Hybrid hydrogel materials and methods of making same

Abstract

The present disclosure provides for a hydrogel composition comprising a polysaccharide and a synthetic polymer crosslinker, wherein the composition comprises one or more characteristics selected from the group consisting of: an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s; and a shear force of at least about 0.45 lbf.

Description

HYBRID HYDROGEL MATERIALS AND METHODS OF MAKING SAMECROSS-REFERENCE

[0001] This application claims benefit of U.S. Provisional Application 63 / 675,116, filed July 24, 2024, which is incorporated herein by reference in its entirety.BACKGROUND

[0002] Early detection of breast cancer and other types of cancer typically result in a higher survival rate. Despite a widely accepted standard of mammography screenings for breast cancer detection, there are many reasons that cancer is often not detected early. In particular, drawbacks of mammography include: limited performance among women with dense breast tissue, a high rate of “false alarms” that lead to unnecessary biopsies that are collectively expensive and result in emotional duress in patients, and low participation in breast screening, as a result of factors such as fear of radiation and discomfort. In particular, the mammography procedure involves compression of the breast tissue between parallel plates to increase the X-ray image quality by providing a more uniform tissue thickness and stabilizing the tissue. However, this compression is typically uncomfortable, or even painful.SUMMARY

[0003] The present disclosure provides for a hydrogel composition comprising a polysaccharide and a synthetic polymer crosslinker, wherein the composition comprises one or more characteristics selected from the group consisting of an ultrasound reflectivity of at most about -260 centibel (cB), a specific sound speed of about 1505 meters per second (m / s) to about 1535 m / s; and a shear force of at least about 0.45 pounds force (Ibf). In some embodiments, the hydrogel comprises two characteristics selected from the group consisting of an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s; and a shear force of at least about 0.45 Ibf. In some embodiments, the hydrogel comprises three characteristics selected from the group consisting of, an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s; and a shear force of at least about 0.45 Ibf. In some embodiments, the synthetic polymer is a synthetic polymer crosslinker. In some embodiments, the polysaccharide is a natural polysaccharide. In some embodiments, the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, and hyaluronic acid. In some embodiments, the natural polysaccharidecomprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, and agar. In some embodiments, the hydrogel composition comprises a natural polysaccharide and a synthetic polymer crosslinker. In some embodiments, the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, and hyaluronic acid. In some embodiments, the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, and agar. In some embodiments, the hydrogel composition comprises carrageenan and a synthetic polymer crosslinker. In some embodiments, the polysaccharide has a molecular weight of about 50,000 dalton (Da) to about 500,000 Da. In some embodiments, the polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 10: 1. In some embodiments, the polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 5: 1. In some embodiments, the polysaccharide is included at about 1 % w / w to about 10 % w / w of the crosslinker.

[0004] The present disclosure provides for a hydrogel composition comprising carrageenan and a synthetic polymer crosslinker. In some embodiments, the composition comprises one or more characteristics selected from the group consisting of: an ultrasound reflectivity of at most about -260 cB; a specific sound speed of about 1505 m / s to about 1535 m / s; and a shear force of at least about 0.45 Ibf. In some embodiments, the hydrogel comprises two characteristics selected from the group consisting of: an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s; and a shear force of at least about 0.45 Ibf. In some embodiments, the hydrogel comprises three characteristics selected from the group consisting of: an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s; and a shear force of at least about 0.45 Ibf. In some embodiments, the composition further comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, and hyaluronic acid. In some embodiments, the composition further comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, and agar. In some embodiments, the carrageenan has a molecular weight of about 50,000 Da to about 500,000 Da. In some embodiments, the carrageenan and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 10: 1. In some embodiments, the carrageenan and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 5: 1. In some embodiments, the carrageenan is included at about 1 % w / w to about 10 % w / w. In some embodiments, the synthetic polymer crosslinker is selected from the groupconsisting of polyethylene glycol) (PEG), PEG derivatives, poly(acrylamide) (PAM), polyvinyl alcohol (PVA), polylactic acid (PLA), and polycaprolactone (PCL). In some embodiments, the synthetic polymer crosslinker is selected from the group consisting of poly(ethylene glycol) (PEG) and PEG derivatives. In some embodiments, PEG derivatives are selected from the group consisting of polyethyleneglycol diacrylate (PEGDA), polyethyleneglycol methacrylate (PEGMA), ethyldiglycol acrylate (EDGA), and polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymers (e.g., Pluronics). In some embodiments, the hydrogel comprises an additional synthetic polymer crosslinker. In some embodiments, the synthetic polymer crosslinker is included at about 0.1 % w / w to about 5 % w / w. In some embodiments, the hydrogel comprises physical crosslinks. In some embodiments, the hydrogel comprises chemical crosslinks. In some embodiments, the hydrogel comprises both physical and chemical crosslinks. In some embodiments, the synthetic polymer crosslinker comprises polyethylene glycol, or a derivative thereof. In some embodiments, the polyethylene glycol has a molecular weight from about 300 Da to about 5000 Da. In some embodiments, the hydrogel has a specific sound speed of about 1505 m / s to about 1535 m / s. In some embodiments, the hydrogel has an ultrasonic reflectivity of at most about -260 cB. In some embodiments, the hydrogel has an ultrasonic reflectivity of about - 800 cB to about -260 cB. In some embodiments, the hydrogel has a shear force of at least about 0.45 Ibf. In some embodiments, the hydrogel has a shear force of about 0.45 Ibf to about 2.0 Ibf. In some embodiments, the hydrogel maintains at least about 90% of its original mass when submerged in an aqueous environment at about 30 °C to about 45 °C for at least about 5 minutes. In some embodiments, the hydrogel further comprises a second polysaccharide. In some embodiments, the hydrogel further comprises a bactericide. In some embodiments, the bactericide is phenol (e.g., sporocidin). In some embodiments, the bactericide is methylparaben. In some embodiments, the bactericide is included at about 0.01 % w / w to about 2 % w / w. In some embodiments, the bactericide is included at about 0.05 % w / w. In some embodiments, the hydrogel further comprises EDTA. In some embodiments, the EDTA is included at about 0.01 % w / w to about 0.1 % w / w. In some embodiments, the EDTA is included at about 0.025 % w / w.

[0005] In certain aspects of the present disclosure is a gel pad for use in an imaging system, the gel pad comprising the hydrogel composition of the present disclosure. In some embodiments, the imaging system is an ultrasound imaging system.

[0006] In other aspects of the present disclosure is an imaging system, wherein the imaging system comprises a tissue interface, wherein the tissue interface comprises a gel pad, whereinthe gel pad comprises the hydrogel composition of the present disclosure. In some embodiments, the imaging system is an ultrasound imaging system.

[0007] In some aspects of the present disclosure is a gel pad for use in an imaging system, wherein the gel pad comprises a hydrogel comprising a natural polysaccharide and a synthetic polymer crosslinker. In some embodiments, the imaging system is an ultrasound imaging system. In some embodiments, the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, and hyaluronic acid. In some embodiments, the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, and agar. In some embodiments, natural polysaccharide comprises carrageenan. In some embodiments, the natural polysaccharide has a molecular weight of about 50,000 Da to about 500,000 Da. In some embodiments, the natural polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 10: 1. In some embodiments, the natural polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 5: 1. In some embodiments, the natural polysaccharide is included at about 1 % w / w to about 10 % w / w. In some embodiments, the composition comprises one or more characteristics selected from the group consisting of: an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s, and a shear force of at least about 0.45 Ibf. In some embodiments, the hydrogel comprises two characteristics selected from the group consisting of: an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s, and a shear force of at least about 0.45 Ibf. In some embodiments, the hydrogel comprises three characteristics selected from the group consisting of: an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s, and a shear force of at least about 0.45 Ibf. In some embodiments, the synthetic polymer crosslinker is selected from the group consisting of polyethylene glycol) (PEG), PEG derivatives, poly(acrylamide) (PAM), PVA, PLA, and PCL. In some embodiments, the synthetic polymer crosslinker is selected from the group consisting of poly(ethylene glycol) (PEG) and PEG derivatives. In some embodiments, PEG derivatives are selected from the group consisting of PEGDA, EPGMA, EDGA, and Pluronics. In some embodiments, the hydrogel comprises an additional synthetic polymer crosslinker. In some embodiments, the synthetic polymer crosslinker is included at about 0.1 % w / w to about 5 % w / w. In some embodiments, the hydrogel comprises physical crosslinks. In some embodiments, the hydrogel comprises chemical crosslinks. In some embodiments, the hydrogel comprises both physical and chemicalcrosslinks. In some embodiments, the synthetic polymer crosslinker comprises polyethylene glycol, or a derivative thereof. In some embodiments, the polyethylene glycol has a molecular weight from about 300 Da to about 5000 Da. In some embodiments, the hydrogel has a specific sound speed of about 1505 m / s to about 1535 m / s. In some embodiments, the hydrogel has an ultrasonic reflectivity of at most about -260 cB. In some embodiments, the hydrogel has an ultrasonic reflectivity of about -800 cB to about -260 cB. In some embodiments, the hydrogel has a shear force of at least about 0.45 Ibf. In some embodiments, the hydrogel has a shear force of about 0.45 Ibf to about 2.0 Ibf. In some embodiments, the hydrogel maintains at least about 90% of its original mass when submerged in an aqueous environment at about 30 °C to about 45 °C for at least about 5 minutes. In some embodiments, the hydrogel further comprises a second polysaccharide. In some embodiments, the hydrogel further comprises a bactericide. In some embodiments, the bactericide is sporocidin or methylparaben. In some embodiments, the bactericide is sporocidin. In some embodiments, the bactericide is methylparaben. In some embodiments, the bactericide is included at about 0.01 % w / w to about 2 % w / w. In some embodiments, the bactericide is included at about 0.05 % w / w. In some embodiments, the hydrogel further comprises EDTA. In some embodiments, the EDTA is included at about 0.01 % w / w to about 0.1 % w / w. In some embodiments, the EDTA is included at about 0.025 % w / w. In some embodiments, the gel pad comprises a center aperture configured to fluidically couple to a low-pressure source of a tissue positioning system. In some embodiments, a vacuum circuit is configured to be closed or completed when a tissue volume makes contact and seals the center aperture of the gel pad. In some embodiments, the gel pad is configured to releasably couple to the tissue positioning system. In some embodiments, the gel pad comprises a frustoconical portion configured to receive a tissue volume. In some embodiments, the tissue volume is a breast. In some embodiments, the frustoconical portion is configured to receive an areola of the breast. In some embodiments, the gel pad is configured to receive the tissue volume without obstructing ultrasound energy directed radially through the gel pad from an ultrasound imaging apparatus.

