Patent Description:
Apparatus and methods are known for accessing a patient's vasculature percutaneously, e.g., to perform a procedure within the vasculature, and for sealing the puncture that results after completing the procedure. For example, a hollow needle may be inserted through a patient's skin and overlying tissue into a blood vessel. A guide wire may be passed through the needle lumen into the blood vessel, whereupon the needle may be removed. An introducer, procedural, or femoral sheath may then be advanced over the guide wire into the vessel, e.g., in conjunction with or subsequent to one or more dilators. A catheter or other device may be advanced through the introducer sheath and over the guide wire into a position for performing a medical procedure. Thus, the introducer sheath may facilitate accessing and/or introducing various devices into the vessel, while minimizing trauma to the vessel wall and/or minimizing blood loss.

Upon completing the procedure, the device(s) and introducer sheath may be removed, leaving a puncture extending between the skin and the vessel wall. To seal the puncture, external pressure may be applied to the overlying tissue, e.g., manually and/or using sandbags, until hemostasis occurs. This procedure, however, may be time consuming and expensive, requiring as much as an hour of a medical professional's time. It is also uncomfortable for the patient, and may require the patient to remain immobilized in the operating room, catheter lab, or holding area. In addition, a risk of hematoma exists from bleeding before hemostasis occurs.

Various apparatus and methods have been suggested for sealing vascular punctures resulting from such procedures, such as those disclosed in <CIT>, <CIT>, <CIT><CIT>, and <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, and <CIT>.

For example, the MATRIX(TM) product included two synthetic polyethylene glycol ("PEG") polymer powders that were mixed with appropriate buffers and injected through a femoral sheath at an arteriotomy site, e.g., as disclosed in <CIT>. The Mynx(R) Vascular Closure Device is another system for sealing vascular punctures, e.g., as disclosed in one or more of the references identified above, such as <CIT>.

As a further example <CIT> discloses coatings for adherence of biomaterials to a tissue. Systems and methods for adapting such coated materials to vascular access closure are disclosed. In particular a biomaterial having a partial and continuous coating is disclosed. An adhesive coating is formed on one portion of a biomaterial, which is then rolled to form a plug with a first portion that is free of a coating and a second portion that is coated.

Accordingly, apparatus for sealing a puncture through tissue would be useful.

According to the present invention there is provided a sealant for sealing a puncture through tissue and a method for making a sealant for sealing a puncture through tissue as claimed in the appended claims. In addition, the present invention is directed to apparatus for providing temporary or permanent hemostasis within a puncture extending through tissue, and/or to apparatus for delivering a sealant into a percutaneous puncture extending from a patient's skin to a blood vessel or other body lumen.

In accordance with another arrangement, a sealant is provided for sealing a puncture through tissue that includes a first section including a proximal end, a distal end, and a cross-section sized for delivery into a puncture through tissue, and a second section fused to and extending from the distal end of the first section. The first section is formed from a freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture. The second section is formed from a solid mass of non-freeze-dried, non-crosslinked hydrogel precursors, the precursors remaining in an unreactive state until exposed to an aqueous physiological, whereupon the precursors undergo in-situ crosslinking with one another to provide an improved adhesion of the sealant to the arteriotomy.

In one arrangement, the first section may consist essentially of freeze-dried hydrogel, and the second section may consist essentially of the non-crosslinked precursors. Alternatively, the second section may include one or more reinforcement elements, e.g., a plurality of filaments or particles, mixed with, embedded in, or surrounding the precursors. In addition or alternatively, the second section may include one or more diluents to enhance one or more properties of the second section.

Optionally, the sealant may include one or more pH adjusting agents, e.g., impregnated into, coated over, or otherwise included in the first and/or section sections. For example, when the sealant is exposed within a puncture, the agent(s) may alter the localized pH on or around the sealant, e.g., to enhance cross-linking of the precursors and/or creation of a desired adhesive material. Alternatively, the materials for the precursors may be selected such that the pH and/or buffering capacity of interstitial body fluids and/or blood are effective to drive or facilitate cross-linking of the precursors and the pH adjusting agents may be omitted.

In accordance with another embodiment, a sealant is provided for sealing a puncture through tissue that includes an elongate first section including a proximal end, a distal end, and a cross-section sized for delivery into a puncture through tissue, the first section consisting essentially of a freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture; and a second section fused to and extending from the distal end of the first section, the second section consisting essentially of a solid mass of non-freeze-dried, non-crosslinked hydrogel precursors, the precursors remaining in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ crosslinking to provide an adhesive layer to bond the first section relative to adjacent tissue.

In accordance with still another embodiment, a sealant is provided for sealing a puncture through tissue that includes an elongate body including a proximal end, a distal end, and a cross-section extending between the proximal and distal ends sized for delivery into a puncture through tissue. The elongate body may consist essentially of a solid mass of non-freeze-dried, non-crosslinked hydrogel precursors, the precursors remaining in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ crosslinking to provide an adhesive material that bonds to adjacent tissue within the puncture. Alternatively, the elongate body may also include one or more reinforcement members, one or more diluents, and/or one or more pH adjusting agents.

In accordance with yet another embodiment, a sealant is provided for sealing a puncture through tissue that includes a first section including a proximal end, a distal end, and a cross-section sized for delivery into a puncture through tissue, and a second section fused to and extending from the distal end of the first section. The first section may be formed from a freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture. The second section may consisting essentially of a solid mass of non-freeze-dried, non-crosslinked hydrogel precursors and one or more pH adjusting agents, reinforcement elements, and/or diluents mixed with the precursors to enhance one or more mechanical properties of the second section.

In accordance with still another embodiment, a method is provided for making a sealant for sealing a puncture through tissue that includes forming an elongated first section including a proximal end, a distal end, and a cross-section sized for delivery into a puncture through tissue. The first section may be formed from a freeze-dried hydrogel or other biocompatible, bioabsorbable material that expands when exposed to physiological fluid within a puncture. A solid mass of non-crosslinked hydrogel precursors may be fused or otherwise attached onto the distal end, the precursors remaining in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ crosslinking with one another to provide an improved adhesion to the arteriotomy. For example, the solid mass may be formed as a substantially uniform solid plug or may be formed as a sintered mass of powder.

In accordance with yet another embodiment, a method is provided for making a sealant for sealing a puncture through tissue that includes forming a sheet of the freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture; rolling the sheet into a tubular roll including a lumen extending between the proximal and distal ends; and loading the tubular roll into a tubular member such the distal end of the tubular roll is offset inwardly from a first end of the tubular member. A plurality of non-crosslinked hydrogel precursors may be mixed and melted, optionally with one or more diluents, the precursors remaining in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ crosslinking; the melted precursors may be applied to the distal end of the tubular roll within the tubular member, and allowed to solidify to create the solid mass fused to the distal end of the tubular roll.

In accordance with another embodiment, an apparatus is provided for sealing a puncture through tissue that includes a tubular member including a proximal end, a distal end sized for insertion into a puncture, a lumen extending between the proximal and distal ends, and a distal opening in communication with the lumen, a sealant within the lumen, and an advancer member within the lumen for deploying the sealant from the lumen out the distal opening, e.g., when the tubular member is retracted from a puncture relative to the advancer member. The sealant may include a first section including proximal and distal ends, and a second section fused to and extending from the distal end. The sealant may be disposed within the lumen such that the second section is disposed closer to the distal opening than the first section. In an exemplary embodiment, the first section may be formed from a freeze-dried hydrogel that expands when exposed to physiological fluid within a puncture, and/or the second section may be formed from non-crosslinked hydrogel precursors, the precursors remaining in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ crosslinking with one another to provide improved adhesion to the arteriotomy.

