Patent Description:
It is with respect to these and other general considerations that the aspects disclosed herein have been made. Also, although relatively specific problems may be discussed, it should be understood that the examples should not be limited to solving the specific problems identified in the background or elsewhere in this disclosure.

<CIT> describes composite materials comprising a hydrogel and a nanostructure for use in methods for reconstruction of soft tissue. <CIT> describes breast templates for delivering stem cell formulations to a breast defect of a patient. <CIT> describes nanofiber-hydrogel composites for cell and tissue delivery and methods for manufacturing.

Examples of the present disclosure describe devices and methods for facilitating post-resection tissue formation to accelerate healing. In an aspect, the technology relates to a method to accelerate healing after a resection of tissue. The method includes preparing a hydrogel scaffold with encapsulated cells corresponding to a type of the tissue resected, and integrating the hydrogel scaffold with a frame to form an implantable device for insertion into a cavity created by the resection.

In an example, a hydrogel precursor solution is prepared, and gelation of the hydrogel precursor solution initiated to form the hydrogel scaffold. In another example, preparing the hydrogel scaffold with the encapsulated cells includes removing a sample of tissue during a biopsy, where the sample of tissue may be a same type of tissue as the tissue resected, isolating cells from the sample of tissue, harvesting and expanding the cells in vitro, mixing the cells in the hydrogel precursor solution to form a precursor-cell solution, and initiating gelation of the precursor-cell solution to form the hydrogel scaffold with the encapsulated cells. In a further example, the sample of tissue is removed during the biopsy of a patient undergoing the resection such that the cells encapsulated in the hydrogel scaffold are cells of the patient, where the sample of tissue removed comprise at least in part a healthy tissue.

In another example, integrating the hydrogel scaffold with the frame includes at least partially surrounding one or more portions of the frame with the hydrogel scaffold. A hydrogel precursor solution is applied to the one or more portions of the frame, and gelation of the hydrogel precursor solution initiated to form the hydrogel scaffold that at least partially surrounds the one or more portions of the frame. In an example, the frame is encapsulated in the hydrogel scaffold by submerging the frame in the hydrogel precursor solution prior to the gelation. In another example, the hydrogel precursor solution is applied to an at least partially open structure of the frame such that the hydrogel scaffold is formed within the frame upon gelation. In a further example, an application of the hydrogel precursor solution to the one or more portions of the frame is determined based on growth patterns of new tissue formed in the cavity. In a yet further example, at least one of a size and a shape of the frame may be selected based at least in part on at least one of a size and a shape of the cavity.

In another aspect, the technology relates to an implantable device to accelerate healing after a resection of tissue. The implantable device includes a hydrogel scaffold including encapsulated cells that correspond to a type of the tissue resected to facilitate tissue formation within a cavity formed by the resection upon insertion of the implantable device into the cavity, and a frame comprising one or more portions that are at least partially surrounded by the hydrogel scaffold.

In an example, the frame is encapsulated in the hydrogel scaffold. In another example, the frame has an at least partially open structure, and the hydrogel scaffold may be formed within the frame. In a further example, the hydrogel scaffold and the frame are bioabsorbable. In a yet further example, the frame includes one or more markers positioned along the one or more portions of the frame, and the one or more markers may be comprised of a non-bioabsorbable, radiopaque material. In an example, at least one of a size and a shape of the frame may be selected based at least in part on at least one of a size and a shape of the cavity formed by the resection.

In a further aspect, the technology relates to a method to accelerate healing after a resection of tissue. The method includes preparing a hydrogel scaffold with encapsulated cells corresponding to a type of the tissue resected, integrating the hydrogel scaffold with a frame to form an implantable device, where one or more portions of the frame are at least partially surrounded by the hydrogel scaffold, and inserting the implantable device into a cavity formed by the resection.

In an example, preparing the hydrogel scaffold with the encapsulated cells includes removing a sample of tissue during a biopsy, where the sample of tissue is a same type of tissue as the tissue resected, isolating cells from the sample of tissue, harvesting and expanding the cells in vitro, mixing the cells in a hydrogel precursor solution to form a precursor-cell solution, and initiating gelation of the precursor-cell solution to form the hydrogel scaffold with the encapsulated cells. In another example, the precursor-cell solution is applied to the one or more portions of the frame, and gelation of the precursor-cell solution is initiated to form the hydrogel scaffold that at least partially surrounds the one or more portions of the frame.

