Patent Description:
Soft tissues within a body may benefit from repair or reinforcement due to a variety of reasons such as disease, enhancement, or trauma.

An implant or medical textile may be used to repair or reinforce a soft tissue such as an unhealthy or modified tissue in the body. The tissue may be, for example, tissue that is no longer able to maintain its shape or physiological function such as a hernia or a tissue for which a shape or size change is desired such as breast size or shape change due to breast enhancement or breast reconstruction. A hernia is a condition in which part of an organ or fatty tissue protrudes through the wall of a surrounding tissue. Abdominal wall hernia surgery is one of the most common surgical procedures, and according to the U. Food and Drug Administration, more than <NUM> million hernia repairs are performed in the United States alone. Common adverse events associated with hernia repair surgery include pain, infection, hernia recurrence, adhesion formation, obstruction, bleeding, and fluid build-up. Breast reconstruction may be performed to reconstruct a breast after a mastectomy has been performed to remove a diseased due to cancer or as a prophylactic measure to prevent cancer. Common adverse events associated with breast reconstruction include infection, pain, delayed healing, and swelling.

Thus there is a need for improved surgical repair materials and medical textiles.

<CIT> discloses a patch comprising an implantable surgical mesh, a cross-linkable protein matrix and a protein cross-linking enzyme in contact with the matrix for cross-linking the cross-linkable protein. The matrix is incorporated into, layered on or surrounding the mesh.

<CIT> discloses a composition of matter comprising liposomes encapsulating in their intraliposomal aqueous compartment at least one active agent. The liposomes are embedded in a water insoluble, water absorbed cross-linked polymeric matrix.

<CIT> discloses sustained-release liposomal anesthetic compositions.

<CIT> discloses a hernia repair graft comprising a first layer comprising a mesh and a second layer comprising a sheet of anti-adhesive material. The second layer is flexibly attached to the first layer with a pattern of discrete attachment sites The pattern of discrete attachment sites alters the compliance of the stacked first and second layers by less than <NUM>% and adjacent regions of the first layer and second layer between the discrete attachment sites may slide relative to each other.

<CIT> discloses a multilaminate or multiple layer implantable surgical graft comprising remodelable collagenous sheet material, the graft including one or more interweaving members to stitch together the graft to help prevent the layers from delaminating or separating during handling and the initial stages of remodeling. In one embodiment, the interweaving members comprise a pharmacologically active substance, such as a drug, growth factors, etc. to elicit a desired biological response in the host tissue.

Further aspects and preferred embodiments of the invention are defined in the dependent claims.

Described herein are surgical repair graft devices and medical textile devices configured to carry an agent (e.g., an active agent such as a drug) and methods of making and using such devices. Such a surgical repair graft may serve to release the agent over a period of time (be time-release). As used herein, a surgical repair graft (or medical textile) refers to a device having more than two biotextile layers and a carrier matrix adhered to at least one layer, the graft configured for implanting into a body (e.g., a mammalian body). Such a surgical repair graft or medical textile may release an agent into the body (in vivo release) or external to or on the body. In general, the surgical repair graft or medical textile maintains advantageous mechanical properties (e.g., strength, flexibility, compliance, etc.) for use in soft tissue reconstruction, regeneration, or repair.

A surgical repair graft as described herein may be useful for supporting or repairing a body tissue such as for breast reconstruction, hernia repair, pelvic organ prolapse treatment, and so forth. In some examples it may be implanted or used to serve as a source of a desired agent.

In some embodiments useful for understanding the invention, the surgical repair graft includes one layer or a plurality of stacked layers (e.g., a plurality of stacked biotextile layers), and a bioabsorbable carrier matrix including a multivesicular liposome attached to one or more than one biotextile layers, the multivesicular liposome including an active agent. In some particular examples, the carrier matrix has a plurality of particles each having a plurality of non-concentric internally aqueous chambers each surrounded by a lipid membrane, wherein at least one or more of the lipid membrane and the aqueous chamber contain an active agent. As used herein, a description of a surgical repair graft may also apply to a medical textile, such as one used for eye treatment, sutures, wound dressing, and so on.

<FIG> show an example useful for understanding the invention of a surgical repair graft with a plurality of attached carrier particles, the surgical repair graft having one or more biotextile layers and a carrier matrix adhered to at least one layer, the graft configured for implanting into a body (e.g., an animal or mammalian body).

A layer or layers of a surgical repair graft as described herein generally have biomechanical properties that match or are similar to the biomechanical properties of the tissues they are replacing or repairing. Such biomechanical properties of a surgical implant may be described, for example by bending stiffness, compliance, elasticity, uniaxial tension, burst strength, roughness, and so on.

A surgical repair graft may be made of any materials or combination of materials that alone or in combination supply desired mechanical properties and other desired characteristics such as biocompatibility and biostability. A graft may serve as a time-release depot for agent (e.g., active agent such as a drug) release. A graft may include multiple components such as one or more biotextile layer(s); a carrier matrix containing an agent; an adhesive that adheres carrier matrix to a biotextile layer, etc.). A component may be made from naturally occurring materials and/or from synthetic materials.

In some examples, a biotextile layer(s) of a surgical repair graft may be made from extracellular matrix (ECM) and/or may be synthesized to mimic the properties of extracellular matrix. In some examples, a biotextile layer may be made from or may include naturally occurring or synthetic extracellular matrix materials such as collagen, elastin, fibronectin, INTERGARD™, laminin, TIGR®, ULTRAPRO™ and so on. In some examples, a biotextile layer (or adhesive) is made from a naturally occurring collagen such as avian collagen, bovine collagen, fish collagen, marine animal collagen, ovine collagen, or porcine collagen. A collagen or other naturally occurring material may be harvested from any source, such as an organ or part of an organ, such as dermis, forestomach, intestine, pericardium, peritoneum, rumen (stomach), skin, stomach, tail, etc. of any organism. In other examples, collagen or another graft component may be manufactured by recombinant or other synthetic processes.

A carrier matrix as used herein includes a plurality of particles configured to carry and hold an agent for use in (or on) the body. In general, an agent in a carrier matrix is an active agent configured for release into the body to have an effect in the body and a carrier matrix is at least partially biodegradable to release the active agent into the body, but this is not necessarily the case. For example, a carrier matrix may hold a fluoroscopic agent for use for imaging purposes and the carrier matrix or part of a carrier matrix may not degrade and the fluoroscopic agent may remain in the carrier matrix. In some embodiments, a carrier matrix attached to a biotextile layer is discontinuous. <FIG> show the same surgical graft under different conditions. <FIG> shows surgical repair graft <NUM> in an unstretched state. Carrier matrix particles <NUM> are attached to substrate or biotextile layer <NUM>. <FIG> shows the same graft shown in <FIG> that has been subjected to a stretching force (shown by the arrow). <FIG> shows the same surgical repair graft <NUM>' that has been subject to a bending force. Due to the space between particles <NUM>', the region of substrate <NUM>' between particles <NUM>' is able to stretch (or compress) and thus allow surgical graft <NUM>' to stretch with little or no change to stretchability or relative to a similar surgical graft lacking such particles. Additionally as shown in <FIG>, substrate <NUM>" is sufficiently flexible to bend and the space between particles <NUM>" and the shape of particles <NUM>" allows room for particles <NUM>" to not interfere with each other as the graft bends and folds towards itself. By comparison, <FIG> show a surgical repair graft with a covering (e.g., a coating or sheet) that limits axial compliance and increases bending stiffness compared with a similar surgical repair graft without a covering. <FIG> shows surgical repair graft <NUM> with covering <NUM> on substrate <NUM> in an unstressed state. <FIG> shows the same surgical repair graft <NUM>' as the one shown in <FIG> that has been subject to a stretching force (shown by the arrow). Although some stretching takes place, coating <NUM>' limits the ability of substrate <NUM>' to stretch. <FIG> shows the same surgical repair graft <NUM>" as shown in <FIG> that has been subject to a bending force. Coating <NUM>" deforms and wrinkles when bent and prevents substrate <NUM>" from bending too far. Because the covering resists an applied axial force and wrinkles on bending, the surgical grafts in <FIG> resist stretching and bending. Bending of such a relatively noncompliant graft may also result in such as wrinkling or separation of the covering from the biotextile.