In accordance with another aspect of the disclosure, which is not part of the invention, a method is provided for sealing a puncture through tissue that includes providing sealant including a first section including proximal and distal ends, and a second section fused to and extending from the distal end. In an exemplary aspect, the first section may be formed from a freeze-dried hydrogel, and/or the second section may be formed from non-crosslinked hydrogel precursors in an unreactive state. The sealant may be introduced into a puncture through tissue with the second section entering the puncture before the first section. The sealant may be exposed to fluid within the puncture, whereupon the precursors of the second section undergo in-situ crosslinking with one another to provide improved adhesion to the arteriotomy, and the freeze-dried hydrogel of the first section expands to fill space within the puncture to provide hemostasis.

Other aspects and features of the present invention will become apparent from consideration of the following description taken in conjunction with the accompanying drawings.

It will be appreciated that the exemplary apparatus shown in the drawings are not necessarily drawn to scale, with emphasis instead being placed on illustrating the various aspects and features of the illustrated embodiments.

Turning to the drawings, <FIG> shows an exemplary embodiment of a sealant <NUM> for sealing a puncture extending through tissue (not shown). Generally, the sealant <NUM> includes a first, proximal, or main section <NUM> including proximal and distal ends 4a, 4b, and a second, distal, or tip section <NUM> formed from a plurality of non-freeze-dried and/or non-crosslinked precursors, e.g., formed as a solid mass or solid plug, fused or otherwise attached to and extending distally from the distal end 4b of the first section <NUM>. As described further below, the non-crosslinked precursors may remain in an unreactive state, e.g., before or until exposure to an aqueous physiological environment, e.g., when deployed or otherwise exposed within a puncture extending through tissue.

For example, this configuration of sealant <NUM> may combine crosslinking of the second section <NUM> to create an adhesive material in-situ with swell characteristics of a freeze-dried hydrogel or other expandable material of the first section <NUM>. By improving the adherence characteristics of the expandable hydrogel, the sealant <NUM> may provide enhanced extravascular closure, e.g., by providing expansion of the first section <NUM> in combination with improved adhesion of the sealant <NUM> to tissue surrounding an arteriotomy or other adjacent tissue structure, e.g., entirely extra-vascularly or extending partially into the arteriotomy and/or vessel, by virtue of the in-situ polymer crosslinking that occurs at the second section <NUM> of the sealant <NUM>.

As shown, the first section <NUM> may be formed generally into an elongate cylindrical shape, e.g., including proximal and distal ends 4a, 4b, and an outer surface 4c extending therebetween. Optionally, as shown in phantom, the sealant <NUM> may include a lumen <NUM> extending between the proximal and distal ends 4a, 4b of the first section <NUM> and through the second section <NUM>, e.g., to facilitate delivery of the sealant <NUM>. For example, the lumen <NUM> may be dimensioned to accommodate receiving a balloon catheter or other positioning member <NUM> (not shown, see, e.g., <FIG> and associated description below) therethrough, e.g., such that the sealant <NUM> may slide relative to or pass over the positioning member <NUM> and/or the positioning member <NUM> may be directed axially relative to the sealant <NUM>, as described further below. Alternatively, the sealant <NUM> may be a substantially continuous rod of material, e.g., such that the sealant <NUM> may be delivered into a puncture using a cartridge or shuttle without a positioning member (not shown).

In an exemplary embodiment, the first section <NUM> may be formed from a sheet of freeze-dried hydrogel rolled into a tubular shape, e.g., as disclosed in <CIT>. It will be appreciated that the first section <NUM> may have other tubular or solid rod cross-sections or shapes, as desired, such as elliptical, triangular, square, conical, disk, polygonic shapes, and the like (not shown).

In exemplary embodiments, the sealant <NUM> may have an overall length between about three and twenty millimeters (<NUM>-<NUM>), e.g., between about five and ten millimeters (<NUM>-<NUM>) or between about fifteen and twenty millimeters (<NUM>-<NUM>), and an outer diameter or other cross-section between about one and eight millimeters (<NUM>-<NUM>), e.g., between about one and three millimeters (<NUM>-<NUM>), e.g., between about <NUM> and two millimeters (<NUM>-<NUM>), e.g., about <NUM> inch (<NUM>). In the embodiment shown in <FIG>, the first section <NUM> is substantially longer than the second section <NUM>, although it will be appreciated that, alternatively, the sections <NUM>, <NUM> may have similar lengths, or the second section <NUM> may be longer than the first section <NUM>. In a further alternative embodiment, the first section <NUM> may be omitted, and the second section <NUM> may provide the entire length of the sealant <NUM> (not shown), e.g., having a length between about three and twenty millimeters (<NUM>-<NUM>).

For example, the first section <NUM> may have a length between about zero (if the sealant <NUM> is formed entirely from the second section <NUM>) and twenty millimeters (<NUM>-<NUM>), e.g., between about five and twenty millimeters (<NUM>-<NUM>), e.g., about fifteen millimeters (<NUM>). The second section <NUM> may have an outer diameter similar to the first section <NUM>, but may have a length that is substantially shorter, e.g., between about zero (if the sealant <NUM> is formed entirely from the first section <NUM>) and eight millimeters (<NUM>-<NUM>), e.g., between about half and five millimeters (<NUM>-<NUM>), e.g., about <NUM> millimeters.

The first section <NUM> may be formed from a biocompatible and/or bioabsorbable material, for example, a porous and/or bioabsorbable hydrogel, that may have desired expansion characteristics when hydrated. In one embodiment, the first section <NUM> may be formed entirely from a freeze-dried and crosslinked hydrogel, e.g., polyethylene glycol ("PEG"), or other synthetic material, as disclosed in <CIT>, although optionally including a transition zone (not shown) where the material of the second section <NUM> has penetrated partially into the distal end 4b of the first section <NUM>, e.g., during fusion, as described further below.

For example, the PEG polymer for the hydrogel sealant may include two components of Polyethylene Glycol Hydrogel, e.g., PEG-Amine: 8A20K-NH2 and PEG-Ester: 4A10K-CM-HBA-NHS, e.g., as disclosed in the references identified above. In an exemplary embodiment, the molar ratio of PEG-Amine/PEG-Ester may be between <NUM>:<NUM> (<NUM>% PEG-Amine: <NUM>% PEG-Ester) and <NUM>:<NUM> (<NUM>% PEG-Amine:<NUM>% PEG-Ester), for example, about a <NUM>:<NUM> ratio.

In alternative embodiments, the first section <NUM> may be formed from other materials, such as pro-thrombotic material, e.g., including one or more biological pro-thrombotics, such as collagen, fibrin, carboxymethylcellulose, oxidized cellulose, alginates, gelatin, or other protein-based material, and/or synthetic materials, e.g., as polyglycolic acids (PGA's), polylactides (PLA's), polyvinyl alcohol (PVA), and the like. The material of the first section <NUM> may be at least partially absorbed by the body over time, e.g., over a period of days, weeks, or months.

Optionally, the first section <NUM> (and/or second section <NUM>) may include therapeutic and/or pharmaceutical agents, e.g., to promote healing, prevent infection and/or other adverse medical events, and the like. Such agents may be embedded in the material and/or applied as one or more coatings or layers. In addition, the material of the first section <NUM> may have a substantially uniform composition or the composition may be varied, e.g., along its length and/or within underlying layers within the first section <NUM>.

In an exemplary embodiment, the first section <NUM> may be formed entirely from freeze-dried hydrogel, e.g., initially formed as a thin sheet of freeze-dried polymer. For example, to fabricate the first section <NUM> from a PEG hydrogel material, PEG-amine and PEG-ester powders intended to form the hydrogel may be filled into separate vials. Phosphate and borate buffers may be made, e.g., by dissolving the sodium borate and sodium phosphate in sterile water for injection (WFI) and adjusting the pH of each solution to meet preestablished requirements. The two PEG powders may then be dissolved in their respective buffer solutions. These precursor solutions may be mixed together, poured into trays, and freeze-dried. The freeze-dried material may be subjected to a series of heat and/or humidity conditioning cycles, e.g., to complete the polymerization reaction.