Additional aspects, features, and/or advantages of examples will be set forth in part in the description which follows and, in part, will be apparent from the description, or may be learned by practice of the disclosure.

The present invention relates to a method for preparing an implantable device and to an implantable device as set forth in the appended claims. The methods of using the implantable device and to accelerate healing after resection of tissue do not form part of the invention.

Based on results of a diagnostic evaluation, a resection surgery may be performed to remove abnormal breast tissue. The removal of the breast tissue may create a cavity at a site of the resection. Over time, new breast tissue may form in the cavity. However, if the cavity is left void while the new breast tissue forms, deformities to the breast may occur that affect the look and/or feel of the breast. Additionally, identification of the site of resection may be important for subsequent procedures and/or imaging, among other examples. Therefore, implantable surgical markers may be inserted into the cavity during the surgery that provide temporary structural support within the cavity as the new breast tissue forms, as well as enable identification of the site for a prolonged period of time post-resection. However, conventional markers fail to facilitate new breast tissue formation within the cavity to accelerate healing post-resection. A bioreactor that induces cell in tissue integration may be one example solution.

Examples as described herein provide a hydrogel-based implantable device for insertion within the cavity. The implantable device may include a hydrogel scaffold with encapsulated cells serving as an example bioreactor to induce cell in tissue integration. The encapsulated cells may correspond to a type of the tissue resected, and may be cells of a patient undergoing the resection. For example, a sample of tissue corresponding to a same type of tissue resected may be removed during a biopsy performed on the patient, where healthy, tissue-specific cells may be isolated from the sample of tissue and harvested in vitro for encapsulation in the hydrogel scaffold. The encapsulated cells may interact with native cells of the breast to facilitate new tissue formation within the hydrogel scaffold and other areas of the cavity upon insertion of the implantable device into the cavity.

The implantable device includes a frame having one or more portions at least partially surrounded by the hydrogel scaffold. The frame may be bioabsorbable providing temporary structural support within the cavity during the tissue formation facilitated by the encapsulated cells of the hydrogel scaffold. Additionally, a plurality of markers comprised of non-bioabsorbable, radiopaque material may be positioned along the frame to enable identification of the site of resection.

For clarity, an implantable device to facilitate tissue reformation and accelerate healing within the breast are described herein. However, a similar implantable device may be inserted within resection cavities formed from the removal of tissues other than breast tissue to facilitate tissue reformation and accelerate healing post-resection.

In describing examples illustrated in the drawings, specific terminology is employed for the sake of clarity. However, the disclosure of this patent specification is not intended to be limited to the specific terminology so selected and it is to be understood that each specific element includes all technical equivalents that operate in a similar manner.

<FIG> depicts an example configuration of an implantable device <NUM> for insertion into a resection cavity <NUM>. <FIG> depicts another example configuration of the implantable device <NUM>. <FIG> depicts a further example configuration of the implantable device <NUM>. Referring concurrently to <FIG>, <FIG>, and <FIG>, a surgical resection of breast tissue may be performed on a patient <NUM>. In one example, a portion of breast tissue may be determined through a diagnostic evaluation to be abnormal (e.g., comprise malignant cells), and the patient <NUM> may have a local wide excision or lumpectomy performed to remove the abnormal breast tissue, as well as at least a small portion of normal breast tissue surrounding the abnormal breast tissue. The removal of the breast tissue creates the cavity <NUM> at a site of the removal (e.g., at a site of resection). If the cavity <NUM> is left void while new breast tissue forms within the cavity <NUM>, deformities to the breast may occur that affect the look and/or feel of the breast. Undergoing the surgical resection and any other necessary post-resection procedures, such as a radiation or chemotherapy, may understandably be a traumatic experience for the patient <NUM>, which may further be exacerbated by such deformities.

The implantable device <NUM> may be inserted into the cavity <NUM> at the site of resection immediately following the removal of the breast tissue as part of the surgical procedure. The implantable device <NUM> may include a hydrogel scaffold <NUM> and a frame <NUM>. The hydrogel scaffold <NUM> may facilitate formation of new breast tissue within the cavity <NUM> to accelerate the post-resection healing process, while the frame <NUM> may provide structural support within the cavity <NUM> to reduce deformities and enable identification of the site of resection during any post-resection procedures.