Carrier matrix particles can be any shape and can be regularly shaped or irregularly shaped. In some examples, a carrier matrix (e.g., of a surgical graft) includes particles that are generally block-shaped, conical, cuboidal, cylindrical, ellipsoidal, helical, pyramidal, spherical, square pyramidal, rectangular prism shaped, rectangular pyramidal, or tetrahedral, etc. and a carrier matrix may include one or more than one different shapes of particles. In some examples, a swath of a textile may have one shape of carrier matrix particles while another swath may have another shape. This may for example be useful to provide a graft that is relatively more compliant or more bendable in a first portion and less compliant or less bendable in a second portion. In some examples, a swath of a textile or an entire textile may have a mixture of different shapes of particles. Such a mixture may be regular or irregular (random). <FIG> show a side view of a surgical repair graft with a plurality of pyramidal shaped carrier particles attached to a biotextile layer at rest and under different types of tension and <FIG> shows a perspective view. <FIG> and <FIG> show surgical repair graft <NUM> at rest without added tension on the graft. <FIG> shows surgical repair graft of <FIG> in which surgical repair graft <NUM>' is axially stretched and <FIG> shows the surgical repair graft of <FIG> when surgical repair graft <NUM>" is bent. <FIG> and <FIG> show carrier particles attached to the biotextile layer at an attachment end and unattached to the biotextile layer at an unattached end. <FIG> show carrier matrix particles larger at an attachment end whereby they are attached (either directly or through an intermediate component such as an adhesive) to a biotextile layer and smaller at an unattached end whereby they are unattached to the biotextile layer. In <FIG> and <FIG>, pyramidal shaped carrier matrix particles <NUM> are attached to layer <NUM> of surgical graft <NUM>. In <FIG>, as a stretching tension shown by the arrow in <FIG> is applied to graft <NUM>' to axially stretch layer <NUM>', sections of layer <NUM>' in between attached particles <NUM>' (particle "nodes") are free to stretch in response to the stretching, allowing the biotextile layer (and graft as a whole) to readily stretch. In some examples, axial compliance of the graft having the carrier matrix attached to the substrate may be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between such as between <NUM>% and <NUM>%) from axial compliance of a similar graft that does not have the carrier matrix attached. In <FIG>, as a force shown by the arrow is applied to graft <NUM>" to bend graft <NUM>", sections of layer <NUM>' between attached particles <NUM>' (particle "nodes") are able to compress and bend and the opposing side of layer <NUM>" away from the particles is free to stretch, and the graft is free to bend. In some examples, bend resistance of the graft having the carrier matrix attached may be or may be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between such as between <NUM>% and <NUM>%) from bend resistance of a similar graft that does not have carrier matrix attached. Additionally, since attached particles <NUM>" are narrower towards their unattached end than at their attached end, attached particles <NUM>" do not bump into each other when graft <NUM>" bends and graft <NUM>" is able to bend without undue interference from attached particles <NUM>". Having a larger attached end may be beneficial for providing space to carry an agent (an active agent) into a body.

<FIG> show side views of another surgical repair graft with a plurality of block shaped attached carrier matrix particles under different degrees of force, such as those that might be experienced in a patient's body. The particles may be for example cuboidal or rectangular prism shaped. <FIG> shows surgical repair graft <NUM> at rest without added tension. <FIG> shows surgical repair graft <NUM>' when the graft is placed under axial tension and stretched. <FIG> shows surgical repair graft <NUM>" of <FIG> when the graft is placed under a bending force. In <FIG> carrier matrix particles <NUM> are attached to layer <NUM>. In <FIG>, as a stretching tension shown by the arrow is applied to graft <NUM>' to axially stretch layer <NUM>', sections of layer <NUM>' in between attached particles <NUM>' (particle "nodes") are free to stretch in response to the stretching. Axial compliance of the graft having the carrier matrix attached may be or maybe not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between such as between <NUM>% and <NUM>%) from axial compliance of a similar graft that does not have the carrier matrix attached. However, in <FIG>, as a force shown by the arrow is applied to graft <NUM>" to bend graft <NUM>", bend resistance of the graft having the carrier matrix attached to it is ultimately increased compared with bend resistance of a similar graft that does not have carrier matrix attached. Sections of layer <NUM>" in between attached particles <NUM>" are able to squeeze together to a limited degree before carrier particles <NUM>" begin to collide and restrict further bending (as shown by the free arrow). Graft <NUM> has an axial compliance that may be minimally affected by the attachment of particles <NUM>, while bend resistance is increased. Particles <NUM> are relatively large and may carry a significant amount of active agent and graft <NUM> (or a portion of a graft <NUM>) may be useful in an area where relatively more bending stiffness is acceptable or desired.

<FIG> show side views of another surgical repair graft with a plurality of attached soft shell carrier particles at rest and under different types of tension. <FIG> shows surgical repair graft <NUM> at rest without added tension. <FIG> shows surgical repair graft <NUM>' when the graft is axially stretched. <FIG> shows surgical repair graft <NUM>" when the graft is bent. <FIG> shows surgical graft <NUM> with soft shell carrier particles <NUM> attached to biotextile layer <NUM>. In <FIG>, as a stretching tension shown by the arrow is applied to graft <NUM>' to axially stretch layer <NUM>', sections of layer <NUM>' in between attached particles <NUM>' (particle "nodes") are free to stretch in response to the stretching. Axial compliance of the graft having the soft shell carrier matrix attached may be or may be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between such as between <NUM>% and <NUM>%) from axial compliance of a similar graft that does not have the carrier matrix attached. In <FIG>, as a force shown by the curved arrow is applied to surgical repair graft <NUM>" to bend surgical repair graft <NUM>", soft shell carrier particles <NUM>" are pressed against one another. Soft shell carrier particles are sufficiently soft or pliable and are configured to deform in response to an applied force. In response to being pressed against one another, the particles readily morph, changing shape, indenting or deforming. Bend resistance of the graft having the soft shell carrier matrix attached may be or may not be significantly different (e.g., between <NUM>% and <NUM>% different or anything in between such as between <NUM>% and <NUM>%) from bend resistance of a similar graft that does not have the carrier matrix attached. Although particle morphing is illustrated as occurring when particles contact one another, particles may also or instead morph in response to contacting a biotextile layer, a body part, etc..

<FIG> show side views of another surgical repair graft with a plurality of attached relatively short carrier particles at rest and under different types of tension. The particles may, for example, be cuboidal or rectangular. Although the particles may be similarly shaped to those of <FIG>, they are shorter and grafts having them generally show less bending resistance. <FIG> shows surgical repair graft <NUM> at rest without added tension. <FIG> shows surgical repair graft <NUM>' when the graft is placed under axial tension and axially stretched. <FIG> shows surgical repair graft <NUM>" when the graft is placed under a bending tension and the graft is bent. In <FIG>, carrier matrix particles <NUM> are attached to biotextile layer <NUM> of surgical graft <NUM>. In <FIG>, as a stretching tension in the direction shown by the large arrow in <FIG> is applied to graft <NUM>' to axially stretch biotextile layer <NUM>', sections of layer <NUM>' in between attached particles <NUM>' (particle "nodes") are free to stretch in response to the stretching. Axial compliance of the graft having the relatively short carrier matrix particles attached may be or may not be significantly different (e.g., between <NUM>% and <NUM>% different or anything in between these values such as between <NUM>% and <NUM>%) from axial compliance of a similar graft that does not have the carrier matrix attached. In <FIG>, as a force shown by the large arrow is applied to surgical repair graft <NUM>" to bend surgical repair graft <NUM>", the relatively short carrier matrix particles do not contact each other. Sections of biotextile layer <NUM>" between attached particles <NUM>" are able to compress and the opposing side of layer <NUM>" is free to stretch apart and the graft is free to bend.

<FIG> show side views of a surgical repair graft with a plurality of relatively tall attached carrier particles at rest and under different types of tension. <FIG> shows surgical repair graft <NUM> at rest without added tension. <FIG> shows surgical repair graft <NUM>' placed under an axial tension wherein the graft is axially stretched. <FIG> shows surgical repair graft <NUM>" when the graft is placed under a bending tension and the graft is bent. In <FIG>, carrier matrix particles <NUM>' are attached to layer <NUM> of surgical graft <NUM>. In <FIG>, as a stretching tension in the direction shown by the arrow in <FIG> is applied to graft <NUM>' to axially stretch layer <NUM>', sections of layer <NUM>' in between attached particles <NUM>' (particle "nodes") are free to stretch in response to the stretching and the graft stretches. Axial compliance of the graft having the relatively tall carrier matrix particles attached may be or may not be significantly different (e.g., between <NUM>% and <NUM>% different or anything in between these values such as between <NUM>% and <NUM>%) from axial compliance of a similar graft that does not have the carrier matrix attached. In <FIG>, as a force shown by the arrow is applied to graft <NUM>" to bend graft <NUM>". The relatively tall particles contact each other even when the graft is bent only slightly and the bend resistance of the graft having the carrier matrix attached to it is significantly greater than the bend resistance of a similar graft that does not have carrier matrix attached. Depending on a patient's needs, a graft or a portion of a graft according to <FIG> may be useful in an area of the body for which greater bend resistance is desired or unimportant. Such a graft with a relatively larger particle size may allow more active agent to be delivered.

<FIG> show views of another surgical repair graft having a relatively homogenous covering of carrier matrix. <FIG> shows surgical repair graft <NUM> at rest without added tension. <FIG> shows surgical repair graft <NUM>' under added tension. <FIG> shows surgical graft <NUM> with covering <NUM> on biotextile layer <NUM>. In <FIG>, as a stretching tension shown by the arrows 157a-157d is applied to graft <NUM>' to axially stretch layer <NUM>'. In <FIG>, covering <NUM>' limits the ability of underlying biotextile layer <NUM>' to stretch, and graft <NUM>' stretches just to the dotted lines. In other examples, a covering and graft may stretch further. Such a covering may be very thin (and reduce a moment of inertia), such as less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM> or more than any of these values (or any values or range of values in between these values) in thickness. A covering may be a lasting (permanent or non-biodegradable) or may be biodegradable in part or in whole. A covering may be relatively uniform or may have regions of differing thickness with a first region with a first thickness and a second region with a second thickness. A carrier matrix covering may be applied to a graft, a biotextile layer or an adhesive as a plurality of separate particles to coat the graft (such as by solution or electrospray) or carrier matrix may be applied to a graft, biotextile layer, or adhesive as a sheet. In some examples, a sheet of carrier matrix may include or be combined with other components, such as an adhesive.