[0008] In some aspects of the present disclosure is an imaging system, wherein the imaging system comprises a tissue interface, wherein the tissue interface comprises the gel pad of the present disclosure. In some embodiments, the imaging system is an ultrasound imaging system. In some embodiments, the gel pad is configured to replaceably attach to an upper surface of an interface plate of a tissue positioning system of the imaging system. In some embodiments, the gel pad comprises a center aperture which fluidly couples to a low pressuresource of the tissue positioning system via at least one perforation in a center region of the interface plate when the gel pad is replaceably attached to the upper surface of the interface plate. In some embodiments, the gel pad is configured to receive a tissue volume without obstructing ultrasound energy directed radially through the gel pad from an ultrasound imaging apparatus coupled to the tissue positioning system. In some embodiments, a vacuum circuit is configured to be closed or completed when the tissue volume makes contact and seals a center aperture of the gel pad. In some embodiments, the interface plate is mounted on a support column of the tissue positioning system. In some embodiments, the gel pad is releasable from the interface plate without disassembly of the interface plate from the support column.INCORPORATION BY REFERENCE

[0009] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and / or take precedence over any such contradictory material.BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The novel features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein) of which:

[0011] Figs. 1 A - 1C illustrate a breast tomography system of the type that can employ the breast shaping device and tissue restrictor ring of the present disclosure.

[0012] Figs. 2A - 2C illustrate a first embodiment of a breast shaping device constructed in accordance with the principles of the present disclosure.

[0013] Figs. 3 A and 3B are detailed views of a gel pad and low pressure connector segment used in the breast shaping device of Figs. 2A - 2C. Fig. 3 A is a top perspective view with a portion cut-away, and Fig. 3B is a bottom perspective view with the low pressure connector segment removed.

[0014] Figs. 3C and 3D illustrate a specific embodiment of an interface pad having a barcode or an RFID label which allows tracking of individual gel pads for a variety of purposes.

[0015] Figs. 3E and 3F illustrate a specific embodiment of an interface plate for removably attaching the interface pad of Figs. 3C and 3D.

[0016] Figs. 4A and 4B are detailed views of a telescoping support for the gel pad and low pressure connector used in the breast shaping device if Figs. 2A - 2C, shown in a vertically extended configuration in Figs 4A and vertically retracted configuration in Fig. 4B.

[0017] Figs. 5A and 5B illustrate an alternative gel pad and low pressure connector configuration having a flat upper surface to enhance cylindrical shaping of the breast.

[0018] Figs. 6A - 6C illustrate a tissue restrictor ring constructed in accordance with the principles of the present disclosure. Fig. 6A shows the tissue restrictor ring itself. Fig. 6B shows placement of the tissue restrictor ring on a ring imaging transducer relative to a telescoping support supporting the alternative gel pad and low pressure connector configuration of Figs. 5 A and 5B. Fig. 6C shows a variation of the telescoping support supporting with a shaper cup intended to more fully cylindricalize smaller breasts.

[0019] Figs. 7A - 7G illustrate the steps of using an assembly of the tissue restrictor ring, ring imaging transducer, and improved breast shaping outcome with alternate gel pad of Figs. 6A and 6B in a breast tomography system of the type shown in Figs. 1 A - 1C to image a breast.

[0020] Figs. 8A - 8D are breast tomography images taken using a breast tomography system having a breast shaping device in accordance with the principles of the methods of the present disclosure.DETAILED DESCRIPTION

[0021] The following description of preferred embodiments of the disclosure is not intended to limit the disclosure to these preferred embodiments, but rather to enable any person skilled in the art to make and use this disclosure.

[0022] A relatively new ultrasound imaging technique, referred to as ultrasound tomography, promises to be a practical alternative to mammography without tissue compression and many other drawbacks. With ultrasound tomography, the patient lies on a support surface in a prone position with a breast depending through an opening in the surface into a water bath. A ring or other ultrasonic transducer assembly is then scanned vertically to acquire the image data to be analyzed. Some of the proposed ultrasound tomography systems employ a magnetic or other device to capture the nipple region of the breast to extend and stabilize thebreast during imaging. While at least partially effective, such prior breast extending apparatus can be uncomfortable, can deform the breast into a conical shape which is not optimum for imaging, do not provide repeatable shaping of the breast, and cannot accommodate breast of differing sizes.

[0023] For these reasons, it would be desirable to provide systems and methods for performing breast and other ultrasound tomography which provide improved positioning of the breast or other tissue body, improved patient comfort, which accommodate size variations of the breasts and other tissue bodies among different patients, and which allow scans to be performed in a repeatable manner in order to monitor changes in a tissue over time in an individual patient. At least some of these objectives will be met by the disclosures described and claimed herein.

[0024] A hydrogel gel pad as disclosed herein offers unique advantages over current systems. By strategically combining natural and synthetic materials, hybrid hydrogels can leverage their respective strengths and mitigate weaknesses, offering tailored solutions for diverse biomedical applications. Hybrid hydrogels have been pioneered to help overcome the inherent limitations of both natural and synthetic polymers, which include relatively deficient mechanical properties and immunogenic risks in the case of natural materials and limited biocompatibility and biodegradability in the case of synthetic materials.

[0025] Referring to Figs. 1 A to 1C, a breast tomography system 100 of the type that can employ the breast shaping device and the tissue restrictor ring of the present disclosure comprises an ultrasonic imaging ring array 102 including a plurality of ultrasound emitters 102 and ultrasonic receivers 106. The ultrasonic imaging ring array 102 may be configured to surround a breast or other tissue volume so that the plurality of ultrasound emitters 102 emits acoustic waveforms 112 toward the volume of tissue. The plurality of ultrasound receivers 106 is configured to receive acoustic waveforms scattered by the volume of tissue, and a processor 108 is configured to generate a tomographic images based on the received acoustic waveforms as described in commonly owned patent nos. 11,071,520; 10,743,837;10,076,304; 18 / 703,746; 10,285,667; 10,123,770; and 9,763,641, the full disclosures of which are incorporated herein by reference. The system 100 can further include a display 110 on which the acoustic data and / or generated image rendering can be displayed, such as to a medical practitioner and / or the patient. The ultrasonic imaging ring array 102 is configured to scan vertically to produce an image of the breast B which depends through an opening or aperture 116 (see Figs 7 A - 7C) in a table 118 having an upper surface for supporting patient P in a prone position. The breast is immersed in water or other ultrasonically transmissiveliquid held in a reservoir enclosure 120 located beneath the table. As described in greater detail below, the breast shaping device and the tissue restrictor ring of the present disclosure are located within the reservoir enclosure 120.

[0026] As shown in Figs. 2A - 2C, a breast or other tissue shaping device (BSD) 130 for positioning a tissue body includes a toroidal pad 132 having an opening 134 for receiving a target region on a tissue body, such as a nipple region N on a breast B. A low-pressure or “suction” source 136 is coupled to the toroidal pad 132 through an interior of, or interior passage within, an extendable / retractable supporting column 138, which is typically a telescoping column including an upper chamber or segment 138a, a middle segment 138b, and a lower segmentl38c. While three segments have been found to be a useful number, it will be appreciated that as few as two or as many as five or more segments might also find use. Other non-telescoping designs, such as accordion designs, could also be employed. In all cases, however, the supporting column should be sufficiently sealed so that the low pressure source coupled to the column can be transmitted into the interior of the column and to the toroidal pad 132.

