Implantable device forming a port in the interstitium and diagnostic, therapeutic and research methods utilizing the port

Abstract

A method for use with a medical activity involving a target area in a human or animal body, the method comprising the steps of: 1) implanting a bioadsorbable portal device in interstitium adjacent the target area, the implanted portal device being made of a bioadsorbable macroporous material and having a hollow core forming at least a part of a passage through the implanted portal device; 2) utilizing the implanted portal device to provide fluid access to the target area via the passage and the interstitium; and 3) performing the medical activity using fluid passing through the implanted portal device.

Description

[0001] Implantable Device Forming a Port in the Interstitium and Diagnostic, Therapeutic and Research Methods Utilizing the Port

[0002] Cross Reference to Related Application

[0003] The present application claims priority to and the benefit of U.S. patent application serial No. 63 / 699,014, filed September 25, 2024, which is hereby incorporated by reference in its entirety.

[0004] Technical Field

[0005] The present application is directed to an implantable device for implantation into the human body within connective tissue and more particularly, to an implantable device, for insertion and implantation into the interstitium, that includes a port that is configured to inject a therapeutic agent into the surgical site (interstitium) or to allow aspiration of fluid from the surgical site.

[0006] Background

[0007] Connective tissue is of mesodermal origin and consists of cellular regions and acellular regions. The primary cells throughout connective tissue are fibroblasts, whose primary function is to produce structural collagen. Fibroblasts are essential in the generation, regeneration, repair, and maintenance of structural tissues of the body. Connective tissue, or fascia, has other cells such as myofibroblasts, which contain actin-myosin fibers, and adipocytes, as well as immune cells such as macrophages. Connective tissue fascia has a system of classification according to function: 1. Linking, 2. Fascicular, 3. Compression, and 4. Separating. It is also frequently termed superficial fascia, between the skin and deep fascia. Deep fascia is made of sheets of connective tissue which surround the surface of muscles, and their individual bundles and fascicles, which, like silk stockings that cover a leg, and make up tendonous and ligamentous connections to the bone. It surrounds blood vessels and nerves throughout their travels through all body parts. Mesodermal cells, chondrocytes and osteocytes can make the extracellular matrix of specialized connective tissue into cartilage and bone.

[0008] Another domain of connective tissue, which is a relatively acellular region, is known as the interstitium. The interstitium is the foundation of all tissue and is present throughout the body. It has cells called interstitial lining cells, which are spindle-shaped, like stem cells but are not stem cells. These cells, sometimes called fasciocytes, tire like endothelial cells but are not endothelial cells; they do not form a continuous lining of the spaces filled with serum and have no basement membrane but are attached directly to the labyrinth of large bundles of collagen, which branch and entangle themselves, forming a sponge-like support structure for the interstitium, Serum fluid that flow's through the spaces between the collagen bundles, called ’interstitial spaces,’ contains glycosaminoglycans (GAGs), primarily hyaluronic acid (HA), and other macromolecules such as hormones, growth factors, and cytokines. Lipid bilayered packets of proteins, or RNA, called extra cellular bound matrix vesicles (EBVs) can attach to the bundles of collagen in the interstitium and steep the microenvironment with local characteristics, which is important in cell signally within the extra-cellular matrix. The interstitial fluid spaces are major highways for the cellular trafficking of immune cells, stem cells, cancer cells, and infectious agents. The interstitium can thus be thought of as being a fluid highway and the present implantable device is designed in view of the composition and functionality of the interstitium and in particular, to take advantage of the fluid highway functionality of the interstitium.

[0009] Thus, the interstitium plays a significant role in cancer by providing a fluid-filled network that acts as a conduit for cancer cells to spread to other parts of the body. It contributes to the tumor microenvironment, affecting tumor progression and potentially increasing interstitial pressure, which can impede drug delivery and correlate with a worse prognosis. As will be understood, once a malignant tumor is discovered, there are a range of different treatments. For example, malignant tumor treatment typically involves a range of therapies like surgery, radiation therapy, and chemotherapy, often used in combination.

[0010] When surgery is a part of the treatment plan, the malignant tumor is resected from the body during a surgical procedure. The purpose of a tumor resection procedure is to: remove the tumor and prevent its growth; to improve symptoms caused by the tumor; and to reduce the risk of the tumor spreading to other parts of the body. The specifics of the tumor resection procedure vary depending on the type, size, and location of the tumor. However, the procedure generally involves: administering anesthesia to the patient; making an incision to access the tumor; removing the tumor and any surrounding tissue that may be affected; and closing the incision.

[0011] Summary

[0012] In one embodiment, an implant for implantation in human or animal tissue to provide access to interstitium adjacent an area of interest is provided. The implant comprises a body made of a bioadsorbable macroporous material that facilitates connective tissue ingrow'th into the body. The body has at least one reservoir formed therein for aceessing the area of interest to introduce a therapeutic to the adjacent interstitium and / or to aspirate fluid and cells therefrom.

[0013] A method for use with a medical activity involving a target area in a human or animal body, the method comprising the steps of: implanting a bioadsorbable portal device in interstitium adjacent the target area, the implanted portal device being made of a bioadsorbable macroporous material and having a hollow core forming at least a pail of a passage through the implanted portal device; utilizing the implanted portal device to provide fluid access to the target area via the passage and the interstitium; and performing the medical activity using fluid passing through the implanted portal device.

[0014] Other aspects and advantages of the present invention will become apparent from the following description of the preferred embodiments taken in conjunction with the accompanying drawings wherein like parts in each of the several figures are identified by the same reference characters.

[0015] Brief Description of the Drawings

[0016] These and other features and advantages of the present invention will be further appreciated, as they become better understood by reference to the detailed description when considered in connection with the accompanying drawings, wherein:

[0017] Fig. 1 shows exemplary connective tissue in the interstitium;

[0018] Fig. 2 shows the interstitium adjacent an exemplary target area of interest (a target surgical site);

[0019] Fig. 3 shows an implantable device in accordance with one embodiment including a central hollow core forming a passage therethrough between distal and proximal surfaces of the implantable device;

[0020] Figs. 4A, 4B, 5 A and 5B show other exemplary implantable devices having different shapes corresponding to the interstitium adjacent to a target area of interest;

[0021] Fig. 6 illustrates one exemplary target implantation site and also illustrates one exemplary implantable device for implantation therein;

[0022] Figs. 7A and 7B illustrate another exemplary target implantation site and also illustrates another exemplary implantable device for implantation therein;

[0023] Figs. 8A-8D illustrate another exemplary implantable device; Fig. 9 illustrates yet another implantable device:

[0024] Fig. 10 illustrates another implantable device that has a folded or accordion shape; and

[0025] Fig. 1 1 depicts a disk-shaped implantable device.