A covering may be a foam and may have a plurality of cells and pores. Cells going through a covering may bend and turn within the covering. In some examples, cells in a covering may be open (e.g., at least half of its cells are open via pores at the surface). In some examples, cells in a covering may be closed (having cells totally enclosed by walls). In general a closed foam covering has less than half of its cells open. Open cells in a covering may better allow bodily fluid to penetrate and may be used to control a rate of degradation. Different ratios of open cells to closed cells may provide advantages for different purposes. In some examples, having more open cells may allow a faster degradation while having fewer open cells may slow down degradation and allow agent release over a longer period of time. The presence of cells and pores in a covering may allow a covering to stretch and bend. In some examples, a covering may have up to <NUM> pores per <NUM><NUM> (square inch (PPI)), from <NUM> to <NUM> pores per <NUM><NUM> (square inch), more than <NUM> and fewer than <NUM> pores per <NUM><NUM> (square inch). Cells (over the whole graft or a region of the graft, such as a <NUM><NUM> (square inch) region) may have an average pore diameter or average cell diameter of between <NUM> and <NUM>, or anything in between, such as between <NUM> and <NUM>, <NUM> and <NUM>, <NUM> and <NUM>, etc. Such pores may also allow a fluid, such as a bodily fluid, to flow through the graft and aid in biodegrading the carrier matrix. The number and sizes of pores or cells may be chosen, for example, to control a rate of carrier matrix biodegradation and active agent release in a time sensitive manner such as releasing from <NUM> % to <NUM>% or of an agent (or any amount in between such as <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>%) in <NUM> hour to <NUM> hours, <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything in between these times (such as between <NUM> days and <NUM> days, <NUM> days, etc.).

<FIG> show views of another surgical repair graft having a relatively homogenous covering with openings. <FIG> shows the repair graft at rest without added tension. <FIG> shows the repair graft under added tension; the openings allow the covering and graft to stretch and bend. In general, openings go through the covering, from one side of the covering to the other side. <FIG> shows surgical graft <NUM> with covering <NUM> on biotextile layer <NUM>. Covering <NUM> can be up any thickness, but in general may be relatively thin (less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, less than <NUM>, or less than <NUM> in thickness or any value or range of values in between these). In <FIG>, as a stretching tension shown by the arrows 167a-167d is applied to graft <NUM>', openings <NUM> open, lengthen, or widen in response to the stretching tension, relieving axial tension, and covering <NUM>' and underlying layer <NUM>' are free to bend, expand, flex, lengthen, stretch or widen (e.g., in the X, Y, and/or Z directions) in response to the stretching force. Axial compliance (in the lengthwise (167a-167b) or widthwise (167c-167d) directions or diagonally) of graft <NUM>' of the graft having a covering with opening may be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between these values such as between <NUM>% and <NUM>%) from axial compliance of a similar graft that does not have the carrier matrix attached. The covering with openings may readily bend when the graft is subject to a bending force and bends. Bend resistance of graft <NUM>' having a carrier matrix covering with openings may be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between these values such as between <NUM>% and <NUM>%) from bend resistance of a similar graft that does not have the carrier matrix attached. A graft having covering with openings may additionally have any of the characteristics or properties indicated above for <FIG>, such as cells, pores, etc..

Openings may be substantially closed (e.g., be slits and the sides of the opening opposed or touching) when a graft is at rest and the openings only open up when the graft is subject to a force, such as an axial force or a bending force or the openings may be open or partially open even in the absence of an applied force. The openings may be any shape when opened, e.g., circular, long rectangular, diamond, etc. The openings in the covering may be randomly spaced from each other or may be regularly (geometrically) spaced from one another such as in an array or matrix. In some examples, a coating may have up to <NUM> openings per <NUM><NUM> (square inch) (e.g., may have <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> openings per <NUM><NUM> (square inch), from <NUM> to <NUM> openings per <NUM><NUM> (square inch), or more than <NUM> openings and less than <NUM> openings per <NUM><NUM> (square inch) (or anything or range in between any of these values). Openings (over an entire graft or a region of a graft, such as <NUM><NUM> ( square inch) region) may have an average opening diameter or maximum dimension between <NUM> and <NUM>, or anything in between, such as from <NUM> to <NUM>, from <NUM> to <NUM>, etc. Such openings may also allow a fluid, such as a bodily fluid, to flow through the graft and aid in biodegrading the carrier matrix. The number and sizes of openings may be chosen, for example, to control a rate of carrier matrix biodegradation and active agent release in a time sensitive manner such as releasing from <NUM> % to <NUM>% or of an agent (or any amount in between such as <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>%) over <NUM> hour to <NUM> hours, <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything or any range in between these values.

<FIG> show side views of a surgical repair graft with carrier matrix attached to a biotextile layer through an intermediate adhesive. <FIG> shows surgical repair graft <NUM> at rest without added tension. <FIG> shows surgical repair graft <NUM>' when the graft is subject to an axial force and the graft is axially stretched. <FIG> shows surgical repair graft <NUM>" when the graft is subject to a bending force and the graft is bent.

In <FIG>, carrier matrix particles <NUM> are attached through adhesive <NUM> to biotextile layer <NUM> of surgical graft <NUM>. In <FIG>, as a stretching (axial) tension in the direction shown by the large arrow in <FIG> is applied to graft <NUM>', sections of adhesive <NUM>' and underlying biotextile layer <NUM>' in between attached particles <NUM>' (particle "nodes") are free to stretch in response to the axial tension. Axial compliance of the graft having an adhesive attached may be or may not be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between these values such as between <NUM>% and <NUM>%) from the axial compliance of a similar graft that does not have the adhesive attached. <FIG> also show carrier particles attached to the biotextile layer at an attachment end and are unattached to the biotextile layer at an unattached end. <FIG> show carrier matrix particles are larger at an attachment end whereby they are attached through an adhesive to a biotextile layer and smaller at a free end whereby they are unattached to the biotextile layer. In <FIG> pyramidal shaped carrier matrix particles <NUM> are attached to adhesive <NUM> and through adhesive <NUM> to biotextile layer <NUM> of surgical graft <NUM>. In <FIG>, as a stretching tension shown by the arrow in <FIG> is applied to graft <NUM>' to axially stretch the graft, sections of adhesive <NUM>' and biotextile layer <NUM>' in between attached particles <NUM>' (particle "nodes") are free to stretch in response to the axial force. Axial compliance of the graft having carrier matrix attached may be or may not be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between these values such as between <NUM>% and <NUM>%) from the axial compliance of a similar graft that does not have the carrier matrix attached. Axial compliance of the graft having both adhesive and carrier matrix attached may be or may not be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between these values such as between <NUM>% and <NUM>%) from the axial compliance of a similar graft that does not have the adhesive and carrier matrix attached.

In <FIG>, a bending force shown by the large curved arrow is applied to graft <NUM>" to bend graft <NUM>". Adhesive <NUM>" may be sufficiently flexible such that bend resistance of graft <NUM>" having either or both adhesive <NUM>" and carrier matrix <NUM>" attached may be or may not be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between these values such as between <NUM>% and <NUM>%) from the bend resistance of a similar graft that does not have either or adhesive and carrier matrix attached. Since attached particles <NUM>" narrow from between an attached end and an unattached end (a free end not attached to the biotextile layer), attached particles <NUM>" do not bump into each other when graft <NUM>" bends. Sections of layer <NUM>" between attached particles <NUM>" are able to compress together and the opposing side of layer <NUM>" is free to stretch apart and the graft is free to bend. In this example, adhesive <NUM>" is sufficiently thin and/or otherwise sufficiently flexible as to allow bending and graft <NUM>" is able to bend without undue interference from either attached particles <NUM>" or adhesive <NUM>". Bend resistance of the graft having both adhesive and carrier matrix attached may be or may not be not significantly different (e.g., between <NUM>% and <NUM>% different or anything in between these values such as between <NUM>% and <NUM>%) from the bend resistance of a similar graft that does not have the adhesive and carrier matrix attached.