The freeze-dried and conditioned sheet of hydrogel sealant may then be trimmed according to size and mass requirements, e.g., cut to a desired length for the finished first section <NUM>. For example, as shown in <FIG>, the trimmed hydrogel may be dried, rolled, and loaded into a transfer tube <NUM> for subsequent attachment to the second section <NUM>. Additional information on materials and methods for making the first section <NUM> may be found in <CIT>.

To fabricate the non-freeze-dried, non-crosslinked distal section <NUM> of the sealant <NUM>, PEG-amine and PEG-ester powders (or other crosslinkable polymer precursors) may be melted in a beaker, mixed, and heated at a pre-determined temperature and duration. For example, the precursors may be melted in a substantially dry air or inert gas environment, e.g., to minimize or prevent entrapment of moisture, which may otherwise cause premature crosslinking. Using a vacuum generator, the melted PEG may then be applied onto the distal end 4b of the rolled freeze-dried first section <NUM>.

For example, as described above, the first section <NUM> may be formed from a rolled sheet and loaded into a transfer tube <NUM>, as shown in <FIG>. The transfer tube <NUM> may have an inner diameter or other cross-section corresponding to the desired outer diameter or cross-section for the finished sealant <NUM>. The transfer tube <NUM> may be formed from any material sufficient to handle the processing parameters of the assembly process, such as polymers, metals, or composite materials, and may optionally include desired coatings, e.g., PTFE to facilitate insertion of the first section <NUM> and/or removal of the sealant <NUM>.

The first section <NUM> may be loaded into the transfer tube <NUM> such that the distal end 4b of the first section <NUM> is offset inwardly a predetermined distance L6 from the end of the transfer tube <NUM>, e.g., corresponding to or greater than the desired length of the second section <NUM>. For example, for a desired finished length of the second section <NUM> of about <NUM> millimeters, the distal end 4b may be offset inwardly about two millimeters (<NUM>) from the end of the transfer tube <NUM> (with any excess material may trimmed off later, as described below). Using the vacuum generator, the melted non-crosslinked PEG is then applied onto the distal end 4b of the rolled freeze-dried sealant, e.g., the vacuum directing the melted PEG into the transfer tube <NUM> and against the distal end 4b of the first section <NUM> (as represented by the arrow labeled "vacuum"). Thus, the transfer tube <NUM> may mold the melted PEG into the desired shape, e.g., diameter and/or length, for the second section <NUM>.

The vacuum may cause the melted precursors to nominally abut the distal end 4b of the first section <NUM>, and/or may partially draw the melted precursors into the pores and/or other open spaces within the first section <NUM>, e.g., due to capillary action and the like. In this situation, a transition zone <NUM> may be created within the distal end 4b of the first section <NUM> in which the melted precursors permeate the freeze-dried hydrogel or other material of the first section <NUM>, which may enhance fusing the second section <NUM> to the first section <NUM>. For example, the melted precursors may quickly cool under ambient conditions such that the penetration into the distal end 4b may be relatively short, e.g., resulting in a transition zone <NUM> of one millimeter (<NUM>) or less.

The melted precursors may be dried under ambient conditions, e.g., simply allowed to cool and solidify, or alternatively, the melted and applied precursors may be exposed to desired conditions to accelerate or facilitate solidification of the melted precursors. The vacuum process effectively fuses the two sections together to provide a length of sealant <NUM>.

If desired, the resulting sealant <NUM> may then be trimmed to length, as desired, e.g., for loading into a delivery apparatus, e.g., a cartridge or shuttle, such as those described further below and in the references identified elsewhere herein. For example, any excess length of the second section <NUM> may be removed, e.g., by mechanical cutting, laser cutting, and the like, to provide the desired length for the final second section <NUM>. In addition or alternatively, the first section <NUM> may be trimmed to a desired length, e.g., by cutting the proximal end 4a before loading the first section <NUM> into the transfer tube <NUM> (as described above) and/or after fusing the second section <NUM> to the distal end 4b.

In addition or alternatively, if the sealant <NUM> and/or first section <NUM> includes a lumen <NUM>, the lumen <NUM> may be created when the first section <NUM> is formed, e.g., if the first section <NUM> is rolled from one or more sheets or layers of material or formed by molding. Alternatively, the lumen <NUM> may be formed by boring into or otherwise removing material from an already formed and solid first section <NUM>, second section <NUM>, or through the entire sealant <NUM>. For example, if the first section <NUM> is formed from a rolled sheet, a rod or other mandrel <NUM> (which may be fabricated similar to the transfer tube <NUM>) may be inserted through the lumen <NUM> before the second section <NUM> is applied to the distal end 4b, e.g., that extends from the transfer tube <NUM>, as shown in <FIG>. Thus, the second section <NUM> may be molded and fused to distal end 4b around the mandrel <NUM>, e.g., within the transfer tube <NUM>. The mandrel <NUM> may be removed once the melted precursors have solidified, resulting in a continuous lumen through the second section <NUM> and the first section <NUM>. Alternatively, the portion of the lumen <NUM> through the second section <NUM> may be bored, drilled, or otherwise created after the second section <NUM> is formed and fused to the first section <NUM>.

In exemplary embodiments, the precursors for the second section <NUM> may include one or more of the following:.

Optionally, the second section may include one or more pH adjusting agents. For example, a pH adjusting agent, e.g., sodium borate, sodium phosphate, sodium bicarbonate, and/or other salts, such as Na<NUM>B<NUM>O<NUM>·<NUM><NUM>O in crystalline or powder form, may be melted with the precursors and then applied with the precursors to the distal end 4b of the first section <NUM>, as described above. Alternatively, the pH adjusting agent may be applied to the second section <NUM> after fusing the melted precursors to the first section <NUM>, e.g., by bonding or impregnating crystals of borate or other salts to the outer surface of the solid mass of non-crosslinked precursors and/or by melting and applying a coating of melted salts to the outer surface, e.g., similar to embodiments disclosed in the references identified elsewhere herein. In addition or alternatively, one or more pH adjusting agents may be provided on the first section <NUM>, if desired.

In this manner, the pH adjusting agent may alter the localized pH on or around the sealant <NUM>, e.g., when deployed within a puncture to enhance cross-linking and/or creation of a desired adhesive material. Alternatively, the pH and/or buffering capacity of interstitial body fluids and/or blood may be effective to drive or facilitate cross-linking of the second section <NUM>. For example, the precursors of the second section <NUM> may be optimized to take into account all of these factors and/or form a robust attachment to tissue.

In addition or alternatively, diluents, such as low molecular PEG and/or glycerol, may be added to the formulation, i.e., the melted precursors before application to the first section <NUM>, e.g., to improve the mechanical strength and/or integrity of the first section <NUM> and/or to minimize the brittleness of the second section <NUM>.

In a further alternative, if desired, one or more reinforcement elements may be provided within the second section <NUM>. For example, as shown in <FIG>, a bioabsorbable mesh 6a' may be embedded within and/or surround the precursors 6b' of a second section <NUM>. ' The mesh 6a' of bioabsorbable material may have greater rigidity, elasticity, and/or other desired properties than the solidified precursors 6b. ' Exemplary materials for the reinforcement elements may include any of the bioabsorbable materials described above for the first section <NUM>.

As shown, the mesh 6a' may include one or more fibers or filaments having a helical configuration (one helical filament shown), or alternatively the mesh 6a' may include a braid of filaments, a rolled porous mat, and the like (not shown). In an exemplary embodiment, the mesh 6a' may be embedded in the precursors 6b' of the second section <NUM>,' e.g., by inserting the reinforcement element(s) into the end of the transfer tube <NUM> (not shown, see <FIG>) before applying the melted precursors (not shown), as described above. Thus, as the applied precursors are drawn into the transfer tube <NUM> and cool (or are otherwise dried and/or solidified), the precursors 6b' may permeate through and/or surround the mesh 6a,' thereby embedding the element(s) in the second section <NUM>.