As described in greater detail with respect to <FIG>, the hydrogel scaffold <NUM> may comprise a three-dimensional (3D) network of cross-linked, hydrophilic polymer chains that mimics a microenvironment of the breast, supporting cell growth. Therefore, cells <NUM> may be encapsulated in the hydrogel scaffold <NUM> to proliferate and differentiate. In some examples, the cells <NUM> may be healthy cells of the patient <NUM> undergoing the resection. For example, the cells <NUM> may be obtained from healthy breast tissue of the patient <NUM> removed during a biopsy performed for diagnostic evaluation of the breast tissue (e.g., to determine whether a resection is necessary). The hydrogel scaffold <NUM> may include growth factors to stimulate growth of the cells <NUM>, among other functions, and may provide one or more of chemical and mechanical cues for directing behavior of the cells <NUM> in order to mirror how the cells <NUM> would behave in the microenvironment present in the breast tissue. For example, chemical cues may indicate a site for cell adhesion and mechanical cues may direct differentiation of the cells. The chemical and/or mechanical cues provided may be based on a type of polymer material from which the hydrogel scaffold <NUM> is formed. Additionally, the hydrogel scaffold <NUM> may be customized to more closely resemble a density of the patient's breast tissue by selecting a particular type of polymer material to form the hydrogel scaffold <NUM>.

While some cell growth is ideal within the hydrogel scaffold <NUM>, it is preferable that tissue formation has not yet occurred before insertion of the implantable device <NUM> into the cavity <NUM> such that the cells <NUM> interact with native cells of the breast to form the new breast tissue. For example, upon insertion of the implantable device <NUM> into the cavity <NUM>, native cells may migrate into the hydrogel scaffold <NUM> to form new breast tissue along with some of the encapsulated cells <NUM> within the hydrogel scaffold <NUM>. Additionally, some of the encapsulated cells <NUM> may migrate out of the hydrogel scaffold <NUM> to form new breast tissue along with native breast cells in other areas within the cavity <NUM>. The interaction between the encapsulated cells <NUM> and the native cells may increase a rate at which new breast tissue is formed, thereby accelerating the healing process.

The frame <NUM> may be an open structure, such as a helix as illustrated in <FIG>, <FIG>, and <FIG>. In other examples, the frame may be a partially open structure or a closed structure. As described in greater detail with respect to <FIG>, the frame <NUM> may be bioabsorbable, providing temporary structural support within the cavity <NUM> to reduce breast deformities created while tissue formation within the cavity <NUM> is being facilitated by the cells <NUM> of the hydrogel scaffold <NUM>. Additionally, the frame <NUM> may include a plurality of markers <NUM> spaced along one or more portions of the frame <NUM>. The markers <NUM> may be comprised of a non-bioabsorbable, radiopaque material such that the markers <NUM> remain at the site of resection for a prolonged period of time post-resection to enable identification of the site via imaging processes.

The hydrogel scaffold <NUM> may be integrated with the frame <NUM> to form the implantable device <NUM>. In some examples, more than one hydrogel scaffold <NUM> may be integrated with the frame <NUM> to form the implantable device <NUM>, as illustrated in <FIG>. To integrate the hydrogel scaffold <NUM> and the frame <NUM>, one or more portions of the frame <NUM> may be at least partially surrounded by the hydrogel scaffold <NUM>. As described in greater detail with respect to <FIG>, formation of the hydrogel scaffold <NUM> may involve preparation of a liquid precursor solution, also referred to herein as a hydrogel precursor solution, that is transitioned into a semi-solid material using physical crosslinking or chemical crosslinking (e.g., via gelation). The cells <NUM> may be mixed into the hydrogel precursor solution prior to gelation. The hydrogel precursor solution may be applied to one or more portions of the frame <NUM>, and gelation may be initiated to form the hydrogel scaffold <NUM>. In some examples, gelation may be initiated using photopolymerization (e.g., by placing the hydrogel precursor solution under ultraviolet light). In other examples, gelation may be initiated by changes in pH or temperature, or ion addition, among other similar methods known to a person having ordinary skill in the art. Upon gelation one or more portions of the frame <NUM> may be at least partially surrounded by the hydrogel scaffold <NUM>.