As indicated above, a surgical repair graft may include an adhesive adhering a carrier matrix to a substrate (a biotextile layer). Carrier matrix may be any such as dendrimers, liposomes, micelles, multivesicular liposomes, nanoparticles, quantum dots, non-concentric internally aqueous chambers, each chamber surrounded by a lipid membrane, the lipid membrane containing an active agent, etc. including those described herein. In some examples, a multivesicular liposome includes non-concentric internally aqueous chambers, each chamber surrounded by a lipid membrane. A carrier matrix may be applied as a coating or sheet, may be painted onto an adhesive (or substrate) electro sprayed on, printed on, <NUM>-D printed, emulsified with an adhesive and applied, mixed with an adhesive and applied, etc. An adhesive for adhering carrier matrix particles to a biotextile layer may be a chemical or mechanical adhesive. An adhesive may hold carrier matrix on its surface or carrier matrix may be contained or embedded in the adhesive. An adhesive may have a smooth surface or may have a rough or textured surface to further hold or entrap a carrier matrix. An adhesive may have a rough surface wherein carrier matrix fills in the roughness to generate a smoother surface with less roughness than found in the adhesive without carrier matrix attached. In some examples, an adhesive may be a gel, such as a dispersion of molecules of a liquid (e.g., the carrier matrix) within a solid. In some examples an adhesive may be a polymer configured to adhere to both carrier matrix particles and to a biotextile layer. In some examples, an adhesive may be a peptide, a polymeric hydrogel or another hydrogel configured to adhere to both carrier matrix particles and to a biotextile layer or to intermediates between such components. Thus a surgical repair graft may include a hydrogel between a carrier matrix and a biotextile layer, the hydrogel adhering the carrier matrix to the biotextile layer. The adhesive (hydrogel) may be chemically bonded to a carrier matrix and may be bonded to a lipid membrane (including to a component embedded in a lipid membrane of a carrier matrix). A chemical bond between a carrier matrix and an adhesive (e.g., a hydrogel) may be a covalent bond or may be a non-covalent chemically bond and held by, e.g., hydrogen bonds, hydrophobic bonds, ionic bonds, or van der Waals interactions. A polymer or hydrogel may be coated or otherwise placed onto a biotextile layer. A hydrogel is generally a hydrophilic three-dimensional polymer swellable by or swelled with an aqueous solution (e.g., water or saline). Such a hydrogel may be naturally occurring or may be synthetic and may contain carbohydrates, nucleic acids, lipids, proteins, etc. Such a hydrogel include a polymer, a polymer mixture, a copolymer, a gradient polymer, an interpenetrating polymer network (IPN), a semi-interpenetrating IPN, or so forth. A hydrogel may be or may be configured to be at least <NUM>% (w/w) aqueous (e.g., by weight of the hydrogel without water), at least <NUM>%, at least <NUM>%, at least <NUM>%, or at least <NUM>% by weight (w/w) water. A polymeric hydrogel adhesive between a carrier matrix and the biotextile layer adhering the carrier to the biotextile layer may be or may include for example, alginate, cellulose, chitosan, collagen, polyhydroxyacids, derivatized cellulose, gelatin, polyanhydrides, polycaprolactone, polyhydroxy acids, polyglycolic acid, polylactic acid, polyorthoester, etc. A surgical repair graft may include a cross-linked polymer (e.g., a cross-linked polymeric hydrogel between a carrier matrix and a biotextile layer adhering carrier matrix to a biotextile layer), the cross-link deriving from acrylamide, allyl methacrylate, dimethacrylate, dimethyl suberimidate, DMS-treated collagen, dimethyl <NUM>, <NUM>'-dithiobispropionimidate, ethylene glycol, glutaraldehyde, N, N methylene-bisacrylamide, transglutaminase, or tripolyphosphate. In some examples, transglutaminase may be utilized to crosslink components (such as adhesive, biotextile or carrier matrix, by self cross-linking (e.g., cross-linking within any of these materials) or between two different materials (e.g., between a carrier matrix such as a multivesicular liposome and an adhesive or between a carrier matrix such as a multivesicular liposome and a biotextile layer). Such an enzyme may catalyze the formation of a covalent bond to effect cross-linking. For example, transglutaminase may be incorporated into a repair graft or otherwise be used to catalyze the formation of a covalent bond between a free amine group and an acyl/alkanoyl group between two different components such as to adhere carrier matrix to a hydrogel adhesive. Such side chains may be found on side chains of certain amino acids such as lysine, glutamate, and aspartate. Amino acids may be part of or be incorporated into any of the components of a surgical graft or medical textile. In some examples, a cross-link that also occurs naturally, such as those between amino acids mediated by transglutaminase may be more readily degraded by in a patient's body by biological processes than is a non-naturally occurring cross-link, and thus the quality and quantity (e.g., amount and locations) of such cross-links may be especially useful to control the stability or degradability of a component or a surgical repair graft to control active agent release. A transglutaminase may be obtained from natural or recombinant sources and may be microbial or non-microbial and may be from fungi, or plants or other eukaryotes. Transglutaminase that may be used to generate adhesion includes transglutaminase (e.g., EC <NUM>. <NUM>, protein-glutamine γ-glutamyltransferase, TGase).

In some examples, an adhesive may have regions (different subregions) having different properties that facilitate attachment to different components, such as to both a carrier matrix and a biotextile. For example, an amphipathic polymer may have a first region that is more biotextile-like and able to attach and/or interpenetrate with a biotextile and may have a second region that is more carrier matrix-like and able to attach and/or interpenetrate with a carrier matrix. For example, an amphipathic polymer may have a first region that is collagen-like region able to interpenetrate and bond to collagen and may have a second region that is lipophilic and able to interpenetrate and bond to lipid membranes of a carrier matrix. In some examples, an adhesive may have one or more material gradients that allow a gradual transition from characteristics of a first region to characteristics of a second region, such as from more biotextile-like properties to more carrier matrix like properties. Materials such as those or similar to those described in <CIT>, <CIT>, <CIT>, <CIT>, <CIT> may be used.

In some examples, an adhesive, such as a polymer, polymeric hydrogel, or other hydrogel may contain a carrier matrix having an encapsulated active agent. Such an adhesive may release carrier matrix and active agent in response to adhesive degradation, diffusion of active agent through the carrier matrix and adhesive, or in response to an applied stimulus, such as a pH change, application of an electric field, application of a magnetic field, change in temperature, treatment with ultrasound and so on.

The surgical grafts described herein may have contain particles in any density, from a homogenous covering to separated particles. Particles may be separated from each other by (on an average) at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM>, or at least <NUM> or any values or range of values in between these.

One or more components in a surgical repair graft may be modified or treated to change the biomechanical properties of the component(s) or graft and / or to join two or more components together. Any of the grafts or graft modifications as described in <CIT>, <CIT>, <CIT>, <CIT>, or <CIT> may be used, alone or in combination. Any of these surgical repair grafts may further include compliance control devices that provide compliance control and / or hold two or more than two layers together. A surgical repair graft such as described herein may have one or more than one biotextile layer with a pattern of reinforced discrete compliance control sites having a density of sites that is fewer than about <NUM> attachments/mm<NUM>. A surgical repair graft as described herein may have one or more than one biotextile layer with a pattern of reinforced discrete compliance control sites having a density of sites that is between <NUM> attachments/mm<NUM> and <NUM> attachments/mm<NUM> or anything in between these values. A surgical repair graft as described herein may have one or more than one biotextile layer biotextile layer with a pattern of reinforced discrete compliance control sites having a density of sites that is less than between <NUM> attachments/mm<NUM> and <NUM> attachments/mm<NUM> or anything in between these values. In some particular examples, stitches are those described in <CIT> and may be sewn or embroidered into one or more biotextile (or adhesive) layers. Such stitches may be compliance control stitch patterns and may be configured to control the compliance of the surgical repair graft. Mechanical properties of a surgical implant may be described by stiffness, breaking strain, and maximum force. For example, material property may be described force per unit width, such as N/cm. For example, compliance strain of the biotextile layer or graft with (or without compliance control stitches) may be between <NUM>-<NUM>% at <NUM> N/cm. Stitches may include a plurality of lines and / or a plurality of repeating angles oriented at one or more axes of a substrate. Stitches may form a corner-lock stitch pattern. Stitches may be non-resorbable (permanent) or may be bioresorbable. Any of these surgical repair grafts may include stitches made from a polymer such as polyethylene or polypropylene and may be a monofilament yarn or thread. Such stitches may form openings that may aid in bioresorbing an active agent from a carrier matrix. Two or more components in a graft may be joined together by an adhesive. For example, two or more biotextile layers may be joined to each other by an adhesive or a carrier matrix may be joined to a biotextile layer by an adhesive. An adhesive may be a chemical adhesive or a material adhesive. The discrete attachment sites may be chemical or material adhesives between the layer and the discrete locations, such as an adhesive or glue material that is biocompatible and adheres a first (e.g., ECM) layer to the second layer. An adhesive may be any appropriate biologically compatible adhesive. The discrete attachment sites may refer to relatively small diameter regions which may be regularly shaped or irregularly shaped and may be uniaxial or biaxial. Any of these surgical repair grafts may further include stitches sewn between two components. Any of these surgical repair grafts include discrete attachment sites with an attachment material (e.g., fiber, thread, yarn, etc.). For example, the discrete attachment sites may have a diameter of between about <NUM> (<NUM> inch) and <NUM> (<NUM> inches) (e.g., between about <NUM> (<NUM> inches) to about <NUM> (<NUM> inches), between about <NUM> to about <NUM> (about <NUM> to about <NUM> inches), etc.). In general, the attachment between the first layer (substrate layer) and the second layer may be configured to flexibly attach the two layers, so that the attachment of the two layers does not change the compliance more than a nominal (e.g., <NUM>% or less) amount. The density of the discrete attachment sites may be uniform or non-uniform. As mentioned above, the discrete attachment sites may be distributed in a pattern such as a grid (or overlapping grids).