[0027] The BSD 130 functions to comfortably immobilize a breast B or other tissue body of a patient, such that the tissue body can be properly scanned e.g., for monitoring, for medical diagnostics, etc. Additionally or alternatively, the BSD 130 can pull breast or other the tissue body away from the body of the patient, e.g., the breast can be pulled away from chest wall of the patient, thereby enabling a larger percentage of the tissue body to be scanned, e.g., for lesions. The BSD 130 can additionally or alternatively function to properly position a breast or other tissue body within a scanning region of an imaging system, thereby increasing efficiency in processing of image data or other data. The BSD 130 can additionally or alternatively function to stretch the tissue body, thereby reducing a thickness of tissue structures (e.g., skin) in order to provide an improved scan of the tissue body. Finally, the BSD 130 can provide a sanitary means for positioning the tissue body, for a scanning system that is used for multiple patients.

[0028] In a specific example, the BSD 130 immobilizes a volume of breast tissue to enable scanning of smaller breasts by elongating and contouring the breast relative to the chest wall to reduce glancing angle effects in relation to incident waves on a tissue surface, enable detection of legions closer to the chest wall by pulling a higher percentage of breast tissue away from the chest wall, improving centering of the breast in a scanning region of interest to reduce computational load in post-processing of scan data ,e.g., with sound speed measurements, with attenuation measurements, with reflection measurements, with time offlight measurements, with density measurements, with stiffness measurements, etc., and induce elongation (e.g., “cylindricalize”) of the volume of breast tissue, thereby inducing a reduction in thickness of skin of the breast to improve scan data.

[0029] The BSD 130 is preferably configured to be used within a volume of an ultrasonically transmissive scanning medium (e.g., water) retained within the reservoir enclosure 120of the ultrasound tomography system 100. The BSD 130 properly immobilizes the breast or other tissue body within the scanning medium so that the tissue body can be properly scanned without disturbance caused by tissue buoyancy. As such, the system can interface with embodiments, variations, and examples of one or more elements of the system for providing scanning medium described in U.S. App. No. 14 / 811,316, entitled “System for Providing Scanning Medium”, and filed on 28-JUL-2015, which is herein incorporated in its entirety by this reference. Additionally or alternatively, the system 100 can interface with embodiments, variations, and examples of one or more elements of the patient interface system configured to support the body of a patient during a scan, as described in U.S. App. No. 14 / 208,181, entitled “Patient Interface System” which has been previously incorporated herein by reference. However, the BSD 130 for positioning a tissue body described herein can additionally or alternatively interface with any other suitable elements / systems.

[0030] As shown in Figs. 3 A and 3B, the toroidal pad 132 is formed from a compliant material, such as a gel as described elsewhere herein, and a bottom surface of the toroidal pad 132 is typically attached to an interface plate 140 with a plurality of holes or perforations 142 therein. The opening 134 is configured to receive a target region of the tissue body, such as the region surrounding the nipple N of the breast B, as seen in Figs. 1 A - 1C. The opening 134 will usually have a funnel or conical portion formed in the upper surface of the toroidal pad 132 and functions to comfortably receive and attach the tissue body during a scan. The funnel or conical portion of the toroidal pad is configured such that a vacuum circuit (as described elsewhere) is closed or completed when the target region of the tissue body, such as the region surrounding the nipple, makes contact and seals the opening 134.

[0031] While preferably toroidal, the pad 132 could have other, non-toroidal geometries, such as ovoid, polygonal, and the like. The pad 132 will have a thickness, a top surface, a bottom surface, and opening 134 through the thickness that allows negative pressure to be transmitted to tissue engaged against the top surface and / or received within the opening. Preferably, the dimensions of the pad 132 (in combination with the material properties) provide a pad with a suitable buoyant behavior for scanning applications in a scanning medium used. For instance, the pad 132 can be configured such that it does not float inscanning medium in an undesired manner. The interface plate can have mechanical features that further prevent the pad from floating off in certain scanning mediums (e.g., water), as described with respect to Figs. 3E and 3F. In one variation, the footprint of the pad 132 is circular; however, the footprint can alternatively have any other suitable shape (e.g., ellipsoidal, rectangular, polygonal, amorphous, etc.). In one variation, the top surface is approximately frustoconical (e.g., shaped as an inverted funnel) in order to comfortably support a portion of the tissue body. The top surface can alternatively have any other suitable profile (e.g., a profile that is complementary to or matched to a specific tissue body). In another variation, the top surface is substantially planar (although a slight degree of convexity or concavity is acceptable) with low pressure plenums about the periphery. The shape of the bottom surface is less critical, usually being substantially planar; however, in alternative variations, the bottom surface can have any other suitable profile. In one variation, an opening in the bottom surface to connect the low pressure sources is circular and centrally located (e.g., concentric with the inverted funnel of the top surface or configured to branch into plenums about the periphery of the top surface); however, in alternative variations, the opening can alternatively have any other suitable cross section (e.g., ellipsoidal, rectangular, polygonal, amorphous, etc.) and / or be non-centrally located relative to the top surface of the pad 132. Furthermore, the pad 132 and / or the opening may not have constant cross sections through the thickness of the pad 132. For instance, the pad 132 can taper in profile from its bottom surface to its top surface, and / or the opening can have a different cross section at the bottom surface in comparison to the cross section of the opening at the top surface, in order to accommodate the reference region of the tissue body and enable immobilization of the tissue body comfortably, by way of the negative pressure generated by the low pressure subsystem 136.

[0032] In specific examples, the pad 132 has a cylindrical outer surface and has an outer diameter from 0.5 cm to 3 cm; the top surface is an inverted frustoconical surface having a base angle a (Fig. 3C) from 5° to 85°, the thickness of the pad is from 1 cm to 5 cm, the bottom surface is substantially planar, and the opening is a circular opening through the thickness of the pad, with a constant cross section having a diameter from 0.5cm to 3 cm. While one opening is described above, the pad 132 can alternatively have multiple openings in order to immobilize the tissue body at multiple points on the surface of the tissue body. In specific examples, the pad 132 is preferably configured as a “one-size-fits-all” element that accommodates a wide variety of breast morphologies; however, the pad 132 can additionallyor alternatively be customized to the morphology of each patient being scanned, or to have a fixed number of configurations that can accommodate a wide range of patient morphologies (e.g., A cup, B cup, etc.).

[0033] In relation to the top surface and the opening, the reference or target region of the tissue body is preferably a most extreme region of the tissue body (e.g. a region that protrudes or otherwise provides an attachment location such as a nipple on a breast), in the orientation in which the patient interfaces with the pad 132. In the context of a volume of breast tissue, the reference region can be a most-anterior region of the breast (e.g., the nipple region), such that the nipple region of the breast is retained at the opening of the pad 132 to properly immobilize the breast of a patient who is in a prone position. However, the target or reference region can additionally or alternatively be any other suitable region of a tissue body that facilitates immobilization of the tissue body.

[0034] The pad 132 is preferably composed of a material having a high degree of acoustic transparency, such that the pad does not interfere with proper scanning of regions of the tissue body within the pad 132. As such, in some variations, the material composition of the pad 132 can thus provide closer focusing at the interface between the tissue body and the pad 132 (e.g., in ultrasound imaging applications). In variations, the pad 132 is composed of a polymeric material (e.g., plastic, hydrogel, etc.), and in specific examples can include a material composed of one or more of: agar, guar bean, and carrageenan; however, the pad 132 can additionally or alternatively comprise any other suitable material (e.g., natural material, synthetic material). For instance, the pad 132 can be composed of a synthetic polymer (e.g., polyurethane) processed to have desired acoustic or other characteristics. The material is preferably substantially stiff, but compliant in supporting the tissue body comfortably and facilitates the completion of the vacuum circuit; however, the material can alternatively have any other suitable properties (e.g., hardness, stiffness, porosity, transparency, thermal characteristics, optical characteristics, electrical conductivity characteristics, rheological characteristics, etc.).

[0035] Furthermore, the pad 132 can be configured for single-use applications (e.g., to provide a sanitary option) and / or can be configured to controllably degrade (e.g., in a manner that does not affect fluid handling components of the scanning system) after a certain number of uses in order to prevent repeated uses of the pad 132. However, the pad 132 can alternatively be configured to be reusable. In a specific example, the pad can comprise a blend of agar, guar bean, and carrageenan, and be configured to have a specific gravity of1.06 (e.g., slightly heavier than water); however, the pad 132 can have any other suitable composition.