In some examples, to apply the hydrogel precursor solution, the frame <NUM> may be placed or positioned in the hydrogel precursor solution that is contained within a receptacle, such as a petri dish or well plate, among other similar receptacles. As one example, the frame <NUM> may be submerged in the hydrogel precursor solution such that each portion of the frame <NUM> may be entirely surrounded by the hydrogel scaffold <NUM> upon gelation, as illustrated in <FIG>. In other words, the frame <NUM> may be encapsulated in the hydrogel scaffold <NUM>. Encapsulation of the frame <NUM> in the hydrogel scaffold <NUM> may allow the breast to feel more natural to the patient <NUM> post-resection. For example, the gel-like feel of the hydrogel scaffold <NUM> may more closely resemble the feel of the breast than the harder feel of the frame <NUM>. Additionally, the encapsulation of the frame <NUM> in the hydrogel scaffold <NUM> may help reduce chances of rejection of the implantable device <NUM> by the patient's body due to the biocompatibility of the hydrogel scaffold <NUM> with the breast environment. As another example, the frame <NUM> may be placed or positioned in the hydrogel precursor solution such that the frame <NUM> is not entirely submerged and only some portions of the frame <NUM> are exposed to the hydrogel precursor solution. Upon gelation, only those portions of the frame <NUM> exposed to the hydrogel precursor solution are at least partially surrounded with the hydrogel scaffold <NUM>.

In other examples, where more than one hydrogel scaffold <NUM> may be integrated with the frame <NUM> to form the implantable device <NUM>, the above described application of hydrogel precursor solution to one or more portions of the frame <NUM> and subsequent gelation may be repeated for each hydrogel scaffold <NUM>. For example, as illustrated in <FIG>, at least two hydrogel scaffolds <NUM> (e.g., first hydrogel scaffold 106A and second hydrogel scaffold 106B) are formed at a different portion or segment of the frame <NUM>. In some examples, each hydrogel scaffold <NUM> is formed such that it surrounds a perimeter of the portion or segment (e.g., forms a hydrogel ring around the portion or segment). For example, a first portion or segment <NUM> of the frame <NUM> may be positioned into the hydrogel precursor solution so that the hydrogel precursor solution surrounds only that first portion or segment <NUM>, and then gelation may be initiated to form the first hydrogel scaffold 106A surrounding the first portion or segment <NUM>. Subsequently, a second portion or segment <NUM> of the frame <NUM> may be positioned into the hydrogel precursor solution so that the hydrogel precursor solution surrounds only that second portion or segment <NUM>, and then gelation may be initiated to form the second hydrogel scaffold 106B surrounding the second portion or segment <NUM>. Additional hydrogel scaffolds <NUM> may be formed to surround additional portions or segments of the frame <NUM> in a same or similar manner.

In further examples, the frame <NUM> may have at least a partially open structure, and the hydrogel precursor solution may be applied to the open structure to form the hydrogel scaffold <NUM> within the frame <NUM>. For example, based on a structure of the frame <NUM>, the frame <NUM> may serve as a mold or be positioned within a mold having a similar shape to the frame <NUM>. As one example, the frame <NUM> may serve as a mold if the frame <NUM> has a partially open structure such as a hollow cone. As another example, the frame <NUM> may be positioned within the mold if the frame <NUM> has an open structure such as a helix. The hydrogel precursor solution may be poured into the open structure, and gelation may be initiated to form the hydrogel scaffold <NUM>. Upon gelation, the hydrogel scaffold <NUM> may be formed within the frame <NUM>, as illustrated in <FIG>. In one example, there may be an additional support structure within the frame <NUM> around which the hydrogel scaffold <NUM> is formed upon gelation.

In some examples, the integration of the hydrogel scaffold <NUM> and the frame <NUM> may be based on growth patterns of new tissue formed in the cavity <NUM> (e.g., based on where growth of breast tissue initially occurs within the cavity <NUM>). For example, if breast tissue naturally grows first in areas surrounding the frame <NUM> within the cavity <NUM>, a frame <NUM> having an open structure may be selected for integration and the hydrogel scaffold <NUM> may be formed within the frame <NUM>, as illustrated in <FIG>. This may promote the migration of native cells into the hydrogel scaffold <NUM> to help facilitate breast tissue growth within the frame <NUM>.