More than two biotextile layers in a graft (such as described herein) are joined together. In some examples a second biotextile layer may be (flexibly) attached to a first biotextile layer in a pattern of discrete attachment sites having a density of <NUM> or fewer than <NUM> attachment sites/mm2 (e.g., <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> attachment sites per mm<NUM>). In some examples, a second biotextile layer may be (flexibly) attached to a first biotextile layer in a pattern of discrete attachment sites having a density of between <NUM> attachment sites/mm<NUM> and <NUM> attachment sites/mm<NUM>. In some examples, a second biotextile layer may be (flexibly) attached to a first biotextile layer in a pattern of discrete attachment sites having a density of more than <NUM> attachment sites/mm<NUM>. In some examples, a carrier matrix is between two biotextile layers and may be adhered to one or both of the layers.

A surgical repair graft that includes a carrier matrix or an adhesive (or both considered together) may alter a compliance (e.g., an axial tensile compliance; force per unit stretch) of a surgical repair graft having similarly stacked layers not having the carrier matrix by less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM> %, less than <NUM>% less than <NUM> %, less than <NUM>% or anything in between. In some examples, the presence of a carrier matrix in a surgical repair graft decreases the compliance of the graft compared with a repair graft having similarly stacked layers not having the carrier matrix. A compliance of surgical repair graft may not change or may increase over time when the carrier matrix is exposed to a bodily fluid or an aqueous fluid. A compliance may increase by up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM> %, up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM>%, or less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM> %, less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM>% or anything in between such as up to <NUM>% and less than <NUM>% compared with a repair graft having similarly stacked layers not having the carrier matrix. The compliance may be measured over any time period, such as one day, from one day to fourteen days, from one week to four weeks, from four weeks to twenty six weeks, from twenty six weeks to fifty two weeks or anything in between these amounts, such as after <NUM> weeks. In some examples, the compliance may be measured after one or more than one more year. In any of these cases, the remainder of the surgical repair graft may remain intact, thus the (stacked) biotextile layers of the surgical repair graft may remain intact and stacked. A compliance strain of a surgical repair graft as described here may between <NUM>-<NUM>% at <NUM> N/cm (e.g., prior to exposure to a bodily fluid for any of the times and conditions described herein, after exposure to a bodily fluid for any of the times and conditions described herein, or both before and after exposure to a bodily fluid for any of the times and conditions described herein).

A surgical repair graft that includes a carrier matrix or an adhesive (or both considered together) including any type of stitch may alter a uniaxial tension of a surgical repair graft having similarly stacked layers not having the carrier matrix by less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM> %, less than <NUM>% less than <NUM> %, less than <NUM>%, less than <NUM>% or anything in between. In some examples, the presence of a carrier matrix in a surgical repair graft decreases the uniaxial tension of the graft compared with a repair graft having similarly stacked layers not having the carrier matrix. A uniaxial tension of a surgical repair graft may increase over time when the carrier matrix is exposed to a bodily fluid or an aqueous fluid. A uniaxial tension may increase by up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM> %, up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM>%, or less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM> %, less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM>% or anything in between such as up to <NUM>% and less than <NUM>% compared with a repair graft having similarly stacked layers not having the carrier matrix. The uniaxial tension may be measured over any time period, such as one day, from one day to fourteen days, from one week to four weeks, from four weeks to twenty six weeks, from twenty six weeks to fifty two weeks or anything in between these amounts, such as after <NUM> weeks. In some examples, the uniaxial tension may be measured after one or more than one more year. In any of these cases, the remainder of the surgical repair graft may remain intact, thus the (stacked) biotextile layers of the surgical repair graft may remain intact and stacked.

A surgical repair graft that includes a carrier matrix or an adhesive (or both considered together) may alter a bending stiffness of a surgical repair graft having similarly stacked layers not having the carrier matrix by less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM> %, less than <NUM>% less than <NUM> %, less than <NUM>%, less than <NUM>% or anything in between. In some examples, the presence of a carrier matrix in a surgical repair graft decreases a bending stiffness of the graft compared with a repair graft having similarly stacked layers not having the carrier matrix. A bending stiffness of a surgical repair graft may increase over time when the carrier matrix is exposed to a bodily fluid or an aqueous fluid. A uniaxial tension may increase by up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM> %, up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM>%, or less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM> %, less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM>% or anything in between such as up to <NUM>% and less than <NUM>% compared with a repair graft having similarly stacked layers not having the carrier matrix. A bending stiffness may be measured over any time period, such as one day, from one day to fourteen days, from one week to four weeks, from four weeks to twenty six weeks, from twenty six weeks to fifty two weeks or anything in between these amounts, such as after <NUM> weeks. In some examples, a bending stiffness may be measured after one or more than one more year. In any of these cases, the remainder of the surgical repair graft may remain intact, thus the (stacked) biotextile layers of the surgical repair graft may remain intact and stacked.

A surgical repair graft that includes a carrier matrix or an adhesive (or both considered together) may alter a burst strength of a surgical repair graft having similarly stacked layers not having the carrier matrix by less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM> %, less than <NUM>% less than <NUM> %, less than <NUM>%, less than <NUM>% or anything in between. In some examples, the presence of a carrier matrix in a surgical repair graft decreases or increases a burst strength of the graft compared with a repair graft having similarly stacked layers not having the carrier matrix. A burst strength of a surgical repair graft may decrease or increase over time when the carrier matrix is exposed to a bodily fluid or an aqueous fluid. A burst strength may change by up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM> %, up to <NUM>%, up to <NUM>%, up to <NUM>%, up to <NUM>%, or less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM> %, less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM>% or anything in between such as up to <NUM>% and less than <NUM>% compared with a repair graft having similarly stacked layers not having the carrier matrix. A burst strength may be measured over any time period, such as one day, from one day to fourteen days, from one week to four weeks, from four weeks to twenty six weeks, from twenty six weeks to fifty two weeks or anything in between these amounts, such as after <NUM> weeks. In some examples, a burst strength may be measured after one or more than one more year. In any of these cases, the remainder of the surgical repair graft may remain intact, thus the (stacked) biotextile layers of the surgical repair graft may remain intact and stacked.

A surgical repair graft that includes a carrier matrix or an adhesive (or both considered together) may alter a roughness of a surgical repair graft having similarly stacked layers not having the carrier matrix by less than <NUM>%, less than <NUM>%, less than <NUM>%, less than <NUM> %, less than <NUM>% less than <NUM> %, less than <NUM>%, less than <NUM>% or anything in between. A roughness of a surgical repair graft may slightly decrease or increase over time when the carrier matrix is exposed to a bodily fluid or an aqueous fluid. Surface roughness may be made by any means, such as categorizing them by height, depth, and/or interval. Linear roughness or areal roughness (over a rectangular range) may be measured using contact or non-contact (e.g., optical) methods.

<FIG> shows carrier matrix particle <NUM> having a plurality of non-concentric internally aqueous chambers <NUM> each surrounded by lipid membrane <NUM> and containing first agent <NUM>. <FIG> shows a partially degraded version of carrier matrix particle <NUM>' of <FIG>. Lipid membrane <NUM>' is partially degraded and the contents of chamber <NUM>' including agent <NUM>' is being released from the particle. In another region of the particle, lipid membrane <NUM>" has reorganized around internally aqueous chamber <NUM>" and agent <NUM>" and part of the contents of the chamber has been released as shown by the presence of agent <NUM>‴ outside the carrier matrix particle. <FIG> also shows an external part of the particle (e.g., chamber <NUM>' and chamber <NUM>") that degrades and/or reorganizes prior to an internal region 208a of the particle degrading or reorganizing. (Internal region 208a is the same as internal region 208a'). In some examples, a carrier matrix particle does not readily degrade or reorganize and the carrier matrix particle may serve to hold an agent in its chambers. Such a particle may have a structure such as that shown in <FIG>, <FIG>, <FIG>, or <FIG> or variations thereof.

<FIG> shows a carrier matrix particle <NUM> having a plurality of non-concentric internally aqueous chambers <NUM> each surrounded by lipid membrane <NUM> and containing first agent <NUM> and second agent <NUM> in different chambers. <FIG> shows a partially degraded version of carrier matrix particle <NUM>' of <FIG>. Lipid membrane <NUM>' is partially degraded and the contents of chamber <NUM>' including first agent <NUM>' and second agent <NUM>' is being released.

<FIG> shows carrier matrix particle <NUM> having a plurality of non-concentric internally aqueous chambers <NUM> each surrounded by lipid membrane <NUM> and containing first active agent <NUM> and second active agent <NUM> in the same chamber <NUM>. <FIG> shows a partially degraded version of carrier matrix particle <NUM>' of <FIG>. Lipid membrane <NUM>' is partially degraded and the contents of chambers <NUM>' including first agent <NUM>' and second agent <NUM>' is being released.