[0036] As shown in Figs. 3C and 3D, the pad may comprise labeling for identification, inventory control, and encoding other types of information. In particular, the pad 132 may have external labeling, such as Id, 2d, and 3d optical labels 133, e.g. barcoding. Such external optical labels may be read by conventional handheld or other scanners, and the scanners could be incorporated as part of the tissue fixating system. Alternatively, the labeling may be provided by radiofrequency identification tags or similar remote electronic scanning means. As RFID tags do not need to be optically scanned, they may be embedded into the pad itself as shown at 135 in Fig. 35. RFID’s may also be scanned by handheld or other scanners.

[0037] The information encoded in a barcode or RFID may include information intended to control use of the replaceable pad, such as to limit the usage to a single patient per gel pad, to ensure that the gel pad is within a useful shelf life, to provide information back to the system manufacturer on utilization patterns, to send a signal to the system manufacturer that could be used for periodic and preventative system maintenance, to send a signal to the system manufacturer to restock inventories at the facility.

[0038] The interface plate 140 functions to allow the pad 132 to be properly seated at a receiving portion of a low pressure system as described below. In more detail, the interface plate can allow the pad 132 and the opening 134 of the pad 132 to be properly aligned and positioned in relation to the segments 138a, 138b, and 138c of the support column 138 for transmission of a low pressure from source 136, thereby allowing the target region of the tissue body to be drawn into the opening of the pad 132.

[0039] Referring now to Figs, 3E and 3F, an alternative interface plate 141 may include a plurality of upwardly projecting anchors 143 formed on its upper surface rather than a continuous peripheral rim of material, as shown in other embodiments herein. Elimination of the rim improves penetration of the ultrasound signal to the tip of the nipple thus improving the image obtained. In this embodiment, the anchors 143 retain the gel pad from floating away and / or sliding off, while minimizing the material that would occlude the ultrasound signals from penetrating the entirety of the breast, particularly in the nipple and retro-areolar region. Small horizontal pins 145 penetrate the gel pad to prevent the gel pad from floating off the platform during scanning, where small patient movements could potentially dislodge the gel pad. The pins 145 are held in posts 147 received in slots 149 formed in the upper surface of the interface plate 141.

[0040] Referring to Figs. 4A and 4B, the lower segmentl38c of the extendable / retractable support column 138 of the BSD 130 is mounted on or through a bottom plate 146 of the reservoir enclosure 120 of the tomography system 100. The lower segmentl38c is connected to the low pressure source 136 (Fig. 2 A) by a connector 148. The middle segment 138b of the extendable / retractable support column 138 is translatable relative to the lower segment 138a, and the upper segment 138c is translatable relative to the middle segment 138b. During operation, the toroidal pad 132 preferably translates with the upper segment 138a to a position that comfortably engages the tissue body, and the target region of the tissue body is preferably retained at the opening 134 of the toroidal pad 132 by way of the negative pressure generated by the low pressure system 136, such that the tissue body is properly immobilized during scanning (e.g., using a tomography system). The low pressure system 136 thus functions to both (1) generate the negative pressure for retaining the tissue body in position and (2) comfortably support the tissue body at an appropriate position during scanning.

[0041] The segments 138a, 138b, and 138c of the column support 138 are preferably substantially cylindrical, having a wall with an appropriate thickness and a longitudinal axis that is parallel to and concentrically aligned with the opening 134 of the pad 132 in assembled system. Furthermore, the upper segment 138a is preferably oriented vertically, such that the support column 138 can properly immobilize a tissue body (e.g., volume of breast tissue) for a patient who is interfacing with the BSD 130 in a prone position.However, in alternative variations, the segments 138a, 13b, and 138c can have any other suitable shapes (e.g., non-cylindrical, polygonal, prismatic, etc.) and / or orientation that provides proper relative motion between the segments.

[0042] The column 138 including segments 138a, 138b, and 138c can be composed of a polymeric material (e.g., a plastic), a metallic material, a composite material, a ceramic material, a glass, and / or any other suitable material. Some or all of the segments 138a, 138b, and 138c are preferably configured to support the negative pressures and / or positive pressures implemented in the BSD 130 without deformation. The segments, however, can alternatively have any other suitable composition and / or be configured with any other suitable mechanical properties. In some cases, one or more of the segments 138a, 138b, and 138c can include stops configured to define limits of the relative range of motion of the segments. Additionally or alternatively, the expansion range of the segments can be defined in any other suitable manner, as described in more detail below.

[0043] The lower segment 138c preferably has a base region and a superior region, wherein the base region is coupled to the base plate 146 of an imaging tank in the reservoir enclosure120 associated with the tomography system 100, and the superior region is open to interface with the middle segment 138b and upper segment 138a. Preferably, the low pressure source 136 connects with the lower segment 138c via the connector 148 near the base, but the low pressure source 136 can additionally or alternatively interface with any of the segments at any level in the column. Still alternatively, the low pressure source 136 can interface with an internal portion of the supporting column 138 or can be connected to the openingl34 in the pad 132 by a separate conduit.

[0044] Preferably, the low pressure source 136 can generate a negative pressure of up to approximately 200 mmHg in order to retain the tissue body in a comfortable manner (and as regulated by the U.S. Food and Drug Administration, in some embodiments). In one variation, the low pressure source can provide a negative pressure over a range that includes the range between 100 and 125 mmHg, which, in a specific embodiment, can properly immobilize the tissue body without causing discomfort. However, the low pressure source 136 can alternatively generate pressures over any other suitable range, and can be configured to generate negative pressures and / or positive pressures. Furthermore, the low pressure source 136 can be configured to generate appropriate pressures during different phases of scanning (e.g., in relation to patient preparation, initialization, mid-scan, scan completion, etc.).

[0045] For instance, in some variations, the low pressure source 136 can provide a higher negative pressure (e.g., 125 mmHg) during initialization phases when the tissue body of the patient is first being immobilized; however, once the tissue body is properly immobilized and scanning initiates, the pressure value can be reduced (e.g., to 50 mmHg), thereby increasing comfort while still allowing the tissue body to be effectively retained in position. Finally, when scanning is completed, the negative pressure can be eliminated, or even reversed (e.g., to expel the tissue body from the low pressure subsystem). In relation to varying the low pressure during operation of the system, the low pressure established by the low pressure source 136 can be adjusted manually (e.g., using an external control module). However, the pressure established by the low pressure source 136 additionally or alternatively can be adjusted automatically (e.g., by using pressure sensors that enable coordination between the low pressure source 136 and phases of scanning established by related systems, by using a mechanism that automatically reduces or increases pressure during scanning phases as described in more detail below, etc.).

[0046] The low pressure source 136 can be controlled with any suitable controller and, as such, can have an associated safety mechanism such that a maximum pressure value is neverexceeded. In a specific example, the maximum pressure can be 200 mmHg; however, in alternative variations, the maximum pressure can be any other suitable pressure value. The low pressure source 136 can additionally or alternatively include a manual shutoff valve and / or any other suitable shutoff system.

[0047] The column segments 138a, 138b, and 138c are configured to be translatable relative to each other in a telescoping manner and the contiguous interiors of the segments coupled the opening 134 of the pad 132 to the low pressure source 136. In some variations, the telescoping structure can also function as a portion of a mechanism that automatically adjusts low pressures provided by the low pressure source 136, during different phases of scanning / patient orientation relative to the system. The segments 138a, 138b, and 138c are preferably configured to form a sufficiently tight sliding fit such that the interface between the segments prevents a significant low pressure leak from occurring, while still allowing sliding motion between the first and the second chambers 130, 140 to occur.

[0048] Preferably, the segments 138a, 138b, and 138c are concentrically aligned, such that each segment can provide a telescoping mechanism that allows the tissue body to be properly supported, at the appropriate depth within the scanning tank during scanning.

[0049] In one variation the support column 138 includes a coil spring 150 which is in extension and which pushes the segments 138a, 138b, and 138c apart so that the column is in its fully extended configuration, as shown in Figs 2A and 4A. The spring 150 also serves to smooth out oscillations resulting from floatation of the pad 132 in water or other ultrasonically transmissive medium. The spring 150 can also provide an appropriate counterforce to facilitate proper latching of the pad 132 to the coupling interface 150 and / or of the tissue body to the pad 132. In smoothing out oscillations, the spring 150 can thus contribute to mass-spring-damper behavior of the low pressure subsystem 136 in interfacing with the tissue volume. In variations, the spring has a spring constant from 0.5 to 10 N / cm; however, the spring 150 can alternatively have any other suitable spring constant. As such, in relation to dynamically supporting the tissue body at a suitable depth within the scanning tank, the spring can allow the segments 138a, 138b, and 138c to passively provide support, while reducing oscillations when the breast or other tissue body interfaces with the pad 132, until the tissue body reaches a natural resting state within the scanning tank.