Alternatively, as shown in <FIG>, reinforcing particles or fillers 6a" may be provided in a second section <NUM>. " For example, similar compositions of bioabsorbable material having greater rigidity, elasticity, and/or other desired properties than the precursors 6b," such as the materials described above, may be mixed into the melted precursor mixture, and then the reinforcing fillers 6a" may be applied to the distal end 4b of the first section <NUM> (not shown) along with the precursors 6b," e.g., using the vacuum process described above. Thus, the filler material 6a" may be distributed randomly, substantially uniformly, or in a desired pattern throughout the second section <NUM>," thereby enhancing the rigidity, reducing the brittleness, and/or otherwise modifiying the properties of the precursors 6b" of the second section <NUM>" in a desired manner.

Once the sealant <NUM> is formed and/or trimmed, as described above, the sealant <NUM> may be loaded onto a delivery apparatus for use in sealing a puncture, e.g., using the methods described below.

Turning to <FIG>, an exemplary embodiment of an apparatus <NUM> is shown for sealing a puncture through tissue, e.g., using the sealant <NUM> (or any of the other embodiments described elsewhere herein). Generally, the apparatus <NUM> includes a positioning member <NUM> and a cartridge or shuttle <NUM> carried on the positioning member <NUM> for delivering a sealant <NUM> therein into a puncture (not shown). Optionally, the apparatus <NUM> may be part of a system, e.g., which may also include a delivery, access, procedure, introducer, or other sheath <NUM> (not shown, see, e.g., <FIG>). Optionally, the apparatus <NUM> and/or system may include one or more other components, e.g., a needle, guidewire, and/or other instrument for creating a puncture, a source of inflation media, and/or a source of additional sealing compound (not shown), for example, to provide a kit for a medical procedure.

As shown in <FIG>, the cartridge <NUM> includes an elongate tubular member <NUM> carrying the sealant <NUM> therein, an advancer tube or member <NUM> adjacent the sealant <NUM> within the tubular member <NUM>, and a handle or hub <NUM> coupled to the tubular member <NUM>. Generally, as best seen in <FIG>, the tubular member <NUM> includes a proximal end <NUM> coupled to the hub <NUM>, a distal end <NUM> sized for introduction into an introducer sheath and/or puncture (not shown), and a lumen <NUM> extending between proximal and distal ends <NUM>, <NUM> of the tubular member <NUM>. The tubular member <NUM> may be substantially rigid, semi-rigid, or flexible, e.g., such that the tubular member <NUM> may be advanced through an introducer sheath or otherwise into a puncture through tissue. Optionally, the hub <NUM> may include one or more detents or other features (not shown) for releasably coupling the cartridge <NUM> to the positioning member <NUM>, e.g., as described in the references identified elsewhere herein.

With additional reference to <FIG>, <FIG>, and <FIG>, the advancer member <NUM> may be an elongate tubular body sized to be slidably received within the lumen <NUM> of the tubular member <NUM>, although the advancer member <NUM> may abut or otherwise interact with the hub <NUM> of the cartridge <NUM>, e.g., such that the advancer member <NUM> is advanced distally when the cartridge <NUM> is advanced. A distal end <NUM> of the advancer member <NUM> may terminate in a substantially blunt distal tip proximal to the tubular member distal end <NUM>, as best seen in <FIG>, e.g., by simply cutting the end of the advancer member <NUM>, which may facilitate contacting and/or otherwise maintaining the sealant <NUM> within a puncture, e.g., when the tubular member <NUM> is retracted during use, as described further below.

The advancer member <NUM> may be substantially rigid, semi-rigid, and/or substantially flexible, e.g., having sufficient column strength to allow proximal movement of the tubular member <NUM> relative to the sealant <NUM> without buckling the advancer member <NUM> and/or to allow the distal end <NUM> of the advancer member <NUM> to be advanced to compress the sealant <NUM> within a puncture, e.g., by pushing from the proximal end <NUM>, as described further below. As best seen in <FIG>, the advancer member <NUM> may also include a lumen <NUM> extending between the proximal and distal ends <NUM>, <NUM>, e.g., to accommodate the positioning member <NUM>, a flowable sealing compound, and/or fluid (not shown).

Optionally, the advancer member <NUM> may include one or more elements (not shown) on the proximal end <NUM>, e.g., for interacting with one or more cooperating elements (also not shown) on the positioning member <NUM>, e.g., to limit movement of the advancer member <NUM> relative to the positioning member <NUM>, e.g., as described in the references identified elsewhere herein.

As shown in phantom in <FIG>, the sealant <NUM> (which, alternatively, may be any of the embodiments herein, e.g., sealant <NUM>-<NUM>) may be disposed within the lumen <NUM> of the tubular member <NUM> proximate to the distal end <NUM>, e.g., immediately adjacent the distal tip. The lumen <NUM> may be sized such that the tubular member <NUM> and sealant <NUM> are slidable relative to one another, e.g., to allow the tubular member <NUM> to be retracted proximally relative to the sealant <NUM> and/or advancer member <NUM>, as described further below.

With continued reference to <FIG>, the positioning member <NUM> generally includes an elongate member <NUM> including a proximal end <NUM> (not shown, see, e.g., <FIG>), a distal end <NUM>, and an occlusion or positioning element <NUM> on the distal end <NUM>. The positioning element <NUM> may be an expandable member, such as a balloon, a wire mesh structure, an expandable frame, and the like, e.g., as disclosed in the references identified elsewhere herein. The positioning element <NUM> may be selectively expandable, e.g., using a source of inflation media, such as syringe <NUM>, a pull wire, and/or other actuator (not shown), operable from the proximal end <NUM> of the positioning member <NUM>.

For example, as shown, the positioning element may be a balloon <NUM>, and the positioning member <NUM> may include a tubular body <NUM> including a lumen (not shown) extending between the proximal and distal ends <NUM>, <NUM> and communicating with an interior of the balloon <NUM>. In this embodiment, the positioning member <NUM> may include a source of inflation media, such as syringe <NUM>, that may be coupled to a housing <NUM> on the proximal end <NUM> of the positioning member <NUM>. Optionally, the positioning member <NUM> may include an internal pull wire (not shown) that causes the balloon <NUM> to shorten during expansion and extend during collapse. Exemplary embodiments of positioning members <NUM> including balloons that may be used are disclosed in <CIT>, <CIT>, <CIT>, and <CIT>.

Alternatively, the positioning element may be biased to an enlarged condition, but may be compressed to a contracted condition, e.g., by an overlying sleeve or other constraint (not shown). The constraint may be removed to expose the positioning element, allowing the expandable element to automatically expand to the enlarged condition. Additional information on expandable structures that may be provided on the positioning member <NUM> may be found in <CIT>, <CIT>, and <CIT>, and in co-pending application Serial No. <CIT>.

With additional reference to <FIG>, the apparatus <NUM> may be used to position and deliver the sealant <NUM> within a puncture, e.g., extra-vascularly just above or otherwise adjacent to an arteriotomy in a blood vessel or other body lumen communicating with a puncture, as described further elsewhere herein. In one embodiment, as shown in <FIG> and <FIG>, the cartridge <NUM> (along with the advancer member <NUM> and sealant <NUM> within the tubular member <NUM>) may be initially provided on the proximal end <NUM> of the positioning member <NUM>. For example, the housing <NUM> on the positioning member <NUM> and the hub <NUM> on the cartridge <NUM> may be initially connected to one another, e.g., using one or more releasable detents (not shown). Alternatively, the cartridge <NUM> may be initially provided such that the distal <NUM> of the tubular member <NUM> is disposed adjacent the balloon <NUM>, e.g., as disclosed in <CIT> and <CIT>.