<FIG> shows carrier matrix particle <NUM> having a plurality of non-concentric internally aqueous chambers <NUM> each surrounded by lipid membrane <NUM> and containing first agent <NUM> which is lipophilic and substantially entrapped or embedded in lipid membrane <NUM>. <FIG> shows a partially degraded version of carrier matrix particle <NUM>' of <FIG>. Lipid membrane <NUM>' is partially degraded and the contents of chamber <NUM>' including first agent <NUM>' which is lipophilic is being released. In some examples, a carrier matrix particle reorganizes as shown by reorganized membrane <NUM>" containing reorganized chamber <NUM>". First agent <NUM>" has moved along with reorganized membrane <NUM>" as it reorganized and is still entrapped or embedded within. First agent <NUM>‴ has been released due to the reorganization of reorganized membrane <NUM>".

A surgical repair graft has a biotextile layer; and a carrier matrix attached to the biotextile layer and comprising a plurality of particles each having a plurality of non-concentric internally aqueous chambers surrounded by a lipid membrane, one or more of the membrane and the aqueous chambers containing an agent. Thus an internally aqueous chamber may carry an (active) agent and/or a lipid membrane may carry an (active) active agent. Alternatively, a carrier matrix may not have such chambers and membrane and may carry an agent. A carrier matrix particle (a liposome) may act as a depot from which an entrapped agent can be slowly released. This may serve to maintain therapeutic levels of the agent in the blood, at the release site, or in another location in a body. In some examples, a therapeutic level of an active agent is from <NUM>% to <NUM>% or anything in between of a Cmax of an immediate release dosage form of an active agent. An internally aqueous chamber may include a buffer, a hydrogel, etc. In some examples, a plurality of particles may be DepoFoam particles. An agent carried in an aqueous chamber may be carried as a colloid in the aqueous material, may be dissolved in the aqueous material, or so on. An agent carried in an aqueous chamber may be charged, hydrophilic, polar etc. such that it is readily carried in an aqueous material. An agent carried in a lipid membrane in general is lipophilic or is coated or otherwise treated to be lipophilic. Such an agent may be hydrophobic or neutral (uncharged). An agent may be an active agent such as an active ingredient or an active pharmaceutical ingredient (API) and may be an agent useful for diagnosing, imaging, managing, preventing or treating such as for diagnosing, imaging, managing, preventing and/or treating anxiety, asthma, attention deficit disorder, bipolar disorder, cancer, diabetes, dementia, depression, a disease, a disorder, an eating disorder, inflammation, infection, mental illness, a neurological disorder, pain, panic, sleep disorder, etc. An agent may be an active agent such as an active pharmaceutical ingredient (API) approved by the United States Food and Drug Administration / Center for Drug Evaluation and Research and may be a brand name, generic or an over-the-counter pharmaceutical agent. An agent may be an antidepressant, an antineoplastic agent, an anxiolytic, antisense oligonucleotide, an antibiotic, an antifungal agent, an antipsychotic, an antithrombolytic, a cell, a drug, a DNA, a fungicide, a hormone, an RNA, an immunoglobulin E blocker (IgG), a non-steroidal anti-inflammatory agent, an opioid, a pain reliever (pain medication), a peptide, a protein, an antirheumatic agent, a sedative, a sense oligonucleotide, a small drug, a steroid. An agent may be radiopaque. In a particular example, an agent is bupivacaine or salts of bupivacaine or variations thereof. An agent may be <NUM>-azacytidine, amikacin, amitriptyline, ampicillin, aripiprazole, betamethasone, chlordiazepoide, chlorpromazine, corticosteroid, cyanocobalamine, cytarabine, daunorubicin, decitabine, delatestryl, delestrogen, desferrioxamine, desferrioxamine mesylate, desmopressin, desmopressin acetate, desoxycorticosterone pivalate, enoxaparin, exenatide, fentanyl, fluphenazine, gentamicin, haloperidol, heparin, hydromorphone, hydromorphone HCL, imitrex, insulin, leuprolide, loflupane, lorazepam, medroxyprogesterone, methotrexate, methylprednisolone, methylprednisolone acetate, morphine, morphine sulfate, naloxone, naltrexone, nandrol decanoate, octreotide acetate, omalizumab, olanzapine, paclitaxel, paliperidone, penicillin, penicillin G benzathine, penicillin G procaine, progesterone, risperidone, terbutaline, testosterone, testosterone cypionate, testosterone enanthate, triamcinolone acetonide, triptorelin, and salts and variations thereof. A carrier matrix may also contain one or more than one inactive ingredients that do not have a pharmacological or therapeutic effect on the body, such as a binding agent, a coating, a coloring agent, a disintegrant, an excipient, enzyme, a filler, a preservative, a stabilizer, etc..

A carrier matrix particle generally has a plurality of aqueous chambers each surrounded by a lipid membrane. A carrier matrix particle has a plurality of non-concentric internally aqueous chambers each surrounded by lipid membrane and containing an agent in at least one of the membrane and the chambers. In general a lipid membrane of a carrier matrix particle is biocompatible and is configured to biodegrade although in some cases it may not biodegrade and instead may be stable over time. In some examples, an enzyme may be present in a surgical graft or carrier matrix and may function to biodegrade the surgical graft or carrier matrix or may change (breakdown) an agent from an inactive form into an active agent. For example, an enzyme may break down a prodrug into a drug that has a therapeutic effect on the body. A biodegradable material, such as a lipid membrane of a carrier matrix particle, is a material may be broken down and cleared by the body's normal metabolic pathways. A lipid membrane of a carrier matrix particle may be naturally occurring lipids or synthetic lipids including synthetic versions of a lipid(s) naturally found in the body. Naturally occurring types of lipids may be those generally found in the body (e.g., a human or mammalian body). A lipid membrane may be a lipid monolayer, a lipid bilayer, a lipid trilayer, etc. A lipid membrane of a carrier matrix particle may be neutral, may be polar, or may be charged. In a particular example a lipid membrane is a phospholipid bilayer. In some examples, a lipid membrane includes an amphipathic lipid or salt thereof, one or more neutral lipids, and optionally cholesterol and / or plant sterols. In some examples a carrier matrix particle includes a multivesicular liposome have at least one amphipathic lipid, at least one neutral lipid, and a therapeutic agent. In some examples, a lipid membrane of a carrier matrix particle includes phospholipids, cholesterol, and triglycerides. In some examples, a phospholipid is dioleoylphosphatidylcholine (DOPC). In some versions, the triglyceride is a synthetic version of a lipid found in the body, such as tricaprylin. In some examples, carrier matrix particle is from <NUM>% (w/w) to <NUM>% (w/w) lipid or anything in between such (<NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w) <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), and <NUM>% (w/w) or from between any of these, such as from <NUM>% (w/w) to <NUM>% (w/w) or from <NUM>% (w/w) to <NUM>% (w/w). In some examples, carrier matrix particle is from <NUM>% (w/w) to <NUM>% (w/w) lipid. Part (e.g., an outer part, an inner facing part) of a carrier matrix particle may be neutral, polar, or charged and another part may have different properties (e.g., an inner facing surface may be neutral while an outer facing surface is charged, etc.). In some examples, an outer facing surface of a lipid membrane is complementary to an adhesive material such that an adhesive membrane adheres to or binds (e.g., chemically binds) to an outer facing surface of a lipid membrane. For example, an outer facing surface of a lipid membrane may be negatively charged and an adhesive positively charged such that the adhesive binds to the outer facing surface of the membrane. An outer facing surface may be modified with proteins or amino groups which may be attached such as through amino groups or sulfhydryl groups.

A carrier matrix particle(s) can be from <NUM>% (w/w) aqueous material to <NUM>% aqueous material or anything or any range in between. In some examples, a carrier matrix particle(s) can be from <NUM>% (w/w) aqueous material to <NUM>% aqueous material of any range in between. Thus a carrier matrix particle can be <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), <NUM>% (w/w), and <NUM>% (w/w) aqueous material or anything in between such as from <NUM>% (w/w) to <NUM>% (w/w), etc. A carrier matrix particle may have a capture volume (an internal volume) of <NUM>% to <NUM>% or anything in between, such as <NUM>% to <NUM>%. A carrier matrix may have any configuration or any materials that carries an agent, such as a polymer such as cellulose esters, ethylcellulose polymer, gelatin, polycaprolactone, poly diaxonone, poly hydroxyl butyrate, poly lactic acid, poly lactide-co-glycolide (PLGA), polyester, poly glycolic acid, polyester amide, polyester urea, polyester urethane, polyethylene oxide, a water soluble resin, and so on. Such materials may be in a liquid dispersion and / or be biodegradable. A carrier matrix may contain one or more than one type of materials. The more than one type of materials may be configured to degrade or otherwise release an active agent over different times. Thus, a carrier matrix may have a first material that degrades more quickly and releases a first active agent quickly and a second material that degrades more slowly and releases a second active agent over a longer period of time. A first active agent and second active agent may be the same or may be different, including any as described herein. In some examples, a surgical graft or carrier matrix does not contain cyclodextrin.