[0050] In similar, but alternative variations, the spring can be replaced with magnetic elements, wherein opposing polarities of the magnetic elements can provide spring-like behavior between the column segments 138a, 138b, and 138c. Still alternatively, the segments 138a, 138b, and 138c can be configured to translate relative to each other with theassistance of an actuator (e.g., a hydraulic actuator, a linear actuator, etc.) that allows the first and the support column 138 to have expanded and contracted configurations. The support column can alternatively be configured to have expanded and contractions in any other suitable manner.

[0051] As mentioned above, in some variations, the segments 138a, 138b, and 138c can also function as a portion of a mechanism that automatically adjusts low pressures provided by the low pressure source 136, during different phases of scanning / patient orientation relative to the system. In one such variation, the middle segment 138b its down stroke, can include appropriate cutout portions that cut off the inlet of the low pressure source 136 into the first chamber 130, thereby automatically reducing the negative pressure as the tissue body settles into the position in which it is immobilized. Additionally or alternatively, in another variation, motion of one segment relative to another segment can open and / or close a valve associated with the low pressure source 136, in order to modulate pressure. Other variations of modulating pressure can, however, operate in any other suitable manner.

[0052] In variations, the pad 132 can translate with the upper segment 138a as low pressure generated within the column retracts the column and pulls down the target region of the tissue body, such as the nipple region N of the breast B, as shown in Figs, 2B (where the nipple is first attached, reducing pressure within the column) and Fig. 2C where the breast is pulled down to a position that comfortably supports the tissue body for scanning. For breast scanning, this pulling cylindricalizes the volume of breast tissue, and draws breast tissue away from the chest wall, such that the tissue body is properly immobilized during scanning (e.g., using a tomography system).

[0053] Referring now to Fig. 5 A and 5B, an alternative interface pad 156 has a flat or planar upper surface 158 which is typically circular with a single hole 161 in the center of the surface. The hole is intended to accommodate a patient’s breast nipple as will be described in detail below. In contrast to toroidal pad 132 described previously which draws the low pressure through a central passage, the interface pad 156 has four annularly placed peripheral plenums 166 to distribute a low pressure about the surface’s periphery. This arrangement allows a larger target region surrounding the patient’s nipple to be secured to the flat surface which in turn improves the cylindricalization of the breast. The peripheral plenums provide improved attached to the peri-areolar region of the breast. In contrast, the smaller low pressure funnel of toroidal pad 132 will shape the breast in a more conical configuration which may be less desirable for overall breast imaging. In some instances, however, theconical breast presentation may allow better visualization of the sub-areolar regions for masses underlying the nipple, e.g., to detect papillomas and other cancerous lesions.

[0054] As best seen in Fig. 5B, each of the peripheral plenums 160 is connected to a lower opening 170 by curved connecting channels which are formed in between an outer shell 162 and a dome-shaped insert 164. The interface 156 may thus be molded from any of the polymers described previously in a simple, two-part molding process where the outer shell 162 and insert 164 may thereafter be joined by adhesives, ultrasonic welding, or other conventional techniques. Interface pad 156 may be connected to an expandable / retractable column 138 in the same manner as was described for toroidal pad 132.

[0055] Referring now to Fig. 6 A and 6B, a restrictor ring or plate 172 may be placed over and attached to the ultrasonic ring imaging array 102 in order to displace breast tissue as the transducer is vertically scanned over the breast, as will be described in greater detail below. The restrictor ring 172 will have an inner aperture or opening 174 which has dimensions which are smaller than those of the inside of the imaging array 102, thus creating an “overhang” or “offset” to push tissue away from the active inner surface of the array. Typically, the restrictor ring 172 will provide an overhang of at least 1 cm, and typical dimensions for both the restrictor ring and the imaging array are set forth in Table 1 below.TABLE 1

[0056] The restrictor ring 172 will be relatively stiff so that it will not bend or deform when engaging the breast tissue. It will also typically have a relatively thin profile, usually being from 2 to 3 mm thick, to minimize any deleterious effect on imaging. In some cases, the restrictor ring 172 may be made from materials, such as Delrin® polymer, to reduce out-of- plane scattering. The interior opening 174 of the ring 172 may be circular but in many embodiments will be ovoid or tear-shaped with the typical dimensions given in Table 1. Tomography systems 100 may be provided with an inventory of differently sized restrictor platesl72 corresponding to different breast sizes. In this way, an imaging system can be optimized for many women with differing anatomies.

[0057] Fig. 6C shows an alternative breast shaper concept where a cylindrical cup 182 is secured to an upper surface of a connector disc 180 which in turn is supported on an extendable / retractable support column 138. The shaper cup 182 may have particular benefit for women with smaller volume breast tissue (e.g., cup size A), whereby even a restrictor ring 172 with the smallest inner diameter (w ) and the peripheral suction alternative gel pad (figure 5A / B) would still lead to a conical overall transition from the chest wall to the peri- areolar region. Therefore, shaper cup 182 could virtually encircle nearly all breast tissue of a smaller breast, engage the entire breast with the gentle suction and elongate the breast upon retraction, while providing near-complete cylindricalization of all available breast tissue. This embodiment could also be envisioned for larger breasts as needed. The shaper cup 182 includes an upper portion 184 having a diameter in the range from 10 cm to 20 cm, where the dimensions of the ultrasonic ring imaging array 102 and the restrictor ring 172 are generally in the ranges set forth in Table 1. A smaller transition region 186 is connected directly to the connector disc 180 so that low pressure induced in the column 138, typically by a recirculating water or other media flow, is transferred to an interior of the upper portion 184. In this way, the region of the breast B surrounding the nipple N can be drawn into the upper portion 184 where the walls of the cup 182 will cylindricalize the breast for optimized imaging, intervention, and the like. The cup 182 will preferably be formed from an ultrasonically transparent material when ultrasonic imaging is being used.

[0058] Referring now to Figs. 7A through 7G, a breast tomography system employing both the tissue shaping device and the breast restrictor ring of the present disclosure will be described. As shown in Fig. 7A, the interface pad 156 is initially supported on the column 138 in its vertically extended position maintained by the spring force of coil spring 150. A low pressure is maintained in the interior of support column by a circulating fluid flow 138 maintained by a pump 136 which draws the water or other ultrasonically transmissive medium downwardly through the peripheral plenums 160. As the patient lowers her breast B through the opening 116 in the table 118, as shown in Fig. 7B, the nipple N is received in the center hole 161 of the flat upper surface 158. As the patient continues to lower her breast, the breast tissue is drawn against the flat surface by the reduced pressure created by the fluid flying through the peripheral plenums 160 until the front region of the breast surrounding the nipple N is flattened against the flat surface 158 of interface pad 156, as shown in Fig. 7C.

[0059] Once the breast B is flattened against the flat surface 158 of the interface pad 156, the pressure within the interior of the support column 138 will be lowered, causing a force which acts against spring 150 which causes the column to vertically retract or collapse, as shown inFig. 7D. The force supplied by the pump 136 against the breast B can be controlled in many ways, and the breast will be lowered and elongated by an amount proper to optimize imaging, as shown in Fig. 7D.

[0060] Once the breast has been properly positioned, the ring imaging array 102 and the restrictor ring 174 will be raised to scan the length of the breast as shown in Figs. 7E through 7G. In Fig 7E, the circumference of the breast is such that the interior edges of the restrictor ring do not contact the breast. As the assembly of the transducer 102 and ring 172 continues to be raised, as shown in Fig. 7F, the interior edge of the ring 172 will begin to contact the breast and displace the breast away from the interior of the transducer ring 102. As the assembly of the imaging array 102 and restrictor ring 174 rises further, as shown in Fig. 7G, the interior edge of the restrictor ring 174 will significantly displace the breast tissue inwardly, avoiding interference with the imaging function of the array 102.

[0061] Example images generated with an ultrasonic tomography system equipped with a BSD of the present disclosure are shown in Figs. 8A-8D.Hydrogel

[0062] Hydrogels represent a class of high water content polymers with physical or chemical crosslinks. Their physical properties are similar to soft tissues. Cross linking is a stabilization process in polymer chemistry which leads to multidimensional extension of polymeric chain resulting in network structure. Cross-link is a bond which links one polymer chain to another. Cross linking can change a polymer from a ‘liquid’ form into ‘solid’ or ‘gel’ by restricting the ability of movement. Hydrogels are three-dimensional networks formed by hydrophilic polymers through chemical cross-linking (covalent bond, ionic bond) or physical crosslinking (hydrogen bond, van der Waals force, physical entanglement). They can swell in water and retain a certain shape while absorbing a large quantity of water.Natural polymers

[0063] Natural polymers, which are formed from photosynthesis or a biochemical reaction in the natural world or extracted from natural products, may be useful skeletons for the fabrication of hydrogels because of their diversified properties such as their biocompatibility, biodegradability, and environmental friendliness. Hydrogels based on natural polymers such as alginate, starch, cellulose, chitosan, gelatin, collagen, hyaluronic acid, and so on show good degradability, biocompatibility, nontoxic degradation products, good flexibility similar to natural tissue, and are in natural abundance, which endow them with widespreadapplications in medicinal fields, for instance, as carriers for drug delivery, wound dressing for wound healing, substrates for cell culture, scaffolds for tissue regeneration, and so on.