As shown in <FIG>, the cartridge <NUM> may be slidable distally along the positioning member <NUM>, e.g., by disconnecting the hub <NUM> from the housing <NUM>, and then advancing the cartridge <NUM>, e.g., until the distal end <NUM> of the tubular member <NUM> is disposed adjacent the positioning element <NUM>. For example, detents on the hub <NUM> and housing <NUM> may simply separate from one another when the hub <NUM> is advanced away from the housing <NUM> with sufficient force. Alternatively, one of the hub <NUM> and housing <NUM> may include an actuator or lock that may be activated (not shown) to separate the detents and/or otherwise allow the cartridge <NUM> to be advanced relative to the positioning member <NUM>.

Optionally, the cartridge <NUM> and/or positioning member <NUM> may include cooperating features that limit distal movement of the cartridge <NUM> relative to the positioning member <NUM>. For example, the hub <NUM> of the cartridge <NUM> may include a pocket and the positioning member <NUM> may include a detent or other feature (both not shown) that may be received within the pocket when the cartridge <NUM> is advanced to a distal position. In addition or alternatively, the positioning member <NUM> and/or advancer member <NUM> may include one or more elements that engage when the cartridge <NUM> reaches a predetermined location when advanced along the positioning member <NUM>, e.g., to limit subsequent proximal movement of the advancer member <NUM> relative to the positioning member <NUM> when the tubular member <NUM> is subsequently retracted, similar to embodiments disclosed in the references identified elsewhere herein.

In addition or alternatively, one or more markers may be provided on the apparatus <NUM>, e.g., to identify when components are located at one or more desired positions or otherwise to facilitate use of the apparatus <NUM>. For example, the positioning member <NUM> may include one or more markers at predetermined locations on the elongate member <NUM>. Such markers may provide visual confirmation when the cartridge <NUM> has been advanced to a desired distal position, e.g., when the marker(s) emerge from the hub <NUM> as the cartridge <NUM> is advanced over the positioning member <NUM>. In addition or alternatively, as shown in <FIG> and <FIG>, the advancer member <NUM> may include one or more markers <NUM> thereon, which may be visible when the cartridge <NUM> is advanced to a distal position and then the tubular member <NUM> is retracted to expose the sealant <NUM>. These markers <NUM> may also provide visual guides to inform the user when the advancer member <NUM> is manipulated, e.g., advanced into a puncture to compress the sealant <NUM> therein, as described further below.

The apparatus <NUM> may be assembled using conventional manufacturing methods and/or using methods disclosed in the references identified elsewhere herein. Although an exemplary process is described below as being performed in an exemplary order, it will be appreciated that the actual order of the assembly steps may be changed, as desired.

For example, the positioning member <NUM> may be formed by providing a length of tubing for the tubular body <NUM> and attaching a balloon <NUM> to the distal end <NUM>. To make the balloon, a section of tubing, e.g., LLDPE or other elastic material, may be cut to a predetermined length that is necked down to a smaller diameter, e.g., using a hot die or hot air necker. The tubing may then be placed into a balloon blower, which may use a split aluminum or other mold (not shown) to form the balloon <NUM>, e.g., at a desired temperature and blow pressure. The resulting balloon subassembly may then be trimmed as desired and attached to the distal end <NUM> of the tubular body <NUM>, which may also be necked down to facilitate attachment of the balloon <NUM>, e.g., by an interference fit, bonding with adhesive, fusing, and the like.

The components of the cartridge <NUM>, the tubular body <NUM>, advancer tube <NUM>, and hub <NUM> may be formed using conventional methods, e.g., extruding, molding, and the like. For example, the hub <NUM> may be formed from a plurality of molded shells that may be attached together and to which the proximal end <NUM> of the tubular body <NUM> may be attached.

In the exemplary embodiment shown, the cartridge <NUM> includes a single tubular body <NUM> attached to the hub <NUM>. In an alternative embodiment, the cartridge <NUM> may include inner and outer cartridge assemblies, including inner and outer tubular bodies (not shown) attached to the hub <NUM>, e.g., similar to embodiments disclosed in the references identified elsewhere herein. For example, an inner cartridge subassembly may include tubing bonded to a molded hub, and an outer cartridge subassembly may include tubing bonded to a molded slider. The inner and outer cartridges may then be captured within halves of a shuttle shell providing the hub <NUM>.

The advancer member <NUM> may include a section of tubing with a thermoformed tapered tip. Once the tubular body <NUM> (or bodies) is assembled to the hub <NUM>, the advancer member <NUM> may be inserted into the lumen <NUM> of the tubular body <NUM> (e.g., into the inner cartridge tubing if inner and outer cartridge tubular bodies are provided).

To provide the hub <NUM> of the positioning member <NUM>, a hub barrel 48a, stopcock 48b, and extension line 48c may be assembled, as shown in <FIG>, similar to embodiments disclosed in the references identified elsewhere herein. One end of the extension line 48c may be bonded or otherwise attached to the stopcock 48b, and the other end of the extension line 48c may be bonded or otherwise attached into the side port of the hub barrel 48a.

To complete the positioning member <NUM>, locking features (not shown) may be bonded onto the tubular body <NUM>, e.g., spaced a predetermined distance from the proximal end <NUM>. The proximal leg of the balloon <NUM> may be bonded to the distal end <NUM> of the tubular body <NUM>. The cartridge <NUM>, hub barrel <NUM> and a core wire with tension plunger (not shown) are all then assembled with the tubular body <NUM>, e.g., similar to embodiments in the references identified elsewhere herein. The core wire may then be bonded into the distal leg of the balloon <NUM>. The hub barrel 48a is bonded to the proximal end <NUM> of the tubular body <NUM> and captured within the halves of the handle shell to provide the hub <NUM>, as shown in <FIG>.

Finally, the sealant <NUM> is loaded onto the assembled apparatus <NUM>. For example, the rolled sealant <NUM> may be coaxially mounted over the tubular body <NUM> from the distal end <NUM> and positioned inside the tubular member <NUM> of the cartridge <NUM>, e.g., adjacent the distal end <NUM> and the advancer member <NUM> therein. For example, the sealant <NUM> stored within a transfer tube <NUM> (not shown, see <FIG>) may be aligned with the balloon <NUM> and distal end <NUM> of the tubular body <NUM> such that the proximal end 4a of the first section <NUM> is oriented towards the proximal end <NUM> of the tubular body <NUM>. The sealant <NUM> may then be transferred from the transfer tube <NUM> over the tubular body <NUM> into the cartridge <NUM> such that the distal section <NUM> is located closest to the distal end <NUM> within the tubular member <NUM>.

Optionally, a thin silicone coating may be applied to the tubular body <NUM>, the tubular member <NUM>, and the balloon <NUM>. A protective sheath (not shown) may then be placed over the balloon <NUM> and at least partially over the tubular body <NUM>.

The apparatus <NUM> and syringe <NUM> may then be placed with appropriate packaging, e.g., into respective cavities within a thermoformed clamshell tray (not shown), and the clamshell tray snaps may be closed. The closed tray may be inserted into a foil pouch or other packaging as desired. Additional processing, such as product labeling, sterilization, and the like, may be completed before the apparatus <NUM> is provided to a user.

Turning to <FIG>, an exemplary method is shown for sealing a puncture <NUM>, e.g., using the apparatus <NUM> to deliver a sealant <NUM> (which again may be any of the exemplary aspects, which are not part of the invention, herein), e.g., to achieve hemostasis within the puncture <NUM>. Generally, the puncture <NUM> extends from a patient's skin <NUM> through intervening tissue, e.g., to a body lumen <NUM>. In an exemplary aspect, the puncture <NUM> may be a percutaneous puncture communicating with a blood vessel <NUM>, such as a femoral artery, carotid artery, and the like.