[0026] Detailed Description

[0027] The present application describes implantable devices that are configured to be implanted into the human or an animal body within connective tissue. More particularly, the present implantable device is a bioabsorbable device for implantation into the human body within the loose areolar connective tissue known as the interstitium. As described herein, the implantable device is engineered to maximize soft tissue ingrowth from the surface of the implantable device, as healing tissues self-organize and render a cast of the meshed construct. In addition, over time, the implantable device is absorbed into the surrounding connective tissue environment.

[0028] As described herein, in one aspect, the present disclosure relates to a method for use with a medical activity involving a target area in a human or animal body. As used herein, the term “medical activity'’ means the performance of a medical or surgical procedure on a body. The method includes the steps of; 1) implanting a bioadsorbable portal device in interstitium adjacent the target area, the implanted portal device being made of a microporous bioadsorbable materialand having a hollow core forming at least a part of a passage through the implanted portal device; 2) utilizing the implanted portal device to provide fluid access to the target area via the passage and the interstitium; and 3) performing the medical activity using fluid passing through the implanted portal device.

[0029] Fig. 1 shows connective tissue 10 in the interstitium. As previously mentioned, the interstitium is a network of fluid-filled spaces 11 that lies between cells and tissues 13 throughout the body. It plays a crucial role in supporting and connecting organs, facilitating nutrient and waste exchange, and maintaining fluid balance. The interstitium is present in all organs and tissues, including: skin, muscles, blood vessels, nerves, and lymphatic system. The interstitium is composed of a matrix of collagen and elastin fibers that define the connective tissue 10, as well as interstitial fluid, which contains proteins, electrolytes, and other substances. The interstitium performs several essential functions, including but not limited to: structural support (it provides a framework for cells and tissues to adhere to and maintain their shape); fluid exchange (it allows for the movement of nutrients, waste products, and immune cells between blood vessels and tissues); lymphatic drainage (the interstitial fluid flows into the lymphatic system, where it is filtered and returned to the bloodstream); and cellular communication (the interstitium facilitates the exchange of signals between cells, which is important for maintaining homeostasis and coordinating cellular activities).

[0030] Fig. 2 shows the interstitium 10 adjacent a target area of interest (target surgical site). In this example, the target area is the terminal duct (ductal) lobular unit (TDLU). As is known, the TDLU is the functional milk-producing unit of the breast. TDLUs are composed of terminal ducts and small sacs called acini, embedded in stromal tissue. Fig. 2 is a transverse section through the acinus (a cluster of cells composing the smallest unit of a compound gland). Fig. 2 depicts a lumen 12, a luminal epithelium 14, a myoepithelium 16, and a basement membrane 18. Adjacent the basement membrane 18 is the interstitium 10 which again includes interstitial spaces 1 1 and bands of collagen 13. Stromal fat is depicted at 15.

[0031] It will be appreciated that Fig. 2 merely illustrates one target area that includes interstitium 10 in which the present implantable device can be implanted.

[0032] Implantable Device 100

[0033] In accordance with the present disclosure, an implantable device 100 is provided and is illustrated in present figures, such as Figs. 3-5B. The implantable device 100 is configured for insertion and implantation into the connective tissue 10 (e.g., interstitium) and the body of the device 100 is made from absorbable macroporous (e.g., pores on the order of 500 microns to 1500 microns and in one embodiment, 750 microns to 1000 microns) polymer scaffolding that assumes a three-dimensional configuration that is selected and / or modeled in view' of the target implantation site. The implantable device 100 is inserted into the human body after sterilization and is allowed to heal over (e.g., healing on the order of one to two months time). In one embodiment, the implantable device 100 takes up a volume between 25 cc to 250 cc and is divided into segments S and sub-segments of the overall volume of space such that the absorbable device 100 (scaffold) takes up very little volume of the space. Subsegmentation of the implantable device 100 is achieved as a quasi-fractal pattern, of low fractal dimension, leaving room for connective tissue ingrowth as part of the healing process. The bioadsorption properties allow, over time, for the implantable device 100 to adsorb into the surrounding connective tissue.

[0034] As will be described herein in more detail, the implantable device 100 is designed to have an open structure which is defined by body segments and sub-segments, with the design being guided by a low density of biosynthetic polymer that leaves ample space in the body for ingrowth of loose areolar connective tissue with the mesh spaces and for parenchymal adipogenesis in the open spaces of the subsegments. The presence of robust vascularity of the engineered space is accomplished by dissection and wrapping of the implant with superficial fascia vessels, such as the artery and venae commicantes of the superficial circumflex artery in the low abdomen or the perforators off the thoraco-acromial artery (below) in the low chest in one embodiment. Incisions for harvesting these vessels are hidden in the creases below the breast or abdomen commonly used for abdominoplasty and mastopexy according to one embodiment.

[0035] As illustrated in the figures, it will be appreciated and understood that the implantable device 100 can take many different shapes and sizes depending on the dimensions and / or location of the implantation (surgical) site. Similar to the makeup of the connective tissue 10, the implantable device 100 has a sponge-like appearance due to its porous nature and the connected nature of its backbone structure. The implantable device 100 can have a symmetric construction or alternatively, can have an asymmetric shape.

[0036] The implantable device 100 can thus generally have a regular shape or can have a custom, irregular shape. For example, depending on the application, the implantable device 100 may take on different shapes. In certain implant locations it can have a spherical shape, in others a flattened star shape, while in some a flat disc may be best. Finally, a tubular structure can be used when the targeted anatomy calls for it. It is expected that the implantable device 100 will contain a centralized hollow core of negative design or white space. This becomes a potential space filled with serum after implantation.

[0037] In the event that the implantable device has an elongated shape, it can be defined as having a first end and an opposing second end. In addition, it can be defined as including a first major surface and a second major surface opposing the first major surface.

[0038] In accordance with one or more embodiments, the implantable device 100 includes one or more voids that define one or more passages 150 within the macroporous polymer structure. In other words, each passage 150 is an open space or open lumen that is formed within the macroporous polymer structure that defines the body of the implantable device 100. The terms passage and channel can be used interchangeably herein.

[0039] In various embodiments, the passage 150 is open along one or more surfaces of the body of the implantable device 100 to permit both ingress and egress from the passage 150 and to allow the passage 150 to be externally accessible as described herein. The open space, or voids, is protected from collapse during the healing process by the initial strength of the body of the implantable device 100. hi certain embodiments, the passage 150 can thus represent a tunnel that is formed through the body of the implantable device 100 and is open at both ends of the passage 150 and the surrounding body of the implantable device 100 has sufficient strength and form that the passage 150 remains open and does not collapse or otherwise become occluded. In some embodiments, the passage 150 is linear in shape and can be centrally located within the body of the implantable device 100.

