosed herein is not limited to filling post biopsy cavities. Indeed, the present post-biopsy cavity treatment implants also find utility in the correction of defects caused by poorly healed cavities, whatever their origin or cause. The present post-biopsy cavity treatment implants may be placed in cavities in which it is desired that the collagen matrices be replaced, over time, with (human or animal) autogenous tissue. Hence, the embodiments of the present invention may be used for the repair of tissue that has been damaged due to tissue removal, thereby providing a favorable tissue scaffold in which autogenous tissue may infiltrate and grow. In addition, embodiments of the post-biopsy cavity treatment implants according to the present invention may serve to absorb exudates within the cavity, thereby further facilitating the healing process.
• While the foregoing detailed description has described preferred embodiments of the present invention, it is to be understood that the above description is illustrative only and not limiting of the disclosed invention. For example, the post-biopsy cavity treatment implants disclosed herein may be configured to have a unique “signaturing” capability, in which a specific code appears under a given imaging modality. The specific code may be formed within or molded into the structure of the collagen matrix or matrices. For example, a combination of the elements with different crosslinking patterns (e.g., bundles of cylindrical fibers or layers of collagen sponges) may be used for both pattern recognition and predictable filling of the post biopsy procedure cavity. Alternatively, the code may be embodied as a discrete echogenic or radiopaque constituent element of the implant. The codes may confer information to the radiologist or treating physician when viewed under X-ray or ultrasound. Alternatively still, the post-biopsy cavity treatment implants having predetermined pore architectures and/or controlled crosslinking densities according to the disclosed embodiments may include a biocompatibly-sealed integrated circuit that may be interrogated electronically to convey information to the physician. Those of skill in this art may recognize other alternative embodiments and all such alternative embodiments are deemed to fall within the scope of the present invention.

Claims (73)

1. A post-biopsy cavity treatment implant, comprising:

a first portion including a first porous matrix defining a first controlled pore architecture, and

a second portion coupled to the first portion, the second portion including a second porous matrix defining a second controlled pore architecture that is different from the first controlled pore architecture to cause the second portion to swell in a different manner than the first portion when the post-biopsy cavity treatment implant is implanted in an aqueous environment.

2. The post-biopsy cavity treatment implant ofclaim 1, wherein the second portion swells faster than the first portion when the implant is implanted in the aqueous environment.

3. The post-biopsy cavity treatment implant ofclaim 1, wherein the second portion swells to a greater extent than the first portion when the implant is implanted in the aqueous environment.

4. The post-biopsy cavity treatment implant ofclaim 1, wherein the first controlled pore architecture differs from the second controlled pore architecture with respect to at least one of: pore density, pore shape, pore orientation and pore dimensions.

5. The post-biopsy cavity treatment implant ofclaim 1, wherein at least one of the first and second portions includes a radiopaque material disposed therein.

6. The post-biopsy cavity treatment implant ofclaim 1, wherein at least one of the first and second portions includes a radioactive material disposed therein.

7. The post-biopsy cavity treatment device ofclaim 1, wherein at least one of the first and second portions includes a paramagnetic material disposed therein.

8. The post-biopsy cavity treatment implant ofclaim 1, wherein at least one of the first and second portions includes a dye disposed therein.

9. The post-biopsy cavity treatment implant ofclaim 1, wherein at least one of the first and second portions includes a pigment disposed therein.

10. The post-biopsy cavity treatment implant ofclaim 1, wherein at least one of the first and second portions includes a contrast media disposed therein.

11. The post-biopsy cavity treatment implant ofclaim 1, wherein at least one of the first and second portions includes a therapeutic agent disposed therein.

12. The post-biopsy cavity treatment implant ofclaim 1, wherein at least one of the first and second portions is biodegradable.

13. The post-biopsy cavity treatment implant ofclaim 1, wherein at least one of the first and second portions includes collagen.

14. The post-biopsy cavity treatment implant ofclaim 1, wherein the first and second portions include at least one of a polylactide (PLA), a polyglycolide (PGA), a poly(lactide-co-glycolide) (PLGA), a polyglyconate, a polyanhydride, PEG, cellulose, a gelatin, a lipids, a polysaccharide, a starches and a polyorthoesters.

15. The post-biopsy cavity treatment implant ofclaim 1, wherein the first and second portions are configured so as to form a laminar structure.

16. The post-biopsy cavity treatment implant ofclaim 1, wherein the first portion defines a first surface and wherein the second portion defines a second surface that faces the first surface to define an interface between the first and second portions.

17. The post-biopsy cavity treatment implant ofclaim 4, wherein the interface is visualizable under ultrasound when the post-biopsy cavity treatment implant is implanted.

18. The post-biopsy cavity treatment implant ofclaim 1, wherein at least the first portion includes a plurality of fibers.

19. The post-biopsy cavity treatment implant ofclaim 1, wherein the first portion forms an inner core and wherein the second portion forms an outer shell disposed at least partially around the first portion.

20. The post-biopsy cavity treatment implant ofclaim 1, wherein at least one of the first and second portions includes an internal reservoir configured to contain at least one of a dye, a pigment and a therapeutic agent.