[0064] For example, carrageenan is a natural linear polysaccharide obtained from red seaweed that consists of a-1,3 and P-l,4-glycosidic bonded D-galactose and 3,6-anhydro- galactose. Carrageenan dissolves in water, yielding a thick solution whose viscosity is contingent on the concentration, temperature, and molecular weight. It undergoes depolymerization through acid-catalyzed hydrolysis. Structurally, carrageenan holds glycosidic linkages between galactose and anhydrogalactose with a twisted helical assembly, where every second unit of d-galactose and 3,6-anhydro-d-galactose attached through the a- 1,3 and P-1,4 glycoside linkages. Carrageenans may be classified based on the degree of substitution on their free hydroxyl groups. Substitutions may involve either the addition of ester sulfate or the presence of the 3,6-anhydride on the 4-linked residue or both.

[0065] Carrageenan-based hydrogels may be prepared by the methods of thermoreversible gelation, ionic cross-linking, ultraviolet (UV) cross-linking, and dual cross-linking. Various forms of carrageenan-based hydrogels can be obtained by these methods and those disclosed elsewhere herein.Synthetic polymers

[0066] Synthetic polymers used in hydrogels preparation can be classified into three main types: non-biodegradable, biodegradable, and bioactive polymers. The term “biodegradable” is art-recognized, and includes polymers, hydrogels, compositions, and formulations that are intended to degrade through biological processes. The term "degradable " is art-recognized, and includes polymers, hydrogels, compositions, and formulations that are capable of being degraded (break down to oligomers or monomers). The term “bioactive” is art-recognized, and includes polymers, hydrogels, compositions, and formulations that elicit specific biological responses within living systems. Examples of synthetic polymers include: poly (lactic acid) (PLA), poly (s-caprolactone) (PCL), poly(glycolic acid) (PGA) and copolymers, poly (ethylene glycol) (PEG) and poly(vinyl alcohol) (PVA) to produce biodegradable hydrogels. Hydrogels may include vinyl monomers like 2-hydroxyethyl methacrylate (HEMA), N-isopropyl acrylamide (NIPAAm), 2-hydroxypropyl methacrylate (HPMA), acrylamide (AAm), acrylic acid (AAc) or macromers, methoxyl poly(ethylene glycol) (PEG), monoacrylates (methoxy polyethylene glycol methacrylate (mPEGMA) or poly ethylene glycol methacrylate (PEGMA)), and diacrylates (polyethylene glycol diacrylate (PEGDA)),ethylene glycol diacrylate (EGDA), and polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymers (e.g., Pluronic®), etc.

[0067] Synthetic polymers such as poly(ethylene glycol) (PEG), poly(acrylamide) (PAM), PVA, PLA, and PCL offer diverse structures and controlled degradation, making them advantageous for various biomedical applications. Synthetic polymers offer a customizable mechanical stability but lack cell adhesion sites, requiring chemical modifications for enhanced cellular interactions. A strategic approach involves combining synthetic polymers with natural counterparts to create hybrid hydrogels with diverse properties, inspired by nature and suitable for versatile applications. Poly(ethylene glycol) (PEG) features hydrophilic -OH groups in its non-degradable, biocompatible chain.

[0068] In some embodiments, the PEG is a primary crosslinker of biocompatible polymers in the hydrogels. In other embodiments, co-crosslinkers can be present, although PEG may be the majority crosslinker, with co-crosslinkers present at minor concentrations (e.g., less than 20 wt. %, less than 10 wt. %, less than 5 wt. % or less than 1 wt. % based on the total weight of crosslinker).

[0069] For example, PEG 400 (polyethylene glycol 400) is a low-molecular-weight grade of polyethylene glycol. It is a clear, colorless, viscous liquid. Due in part to its low toxicity, PEG 400 may be used in a variety of pharmaceutical formulations. Poly(ethylene glycol) (PEG) is a synthetic, hydrophilic, biocompatible polymer with widespread use in biomedical and other applications.Hybrid Natural and Synthetic Hydrogels

[0070] By strategically combining natural and synthetic materials, hybrid hydrogels can leverage their respective strengths and mitigate weaknesses, offering tailored solutions for diverse biomedical applications. Hybrid hydrogels may help overcome the inherent limitations of both natural and synthetic polymers, which include relatively deficient mechanical properties and immunogenic risks in the case of natural materials and limited biocompatibility and biodegradability in the case of synthetic materials.

[0071] Hybrid hydrogels disclosed herein exhibit a remarkable performance, combining robust mechanical properties with favorable biocompatibility and degradability. For instance, natural hydrogels may often suffer from mechanical weakness and rapid degradation by endogenous enzymes. Similarly, natural hydrogels may suffer from insufficient physical strength, prompting the development of hybrid hydrogels comprising natural and synthetic materials.

[0072] For example, the chemical structure of the polymer may allow for more or less swelling by affecting the crosslinking densities and the hydrophilic potential. Crosslinking density, the number of crosslinks between the polymeric backbone, can increase with more crosslinker and lower molecular weight crosslinker and tightens the network, allowing less swelling and liquid uptake and often a stronger material (higher tensile strength).

[0073] Hydrogel material disclosed herein may combine both natural and synthetic polymers together while retaining the bioactive properties of natural polymers accompanying with good mechanical features, durability, and controlled biodegradability of synthetic polymers. For example, the biological properties of polyethylene glycol (PEG) may comprise excellent biocompatibility, biodegradability, elastomeric nature, and antifouling nature. In another example, the combination of polyvinylpyrrolidone (PVP), kappa-carrageenan, and polyethylene glycol (PEG) using gamma radiation for crosslinking may show reduced bioadhesion energy, high tensile strength, flexibility, and longer shelf life. In some cases, PEG as a blended material may enhance the physicochemical properties of natural polymers. In some cases, PEG may impart sufficient mechanical features and biocompatibility and a natural material (e.g., carrageenan or other materials disclosed herein) provides hydrogel nature with adequate exudate absorption and maintains stability in a moist environment.

[0074] Disclosed herein are gel formulations based on hybrid natural and synthetic crosslinking polymers. Such a hybrid gel pad may have the advantage over natural only or synthetic only crosslinked polymers for this use. Advantageous properties may include specific sound speed (1505-1535 m / s), low ultrasonic reflectivity to avoid artifacts in the image, durability in body temperature aqueous environments for extended time as measured by shear force, and combinations thereof. Gel formulations of the present disclosure may be integrated in to gel pads as disclosed herein and imaging systems as disclosed herein, for example, as illustrated in any of Figs. 1 A to 7G.

[0075] In an aspect of the present disclosure is a hydrogel composition comprising a polysaccharide and a synthetic polymer, wherein the hydrogel has one or more characteristics selected from the group consisting of an ultrasound reflectivity of at most about -260 centibel (cB), a specific sound speed of about 1505 meters per second (m / s) to about 1535 m / s; and a shear force of at least about 0.45 pounds force (Ibf).

[0076] In some embodiments, the hydrogel comprises two characteristics selected from the group consisting of an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s, and a shear force of at least about 0.45 Ibf.

[0077] In some embodiments, the hydrogel comprises an ultrasound reflectivity of at most about -260 cB, a specific sound speed of about 1505 m / s to about 1535 m / s, and a shear force of at least about 0.45 Ibf.

[0078] In an aspect of the present disclosure is a hydrogel composition comprising a natural polysaccharide and a synthetic polymer crosslinker.

[0079] In an aspect of the present disclosure is a hydrogel composition comprising carrageenan and a synthetic polymer crosslinker.

[0080] In some embodiments, the polysaccharide comprises carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, hyaluronic acid, or a combination thereof. In some embodiments, the polysaccharide comprises carrageenan, konjac, xanthan, guar, agar, or a combination thereof. In some embodiments, the polysaccharide comprises carrageenan, konjac, or a combination thereof. In some embodiments, the polysaccharide comprises carrageenan. In some embodiments, the polysaccharide is selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, hyaluronic acid, and a combination thereof. In some embodiments, the polysaccharide is selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, and a combination thereof. In some embodiments, the polysaccharide is selected from the group consisting of carrageenan, konjac, and a combination thereof. The polysaccharide may be naturally occurring or synthetically produced. The polysaccharide may be synthetically modified. Polysaccharides have several reactive groups that are available for chemical modification. These include the hydroxyl (OH), carboxyl (COOH), and acetamido (COCH3) groups. In some embodiments, the polysaccharide is a natural polysaccharide. In some embodiments, a natural polysaccharide refers to a polysaccharide as found in nature. In some embodiments, a natural polysaccharide refers to a polysaccharide without chemical modification.