<FIG> depicts an example hydrogel scaffold <NUM> with encapsulated cells <NUM>. The hydrogel scaffold <NUM> comprises a bioabsorbable, 3D network of hydrophilic polymer chains held together by cross-links. Formation of the hydrogel scaffold <NUM> may involve preparation of a hydrogel precursor solution comprised of at least one or more hydrophilic polymers that is transitioned into a semi-solid material using physical crosslinking or chemical crosslinking (e.g. via gelation). In some examples, the hydrogel scaffold <NUM> may be formed from one or more synthetic polymer materials, including one or more of poly(<NUM>-hydroxyethyl methacrylate) (pHEMA), polyvinylpyrrolidone (PVP), polyethylene glycol diacrylate (PEGDA) and poly(vinyl alcohol) (PVA), among other similar polymers. In other examples, the hydrogel scaffold <NUM> may be formed from one or more natural polymer materials such as collagen, fibrin, and alginate, among other natural polymer materials. In further examples, the hydrogel scaffold <NUM> may be formed from hydrophilic polymer materials that are a hybrid of natural and synthetic polymer materials. These polymer materials are provided merely as examples, and those having skill in the art will recognize and understand additional or different polymer materials that may be used to form a hydrogel scaffold, such as the hydrogel scaffold <NUM>.

A type of crosslinking performed may be based on the type of polymer materials selected. Additionally, depending on the type of polymer material selected and the crosslinking to be performed, additional chemical modifications may be made to the hydrogel precursor solution, such as an addition of cross-linking agents and/or initiators. In some examples, the polymer materials may be selected based on factors associated with an anatomy of the breast of the patient <NUM>. For example, if the breast of the patient <NUM> is dense, particular types of polymer materials may be selected to more closely resemble the dense breast tissue.

The hydrogel scaffold <NUM> may mimic a microenvironment of the breast, supporting cell growth. Therefore, cells <NUM> may be encapsulated in the hydrogel scaffold <NUM> to proliferate and differentiate. In some examples, the cells <NUM> may be healthy cells of the patient <NUM> undergoing the resection. For example, the cells <NUM> may be obtained from healthy breast tissue of the patient <NUM> removed during a biopsy performed for diagnostic evaluation of the breast tissue (e.g., to determine whether the resection was necessary). A method for isolating and encapsulating the cells <NUM> in the hydrogel scaffold <NUM> is described in greater detail in <FIG>. Additionally, the hydrogel scaffold <NUM> may include growth factors to stimulate growth of the cells <NUM>, among other functions, and provide one or more of chemical and mechanical cues for directing behavior of the cells <NUM> in order to mirror how the cells <NUM> would behave in the microenvironment present in the breast tissue. For example, chemical cues may indicate a site for cell adhesion and mechanical cues may direct differentiation of the cells. The chemical and/or mechanical cues provided may be based on the type(s) of polymer materials from which the hydrogel scaffold <NUM> is formed.

While some cell growth is ideal within the hydrogel scaffold <NUM>, it is preferable that tissue formation has not yet occurred before insertion of the implantable device <NUM> into the cavity <NUM> such that the cells <NUM> interact with native cells to form the new breast tissue. For example, once the implantable device <NUM> is inserted into the cavity <NUM>, some of the cells <NUM> may migrate out of the hydrogel scaffold <NUM> to other areas of the cavity <NUM>, and native cells may migrate into the hydrogel scaffold <NUM> to engage in intercellular communication. The migration occurring in and out of the hydrogel scaffold <NUM> may promote and accelerate breast tissue formation within the hydrogel scaffold <NUM> as well as other areas within the cavity <NUM>. The acceleration of the breast tissue formation may correspondingly accelerate the post-resection healing process. Over time, the hydrogel scaffold <NUM> may be absorbed by the patient's body.

<FIG> depicts an example process <NUM> for preparing a hydrogel scaffold with encapsulated cells. If a suspicious area within the breast is discovered through screening procedures, for example, a breast biopsy may be performed to remove a sample of breast tissue from the suspicious area for diagnostic evaluation at operation <NUM>. The sample of breast tissue removed during the breast biopsy may include the suspicious area, as well as portions of healthy breast tissue surrounding the suspicious area.