21. The post-biopsy cavity treatment implant ofclaim 20, wherein the internal reservoir is configured to deliver the at least one of dye, pigment and therapeutic agent through elution when the implant is implanted in the aqueous environment.

22. The post-biopsy cavity treatment implant ofclaim 20, wherein the internal reservoir is configured to deliver the at least one of dye, pigment and therapeutic agent at a first rate when the reservoir is breached and at a second rate that is lower than the first rate when the reservoir is not breached.

23. The post-biopsy cavity treatment implant ofclaim 1, further including a third portion, the third portion being radiopaque.

24. The post-biopsy cavity treatment implant ofclaim 23, wherein the third portion includes a metal.

25. The post-biopsy cavity treatment implant ofclaim 1, further including a third portion including a third porous matrix defining a third controlled pore architecture, the first, second and third portions collectively defining a predetermined pore density gradient.

26. The post-biopsy cavity treatment implant ofclaim 1, wherein the second portion is configured to have a second crosslinking density and wherein the first portion is configured to have a first crosslinking density that is greater than the second crosslinking density.

27. The post-biopsy cavity treatment implant ofclaim 26, wherein the second portion is configured to swell to a greater degree than the first portion when the implant is implanted in the aqueous environment.

28. The post-biopsy cavity treatment implant ofclaim 1, wherein the first and second portions include collagen and wherein a crosslinking density of at least one of the first and second portions is controlled through adding a selected amount of a bifunctional reagent to the collagen.

29. The post-biopsy cavity treatment implant ofclaim 28, wherein the bifunctional reagent includes at least one of a aldehyde and a cyanamide.

30. The post-biopsy cavity treatment implant ofclaim 29, wherein the aldehyde includes a glutaraldehyde.

31. The post-biopsy cavity treatment implant ofclaim 1, wherein the first and second portions include collagen and wherein a crosslinking density of the first and second portions is controlled by an application of energy to the collagen.

32. The post-biopsy cavity treatment implant ofclaim 31, wherein the application of energy includes at least one of dehydrothermal processing, exposure to UV light and radiation.

33. The post-biopsy cavity treatment implant ofclaim 1, wherein the first and second portions include collagen and wherein a crosslinking density of at least one of the first and second portions is controlled by a combination of dehydrothermal processing and exposure to cyanamide.

34. A method for mapping a lymphatic system following a cavity generating procedure, comprising:

providing a post-biopsy cavity treatment implant, the implant including a collagenous matrix having a non-uniform cross-linking density that is configured to cause the implant to swell non-uniformly when placed within an aqueous environment, the implant including a dye or a pigment contained therein;

implanting the provided post-biopsy cavity treatment implant into the cavity;

closing the cavity with the post-biopsy cavity treatment implant implanted therein;

causing the dye/pigment to be released from the implant and to propagate through the lymphatic system, and

visualizing the propagated dye/pigment in the lymphatic system using a selected visualization mode.

35. The method ofclaim 34, wherein the implant in the providing step includes a reservoir disposed within the collagenous matrix, the reservoir containing a volume of the dye/pigment and wherein the causing step includes a step of breaching the reservoir to release the dye/pigment.

36. The method ofclaim 35, wherein the breaching step includes a step of squeezing the implanted post-biopsy cavity treatment implant.

37. The method ofclaim 34, wherein the causing step includes a step of waiting for a predetermined period of time during which the implant degrades within the cavity and releases the dye/pigment.

38. The method ofclaim 34, wherein the at least one of dye and pigment is loaded within the collagenous matrix of the implant.

39. The method ofclaim 34, wherein visualizing mode in the visualizing step includes at least one of ultrasound, X-ray, MRI, elastography, microwave and the unaided eye.

40. A post-biopsy cavity treatment implant, comprising:

a first portion comprising a first collagenous matrix, the first collagenous matrix being controlled to have a first crosslinking density, and

a second portion in contact with the first portion, the second portion comprising a second collagenous matrix, the second collagenous matrix being controlled to have a second crosslinking density, the first crosslinking density being controlled to be different than the second cross-linking density.

41. The post-biopsy cavity treatment implant ofclaim 40, wherein the second portion swells faster than the first portion when the implant is implanted in the aqueous environment.

42. The post-biopsy cavity treatment implant ofclaim 40, wherein the second portion swells to a greater extent than the first portion when the implant is implanted in the aqueous environment.

43. The post-biopsy cavity treatment implant ofclaim 40, wherein at least one of the first and second collagenous matrices includes a radiopaque material disposed therein.

44. The post-biopsy cavity treatment implant ofclaim 40, wherein at least one of the first and second collagenous matrices includes a radioactive material disposed therein.

45. The post-biopsy cavity treatment device ofclaim 40, wherein at least one of the first and second collagenous matrices includes a paramagnetic material disposed therein.

46. The post-biopsy cavity treatment implant ofclaim 40, wherein at least one of the first and second collagenous matrices includes a dye disposed therein.

47. The post-biopsy cavity treatment implant ofclaim 40, wherein at least one of the first and second collagenous matrices includes a pigment disposed therein.