[0040] Fig. 3 illustrates a single void 150 formed in the body of the implantable device 100. In this case, the single void 150 can either be in the form of a well or reservoir that is centrally located within the body of the implantable device 100 or it can be an open-ended passage formed in the body. The terms well and reservoir can be used interchangeably herein. As shown in Fig. 3, in this embodiment, the implantable device 100 is a spherical body defined by a center core 160 in which the single void 150 is formed. The center core 160 is surrounded by a plurality of fingers 162 that extend radially outward from the center core 160. Given the overall porosity of the device 100, the fingers 162 are not rigid but are freely movable. The fingers 162 like the center core 160 is formed of the same material and thus, can have a sponge-like appearance and feel. The fingers 162 can have the same shape and size or, as shown, the fingers 162 can have different shapes and sizes. In this particular embodiment, the fingers 162 do not have any internal dedicated channeling or passageways that are in fluid communication with the single void 150 in the center core 160. However, due to the material and construction of the device 100, and in particular, the porosity thereof including the porous center core 160 that defines the void (well) 150, a fluid that is within the void 150 is transported radially outward through the fingers 162 as by diffusion or other principles.

[0041] When there are two or more passages 150, the passages 150 can be independent from one another (non-intersecting) or they can intersect at one or more locations, w'hereby there is fluid communication between the two or more passages 150.

[0042] Figs. 4A and 4B illustrate other implantable devices 200 that are similar to the implantable device 100; however, these devices 200 have different shapes and different internal architectures. In particular, the implantable device 200 has more of a pill shape and more specifically a pill shape with truncated ends 202, 204. Like the implantable device 100, the implantable device 200 has a sponge-like construction formed by an interconnected network of polymer segments. The outer surface of the implantable device 200 is not smooth but instead is textured and / or contoured (e.g., undulating appearance, ribbed, folded construction, petal shaped, etc.). As mentioned, the ends 202, 204 can be truncated and thus, are generally flat, while the rest of the body is pill-shaped. The implantable device 200 has a void in the form of a central passage 210 that is open at and extends from the end 202 to the end 204. In addition, as shown, the passage 210 is intersected by one or more wells (reservoirs) 220 and in the illustrated embodiment, there are two wells 220 formed along the length of the passage 210 with the wells 220 segmenting the central passage 210 into three passage segments (one at end 202, one at end 204 and one between the wells 220).

[0043] It will also be appreciated that while the wells 220 are shown as being spherical in shape, the wells 220 can have any number of shapes and sizes so long as the well 220 is distinguishable from the central passage 210. Both wells 220 are thus in fluid communication with the two open ends 202, 204 of the implantable device 200, as well as being in fluid communication with each other. It will be understood that the volume of each well 220 varies depending upon the application and depending upon the size of the overall implantable device. For example, in at least one embodiment, the well 220, individually or combined, can hold about 40 cc to about 50 cc of fluid.

[0044] As in the previous embodiment, each of the well 220 and the central passage 210 is defined by a porous w all structure (perforated) that allow s for fluid to be transported across the porous wal 1 structure into the surrounding polymer material and / or into the surrounding tissue environment. Thus, fluid is held and / or flows within these structures and can be transported to different locations but also there is a radial transport (diffusion) of the fluid away from these structures.

[0045] The well 220 in Figs. 4A and 4B are slightly different in shape.

[0046] Figs. 5A and 5B are yet additional embodiments in w'hich an implantable device 300 is show'n. The implantable device 300 is similar to the others described herein and is generally spherically shaped wdth truncated first and second ends 302, 304. In this case, the void is in the form of a central passage 310 that is bisected by a well (reservoir) 320. As illustrated, the well 320 is centrally located within the body of the device 300. The well 320 can have a spherical shape in Fig, 5A, while, it can have a different, irregular shape as in Fig. 5B. The central passage 310 is open at both the first and second ends 302, 304. Thus fluid can travel within the central passage 310 and enter and exit at ends 302, 304 and can diffuse radially outw'ard from the central passage 310 and the w'ell 320.

[0047] Figs. 4A, 4B, 5A and 5B illustrate embodiments in which there is a single passage and one or more wells. However, in other embodiments, such as those described below, the implantable device includes primary and secondary passages, as w'ell as one or more wells. Fig. 6 illustrates another implantable device 400 that has a frustoconical shape. The device 400 has a first face 402 defining a first end and an opposing second face 404 defining an opposite second end. Due to the frustoconical shape, the first face 402 has a smaller surface area than the second face 404 and the side wall connecting the two faces is outwardly tapered toward the second face 404. The body of the implantable device 400 is generally ribbed shape along its outer surface. While not shown, the implantable device 400 includes a well, one or more passages, or a combination thereof. In the event that the implantable device 400 includes a central passage, it can be centrally located with respect to the first face 402 and the second face 404.

[0048] Figs. 7A and 7B illustrate another implantable device 500 that is similar to those described herein. Fig. 7A shows one exemplary target implantation site, while Fig. 7B shows the structure of the implantable device 500. As depicted in Fig. 7B, the implantable device 500 is implanted within the interstitium 10. The implantable device 500 is similar to the implantable device 300 of Fig. 5 and includes a central passage 510 and a center well 520 that bisects the central passage 510. As will be described in more detail herein, Fig. 7B also shows one exemplary use of the implantable device in that it illustrates using the implantable device to deliver a therapeutic by using a needle or other therapeutic delivery device. As shown, the implantable device 500 acts as a therapeutic delivery port by permitting a needle tip 7 of a needle 5 to be inserted into one end of the central passage 510 for injecting a therapeutically effective amount of the therapeutic into the central passage 510 and the well 520. As mentioned, the central passage 510 defines a flow path for the therapeutic and the porosity of the implantable device 500 permits radial diffusion of the therapeutic through the porous body of the implantable device 500. Unlike traditional therapeutic delivery through a needle tip to a very localized site, the construction and architecture of the implantable device described herein, including the implantable device 500, delivers therapeutic to a much greater tissue area due to the multi -direction diffusion and delivery of the therapeutic from the body of the implantable device 500 to the surrounding environment (i.e., the interstitium). Since the interstitium acts as fluid highway within the body, the therapeutic delivered by the implantable device enters into this fluid highway and is effectively circulated throughout the body including the local area at which the implantable device is implanted. It will also be understood that the construction of the present device prevents the needle from being clogged which occurs using the traditional needle tip delivery technique. Since the needle tip is within the reservoir and / or passage, it is protected from undesired clogging by matter and the injection site. Since the implantable device acts as a portal, it protects the needle tip from clogging.

[0049] The implantable device 500 of Fig. 7B can be the same as or similar to the implantable device of Fig. 5B.

[0050] Figs. 8A-8D illustrate another embodiment in which a star-shaped or spiked ball shaped implantable device 600 is shown. As best shown in Fig. 8C, the implantable device 600 has a porous body in the form of a star. The body has a center region 610 and a plurality of pointed regions 620 that extend radially outward from the center region 610. Given the 3D nature of the implantable device 600, it can be thought of as resembling a spiked ball (spiked mace or a morning star). The center region 610 includes a reservoir (well) 630. Unlike in other embodiment, there is not a large primary passage leading to the well 630. The well 630 is shown as being spherical shape; however, other shapes are possible.