In an exemplary method, the puncture <NUM> may be created using known procedures, e.g., using a needle, guidewire, one or more dilators, and the like (not shown). An introducer sheath <NUM> may be advanced through the puncture <NUM> into the vessel <NUM>, e.g., over a guidewire (not shown) placed through the puncture <NUM> into the vessel <NUM>. The introducer sheath <NUM> may provide access into the vessel <NUM> for one or more instruments (not shown), e.g., to allow one or more diagnostic and/or interventional procedures to be performed via the vessel <NUM>. Upon completing the procedure(s) via the vessel <NUM>, any such instrument(s) may be removed from the puncture <NUM>, leaving the introducer sheath <NUM> extending through the puncture <NUM> into the vessel <NUM>.

With reference to <FIG>, the positioning member <NUM> may be introduced into and/or through the lumen of the introducer sheath <NUM>, e.g., with the expandable positioning element <NUM> in a collapsed condition. The cartridge <NUM>, along with the sealant <NUM> and advancer member <NUM>, may be provided initially on the proximal end <NUM> of the positioning member <NUM>, e.g., as shown in <FIG> and <FIG>. Thus, the distal end <NUM> of the tubular member <NUM> may initially be located outside the puncture <NUM> when the positioning member <NUM> is advanced into the puncture <NUM>.

Still referring to <FIG>, the distal end <NUM> of the positioning member <NUM> may be inserted through the puncture <NUM> (via the introducer sheath <NUM>) and into the vessel <NUM>. Once the positioning element <NUM> is disposed within the vessel <NUM>, i.e., beyond a distal end <NUM> of the introducer sheath <NUM>, the positioning element <NUM> may be expanded to an enlarged condition, as shown.

After expanding the positioning element <NUM>, the positioning member <NUM> may be at least partially withdrawn until the positioning element <NUM> contacts the wall of the vessel <NUM>, e.g., to substantially seal the vessel <NUM> from the puncture <NUM>. In an exemplary method, shown in <FIG>, this may involve a two-step process (although it may be completed in a single substantially continuous action). First, with the positioning element <NUM> expanded within the vessel <NUM>, the positioning member <NUM> may be withdrawn until the positioning element <NUM> contacts the distal end <NUM> of the introducer sheath <NUM>, which may provide a first tactile feedback to the user (i.e., that the positioning element <NUM> has contacted the introducer sheath <NUM>, e.g., based upon the increased weight and/or resistance to proximal movement). The positioning member <NUM> may be withdrawn further until the positioning element <NUM> contacts the wall of the vessel <NUM> and resists further withdrawal, thereby providing a second tactile feedback. The introducer sheath <NUM> may be pulled proximally by the positioning element <NUM> as the positioning member <NUM> is withdrawn, e.g., until the distal end <NUM> of the introducer sheath <NUM> is withdrawn from the vessel <NUM> into the puncture <NUM>, as shown in <FIG>.

Proximal tension may be applied and/or maintained on the positioning member <NUM> to hold the positioning element <NUM> against the wall of the vessel <NUM>, e.g., to seal the puncture <NUM> from the vessel <NUM> and/or prevent further removal of the positioning member <NUM>. The proximal tension may be maintained manually or using a tensioner device (not shown) to provide temporary hemostasis, e.g., during the subsequent steps. Exemplary tension devices are disclosed in <CIT>.

Turning to <FIG>, the cartridge <NUM> (carrying the sealant <NUM>) may then be advanced distally over the positioning member <NUM> into the puncture <NUM>. As shown, the distal end <NUM> of the tubular member <NUM> may enter the introducer sheath <NUM> and be advanced towards the positioning element <NUM>. The cartridge <NUM> may be advanced until a component of the cartridge <NUM> encounters a stop on the positioning member <NUM>, thereby preventing further advancement of the cartridge <NUM> and/or spacing the sealant <NUM> a predetermined distance from the positioning element <NUM>. Alternatively, the cartridge <NUM> may be advanced into the introducer sheath <NUM> until the distal end <NUM> contacts the expanded positioning element <NUM>, which may provide tactile feedback that the cartridge <NUM> has been advanced sufficiently, or the sealant <NUM> is otherwise positioned within the puncture <NUM>.

Thereafter, as shown in <FIG>, the tubular member <NUM> of the cartridge <NUM> and introducer sheath <NUM> may be retracted, e.g., by pulling proximally on a hub <NUM> of the introducer sheath <NUM>, to withdrawn the introducer sheath <NUM> and tubular member <NUM> from the puncture <NUM> and expose the sealant <NUM> within the puncture <NUM> beyond the introducer sheath distal end <NUM>. Optionally, a sleeve or locking device (not shown) may be provided on the cartridge <NUM> that may couple the introducer sheath <NUM> to the tubular member, similar to embodiments disclosed in <CIT>. Thus, in this alternative, if the user pulls proximally on the hub <NUM> or tubular member <NUM> rather than the hub <NUM> of the introducer sheath <NUM>, the introducer sheath <NUM> and tubular member <NUM> may still be withdrawn together from the puncture <NUM>.

As the tubular member <NUM> is retracted, the advancer member <NUM> may prevent substantial proximal movement of the sealant <NUM>, thereby exposing the sealant <NUM> within the puncture <NUM>, as shown in <FIG> and <FIG>. For example, as described above, as the cartridge <NUM> is advanced, one or more features (not shown) on the proximal end <NUM> of the advancer member <NUM> may pass over a reduced region or other feature (also not shown) on the positioning member <NUM>, thereby preventing subsequent proximal withdrawal of the advancer member <NUM> relative to the positioning member <NUM>. Thus, when the cartridge <NUM> is then retracted, the features may prevent substantial proximal movement of the advancer member <NUM>, and the sealant <NUM> adjacent the distal end <NUM> of the advancer member <NUM>.

When the sealant <NUM> is exposed within the puncture <NUM>, the sealant <NUM> may be exposed to blood and/or other body fluids within the puncture <NUM>. This exposure may cause the sealant <NUM> to absorb fluid and activate to provide hemostasis, as described further elsewhere herein. Optionally, as shown in <FIG>, once the sealant <NUM> is exposed within the puncture <NUM>, the advancer member <NUM> may be advanced to compress or tamp the sealant <NUM>, e.g., against the positioning element <NUM>. Optionally, the advancer member <NUM> may include one or more markers <NUM>, e.g., on or adjacent the proximal end <NUM>, and the advancer member <NUM> may be advanced into the puncture <NUM> a desired distance, which may be confirmed by monitoring the markers <NUM>. In addition or alternatively, the positioning member <NUM> may include a second feature (not shown) over which the advancer member <NUM> may pass when advanced a predetermined distance. The second feature may provide an audible confirmation that the advancer member <NUM> has been advanced the predetermined distance (in addition or instead of the visible confirmation provided by the markers <NUM>). In addition, the second detent 41b may ensure that the advancer member <NUM> is not subsequently withdrawn once advanced the predetermined distance.

Once the sealant <NUM> has been exposed for sufficient time and/or tamped by the advancer member <NUM>, the positioning element <NUM> may be collapsed, and the positioning member <NUM> withdrawn from the vessel <NUM> and puncture <NUM>, e.g., pulling the collapsed positioning element <NUM> through the sealant <NUM> and advancer member <NUM>, as shown in <FIG>. The advancer member <NUM> may be maintained substantially stationary during withdrawal of the positioning member <NUM>, e.g., to prevent migration and/or dislodgment of the sealant <NUM> within the puncture <NUM>. Once the positioning member <NUM> is completely removed, the advancer member <NUM> may be removed from the puncture <NUM>, leaving the sealant <NUM> within the puncture <NUM>, as shown in <FIG>.

Optionally, after removing the positioning member <NUM>, liquid hydrogel or other sealing compound, or other material may be delivered into the puncture <NUM>, e.g., above and/or around the sealant <NUM>, to assist in achieving hemostasis. For example, such material may be delivered via the lumen <NUM> of the advancer member <NUM> and/or by introducing another delivery device (not shown) into the puncture <NUM>, e.g., after removing the advancer member <NUM>.