If a resection is determined to be necessary based on the diagnostic evaluation, the cells <NUM> to be encapsulated in the hydrogel scaffold <NUM> may be obtained from the portions of healthy breast tissue from the breast biopsy sample. For example, at operation <NUM>, tissue-specific cells may be isolated from the portions of healthy breast tissue. At operation <NUM>, the cells may be harvested and expanded in vitro to increase a number of cells to be encapsulated in the hydrogel scaffold <NUM> (e.g., encapsulated cells <NUM>).

At operation <NUM>, the hydrogel scaffold <NUM> may be prepared. For example, a hydrogel precursor solution may be prepared, and the hydrogel precursor solution may undergo gelation to form the hydrogel scaffold <NUM>. The hydrogel precursor solution may be comprised of one or more hydrophilic polymers, where the polymers may be natural, synthetic, or a hybrid of natural and synthetic. In some examples, the hydrogel scaffold <NUM> may be formed from one or more of pHEMA, PVP, PEGDA, and PVA, among other similar polymers. During gelation, the polymers may undergo physical or chemical crosslinking to form a 3D network of cross-linked, polymer chains that mimics a microenvironment of the breast, supporting cell growth. A type of crosslinking performed may be based on the type of polymers used to prepare the hydrogel precursor solution. Additionally, depending on the type of polymer selected and the crosslinking to be performed, additional chemical modifications may be made to the hydrogel precursor solution, such as the addition of cross-linking agents and/or initiators.

Prior to gelation, the cells <NUM> may be mixed into the hydrogel precursor solution (e.g., forming a precursor-cell solution) to enable even distribution of the cells <NUM> throughout an entirety of the hydrogel scaffold <NUM> upon gelation. Additionally, growth factors <NUM> may be incorporated in the precursor solution that stimulate growth of the cells <NUM>, among other functions. In some examples, the hydrogel precursor solution may also include a buffer solution to control a pH level of the hydrogel precursor solution.

Additionally, the hydrogel scaffold <NUM> may provide one or more of chemical and mechanical cues <NUM> for directing behavior of the cells <NUM> in order to mirror how the cells <NUM> would behave in the microenvironment present in the breast tissue. For example, chemical cues may indicate a site for cell adhesion and mechanical cues may direct differentiation of the cells <NUM>. The chemical and/or mechanical cues <NUM> provided may be based on the type(s) of polymer from which the hydrogel scaffold <NUM> is formed.

At operation <NUM>, the hydrogel scaffold <NUM> may be integrated with the frame <NUM> to form the implantable device <NUM>. The integration may occur prior to the gelation of the precursor-cell solution. In some examples, the precursor-cell solution may be placed within a receptacle, such as a petri dish or a well plate, among other similar receptacles. The frame <NUM> may then be positioned in the receptacle such that one or more portions of the frame <NUM> are at least partially exposed to the precursor-cell solution. Gelation may be initiated causing the hydrogel scaffold to at least partially surround the one or more portions of the frame <NUM>. In some examples, gelation may be initiated using photopolymerization (e.g., placing the hydrogel precursor solution under ultraviolet light). In other examples, gelation may be initiated by changes in pH or temperature, or ion addition, among other similar methods known to a person having ordinary skill in the art.

In one example, the frame <NUM> may be submerged within the precursor-cell solution such that the frame <NUM> is encapsulated in the hydrogel scaffold <NUM> upon gelation. In other examples, the frame <NUM> may have an at least partially open structure. The precursor-cell solution may be applied to (e.g., poured into) the open structure, and gelation may be initiated such that the hydrogel scaffold <NUM> is formed within the frame <NUM>.

Once the hydrogel scaffold <NUM> and the frame <NUM> have been integrated to form the implantable device, the implantable device <NUM> may then be inserted into the cavity <NUM> at operation <NUM>. The implantable device <NUM> may be inserted immediately following the removal of breast tissue that created the cavity <NUM>.