[0051] The pointed regions 620 can be thought of as being tubules and the pointed regions 620 are in fluid communication with the well 630 by means of internal channeling / passages. For example, each pointed region 620 can include at least one primary passage or channel 640 that is in direct fluid communication with the well 630. The primary passage 640 thus extends radially outward from the well 630. There are also a plurality of secondary passages 650 that are in fluid communication with one primary passage 640 and thus, are in fluid communication therewith. These secondary passages 650 can be thought of as being side channels or branches. In the illustrated embodiment, the secondary passages 650 are formed perpendicular to the primary passage 640. The primary and secondary passages 640, 650 thus serve to transport fluid to or from the outer surface of the body depending if tin injection action or aspiration action is being performed. In Fig. 8B, an injection of a therapeutic is shown in which a needle tip 7 of a needle 5 is inserted through the body of the implantable device 600 until the needle tip 7 is in the well 630 at which time the therapeutic is injected. The channel architecture described above facilities a radially outward flow of the therapeutic from the well 630 to the outer surface of the device. Because of the channeling, optimal diffusion occurs since the primary and secondary passages have numerous end points along the optimized outer surface area of the device. Thus, while the needle tip 7 delivers the therapeutic to a needle tip location, the portal construction of the device results in extensive delivery coverage of the therapeutic due to the porous nature of the device, the extensive surface area of the device, and the internal channeling.

[0052] The terms ‘‘therapeutic” and “therapeutic agent” each generally refers to any agent that, when administered to a subject, has a therapeutic, diagnostic, and / or prophylactic effect and / or elicits a desired biological and / or pharmacological effect. Therapeutic agents are also referred to as “actives” or “active agents.” Such agents include, but are not limited to, cytotoxins, radioactive ions, chemotherapeutic agents, small molecule drugs, proteins, and nucleic acids, or other substance that is effective in treating a condition, disease, etc. As used herein, the term “therapeutically effective amount” means an amount of an agent to be delivered (e.g., nucleic acid, drug, composition, therapeutic agent, diagnostic agent, prophylactic agent, etc.) that is sufficient, when administered to a subject suffering from or susceptible to an infection, disease, disorder, and / or condition, to treat, improve symptoms of, diagnose, prevent, and / or delay the onset of the infection, disease, disorder, and / or condition. It will also be understood that the therapeutic / therapeutic agent can come in many different forms so long as they are suitable for injection into the implantable device and for transport from the implantable device to the surrounding connective tissue. For example, the therapeutic I therapeutic agent can be a solution, a gel, etc.

[0053] Fig. 9 illustrate an implantable device 700 that has an irregular shape. The body of the device 700 has a center region (section) 710 that includes a well 730 and has a plurality of legs or fingers 720 extending radially outward therefrom. Unlike the star or spiked ball construction of Fig. 8A, the device 700 does not having pointed appendages but rather the fingers 720 are more trunk-like. However, like the device 600, each leg 720 includes at least one primary passage or channel 740 that is in direct fluid communication with the well 730. The primary passage 740 thus extends radially outward from the well 730. There are also a plurality of secondary passages 750 that are in fluid communication with one primary passage 740 and thus, are in fluid communication therewith. These secondary passages 750 can be thought of as being side channels or branches. In the illustrated embodiment, the secondary passages 750 are formed perpendicular to the primary passage 740. The primary and secondary passages 740, 750 thus serve to transport fluid to or from the outer surface of the body depending if an injection action or aspiration action is being performed.

[0054] The dimensions of the primary and secondary passages 740, 750 can vary in that one can have a greater width or diameter relative to the others; or they can have the same width or diameter.

[0055] It will be understood and appreciated that all of the implantable devices described and illustrated herein are made from absorbable macroporous polymer scaffolding that assumes a three-dimensional configuration that is selected and / or modeled in view of the target implantation site. Each has optimal surface area to permit both diffusion of the injected therapeutic and aspiration of surrounding tissue fluid.

[0056] It will also be appreciated that post implantation and as healing cells engulf the structure, the implantable device is cast in connective tissue collagen fibers of the interstitium. In other words, the implantable device becomes integrated within the connective tissue 10 of the interstitium. The central hollow space or core (passage 150) fills with the proteinaceous exudate of the healing wound environment and becomes part of the interstitial space. As the macroporous implantable device absorbs, the designed structure persists in a relief of spaces which connect the hollow core (passage 150) to the interstitium surrounding the implantable device. The adjacent areas, around and within the design of the implantable device, heal with adipogenesis, a fatty connective tissue which has normal vascularization.

[0057] The passage 150 (hollow core) can be accessed with large bore needles or cannulas, to aspirate fluid and cells for diagnostic testing or it can be used to infuse therapeutic substances such as: cells, proteins, RNA, DNA, immune modulators, radiation enhancers, or probiotics. The substances are not limited to those listed above but serve to exemplify the way fluid, with everything from immune cells to nanoparticles, can be introduced into the designed passage 150 (hollow core space) of the implantable device and then perfuse into the interstitial spaces of the surrounding tissues.

[0058] In the event that passage 150 is intended to receive an external instrument, like a needle or cannula, the passage 150 preferably has a linear construction to allow for easy insertion and guidance and removal of the instrument.

[0059] In at least one embodiment, the implantable device is constructed such that any agent that is injected into the passage 150 is at least substantially contained within and flows within the passage 150 as opposed to substantially diffusing out through the surrounding body of the implantable device 100. In other words, the body walls that define the passage 150 and the material properties of the body are selected to provide the aforementioned feature. For example, in one embodiment, the walls of the passage 150 can have a different porosity than the porosity of the surrounding body structure of the implantable device. In particular, the passage 150 can have a lower porosity compared to the surrounding body structure to promote flow of the fluid within the passage 150. However, it will be appreciated that in other embodiments, the body of the implantable device is homogenous in that there are no material differences between the material defining the passage 150 and the material defining the surrounding body.

[0060] As an example, in one preferred embodiment, the implantable device is implanted into the surgical space that remains after resection of a cancerous tumor.

[0061] The device of the present invention provides an accessible portal into the desired tissue space adjacent a target area of the human body for medical purposes, such as diagnostic aspiration or therapeutic infusion; and thus provides a mechanism for changing the nature of medical human research. Instead of scientific models of disease in cellular cultures or animal models, real time information is obtained in a non-invasive manner over the course of the disease by diagnostic aspirations from the device. The device of the present invention also provides a window into the tissue microenvironment that allows monitoring of the dynamic changes involved with tissue humors (bodily fluids) over time giving a whole new meaning to the concept of “real world data.” The present device thus has applicability beyond therapeutic treatments and therapy.