With additional reference to <FIG>, with the freeze-dried hydrogel proximal section <NUM> of the sealant <NUM> delivered into the puncture <NUM> adjacent vessel <NUM>, hydration may occur substantially immediately as the sealant <NUM> is exposed from the tubular member <NUM> and begins to uptake local fluids (blood or interstitial fluids). For example, the proximal section <NUM> of the sealant <NUM> may begin to swell rapidly such that the swelling and the increase in the radial dimension of the proximal section <NUM> substantially fills a portion of the available space in the puncture <NUM> above the vessel <NUM>, e.g., above the arteriotomy in the vessel wall. The end result is a discrete, optimally targeted deposition of hydrogel sealant <NUM> that provides a seal over the arteriotomy.

In addition, the non-freeze-dried distal section <NUM> of non-crosslinked precursors absorbs local fluids, which initiates crosslinking in-situ and results in a more secure mechanical hold on the surrounding tissue as the freeze-dried hydrogel conforms to the spaces in the tissue tract. Optionally, if the sealant <NUM> includes salts or other pH adjusting agents, exposure of the sealant <NUM> may dissolve the agent(s) in the local fluids, which may enhance or facilitate crosslinking of the precursors.

In an exemplary, if the sealant <NUM> is compressed against the arteriotomy over the vessel <NUM>, the distal section <NUM> may bond to the outer surface of the vessel wall <NUM> and/or other tissue adjacent the arteriotomy, or may fill or otherwise penetrate into the arteriotomy, e.g., optionally extending into the interior of the vessel <NUM>, which may enhance the resulting seal and/or prevent migration of the proximal section <NUM> of the sealant <NUM>, e.g., away from the arteriotomy and vessel wall <NUM>. Thus, the end result may be a discrete, optimally targeted deposition of hydrogel sealant that provides a durable seal over or within the arteriotomy, as shown in <FIG>.

Several alternative embodiments of sealants are shown in <FIG> and described below that may be delivered, e.g., using the apparatus and methods described elsewhere herein and/or in the references identified elsewhere herein. The sealants described below may be formed from any of the materials and methods described above for sealant <NUM>.

For example, turning to <FIG>, an exemplary embodiment of a sealant <NUM> is shown that includes a proximal section <NUM> of freeze-dried hydrogel and a distal section <NUM> of non-crosslinked precursors, generally similar to other embodiments herein. In an exemplary embodiment, uncoated biomaterial, e.g., freeze-dried hydrogel, may be rolled or otherwise formed, similar to other embodiments described herein, for the proximal section <NUM>. Thus, the sealant <NUM> may include a lumen (not shown) extending longitudinally between the proximal and distal sections <NUM>,<NUM>, e.g., to allow delivery of the sealant <NUM> over a positioning member <NUM>, similar to other embodiments herein.

As shown in <FIG>, a cylindrical plug or bolus <NUM> of substantially dry non-crosslinked hydrogel precursors may be fused or otherwise provided on or adjacent the distal end of the proximal section <NUM>. For example, the distal section <NUM> may be a solid mass or plug, e.g., a melted and solidified form attached to the proximal section <NUM>, similar to the processes described above. Alternatively, the distal section <NUM> may be a bolus of powder provided adjacent but separate from the proximal section <NUM>, e.g., sintered or otherwise compressed together, while remaining in a powder form, or simply loaded into a delivery cartridge distal to the proximal section <NUM> such that the powder is released when the sealant <NUM> is delivered from the cartridge. For example, if the precursor powder is sintered into a desired shape, the powder particles may behave as a solid mass yet may easily separate from one another, e.g., when delivered within a puncture, which may increase surface contact between the powder and physiologic fluids, which may accelerate and/or otherwise enhance crosslianking of the precursors.

Optionally, the non-crosslinked precursors of the distal section <NUM> and/or the uncoated biomaterial of the proximal section <NUM> may have salts or other pH adjusting agents impregnated therein or applied thereto such that, when physiological fluids wet the biomaterial and/or unreacted hydrogel precursors, a favorable pH may be obtained for cross-linking the distal section <NUM>. The ratio of the lengths of unreacted hydrogel precursors to uncoated biomaterial, i.e., distal to proximal sections <NUM>, <NUM>, may range from <NUM>-<NUM>% for the respective materials, and the length of the overall sealant <NUM> may vary, similar to other embodiments herein.

During use, the sealant <NUM> may be advanced into position, e.g., over a positioning member <NUM> and/or towards a positioning element <NUM>, in apposition to the surface <NUM> of an artery at the arteriotomy within a puncture (not shown), e.g., using apparatus and methods similar to those described elsewhere herein. The local fluids within the puncture may initiate crosslinking of the precursors of the distal section <NUM>, which may cause the crosslinking precursors to soften, flow into available space within the puncture, e.g., into the arteriotomy and/or into the vessel itself, and begin to crosslink to form a hydrogel. The "setting" action of the non-crosslinked precursors as the in-situ crosslink occurs may act as a glue to substantially fix the sealant <NUM> in position over the arteriotomy.

The distal section <NUM> may also form a patch over the arteriotomy, e.g., against or into the vessel wall <NUM>, e.g., with the sealant <NUM> acting as a sponge to absorb any blood in the immediate area, e.g., to minimize subsequent oozing. For example, as shown in <FIG>, the distal section <NUM> may be compressed against the vessel wall <NUM>, e.g., using a tamping member (not shown), similar to other embodiments herein, which may cause deformation of the crosslinking precursors, potentially enhancing the coverage area of the adherent material and/or increasing the surface area for the cross-linking reaction.

Turning to <FIG>, an alternative embodiment of a sealant <NUM>' is shown that includes a proximal secton <NUM>' and a distal section <NUM>' generally similar to the sealant <NUM> of <FIG>. However, as shown in <FIG>, unlike the previous embodiment, the proximal section <NUM>' may include a pocket 104d' formed in the distal end of the uncoated biomaterial within which the non-crosslinked precursors of the distal section <NUM>' may be formed or deposited. For example, a solid mass of non-crosslinked precursors or a bolus of precursor powders may be loaded into the pocket 104d,' e.g., loosely or fused to the distal end of the first section 104a,' similar to previous embodiments.

As shown in <FIG>, the sealant <NUM>' may be compressed within a puncture and/or against an arteriotomy in the vessel wall <NUM>, similar to other embodiments herein, which may cause an annular wall of the first section <NUM>' defining the pocket 104d'to splay out over the flattened distal section <NUM>,' e.g., providing improved adhesion between the uncoated biomaterial of the proximal section <NUM>' and the adherent material of the distal section <NUM>.

Turning to <FIG>, another alternative embodiment of a sealant <NUM>" is shown, similar to the sealant <NUM>' of <FIG> (or the sealant <NUM> of <FIG>) including a proximal section <NUM>" of freeze-dried hydrogel and a distal section <NUM>" of non-crosslinked polymers. Similar to the sealant <NUM>,' the proximal section <NUM>" includes a pocket 104d" for receiving the non-crosslinked precursors of the distal section <NUM>. " Unlike the previous embodiments, the proximal section <NUM>" may include one or more longitudinal slits 104e" formed laterally through the uncoated biomaterial and extending only partially between and spaced apart from the proximal and distal ends of the proximal section <NUM>. " Such a slit 104e" through the side of the proximal section <NUM>" may facilitate collapsing the sealant <NUM>" during compression, e.g., into a "lantern" shaped body, as shown in <FIG>. For example, these drawings show how compression may result in a substantially flattened low profile for the delivered sealant <NUM>," which may provide maximum surface area coverage against the vessel wall <NUM>.

Turning to <FIG>, still another embodiment of a sealant <NUM> is shown that includes two distinct sections of sealant material. The distal section <NUM> may be formed from a relatively softer, rapidly swelling composition, e.g., freeze-dried hydrogel, while the proximal section <NUM> may be formed from a relatively harder, slower swelling composition. As shown, the proximal section <NUM> may be nested to some degree into the distal section <NUM>, e. g, including a tapered distal tip 206f that is initially provided within a similar shaped pocket <NUM> in the proximal end of the distal section <NUM>, as shown in <FIG>.