[0081] Chitosan is a linear polysaccharide composed of randomly distributed P-linked D- glucosamine and N-acetyl-D-glucosamine monomers. Xanthan gum is composed of pentasaccharide repeat units, comprising glucose, mannose, and glucuronic acid in the molar ratio of about 2.0:2.0: 1.0. Carrageenan is a linear sulfated polysaccharide that are extracted from red edible seaweeds. There are three main varieties of carrageenan, which differ in their degree of sulfation: kappa-carrageenan has one sulfate group per disaccharide; iota- carrageenan has two sulfates per disaccharide; lambda carrageenan has three sulfates per disaccharide. All carrageenans are high-molecular weight polysaccharides made up of repeating galactose units and 3,6-anhydrogalactose, both sulfated and non-sulfated. The units are joined by alternating a-1,3 and P-1,4 glycosidic linkages. Guar gum is a polysaccharidecomposed of the sugars galactose and mannose: the backbone is a linear chain of P 1,4-linked mannose residues to which galactose residues are 1,6-linked at every second mannose, forming short side-branches. Guar gum is primarily the ground endosperm of guar beans. Alginate may also be referred to in the literature as algin or alginic acid. Alginate is an anionic polysaccharide derived from brown algae and is a linear copolymer with homopolymeric blocks of (l-4)-linked P-D-mannuronate residues and a-L-guluronate residues.

[0082] In some embodiments, the polysaccharide has a molecular weight of about 50,000 dalton (Da) to about 500,000 Da. In some embodiments, the polysaccharide has a molecular weight of about 50 kilodalton (kDa) to about 750 kDa. In some embodiments, the polysaccharide has a molecular weight of about 50 kDa to about 100 kDa, about 50 kDa to about 150 kDa, about 50 kDa to about 200 kDa, about 50 kDa to about 250 kDa, about 50 kDa to about 300 kDa, about 50 kDa to about 400 kDa, about 50 kDa to about 500 kDa, about 50 kDa to about 750 kDa, about 100 kDa to about 150 kDa, about 100 kDa to about 200 kDa, about 100 kDa to about 250 kDa, about 100 kDa to about 300 kDa, about 100 kDa to about 400 kDa, about 100 kDa to about 500 kDa, about 100 kDa to about 750 kDa, about 150 kDa to about 200 kDa, about 150 kDa to about 250 kDa, about 150 kDa to about 300 kDa, about 150 kDa to about 400 kDa, about 150 kDa to about 500 kDa, about 150 kDa to about 750 kDa, about 200 kDa to about 250 kDa, about 200 kDa to about 300 kDa, about 200 kDa to about 400 kDa, about 200 kDa to about 500 kDa, about 200 kDa to about 750 kDa, about 250 kDa to about 300 kDa, about 250 kDa to about 400 kDa, about 250 kDa to about 500 kDa, about 250 kDa to about 750 kDa, about 300 kDa to about 400 kDa, about 300 kDa to about 500 kDa, about 300 kDa to about 750 kDa, about 400 kDa to about 500 kDa, about 400 kDa to about 750 kDa, or about 500 kDa to about 750 kDa. In some embodiments, the polysaccharide has a molecular weight of about 50 kDa, about 100 kDa, about 150 kDa, about 200 kDa, about 250 kDa, about 300 kDa, about 400 kDa, about 500 kDa, or about 750 kDa. In some embodiments, the polysaccharide has a molecular weight of at least about 50 kDa, about 100 kDa, about 150 kDa, about 200 kDa, about 250 kDa, about 300 kDa, about 400 kDa, or about 500 kDa. In some embodiments, the polysaccharide has a molecular weight of at most about 100 kDa, about 150 kDa, about 200 kDa, about 250 kDa, about 300 kDa, about 400 kDa, about 500 kDa, or about 750 kDa.

[0083] In some embodiments, the synthetic polymer comprises poly(ethylene glycol), poly(ethylene glycol) derivatives, poly(ethylene oxide), poly(vinyl alcohol), poly(acrylamide), poly(lactic acid), poly(caprolactone), poly(allyl alcohol),poly(vinylpyrrolidone), poly(alkylene oxides), poly(oxyethylated polyols), poly(ethyleneimine), poly(allylamine), poly(vinyl amine), poly(aminoacids), poly(ethyloxazoline), poly(ethylene oxide)-co-poly(propylene oxide) block copolymers, polysaccharides, carbohydrates, oligopeptides, and polypeptides. In some embodiments, the synthetic polymer comprises polyethylene glycol), poly(ethylene glycol) derivatives, poly(vinyl alcohol), poly(acrylamide), poly(lactic acid), poly(caprolactone), or a combination thereof. In some embodiments, the synthetic polymer comprises poly(ethylene glycol), poly(ethylene glycol) derivatives, poly(vinyl alcohol), poly(acrylamide), or a combination thereof. In some embodiments, the synthetic polymer comprises poly(ethylene glycol), poly(ethylene glycol) derivatives, or a combination thereof. The polymer chains may include homo-, co-, or terpolymers of the above materials, in a linear, multi-arm, dendrimer, or branched form, and derivatives thereof. These materials may crosslink into a hydrogel through the formation of covalent bonds through the action of chemically active groups that are present on the polysaccharide and the counterpart synthetic polymer crosslinker. In some embodiments, the synthetic polymer has one or more reactive moieties. In some embodiments, the one or more reactive moieties comprise -OH, -NH2, -SH, aldehyde, acrylate, methacrylate, acrylamide, methacrylamide, allyl, or derivatives thereof.

[0084] In some embodiments, the synthetic polymer crosslinker comprises polyethylene glycol, or a derivative thereof. In some embodiments, the polyethylene glycol or a derivative thereof has a molecular weight of about 300 Da to about 10,000 Da. In some embodiments, the polyethylene glycol or a derivative thereof has a molecular weight of about 300 Da to about 10,000 Da. In some embodiments, the polyethylene glycol or a derivative thereof has a molecular weight of about 300 Da to about 500 Da, about 300 Da to about 1,000 Da, about 300 Da to about 2,000 Da, about 300 Da to about 4,000 Da, about 300 Da to about 5,000 Da, about 300 Da to about 7,000 Da, about 300 Da to about 8,000 Da, about 300 Da to about 10,000 Da, about 500 Da to about 1,000 Da, about 500 Da to about 2,000 Da, about 500 Da to about 4,000 Da, about 500 Da to about 5,000 Da, about 500 Da to about 7,000 Da, about 500 Da to about 8,000 Da, about 500 Da to about 10,000 Da, about 1,000 Da to about 2,000 Da, about 1,000 Da to about 4,000 Da, about 1,000 Da to about 5,000 Da, about 1,000 Da to about 7,000 Da, about 1,000 Da to about 8,000 Da, about 1,000 Da to about 10,000 Da, about 2,000 Da to about 4,000 Da, about 2,000 Da to about 5,000 Da, about 2,000 Da to about 7,000 Da, about 2,000 Da to about 8,000 Da, about 2,000 Da to about 10,000 Da, about 4,000 Da to about 5,000 Da, about 4,000 Da to about 7,000 Da, about 4,000 Da to about 8,000 Da, about 4,000 Da to about 10,000 Da, about 5,000 Da to about 7,000 Da, about 5,000 Da toabout 8,000 Da, about 5,000 Da to about 10,000 Da, about 7,000 Da to about 8,000 Da, about 7,000 Da to about 10,000 Da, or about 8,000 Da to about 10,000 Da. In some embodiments, the polyethylene glycol or a derivative thereof has a molecular weight of about 300 Da, about 500 Da, about 1,000 Da, about 2,000 Da, about 4,000 Da, about 5,000 Da, about 7,000 Da, about 8,000 Da, or about 10,000 Da. In some embodiments, the polyethylene glycol or a derivative thereof has a molecular weight of at least about 300 Da, about 500 Da, about 1,000 Da, about 2,000 Da, about 4,000 Da, about 5,000 Da, about 7,000 Da, or about 8,000 Da. In some embodiments, the polyethylene glycol or a derivative thereof has a molecular weight of at most about 500 Da, about 1,000 Da, about 2,000 Da, about 4,000 Da, about 5,000 Da, about 7,000 Da, about 8,000 Da, or about 10,000 Da.

[0085] In some embodiments, the polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 10: 1. In some embodiments, the polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1, 2: 1, 3: 1, 4: 1, 5: 1, 6: 1, 7: 1, 8: 1, 9: 1, or 10: 1. In some embodiments, the polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of at least about 1 : 1, 2: 1, 3 : 1, 4: 1, 5:1, 6: 1, 7: 1, 8: 1, 9: 1, or 10: 1. In some embodiments, the polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of at most about 10: 1, 9: 1, 8: 1, 7: 1, 6: 1, 5: 1, 4: 1, 3: 1, 2: 1, or 1 : 1. In some embodiments, the polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 5: 1.