[0062] The bioadsorbable device can be designed using absorbable monofilament polymers, knitted or otherwise constructed, with perforated surfaces arranged in three Cartesian dimensions. The absorption of the knitted monofilaments of the mesh leaves behind an empty space that becomes pail of the interstitial space. Thus, an infusion portal is created in a tissue-engineered organ and can, over time, manipulate the organ function depending on what is infused. Within the various shapes and sizes of the device is a hollow core, which can be accessed clinically via ultrasound-guided needles to inject therapeutic cells, such as stem cells, colonized immune cells, CRISPR edited cells, biological therapies, such as monoclonal antibodies and other proteins, or mRNA, etc. The central hollow core becomes integrated into the interstitium of the tissue it is implanted in and can be accessed with a needle to aspirate fluid and cells. These cells can include circulating tumor cells that can be analyzed with multi-omics, over time to guide a patient's response to therapy and target new therapies longitudinally. External negative pressure can be applied via a passage in the implanted device prior to aspiration of cells from the hollow core to facilitate pulling cells from the interstitium of the original tumor bed into the device's core. The device is oriented along the meridians of an original tumor prior to excision from the body, and the device can have a plurality of central hollow chambers going into different poles of the device to allow different therapies to be infused to different spatial areas of the tumor bed.

[0063] Markers

[0064] In accordance with one aspect of the present application, the implantable device 100 includes one or more markers that are visible under imaging to allow the user to visualize the location and / or orientation of the implantable device 100. As mentioned herein, there are at least several different types of imaging devices that can be used to detect tumors. For example, depending on the tumor’s location and type, the following imaging devices can be used to detect tumors: Computed Tomography (CT) scans, which use X-rays to create detailed cross-sectional images; Magnetic Resonance Imaging (MRI) scans, which use magnetic fields and radio waves for soft tissue visualization; Positron Emission Tomography (PET) scans, which identify metabolically active cells, often used in combination with CT (PET / CT); and Ultrasound, which uses sound waves. It will be appreciated that these imaging devices can be used to not only initially detect the tumor but also track the post- surgical recovery and in the instance of the present disclosure, can be used to visualize the location of the implantable device 100.

[0065] In order to assist the user in locating the implantable device 100 under imaging, one or more markers can be used. As is known, the type of marker that is used depends on the type of imaging that is likewise being used. For example, in the case in which ultrasound is being used, the implantable device 100, as well as any of the other devices described herein, can include one or more markers 90 that are designed to be visible under ultrasound. It will also be appreciated that such markers can also be used on the surgical instruments, such as the tip of a needle, thereby helping surgeons confirm accurate localization. In one embodiment, when the implantable device 100 and the surgical instrument both include surgical markers, the two can be formed so as to be distinguishable from one another to allow the user (surgeon) to differentiate between say the tip of the instrument and the implantable device 100 itself.

[0066] In one embodiment, the surgical marker 90 comprises a metal marker that is visible under ultrasound, such as a titanium marker or other metal component that is visible under ultrasound. For example, one or more small metallic marker can be part of and associated with the body of the implantable device 100. It is also possible that the marker can incorporate a hydrogel, which provides long-term ultrasound visibility by hydrating and enhancing echogenicity. In addition, the marker can be coated with pyrolytic carbon or can be embedded in a material like hydrogel (e.g., lyophilized beta-glucan gel) to increase its acoustic echogenicity and visibility.

[0067] In one embodiment, the implantable device includes one or more markers 90 that identify the passage 150. For example, in the case in which the passage 150 is an open ended passage, there can be a first marker 90 at the first end of the passage 150 and similarly, there can be a second marker 90 at the opposite second end of the passage 150. This allow s the user to visualize the open ends of the passage. Fig. 5A shows an exemplary marker 90 which in the case of device 300, the marker can be an annular shaped marker that surrounds the open end of the passage 150. Thus, the open center of ring-shaped marker 90 is axially aligned with the open lumen of the passage 150 for assisting in delivery of a surgical instrument to or into the open end of the passage 150.

[0068] It will also be appreciated that only one end of the passage 150 can include a marker 90. For example, the marker 90 that is closest to the skin of the patient. This end of the passage 150 comprises an ingress of the passage that can receive a surgical instrument, such as a needle or cannula, that, as described herein, can be used for injection of an agent and / or aspiration of a fluid.

[0069] Other types of markers that permit visualization of the implantable device, and / or permits identification of the internal voids, such as a well, are equally possible as well.

[0070] Optimized Surface Area Design

[0071] Both the ontogeny (generation from the embryonic to adult form) and regeneration of lost or damaged human tissues takes place through a process of self-organization of connective tissues, that specialized epithelium build on to form organs. This self-organizing is largely affected by physical forces at the scale of mesoscopic and microscopic tissue levels. One important consideration for self-organizing tissues is surface tension and minimal surfaces that reduce the tension as much as possible. Triply periodic minimal surfaces (TPMS) are patterns of geometry that repeat in three dimensions, like soft crystals, but minimize surface tension by having a zero-mean curvature. This is because they are like the bicontinuous phase surfaces seen in spontaneously forming stacked sheets, or lamina, of surfactants and phospholipids. Under certain conditions, pores form between the layers as a way of reducing the energy of the system. This leads to the stack with pores breaking up to a web of 3-D tunnels that divide the system into two distinct subspaces sometimes called a ■‘sponge phase”, whose curved surface cancel each other out and achieve the lowest energy state of the system. Some of the common designs, used in nature and industry involved with nanotechnology, include the cubic P-phase, the diamond or D-phase, and the gyroid G-phase. This becomes of interest because nature will use TPMS membrane designs, which are the lowest energy states for the job, w'hen self-organization heals tissues.

[0072] In constructing the present design and when designing a polymer implant for tissue interaction it is important what you put in the surgical site, namely, absorbable materials that have extremely low inflammatory reaction; but it is even more important what you leave out. In tissue regenerative scaffolds, such as the present implantable devices, there must be designed empty space for the body to grow into. Nature uses this principle when designing branching structures like arteries.

[0073] The design and material selection of the implantable devices are guided by a desire to use the least amount of material and leave open the most amount of open space for tissue ingrowth, all while maintaining a device strength that allows room for the ingrowth of healing tissue. In one embodiment, this can be accomplished by using a tensegrity system and the device can be formed so as to resemble a famous triply periodic minimal surface, the Calabi-Yau manifold, which resembles a lotus flower. In the present disclosure, the implantable devices each utilizes a mesh polymer design around a central hollow core reservoir. The exact design depends on the targeted tissue location in the body, but looks to create maximum surface area, per volume of the implant, to interact with the surrounding tissues of interest. The open mesh design heals with interstitial collagen bundles forming a three-dimensional labyrinth of interstitial spaces that then become in direct flow with fluids moving out of the tissue and through the device when aspiration from the reservoir is performed, as well as in the reverse direction when therapies are infused.