A carrier matrix particle is generally a microscopic particle and as indicated elsewhere herein, a carrier matrix particle can be any shape. A carrier matrix particle may be from between <NUM> to <NUM> or longer in a longest dimension (or diameter), from <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> in a longest dimension (or diameter) or any value or range of values in between these values. In some examples, a particle is between <NUM> and <NUM>, between <NUM> and <NUM>, between <NUM> and <NUM> and so on. A carrier matrix particle may contain from <NUM> to <NUM> or more than <NUM> internal chambers, such as at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM>, at least <NUM> internal chambers or may have fewer than <NUM>, fewer than <NUM>, fewer than <NUM>, fewer than <NUM>, fewer than <NUM>, fewer than <NUM>, fewer than <NUM>, fewer than <NUM>, fewer than <NUM>, fewer than <NUM> or anything in between such as at least <NUM> and fewer than <NUM>, at least <NUM> and fewer than <NUM> and so on.

Manipulation of the amounts, types and compositions of adhesives, lipids, aqueous material, and agent material may be used to control the rate and time of degradation and/or lipid membrane reorganization. Controlling the particle size may be used to control the rate and time of degradation and/or the rate and time of lipid membrane reorganization. The amounts and types of materials and other characteristics of the carrier matrix and surgical graft may be chosen, for example, to control a rate of carrier matrix biodegradation and active agent release in a time sensitive manner such as releasing from <NUM> % to <NUM>% or of an agent (or any amount in between such as <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, or <NUM>%) in <NUM> hour to <NUM> hours, <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything in between these times (such as <NUM> days, <NUM> days, etc.) upon continuous exposure to a bodily fluid. In some particular examples, a carrier matrix is at least <NUM>% degraded after <NUM> days upon continuous exposure to a bodily fluid or bodily fluid substitute (e.g., a synthetic version of a bodily fluid), at least <NUM>% degraded within one day of continuous exposure to a bodily fluid, at least <NUM>% degraded after <NUM> days of continuous exposure to a bodily fluid, between <NUM>% and <NUM>% degraded at <NUM> days of continuous exposure to a bodily fluid, between <NUM>% and <NUM>% degraded at <NUM> days of continuous exposure to a bodily fluid. A bodily fluid may be, for example, ascites, blood, breast milk, gastric fluid, intestinal fluid, interstitial fluid, lymph fluid, menstrual fluid, peritoneal fluid, perspiration, urine, wound exudate and so forth.

Described herein is a method useful for understanding the invention for controlled release an active agent from a surgical repair graft, including exposing a surgical repair graft having one or more than one stacked biotextile layers and a bioabsorbable carrier matrix attached to the one or at least one of the biotextile layers, the carrier matrix comprising a plurality of particles each having a plurality of non-concentric internally aqueous chambers surrounded by lipid membranes, at least one of the membrane and the aqueous chambers containing an active agent; and degrading over time the lipid membrane by the aqueous fluid to thereby release the active agent from the carrier matrix.

Also described herein is a method useful for understanding the invention for diagnosing, treating or otherwise relieving the symptoms of an affliction, disease, or disorder (including any of those described herein) comprising administering a formulation to a subject in need thereof by implanting a surgical repair graft having the formulation attached, wherein the formulation comprises multivesicular liposomes, the multivesicular liposomes comprising an amount of an active pharmaceutical ingredient (API), one or more amphipathic lipids or salts thereof, one or more neutral lipids, and optionally cholesterol or plant sterols, wherein the formulation is substantially cyclodextrin free, wherein administration of a single dose of said formulation to the subject in need thereof results in a plasma C max of the active pharmaceutical ingredient of from <NUM>% to <NUM>% of the plasma C max an of immediate release dosage forms of the active pharmaceutical ingredient, and wherein a duration of the active pharmaceutical ingredient in the subject is from about <NUM> to about <NUM> days.

Also described herein is a method useful for understanding the invention of treating post-operative or post-trauma pain in a subject in need thereof comprising administering a multivesicular liposome comprising a therapeutically effective amount of an analgesic attached to a surgical repair graft, wherein the multivesicular liposome comprises the analgesic; a lipid component comprising at least one amphipathic lipid and at least one neutral lipid lacking a hydrophilic head group; and, optionally, a cholesterol and/or a plant sterol. In some particular examples, the analgesic comprises bupivacaine or a salt or derivative thereof such as bupivacaine phosphate.

In some such methods, wherein a first set of chambers is on the exterior of the particle and a second set of chambers is on the interior of the particle, lipid walls on the first set of chambers are degraded first and lipid walls on the second set of chambers are degraded later. In some such methods, wherein the one or more biotextile layer comprises pores, the method further includes flowing active agent through the pores to thereby release it to a body region adjacent one biotextile layer of the one or more biotextile layers. A body may be that of an animal or plant and a body region may be part of a body system, a body organ or part of a body organ, such as a breast, an intestine, a muscle, a stomach etc., In some such methods, wherein a hydrogel is adhered to at least one of the layers, the method further includes flowing active agent through the hydrogel to thereby release it to a body region adjacent the surgical repair graft. In some such methods, the aqueous fluid includes a bodily fluid, such as ascites, blood, breast milk, gastric fluid, intestinal fluid, interstitial fluid, lymph fluid, menstrual fluid, peritoneal fluid, perspiration, urine, wound exudate, etc.. In some such methods, a compliance strain of the surgical repair graft is between <NUM>-<NUM>% at <NUM> N/cm prior to the degrading step. In some such methods, a compliance strain of the surgical repair graft is between <NUM>-<NUM>% at <NUM> N/cm after the degrading step. In some such methods, a compliance strain of the surgical repair graft is between <NUM>-<NUM>% at <NUM> N/cm after the degrading step. In some such methods, a compliance strain of the surgical repair graft is between <NUM>-<NUM>% at <NUM> N/cm both before and after the degrading step. Such compliance after the degrading step may be measured after <NUM> hour to <NUM> hours, <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything in between these times (such as <NUM> days, <NUM> days, etc.) of continuous exposure to a bodily fluid.

In some methods useful for understanding the invention for controlled release an active agent from a surgical repair graft, carrier matrix is at least <NUM>% (or at least <NUM>% or between <NUM>% and <NUM>%) degraded one day after beginning the exposing step. In some methods for controlled release an active agent from a surgical repair graft, carrier matrix at least <NUM>% (or at least <NUM>% or between <NUM>% and <NUM>%) degraded <NUM> days after beginning the exposing step. In some methods for controlled release an active agent from a surgical repair graft, carrier matrix at least <NUM>% (or at least <NUM>% or between <NUM>% and <NUM>%) degraded <NUM> days after beginning the exposing step. In some methods for time releasing an active agent from a surgical repair graft, carrier matrix particles are at least <NUM>% (or at least <NUM>% or between <NUM>% and <NUM>%) degraded <NUM> hour to <NUM> hours, <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything in between these times (such as <NUM> days, <NUM> days, etc.) after beginning the exposing step.

In some methods useful for understanding the invention for controlled release an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) lipid prior to the degrading step. In some methods for controlled release an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) lipid one day after beginning the exposing step. In some methods for controlled release an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) lipid <NUM> days after beginning the exposing step. In some methods for controlled release of an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) lipid <NUM> days after beginning the exposing step. In some methods for time releasing an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) lipid <NUM> hour to <NUM> hours, <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything in between these times (such as <NUM> days, <NUM> days, etc.) after beginning the exposing step.

In some methods useful for understanding the invention for controlled release of an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) aqueous prior to the degrading step. In some methods for controlled release of an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) aqueous one day after beginning the exposing step. In some methods for controlled release of an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) aqueous <NUM> days after beginning the exposing step. In some methods for controlled release of an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) aqueous <NUM> days after beginning the exposing step. In some methods for time releasing an active agent from a surgical repair graft, carrier matrix particles are between <NUM>% (w/w) and <NUM>% (w/w) aqueous <NUM> hour to <NUM> hours, <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything in between these times (such as <NUM> days, <NUM> days, etc.) after beginning the exposing step.

In some methods useful for understanding the invention for controlled release of an active agent from a surgical repair graft, carrier matrix particles have at least <NUM> (or at least <NUM> or at least <NUM>) internally aqueous chambers prior to the degrading step. In some methods for controlled release of an active agent from a surgical repair graft, carrier matrix particles have at least <NUM> (or at least <NUM> or at least <NUM>) internally aqueous chambers one day after beginning the exposing step. In some methods for controlled release of an active agent from a surgical repair graft, carrier matrix particles have at least <NUM> (or at least <NUM> or at least <NUM>) internally aqueous chambers <NUM> days after beginning the exposing step. In some methods for controlled release of an active agent from a surgical repair graft, carrier matrix particles have at least <NUM> (or at least <NUM> or at least <NUM>) internally aqueous chambers <NUM> days after beginning the exposing step. In some methods for time releasing an active agent from a surgical repair graft, carrier matrix particles have at least <NUM> (or at least <NUM> or at least <NUM>) internally aqueous chambers <NUM> hour to <NUM> hours, <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything in between these times (such as <NUM> days, <NUM> days, etc.) after beginning the exposing step. In some methods for time releasing an active agent from a surgical repair graft, carrier matrix particles have at least <NUM> (or at least <NUM> or at least <NUM>) internally aqueous chambers both before the exposing step and <NUM> hour to <NUM> hours, <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything in between these times (such as <NUM> days, <NUM> days, etc.) after beginning the exposing step.