<FIG> depicts an example frame <NUM> integrated with a hydrogel scaffold <NUM> to form an implantable device <NUM>. The frame <NUM> may have an open structure, as illustrated in <FIG>. In other examples, the frame <NUM> may be a partially open structure or a closed structure. In some examples, for any structure type, one or more portions of the frame <NUM> may be placed or positioned in a hydrogel precursor solution that is contained within a receptacle, and gelation may be initiated to form the hydrogel scaffold <NUM> such that the one or more portions of the frame <NUM> are at least partially surrounded by the hydrogel scaffold <NUM>. In other examples, the frame <NUM> may serve as a mold (e.g., if the frame <NUM> is a partially open structure such as a hollow cone) or be positioned within a mold having a similar shape to the frame (e.g., if the frame <NUM> is an open structure such as a helix as illustrated in <FIG>). The hydrogel precursor solution may be poured into the open structure, and gelation may be initiated to form the hydrogel scaffold <NUM> within the frame <NUM>.

The frame <NUM> may be formed from a bioabsorbable material and provide temporary structural support within the cavity <NUM>. Due to the bioabsorbable nature of the hydrogel scaffold <NUM>, the hydrogel scaffold <NUM> at least partially surrounding the one or more portions of the frame <NUM> does not interfere with the absorption of the frame <NUM> by the body, even when the frame <NUM> is encapsulated in the hydrogel scaffold <NUM>. A rate at which the frame <NUM> absorbs may be based on a type of the bioabsorbable material. In some examples, the bioabsorbable material may be selected such that the frame <NUM> is absorbed at a faster or slower rate than the hydrogel scaffold <NUM>. In other examples, the bioabsorbable material may be selected such that the frame <NUM> is absorbed at a same rate as the hydrogel scaffold <NUM>.

A size and shape of the frame <NUM>, as well as structure, may be selected based at least in part on a size and shape of the cavity <NUM>. For example, a size of frame <NUM> may be slightly smaller than the size of the cavity <NUM> so that the implantable device <NUM> may fit within the cavity, but may otherwise be similar in size and shape of the cavity <NUM> to provide adequate structural support.

In some examples, the frame <NUM> may include a plurality of markers <NUM> spaced along one or more portions of the frame <NUM>. The markers <NUM> may be comprised of a non-bioabsorbable, radiopaque material such that the markers <NUM> remain at the site of resection for a prolonged period of time post-resection to enable identification of the site via imaging processes. In one example, the markers <NUM> may be comprised of titanium or other similar metal.

<FIG> depicts example frame configurations. The frame <NUM> may be formed in many different shapes and sizes. A size and shape of the frame <NUM>, as well as structure, may be selected based at least in part on a size and a shape of the cavity <NUM>. Additionally, in some examples, the size, shape, and structure selection for the frame <NUM> may be based on where growth of breast tissue initially occurs within the cavity <NUM>.

Example shapes include a 3D cross <NUM>, a 3D concave structure <NUM>, a solid or hollow cone <NUM>, a solid or hollow pyramid <NUM>, a spherical or elliptical structure <NUM>, and a 3D star <NUM>. In some examples, the shape of the frame <NUM> may yield an open structure, such as the helix shape illustrated in <FIG>. In other examples, the shape of the frame <NUM> may yield a partially open structure, such as the 3D concave structure <NUM>, the hollow cone <NUM> or the hollow pyramid <NUM>. In further examples, the shape of the frame <NUM> may yield a closed structure, such as the 3D cross <NUM>, the solid cone <NUM>, the solid pyramid <NUM>, the spherical or elliptical structure <NUM>, and the 3D star <NUM>.

The example shapes provided in the figures are for illustrative purposes only, and are not intended to be limiting. An alternatively shaped frame <NUM> may be integrated with the hydrogel scaffold <NUM> to form the implantable device <NUM>.

<FIG> depicts a method <NUM> to accelerate healing after a resection of tissue. At operation <NUM>, a hydrogel scaffold <NUM> with encapsulated cells <NUM> corresponding to a type of the tissue resected is prepared. In some examples, the type of tissue resected is breast tissue. The cells <NUM> may be healthy cells of a patient <NUM> undergoing the resection. For example, the cells <NUM> may be obtained from healthy breast tissue of the patient <NUM> removed during a biopsy performed for diagnostic evaluation of the breast tissue (e.g., to determine whether the resection was necessary). The cells may be obtained by isolating tissue-specific cells from the healthy breast tissue, harvesting and expanding the cells in vitro, and mixing the cells with a hydrogel precursor solution to form a precursor-cell solution. The precursor-cell solution may be transitioned into a semi-solid material using physical crosslinking or chemical crosslinking (e.g. via gelation) to form the hydrogel scaffold <NUM> after the frame <NUM> has been integrated, as described in operation <NUM>.