[0074] The implantable device can have shape and appearance that resembles a shower pouf or scrunchie that has a mesh construction and appearance. The shape can be described as being one of: 1) a "fluffed ball" or sphere with the body of the implantable device, which can have a mesh netting construction, being gathered and pulled tight at the center, causing the rest of the material to "fluff" outwards into a roughly spherical shape; 2) a "mesh ball" or "scrubber ball" in which a tightly knotted mesh forms a dense, compact ball: 3) an "accordion-folded" mesh construction in which the body is folded into an accordion-like structure, which defines many layers and ruffles; and 4) a "flower shape" in which the body looks like flower blossoms.

[0075] Fig. 10 shows an implantable device 800 that is similar to the others described herein. Fig. 10 shows the accordion-folded mesh appearance in that the body, which is formed of a porous (e.g., mesh) material is then folded to define a plurality of folds 810. A center core of the body includes at least one passage or void defining an empty space, such as a well 820. As previously described, since the material surrounding the well 820 has a mesh / porous construction, the wall of the well 820 is porous and the well 820 is in fluid communication therewith and more specifically, an injected therapeutic into the well 820 will diffuse radially outward through the mesh folds 810 to the outer surface / outer periphery of the device.

[0076] It will be understood that the size of the well 820 depicted by the broken circular line is not limiting and only exemplary since the size (volume) of the well 820 can be smaller or larger.

[0077] Fig. 11 illustrates another implantable device 900 that is generally disk-shaped. The implantable device 900 has a disk-shaped center section 910 that can have a relatively planar first major surface and a relatively planar opposite second major surface. Extending radially outward from the center section 910 is a peripheral folded or ribbon section 920. This ribbon section 920 extends around the complete periphery of the center section 910 and extends radially outward therefrom. As the name suggests, the ribbon section 920 is defined by a series of folds to define a ribbon-like structure that extends between the first major surface 912 and the second major surface 914.

[0078] The first and second major surfaces are described as being relatively planar since unlike the ribbon, folded structure (undulating surface), the first and second major surfaces can be relatively flat with a porous outer surface.

[0079] A center well or reservoir 915 is formed in the center section 910.

[0080] It will be understood that as in all embodiments described herein, the entire device 900 is formed of a porous bioadsorbable material and thus, both the center section 910 and the peripheral ribbon section 920 is porous and can be mesh-like to act Eke a sponge and freely transport fluid.

[0081] Design and Fabrication of the Implantable Device

[0082] In one or more embodiments, fabrication of the implantable device 100 employs hardware and software that models a resection site and then customizes an implantable device 100 for implantation within the resection site. For example, as previously mentioned, during a surgical procedure to remove a tumor, a resection site is formed defined as the area in which the tumor and any surrounding tissue was removed, thereby leaving a void.

[0083] An imaging device can be used to not only visualize and assess the results of the resection procedure, but also, to model the implantable device 100 that is subsequently implanted into the resection site. As described herein, in one embodiment, the implantable device 100 is manufactured using an additive manufacturing technique that allows the implantable device 100 to be manufactured quickly on-site at least in one embodiment.

[0084] Imaging devices for tumor resection sites include traditional modalities like intraoperative MRI and CT scans (often used in neurosurgery), as well as newer optical technologies such as the Lumicell DVS (for breast cancer), DOCI system (for head and neck cancers), and other fluorescence imaging systems. These advanced systems allow surgeons to visualize residual cancer cells or delineate tumor margins in real-time within the operating room, helping to ensure complete tumor removal and reduce the need for subsequent surgeries.

[0085] In one preferred embodiment, the imaging device comprises ultrasound imaging. In accordance with the present disclosure, these imaging technologies allow for 3D modeling of the resection site and surrounding structures and this information can then be used to model and design the implantable device such that an optimal fit results between the implantable device and the resection site. In one embodiment, the selection can be as simple as selection of a shape and size of the implantable device from a database of different shapes and different sized implantable devices. For example, the modeling and implant selection (module) software can select first a shape of the implantable device amongst those in the database and then a size. Alternatively, the software can be configured to build a custom fit implantable device for insertion into the resection site. This modeling of the shape and size of the implantable device can be based on the 3D model of the resection site generated from the captured images of the site and can also be based on input from the surgeon. For example, the surgeon can input the anatomical location of the resection site, the type of planned treatment (e.g., therapeutic delivery over a condensed or extended period of time, etc.), etc.

[0086] Computer programs (and other executable instructions) and data, such as the above database, can be stored on a machine-readable medium that is accessible by one or more processors for providing functionality shown and described herein. Various forms of computing devices are accessible to the network and can communicate over the network to the various machines that are configured to send and receive content, data, as well as instructions that, when executed, enable operation of the modeling and implant selection. The content and data can include information in a variety of forms, including, as non-limiting examples, text, audio, images, and video, and can include embedded information such as links to other resources on the network, metadata, and / or machine executable instructions. Each computing device can be of conventional construction, and while discussion is made in regard to servers that provide different content and services to other devices, such as mobile computing devices, one or more of the server computing devices can comprise the same machine or can be spread across several machines in large scale implementations, as understood by persons having ordinary skill in the art. In relevant part, each computer server has one or more processors, a computer-readable memory that stores code that configures the processor to perform at least one function, and a communication port for connecting to the network. The code can comprise one or more programs, libraries, functions or routines which, for purposes of this specification, can be described in terms of a plurality of modules, residing in a representative code / instructions storage, that implement different parts of the process described herein. Further, computer programs (also referred to herein, generally, as computer control logic or computer readable program code) can be stored in a main and / or secondary memory and implemented by one or more processors (controllers, or the like) to cause the one or more processors to perform the functions of the invention as described herein. In this document, the terms ‘‘memory,” “machine readable medium,” “computer program medium” and “computer usable medium” are used to generally refer to media such as a random access memory (RAM); a read only memory (ROM); a removable storage unit (e.g., a magnetic or optical disc, flash memory device, or the like); a hard disk; or the like.

[0087] In one embodiment, the imaging system communicates with a main or server computing device and / or a mobile computing device (e.g., a tablet) over a communications network to allow' the surgeon (or other user) to view the images (ultrasound or CT / MRI images) generated by the imaging device and also permit, via a user interface, the user to provide input that can be used to select the implantable device.

[0088] As noted herein, the control console, server computing device and / or mobile computing device includes memory (e.g., non-transitory processor readable media) which is accessible and / or coupled to the processor(s). The memory may be used for storing data, metadata, and programs for execution by the microprocessor(s) 150. The memory may include one or more of volatile and non-volatile memories, such as Random Access Memory (“RAM”), Read Only Memory (“ROM”), Flash, Phase Change Memory (“PCM”), or other type.

[0089] Moreover, a display controller and display device can provide a visual user interface for the user; this user interface may include a graphical user interface which, for example, is similar to that shown on a desktop, laptop, tablet or mobile device when running Mac OS, Windows OS, Android, Linux, or other common operating system software. Further, one or more buses can be included that interconnect various modules.