The act of placing a compressive load on the proximal section <NUM> of the sealant <NUM> while holding the distal face of the distal section <NUM> substantially fixed (e.g., in this case using a balloon <NUM> as a backstop), may drive the proximal section <NUM> into the distal section <NUM>. As shown in <FIG>, this action may expand the distal section <NUM> into a shape that is wider than its original configuration. For example, as shown in <FIG>, the distal section <NUM> may be designed to split during compression, bulge, or otherwise deform under the compressive load.

Turning to <FIG>, still another embodiment of a sealant <NUM> is shown that includes a proximal end 304a, a distal end 304b and a longitudinal slit 304e extending partially between the proximal and distal ends 304a, 304b, e.g., similar to the proximal section <NUM>" of the sealant <NUM>" of <FIG>. In this embodiment, the freeze-dried hydrogel or other sealant may include one or more slits to enable a controlled deformation of the sealant <NUM> under a compressive load. For example, the sealant <NUM> may include two longitudinal slits 304e (only one visible in the side view shown in <FIG>), e.g., offset one hundred eighty degrees (<NUM>°) apart from one another around the circumference of the sealant <NUM>. Alternatively, the number and/or orientation of the slits 304e may be modified, e.g., to attain a desired morphology after compression.

It will be appreciated that the shape of any of the sealants herein may be modified to have a shape that is conducive to controlled deformation. Examples include an inverted golf tee, an hourglass, swept or wavy surfaces, and the like.

Turning to <FIG>, additional alternative embodiments of sealants are shown that include non-crosslinked precursor sections 406a-<NUM> and freeze-dried hydrogel main sections 404a-<NUM>. The location of the non-crosslinked precursors 406a-<NUM> may be proximal to, distal to, or both proximal and distal to the hydrogel main sections 404a-<NUM>. The precursors 406a-<NUM> may be provided as a solid mass fused or otherwise attached to the main section 404a-<NUM> or as a bolus of powder, similar to other embodiments herein. For example, a sealant 402a may be provided that includes precursor sections 406a within pockets in both proximal and distal ends of the main section 404a, while the sealant 402b may include a precursor section 406b within a pocket on the proximal end of the main section 404b.

Sealants 402c and 402d include a main section 404c, 404d,e.g., formed from freeze-dried hydrogel, and non-crosslinked precursor sections on either both ends 406c or one end 406d of the main section 404c, 404d. In these embodiments, the non-crosslinked sections 406c, 406d may be a solid mass fused to the main sections 404c, 404d or a bolus or sintered mass of precursor powders.

Sealants 402e-<NUM> include main sections 404e-<NUM>, e.g., formed from freeze-dried hydrogel, and distal sections 406e-<NUM>, e.g., solid masses of non-crosslinked precursors fused or otherwise attached to the main sections 404a-<NUM>. For example, in sealant 402e, the main section 404e may include a recess, e.g., a conical recess in one end for receiving the distal section 406e substantially flush with the end of the main section 404e. Alternatively, the distal section 406f may extend from the recess in the main section 404f, as shown for the sealant 402f. In a further alternative, the sealant <NUM> includes a smaller tab or other feature extending from the main section <NUM> around which the distal section <NUM> may be formed and/or extend.

Turning to <FIG>, another embodiment of a sealant <NUM> is shown, which may include a section of rolled hydrogel or other base material <NUM>, such as any of the materials described above, including proximal and distal ends 504a, 504b. A plurality of slits <NUM> may be formed in the distal end 504b, e.g., by mechanical cutting, laser cutting, stamping, and the like, as shown in <FIG>. The distal end 504b may then be coated, e.g., with non-crosslinked precursors, as shown in <FIG>, similar to other embodiments herein and in the references identified elsewhere herein. Optionally, pH controlling salts and the like may be embedded in the coating or in the non-coated biomaterial, e.g., as shown in <FIG>. The slits <NUM> may facilitate collapsing the coated end 504b of the sealant <NUM>, e.g., resulting in a wider footprint to cover an arteriotomy or other vessel puncture, as shown in <FIG>. The sealant <NUM> may be delivered using apparatus and methods similar to those described elsewhere herein.

Turning to <FIG>, an exemplary embodiment of a pliable patch-like material <NUM> is shown, e.g., having lateral dimensions (from the perspective of <FIG>), e.g., a width, height, diameter, and the like depending on the desired shape for the patch, formed from material with minimal stretch in the lateral directions. The patch <NUM> may include a weave or other arrangement <NUM> of synthetic biocompatible and/or bioresorbable fibers, such as PLG, PLA or PGA, e.g., defining a first or base layer, as shown in <FIG>. Alternatively, the patch <NUM> may also be formed from naturally occurring proteins, such as collagen, or other bioabsorbable materials, such as those described above.

As shown in <FIG>, the patch <NUM> may be covered on one or both sides with non-crosslinked precursors, similar to other embodiments herein, e.g., to provide an adhesive layer <NUM> for the patch <NUM>. As shown, the coating <NUM> has been provided on only the bottom side of the base layer <NUM> of the patch <NUM>. In the case of coating <NUM> on only one side, a layer <NUM> of freeze-dried hydrogel or other expandable, bioabsorbable material may be provided on the top side of the base layer <NUM>, e.g., to absorb excess fluid and/or expand to fill a space above the delivery site. Optionally, salts to control the pH (not shown) may be blended with the coating <NUM>, embedded in the base material <NUM>, embedded in the freeze-dried hydrogel <NUM>, and/or dissolved in a buffer solution that is used to saturate the assembly immediately before or after the patch <NUM> is applied to a arteriotomy or other tissue surface.

The patch <NUM> may be delivered using the apparatus and methods described elsewhere herein, e.g., where the patch <NUM> is small enough to be loaded into a cartridge. Alternatively, the patch <NUM> may be applied manually, e.g., if the tissue surface is sufficiently exposed.

For example, upon application to a vessel or other tissue surface or structure, e.g., over an arteriotomy or other puncture (not shown), adhesion to the vessel may occur due to the coating <NUM>, but the non-stretch nature of the base layer <NUM> of the substrate patch <NUM> may prevent the expanding pressurized vessel from substantially opening or enlarging the arteriotomy because of the lateral resistance of the patch <NUM> to expansion. The dense weave of the base layer <NUM> and the cross-linking of the coating <NUM> may prevent blood or other fluid from the vessel from leaking though the patch <NUM>. The size of the patch <NUM> may vary from being large enough to surround all or a portion of vessel having a puncture therethrough, e.g., adhering the patch all around the puncture to only pulling together the mid-point of the vessel puncture for achieving substantial hemostasis. Optionally, after applying the patch, another hemostatic material, such as freeze-dried hydrogel (or any other sealant, such as those described elsewhere herein) may be applied over the top to achieve complete hemostasis.

Claim 1:
A sealant for sealing a puncture through tissue, comprising:
an elongate first section (<NUM>) including a proximal end (4a), a distal end (4b), and a cross-section sized for delivery into a puncture through tissue,
wherein the first section (<NUM>) is formed from a rolled freeze-dried hydrogel that expands when exposed to physiological fluid within the puncture; and
a second section (<NUM>) extending from the distal end (4b) of the first section (<NUM>), the second section (<NUM>) comprising PEG-precursors comprising PEG-ester and PEG-amine precursors, at least some of the precursors remaining in an unreactive state until exposed to an aqueous physiological environment, whereupon the precursors undergo in-situ cross-linking with one another to provide adhesion to tissue adjacent the puncture,
and characterized in that the second section (<NUM>) is a solid mass of the precursors remaining in the unreactive state fused to and extending from an end face of the distal end (4b) of the rolled first section (<NUM>), wherein the solid mass comprises a uniform solid plug of precursors remaining in the unreactive state.