At operation <NUM>, the hydrogel scaffold <NUM> may be integrated with a frame <NUM> to form an implantable device <NUM>. A shape, size, and structure of the frame <NUM> may be selected based at least in part on a size and shape of a cavity <NUM> into which the implantable device <NUM> is to be inserted at optional operation <NUM>. The frame <NUM> may be bioabsorbable and include one or more non-bioabsorbable, radiopaque markers <NUM> spaced along one or more portions of the frame <NUM>. The one or more non-bioabsorbable, radiopaque markers can be made from any biocompatible, radio-opaque material (e.g., titanium, stainless steel, gold, or composite polymer materials) and may be attached to the portions of frame <NUM> using preformed holes in the frame into which the markers can be attached.

To integrate the hydrogel scaffold <NUM> with the frame <NUM>, the precursor-cell solution may be applied to one or more portions of the frame <NUM>, and gelation may be initiated. In some examples, the one or more portions of the frame <NUM> may be placed or positioned in the hydrogel precursor solution, which is contained within a receptacle, such as a petri dish or well plate, among other similar receptacles. Upon gelation, the one or more portions of the frame <NUM> may be at least partially surrounded by the hydrogel scaffold <NUM>. To encapsulate the frame <NUM> in the hydrogel scaffold <NUM>, the frame <NUM> may be submerged in the hydrogel precursor solution prior to gelation. In other examples, if the frame <NUM> has at least a partially open structure, the hydrogel precursor solution may be applied to the open structure, and gelation may be initiated to form the hydrogel scaffold <NUM>. Upon gelation, the hydrogel scaffold <NUM> may be formed within the frame <NUM>. In some examples, the integration of the hydrogel scaffold <NUM> and the frame <NUM> may be based on where growth of breast tissue initially occurs within the cavity <NUM>.

At optional operation <NUM>, the implantable device <NUM> may be inserted into a cavity <NUM> created by the resection. The bioabsorbable frame <NUM> may provide temporary structural support in the cavity <NUM> to reduce deformities in the look and appearance of the breast, while the encapsulated cells <NUM> within the bioabsorbable hydrogel scaffold <NUM> interact with native cells to facilitate new tissue formation within the hydrogel scaffold and other areas of the cavity. Additionally, the markers <NUM> may remain at a site of the resection for a prolonged period of time (e.g., remain after the hydrogel scaffold <NUM> and frame <NUM> have been absorbed) to enable identification of the site via imaging processes, which may be important for subsequent procedures and screenings.

In light of the foregoing, it should be appreciated that the present technology is able to accelerate healing post-resection using a hydrogel-based implantable device to facilitate tissue formation within a resection cavity. For example, the implantable device may include a hydrogel scaffold having healthy cells of the patient undergoing the resection encapsulated within that interact with native cells to facilitate new tissue formation within the hydrogel scaffold and other areas of the cavity. Additionally, the hydrogel scaffold may be integrated with a bioabsorbable frame to provide temporary structural support in the cavity while the tissue formation is being facilitated to reduce deformities in the look and appearance of the breast. The frame may also include non-bioabsorbable, radiopaque markers to enable identification of a site of the resection for subsequent procedures, screenings, or other imaging purposes.

The examples described herein may be employed using software, hardware, or a combination of software and hardware to implement and perform the systems and methods disclosed herein. Although specific devices have been recited throughout the disclosure as performing specific functions, one of skill in the art will appreciate that these devices are provided for illustrative purposes, and other devices may be employed to perform the functionality disclosed herein without departing from the scope of the disclosure.

Claim 1:
A method for preparing an implantable device to accelerate healing after a resection of tissue, the method comprising:
preparing a hydrogel precursor solution;
forming a hydrogel scaffold with encapsulated cells corresponding to a type of the tissue resected by initiating gelation of the hydrogel precursor solution; and
integrating the hydrogel scaffold with a frame to form an implantable device for insertion into a cavity created by the resection;
wherein integrating the hydrogel scaffold with the frame comprises:
applying the hydrogel precursor solution to the one or more portions of the frame; and
initiating the gelation of the hydrogel precursor solution applied to the one or more portions of the frame to form the hydrogel scaffold that at least partially surrounds one or more portions of the frame.