[0090] The computer-implemented methods may be carried out in a computer system or other data processing system in response to its processor or processing system executing sequences of instructions contained in a memory, such as memory or other machine-readable storage medium. In various embodiments, fiard wired circuitry may be used in combination with the software instructions to implement the present embodiments. Thus, the techniques are not limited to any specific combination of hardware circuitry and software, or to any particular source for the instructions executed by the control console.

[0091] Cancer Therapy Applications The implantable devices described herein are particularly suited for use in cancer therapy. First, the implantable device can be used to aspirate fluid from tissue at the implant site using the implantable device and in particular, the fluid can be drawn from the central hub reservoir (the well) through a percutaneously placed large gauge needle (e.g., 12-14 g) that is in fluid communication with one void formed in the implantable device, such as a passage or well. This is performed in the clinic, starting one to two months after the surgical resection of the solid tumor and implantation of the implantable device in the tumor bed. A low negative pressure aspiration ( -15 to -25 mm Hg) is used for 15 to 20 minutes and collected to be sent to the lab. Once the tissue diagnostic fluids are obtained, the laboratory can subject it to various “multiomics” (genome, epigenome, transcriptome, proteome, metabalome, exposome, and microbiome) that interrogate the fluid of the tissue surrounding the implantable device. Following the results and trends of these studies can alert physicians to the possibility of local cancer activity, in the resected tumor bed, before standard serum testing from the systemic circulation, such as elevations in the tumor marker CA 19-9, suggests recurrent cancer activity in a patient. This early warning in asymptomatic patients w ould alert the clinician of the need for therapeutic interventions before scans, such as CAT scans, MRI, and nuclear medicine / PET scans, would show a positive finding.

[0092] Secondly, the reservoir (w ell) in the center of the portal (implantable device) can be accessed percutaneously with a large gauge needle (12-14g). The reservoir is then filled with a fluid or a plasma as part of a therapeutic medical activity. The therapy flows directly from the central reservoir, which has perforated surfaces containing a large porous makeup, which allows the therapy to diffuse unobstructed into the surrounding interstitial tissues. The central reservoir has radiating canals coming off of the central hub, like spokes on a wheel, which are also designed to be porous. These spoke dived the device into segments, which can be further divided by branches off the canals into subsegments. The therapeutic(s) can be such things as cellular therapies, such as CAR T Cell therapies, immune adjuvant designed to vaccinate the patient against the cancer cells, monoclonal antibodies such as Herceptin, nanoparticle therapies, time released chemotherapies and hormone blockers. The therapies may also consist of enzymes known to phosphorylate extracellular matrix proteins and thus alter the malignant tumor environment towards less malignant states. This also could include therapies directed at changing the electrolyte and ion makeup of the extracellular fluid in the interstitial space fluids. This may, in addition, involve therapies that alter the makeup of the interstitial hyaluronic acid and proteoglycan characteristics to make them less viscous and promote diffusion of therapies into the tissue environment- such as enzymes like hydaluronodase. Other therapies may involve infusing designed DNA or RNA in vesicles or extracellular bound vesicles to change the character of the extracellular matrix protein environment into one intolerant of cancer behavior. Finally, therapeutic infusions could change the bioelectric membrane potentials of cells living on the interstitial ecotone and thus shut off carcinogenic proclivity.

[0093] The final leg of the present implantable device is its use for scientific studies of the biology of cancer in vivo. This would be done in preclinical animal studies, such as in vivo murine models of cancer. Using a tissue portal in the form of the present implantable device would allow diagnostic and therapeutic treatments as outlined above in the research animal model to be done in vivo longitudinally. No longer would the outcome of chemical and pamiocologic therapies be performed after euthanizing the subject animal to look for local and distant cancer effects, but the study data could be drawn every day from the tissue port to see changes in multiomics. Therapeutic infusions through the port would then be performed and once again longitudinal study of tissue fluid aspirated from the device would aid the scientific effects of the particular therapy over time.

[0094] Thus, the implantable devices described and illustrated herein can be implanted in either a human body or an animal, such as a mouse.

[0095] Tumor Infiltrating Lymphocyte Therapy

[0096] Tumor infiltrating lymphocyte (TIL) therapy is similar to CAR T cell therapy, which is usually given for blood cancers like lymphoma, but the TIL therapy is designed for solid tumors. The tumor is resected and in the lab, TILs are selected and cloned up to significant numbers then infused back into the patient with an intravenous catheter or port. If a tissue port (InpOUrT) was put in place of the solid tumor when it was resected, those cloned TILs could be infused to the central reservoir of the present invention and enter the interstitium at the ground zero of the cancerous solid tumor, to treat and clean up any residual cancer cells in the local or regional setting. Of course some TILs would make their way through the interstitium and into the lymphatic system and thereby into the circulatory system- but at a much safer dose that would help mitigate systemic complications of TIL therapy that is first infused through a vein.

[0097] The implantable devices described herein have applicability to this treatment. It is to be understood that any structural and functional details disclosed herein are not to be interpreted as limiting the systems and methods, but rather are provided as a representative embodiment and / or arrangement for teaching one skilled in the art one or more ways to implement the methods.

[0098] It is to be further understood that like numerals in the drawings represent like elements through the several figures, and that not all components and / or steps described and illustrated with reference to the figures are required for all embodiments or arrangements.

[0099] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the disclosure. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising", when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0100] Terms of orientation are used herein merely for purposes of convention and referencing and are not to be construed as limiting. However, it is recognized these terms could be used with reference to a viewer. Accordingly, no limitations are implied or to be inferred.

[0101] Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having," "containing," "involving," and variations thereof herein, is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.

[0102] While the disclosure has been described with reference to exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the disclosed invention. In addition, many modifications will be appreciated by those skilled in the art to adapt a particular instrument, situation or material to the teachings of the disclosure without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention includes all embodiments falling within the scope of the appended claims.

Claims

What is claimed is:

1. An implant for implantation in human or animal tissue to provide access to interstitium adjacent an area of interest, the implant comprising: a body made of a bioadsorbable macroporous material that facilitates connective tissue ingrowth into the body, the body having at least one reservoir formed therein for accessing the area of interest to introduce a therapeutic to the adjacent interstitium and / or to aspirate fluid and cells therefrom.

2. The implant of claim 1, wherein the bioadsorbable macroporous material has pores with a pore size from 500 microns to 1500 microns.

3. The implant of claim 1, wherein the bioadsorbable macroporous material comprises a 3D polymer scaffolding structure.

4. The implant of claim 1. wherein an outer surface of the body has an undulating construction.

5. The implant of claim 1, wherein the body has a homogenous porosity.

6. The implant of claim 1, wherein the body has a plurality of folds to increase surface area.

7. The implant of claim 1. wherein the body further includes a first passage that has a first open end at a first location of the body and an opposite second open end at a second location of the body.