48. The post-biopsy cavity treatment implant ofclaim 40, wherein at least one of the first and second collagenous matrices includes a contrast media disposed therein.

49. The post-biopsy cavity treatment implant ofclaim 40, wherein at least one of the first and second collagenous matrices includes a therapeutic agent disposed therein.

50. The post-biopsy cavity treatment implant ofclaim 40, wherein at least one of the first and second portions is biodegradable.

51. The post-biopsy cavity treatment implant ofclaim 40, wherein at least one of the first and second portions includes collagen.

52. The post-biopsy cavity treatment implant ofclaim 40, wherein the first and second portions include at least one of a polylactide (PLA), a polyglycolide (PGA), a poly(lactide-co-glycolide) (PLGA), a polyglyconate, a polyanhydride, PEG, cellulose, a gelatin, a lipids, a polysaccharide, a starches and a polyorthoesters.

53. The post-biopsy cavity treatment implant ofclaim 40, wherein the first and second portions are configured so as to form a laminar structure.

54. The post-biopsy cavity treatment implant ofclaim 40, wherein the first portion defines a first surface and wherein the second portion defines a second surface that faces the first surface to define an interface between the first and second portions.

55. The post-biopsy cavity treatment implant ofclaim 54, wherein the interface is visualizable under ultrasound when the post-biopsy cavity treatment implant is implanted in the aqueous environment.

56. The post-biopsy cavity treatment implant ofclaim 40, wherein at least the first portion includes a plurality of fibers.

57. The post-biopsy cavity treatment implant ofclaim 40, wherein the first portion forms an inner core and wherein the second portion forms an outer shell disposed at least partially around the first portion.

58. The post-biopsy cavity treatment implant ofclaim 40, wherein at least one of the first and second portions includes an internal reservoir configured to contain at least one of a dye, a pigment and a therapeutic agent.

59. The post-biopsy cavity treatment implant ofclaim 58, wherein the internal reservoir is configured to deliver the at least one of dye, pigment and therapeutic agent through elution when the implant is implanted in the aqueous environment.

60. The post-biopsy cavity treatment implant ofclaim 58, wherein the internal reservoir is configured to deliver the at least one of dye, pigment and therapeutic agent at a first rate when the reservoir is breached and at a second rate that is lower than the first rate when the reservoir is not breached.

61. The post-biopsy cavity treatment implant ofclaim 40, further including a third portion disposed between the first and second portions, the third portion being radiopaque.

62. The post-biopsy cavity treatment implant ofclaim 61, wherein the third portion includes a metal.

63. The post-biopsy cavity treatment implant ofclaim 40, further including a third portion including a third porous matrix defining a third controlled pore architecture, the first, second and third portions collectively defining a predetermined pore density gradient.

64. The post-biopsy cavity treatment implant ofclaim 1, wherein the first and second portions include collagen and wherein the crosslinking density of the at least one of the first and second portions is controlled through adding a selected amount of a bifunctional reagent to the collagen.

65. The post-biopsy cavity treatment implant ofclaim 64, wherein the bifunctional reagent includes at least one of a aldehyde and a cyanamide.

66. The post-biopsy cavity treatment implant ofclaim 65, wherein the aldehyde includes a glutaraldehyde.

67. The post-biopsy cavity treatment implant ofclaim 40, wherein the first and second portions include collagen and wherein a crosslinking density of the first and second portions is controlled by an application of energy to the collagen.

68. The post-biopsy cavity treatment implant ofclaim 67, wherein the application of energy includes at least one of dehydrothermal processing, exposure to UV light and radiation.

69. The post-biopsy cavity treatment implant ofclaim 40, wherein the first and second portions include collagen and wherein the crosslinking density of at least one of the first and second portions is controlled by a combination of dehydrothermal processing and exposure to cyanamide.

70. A post-biopsy cavity treatment implant, comprising:

a first portion including a first collagenous matrix defining a first controlled pore architecture, and

a second portion coupled to the first portion, the second portion comprising a second collagenous matrix, the second collagenous matrix being controlled to have a first controlled crosslinking density to cause the second portion to swell in a different manner than the first portion when the post-biopsy cavity treatment implant is implanted in an aqueous environment.

71. Method of filling a cavity created by an excisional procedure, the cavity having a predetermined shape, the method comprising the steps of:

providing an implant, the implant including at least a first portion and a second portion, the first portion comprising a first collagenous matrix that defines a first selected crosslinking density, the second portion comprising a second collagenous matrix that defines a second selected crosslinking density that is different than the second cross-linking density, the first and second cross-linking densities being selected so as to cause the first and second portions to swell into a size and a shape that is similar to the predetermined shape of the cavity when the implant is implanted;

implanting the implant within the cavity through an incision;

adding an aqueous solution to the cavity if the cavity is not sufficiently aqueous to cause the implant to swell, and

closing the incision with the implant implanted in the cavity.

72. The method ofclaim 71, wherein the first portion comprises a plurality of first collagenous fibers, each of the plurality of first collagenous fibers having the first selected crosslinking density.

73. The method ofclaim 71, wherein the second portion comprises a plurality of second collagenous fibers, each of the plurality of second collagenous fibers having the second selected crosslinking density.

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