In some methods useful for understanding the invention for controlled release of an active agent from a surgical repair graft, the active agent comprises any active agent as described herein. In some methods for controlled release of an active agent from a surgical repair graft, the active agent includes an active pharmaceutical ingredient. In some methods for controlled release of an active agent from a surgical repair graft, the active agent includes an antifungal agent, antineoplastic agent, or an antibiotic. In some methods for controlled release of an active agent from a surgical repair graft, the active agent includes a pain reliever, e.g., an analgesia. In some methods for controlled release of an active agent from a surgical repair graft, the active agent includes bupivacaine.

In some examples, a surgical repair graft or carrier matrix may be configured to release active agent such that a therapeutic level of active agent is released into the bloodstream. In such cases, the plasma concentration of the active agent may spike at a particular concentration or may be sustained at a therapeutic concentration for one hour, from one hour to <NUM> hours (or anything in between, such as <NUM> hours or <NUM> hours), <NUM> day to <NUM> days, <NUM> week to <NUM> weeks or <NUM> month to <NUM> year or anything in between these times (such as <NUM> days, <NUM> days, etc.) after beginning the exposing step. For example, a drug may be bupivacaine (e.g., Exparel) and the plasma level of bupivacaine may be at least <NUM> ng/mL, at least <NUM> ng/mL, at least <NUM> ng/mL, at least <NUM> ng/mL, at least <NUM> ng/mL, at least <NUM> ng/mL, at least <NUM> ng/mL, at least <NUM> ng/mL or anything in between, such as at least <NUM>,<NUM> ng/mL or between <NUM> ng/mL and <NUM> ng/mL. The concentration may be an FDA approved dosage. In some examples, a surgical repair graft or carrier matrix may be configured to release a therapeutic amount of an active agent, such as releasing <NUM> bupivacaine, <NUM> bupivacaine, <NUM> bupivacaine, <NUM> bupivacaine, <NUM> bupivacaine, <NUM> bupivacaine, <NUM> bupivacaine, or <NUM> bupivacaine in a certain time period, such as in <NUM> hours, In some methods for controlled release of an active agent from a surgical repair graft, the method further includes an adhesive, such as a chemical or physical adhesive (and including those described herein) adhering the carrier matrix to the biotextile layer. In some methods for controlled release of an active agent from a surgical repair graft, the method further includes a polymer (e.g., a hydrogel) adhering the carrier matrix to the biotextile layer. In some methods, the hydrogel is chemically bonded (e.g., either covalently bonded or non-covalently bonded) to the biotextile layer. In some methods for controlled release of an active agent from a surgical repair graft, the method further includes a polymer (e.g., alginate, cellulose, chitosan, collagen, polyhydroxyacids, derivatized cellulose, gelatin, polyanhydrides, polycaprolactone, polyhydroxy acids, polyglycolic acid, polylactic acid, or polyorthoester) adhering the carrier matrix to the biotextile layer. In some methods for controlled release of an active agent from a surgical repair graft, the method further includes a cross-linked polymeric hydrogel between the carrier and the biotextile layer adhering the carrier to the biotextile layer, the cross-link derived from acrylamide, allyl methacrylate, dimethacrylate, dimethyl suberimidate, DMS-treated collagen, dimethyl <NUM>, <NUM>'-dithiobispropionimidate, ethylene glycol, glutaraldehyde, N, N methylene-bisacrylamide, transglutaminase, or tripolyphosphate.

In some methods useful for understanding the invention for controlled release of an active agent from a surgical repair graft, the method further includes a second of the biotextile layers which is flexibly attached to a first of the biotextile layers with a pattern of discrete attachment sites. In some methods, a density of discrete attachment sites that is less than about <NUM> attachments/mm<NUM> and the number of attachment sites is substantially unchanged <NUM> days after the beginning of the degrading step. In some methods, a compliance of the stacked layers increases up to <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a compliance of the stacked layers changes by less than <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a uniaxial tension of the stacked layers changes by less than <NUM>% <NUM> days after the beginning of the degrading step. In some methods, uniaxial tension of the stacked layers changes by less than <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a bending stiffness of the stacked layers changes to <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a bending stiffness of the stacked layers changes by less than <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a burst strength of the stacked layers increases up to <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a burst strength of the stacked layers changes by less than <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a roughness of the stacked layers changes by less than <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a roughness of the stacked layers increases up to <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a roughness of the stacked layers changes by less than <NUM>% <NUM> days after the beginning of the degrading step. In some methods, a stiffness of the surgical mesh changes by less than <NUM>% when at least <NUM>% of the carrier matrix is degraded by exposure to aqueous fluid for at least <NUM> days.

Also described herein are methods useful for understanding the invention of manufacturing a surgical repair graft. A method of manufacturing a surgical repair graft includes hydrating a biotextile layer having a first compliance; adhering to the biotextile layer a carrier matrix comprising a plurality of particles having non-concentric internally aqueous chambers containing a lipid- encapsulated drug to create an attached biotextile layer having a second compliance to thereby form a surgical mesh, wherein the first compliance and the second compliance differ by less than <NUM>% (or less than <NUM>, less than <NUM>% , less than <NUM>%, less than <NUM>%, less than <NUM>% , less than <NUM>%, or less than <NUM>% ). A biotextile may be hydrated in any aqueous solution, such a biocompatible saline (e.g., half normal or normal saline with about <NUM> mEq/L or <NUM> mEq/L sodium and about <NUM> mEq/L or <NUM> mEq/L chloride or anything near or between these values, at pH <NUM> to <NUM> though other aqueous solutions may be used for the hydrating step). Some methods include the step of attaching a hydrogel to the biotextile layer and to the carrier matrix such that the hydrogel is between the biotextile layer and the carrier matrix. Some such methods include the step of swelling a hydrogel prior to the attaching a hydrogel step. Some methods include the step of diffusing a carrier matrix through a hydrogel, prior to, concomitant with, or after swelling the hydrogel. In some cases, a liposome may be coated with a hydrogel. In some methods the biotextile layer comprises one or more than one layer of collagen such as described elsewhere herein.

In a surgical repair graft as described herein, carrier matrix is attached to at least one of the biotextile layers (e.g., be sandwiched in between two biotextile layers). Carrier matrix particles made by emulsifying lipids with an active agent, forming a suspension of multivesicular liposomes having a plurality of non-concentric chambers and including at least one amphipathic lipids, at least one neutral lipid, and a therapeutic agent, or other methods. Carrier matrix particles may be formed any method or modifications of such methods, such as those described in <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, and <CIT>.

Carrier matrix may be attached to a biotextile layer in islands or as a covering. In some examples, carrier matrix may be attached in islands, at a plurality of discrete attachment sites. Such an attachment site may correspond to a single particle or may correspond to a plurality of particles at that site and there may be one or more than one islands or attachment sites. Carrier matrix may form a depot of increased size. The size may be a depot of greater length or width and in some cases. In some cases carrier matrix may form a depot containing many particles agglomerated together and carrier matrix may not be a single layer. For example, such a depot may be <NUM>, <NUM>, <NUM>, <NUM> or more particles high (e.g., perpendicular or more or less perpendicular to a plane defined by a biotextile layer. Carrier matrix is attached to at least one of the biotextile layers in a random configuration at a plurality of discrete attachment sites or in a regular configuration (regular pattern) at a plurality of discrete attachment sites. Some areas of a biotextile layer, such as along an edge, may be free or have less carrier matrix. In other examples, a region of a surgical repair graft that needs to bend may have fewer islands of carrier matrix or less carrier matrix to increase bendability in that region. In some cases, carrier matrix may be layer on over another material, such over a biotextile layer or over an adhesive layer. It may be layer in a solution or may be <NUM>-printed. It may have a random pattern or a regular array pattern.

Claim 1:
A surgical repair graft comprising:
more than two stacked biotextile layers made of collagen and joined together; and
a bioabsorbable carrier matrix comprising multivesicular liposomes attached to at least one of the biotextile layers, the multivesicular liposomes comprising an active agent, wherein the multivesicular liposomes comprise a plurality of particles (<NUM>) each having a plurality of non-concentric internally aqueous chambers (<NUM>) each surrounded by a lipid membrane (<NUM>), at least one of the aqueous chambers and the lipid membrane containing the active agent (<NUM>), wherein the carrier matrix is attached to the biotextile layer at a plurality of discrete attachment sites, and wherein a first set of the aqueous chambers are on an exterior of the particles and a second set of aqueous chambers are on an interior of the particles, wherein lipid membranes on the first set of aqueous chambers are configured to degrade before the lipid membranes on the second set of aqueous chambers.