8. The implant of claim 7, wherein the first passage comprises a linear channel.

9. The implant of claim 7, wherein the at least one reservoir comprises a first reservoir that bisects the first passage and is centrally formed in the body.

10. The implant of claim 9, wherein the first reservoir has at least one dimension greater than dimensions of the first passage.1 1 . The implant of claim 9, wherein each of the first reservoir and the first passage is defined by porous walls to permit fluid to flow radially outward therefrom toward an outer surface of the body.

12. The implant of claim 1, wherein the at least one reservoir comprises a plurality of reservoirs spaced apart from one another and the body includes a fust passage that has a first open end at a first location of the body and an opposite second open end at a second location of the body, the first passage intersecting each of the plurality of reservoirs.

13. The implant of claim 1, wherein the body has a frustoconical shape.

14. The implant of claim 1, wherein the body has a center core in which the at least one reservoir is formed and has a plurality of fingers extending radially outward from the center core.

15. The implant of claim 14, wherein the center core has a spherical shape and the plurality of fingers have a spherical shaped coverage.

16. The implant of claim 1 , wherein the body has an elongated pill-shaped with truncated first and second ends that are opposite one another and further includes a first passage that has a first open end at the first end and an opposite second open end at the second end.

17. The implant of claim 1, wherein the body includes a plurality of primary channels that are each in fluid communication with the at least one reservoir and a plurality of secondary channels, each secondary channel being in fluid communication with one primary channel of the plurality of primary channels.

18. The implant of claim 1 , w'herein the at least one reservoir is formed in a center core of the body and the body includes a plurality of appendages extending radially outward from the center core, each appendage having at least one primary channel and a set of secondary channels of the plurality of secondary channels.

19. The implant of claim 1 , wherein the body has a spiked ball construction.

20. The implant of claim 19, wherein the at least one reservoir is formed in a center core of the body and the body includes a plurality of appendages extending radially outward from the center core, each appendage having at least one primary channel and a set of secondary channels of the plurality of secondary channels.

21. The implant of claim 1 , further including a marker that is visible under imaging.

22. The implant of claim 21, wherein the marker is visible under ultrasound.

23. The implant of claim 21, wherein the marker identifies a location of the at least one passage.

24. The implant of claim 1 , wherein the body has a lotus flower shape.

25. The implant of claim 1 , w'herein the body has an accordion-folded construction defined by a plurality of ruffles or folds that define an outer surface of the body.

26. The implant of claim 1, wherein the body has a mesh construction.

27. The implant of claim 1 , wherein the body has a volume between 25 cc to 250 cc.

28. A method for use with a medical activity involving a target area in a human or animal body, the method comprising the steps of: implanting a bioadsorbable portal device in interstitium adjacent the target area, the implanted portal device being made of a bioadsorbable macroporous material and having a hollow' core forming at least a part of a passage through the implanted portal device; utilizing the implanted portal device to provide fluid access to the target area via the passage and the interstitium; and performing the medical activity using fluid passing through the implanted portal device.

29. The method of claim 28, w'herein the medical activity comprises one of an injection of a therapeutic agent and aspiration of a fluid from the target area.

30. The method of claim 29, wherein the injection of the therapeutic agent comprises inserting a needle tip into the hollow core and injecting the therapeutic agent into the hollow core.

31. The method of claim 29, w'herein the aspiration of the fluid comprises inserting a needle tip of a needle into the hollow core and generating negative pressure with the hollow core using the needle to aspirate the fluid.

32. The method of claim 28, wherein the bioadsorbable macroporous material has pores with a pore size from 500 microns to 1500 microns.

33. The method of claim 28, w'herein the bioadsorbable macroporous material comprises a 3D polymer scaffolding structure.

34. The method of claim 28, wherein an outer surface of the body has an undulating construction.

35. The method of claim 28, w'herein the body has a homogenous porosity.

36. The method of claim 28, wherein the body has a plurality of folds to increase surface area.

37. The method of claim 28, w'herein the passage has a first open end at a first location of the body and an opposite second open end at a second location of the body.

38. The method of claim 37. w herein the passage comprises a linear channel.

39. The method of claim 37, wherein the hollow core comprises a first reservoir that bisects the passage and is centrally formed in the body.

40. The method of claim 39, w'herein the first reservoir has at least one dimension greater than dimensions of the passage.41 . The method of claim 39, wherein each of the first reservoir and the passage is defined byporous walls to permit fluid to flow radially outward therefrom toward an outer surface of the body.

42. The method of claim 28, wherein the hollow core comprises a plurality of reservoirs spaced apart from one another and the passage includes a first passage that has a first open end at a first location of the body and an opposite second open end at a second location of the body, the first passage intersecting each of the plurality of reservoirs.

43. The method of claim 28, wherein the body has a frustoconical shape.

44. The method of claim 28, wherein the body has a center section in which hollow core is formed and has a plurality of fingers extending radially outward from the center section.

45. The method of claim 44, wherein the center section has a spherical shape and the plurality of fingers have a spherical shaped coverage,46. The method of claim 28, wherein the body has an elongated pill-shaped with truncated first and second ends that are opposite one another and the passage has a first open end at the first end and an opposite second open end at the second end.

47. The method of claim 28, wherein the body includes a plurality of primary channels that are each in fluid communication with the hollow core and a plurality of secondary channels, each secondary channel being in fluid communication with one primary channel of the plurality of primary channels.

48. The method of claim 28. wherein the body includes a plurality of appendages extending radially outward from the hollow core, each appendage having at least one primary channel and a set of secondary channels of the plurality of secondary channels.

49. The method of claim 28, wherein the body has a spiked ball construction.

50. The method of claim 49, wherein the body includes a plurality of appendages extending radially outward from the hollow core, each appendage having at least one primary channel and a set of secondary channels of the plurality of secondary channels.51 . The method of claim 28, further including a step of visualizing a marker that is on an outer surface of the body under imaging to locate the hollow core.

52. The method of claim 51, wherein the imaging comprises ultrasound.

53. The method of claim 28. wherein the body has an accordion-folded construction defined by a plurality of ruffles or folds that define an outer surface of the body.

54. The method of claim 28, wherein the body has a mesh construction.

55. The method of claim 28, wherein the body has a volume between 25 cc to 250 cc.

56. The method of claim 28, wherein the medical activity comprises aspiration of a fluid from the target area; and performing a diagnostic test on the aspirated fluid.

57. A method of accessing a target area of the human body for medical purposes comprising, the steps of implanting a tissue engineered device in the interstitium adjacent the target area, the device being made of bioabsorbable material and having distal and proximal portions, hollow portions forming a part or all of a passage through the implanted device, and accessing the target area to introduce therapeutics to the adjacent interstitium area and / or to aspirate fluid and cells.

Images