[0086] In some embodiments, the polysaccharide is included at about 1 % w / w to about 10 % w / w. In some embodiments, the polysaccharide is included at about 1 % w / w to about 15 % w / w. In some embodiments, the polysaccharide is included at about 1 % w / w to about 2 % w / w, about 1 % w / w to about 3 % w / w, about 1 % w / w to about 4 % w / w, about 1 % w / w to about 5 % w / w, about 1 % w / w to about 6 % w / w, about 1 % w / w to about 7 % w / w, about 1 % w / w to about 8 % w / w, about 1 % w / w to about 9 % w / w, about 1 % w / w to about 10 % w / w, about 1 % w / w to about 15 % w / w, about 2 % w / w to about 3 % w / w, about 2 % w / w to about 4 % w / w, about 2 % w / w to about 5 % w / w, about 2 % w / w to about 6 % w / w, about 2 % w / w to about 7 % w / w, about 2 % w / w to about 8 % w / w, about 2 % w / w to about 9 % w / w, about 2 % w / w to about 10 % w / w, about 2 % w / w to about 15 % w / w, about 3 % w / w to about 4 % w / w, about 3 % w / w to about 5 % w / w, about 3 % w / w to about 6 % w / w, about3 % w / w to about 7 % w / w, about 3 % w / w to about 8 % w / w, about 3 % w / w to about 9 % w / w, about 3 % w / w to about 10 % w / w, about 3 % w / w to about 15 % w / w, about 4 % w / w to about 5 % w / w, about 4 % w / w to about 6 % w / w, about 4 % w / w to about 7 % w / w, about4 % w / w to about 8 % w / w, about 4 % w / w to about 9 % w / w, about 4 % w / w to about 10 %w / w, about 4 % w / w to about 15 % w / w, about 5 % w / w to about 6 % w / w, about 5 % w / w to about 7 % w / w, about 5 % w / w to about 8 % w / w, about 5 % w / w to about 9 % w / w, about 5 % w / w to about 10 % w / w, about 5 % w / w to about 15 % w / w, about 6 % w / w to about 7 % w / w, about 6 % w / w to about 8 % w / w, about 6 % w / w to about 9 % w / w, about 6 % w / w to about 10 % w / w, about 6 % w / w to about 15 % w / w, about 7 % w / w to about 8 % w / w, about 7 % w / w to about 9 % w / w, about 7 % w / w to about 10 % w / w, about 7 % w / w to about 15 % w / w, about 8 % w / w to about 9 % w / w, about 8 % w / w to about 10 % w / w, about 8 % w / w to about 15 % w / w, about 9 % w / w to about 10 % w / w, about 9 % w / w to about 15 % w / w, or about 10 % w / w to about 15 % w / w. In some embodiments, the polysaccharide is included at about 1 % w / w, about 2 % w / w, about 3 % w / w, about 4 % w / w, about 5 % w / w, about 6 % w / w, about 7 % w / w, about 8 % w / w, about 9 % w / w, about 10 % w / w, or about 15 % w / w. In some embodiments, the polysaccharide is included at least about 1 % w / w, about 2 % w / w, about 3 % w / w, about 4 % w / w, about 5 % w / w, about 6 % w / w, about 7 % w / w, about 8 % w / w, about 9 % w / w, or about 10 % w / w. In some embodiments, the polysaccharide is included at most about 2 % w / w, about 3 % w / w, about 4 % w / w, about 5 % w / w, about 6 % w / w, about 7 % w / w, about 8 % w / w, about 9 % w / w, about 10 % w / w, or about 15 % w / w.

[0087] In some embodiments, the synthetic polymer crosslinker is included at about 0.1 % w / w to about 5 % w / w. In some embodiments, the synthetic polymer crosslinker is included at about 0.1 % w / w to about 7.5 % w / w. In some embodiments, the synthetic polymer crosslinker is included at about 0.1 % w / w to about 0.5 % w / w, about 0.1 % w / w to about 1 % w / w, about 0.1 % w / w to about 2 % w / w, about 0.1 % w / w to about 3 % w / w, about 0.1 % w / w to about 4 % w / w, about 0.1 % w / w to about 5 % w / w, about 0.1 % w / w to about 7.5 % w / w, about 0.5 % w / w to about 1 % w / w, about 0.5 % w / w to about 2 % w / w, about 0.5 % w / w to about 3 % w / w, about 0.5 % w / w to about 4 % w / w, about 0.5 % w / w to about 5 % w / w, about 0.5 % w / w to about 7.5 % w / w, about 1 % w / w to about 2 % w / w, about 1 % w / w to about 3 % w / w, about 1 % w / w to about 4 % w / w, about 1 % w / w to about 5 % w / w, about 1 % w / w to about 7.5 % w / w, about 2 % w / w to about 3 % w / w, about 2 % w / w to about 4 % w / w, about 2 % w / w to about 5 % w / w, about 2 % w / w to about 7.5 % w / w, about 3 % w / w to about 4 % w / w, about 3 % w / w to about 5 % w / w, about 3 % w / w to about 7.5 % w / w, about 4 % w / w to about 5 % w / w, about 4 % w / w to about 7.5 % w / w, or about 5 % w / w to about 7.5 % w / w. In some embodiments, the synthetic polymer crosslinker is included at about 0.1 % w / w, about 0.5 % w / w, about 1 % w / w, about 2 % w / w, about 3 % w / w, about 4 % w / w, about 5 % w / w, or about 7.5 % w / w. In some embodiments, the synthetic polymer crosslinker is included at least about 0.1 % w / w, about 0.5 % w / w, about 1 % w / w, about 2 %w / w, about 3 % w / w, about 4 % w / w, or about 5 % w / w. In some embodiments, the synthetic polymer crosslinker is included at most about 0.5 % w / w, about 1 % w / w, about 2 % w / w, about 3 % w / w, about 4 % w / w, about 5 % w / w, or about 7.5 % w / w.

[0088] In some embodiments, the hydrogel comprises a bactericide. In some embodiments, the bactericide is phenol. In some embodiments, the bactericide is Sporicidin or methylparaben. In some embodiments, the bactericide is Sporicidin. In some embodiments, the bactericide is methylparaben. In some embodiments, the hydrogel comprises phenol. In some embodiments, the hydrogel comprises Sporicidin. In some embodiments, the hydrogel comprises methylparaben.

[0089] In some embodiments, the hydrogel comprises Ethylenediaminetetraacetic acid (EDTA). In some embodiments, EDTA is included at about 0.01 % w / w to about 0.1 % w / w. In some embodiments, EDTA is included at about 0.025 % w / w. In some embodiments, EDTA is included at about 0.01 % w / w to about 0.5 % w / w. In some embodiments, EDTA is included at about 0.01 % w / w to about 0.025 % w / w, about 0.01 % w / w to about 0.05 % w / w, about 0.01 % w / w to about 0.075 % w / w, about 0.01 % w / w to about 0.1 % w / w, about 0.01 % w / w to about 0.25 % w / w, about 0.01 % w / w to about 0.5 % w / w, about 0.025 % w / w to about 0.05 % w / w, about 0.025 % w / w to about 0.075 % w / w, about 0.025 % w / w to about 0.1 % w / w, about 0.025 % w / w to about 0.25 % w / w, about 0.025 % w / w to about 0.5 % w / w, about 0.05 % w / w to about 0.075 % w / w, about 0.05 % w / w to about 0.1 % w / w, about 0.05 % w / w to about 0.25 % w / w, about 0.05 % w / w to about 0.5 % w / w, about 0.075 % w / w to about 0.1 % w / w, about 0.075 % w / w to about 0.25 % w / w, about 0.075 % w / w to about 0.5 % w / w, about 0.1 % w / w to about 0.25 % w / w, about 0.1 % w / w to about 0.5 % w / w, or about 0.25 % w / w to about 0.5 % w / w. In some embodiments, EDTA is included at about 0.01 % w / w, about 0.025 % w / w, about 0.05 % w / w, about 0.075 % w / w, about 0.1 % w / w, about 0.25 % w / w, or about 0.5 % w / w. In some embodiments, EDTA is included at least about 0.01 % w / w, about 0.025 % w / w, about 0.05 % w / w, about 0.075 % w / w, about 0.1 % w / w, or about 0.25 % w / w. In some embodiments, EDTA is included at most about 0.025 % w / w, about 0.05 % w / w, about 0.075 % w / w, about 0.1 % w / w, about 0.25 % w / w, or about 0.5 % w / w.

[0090] In some embodiments, the hydrogel comprises a specific sound speed of about 1505 m / s to about 1535 m / s. In some embodiments, the hydrogel comprises a specific sound speed of about 1,505 m / s to about 1,535 m / s. In some embodiments, the hydrogel comprises a specific sound speed of about 1,505 m / s to about 1,510 m / s, about 1,505 m / s to about 1,515 m / s, about 1,505 m / s to about 1,520 m / s, about 1,505 m / s to about 1,525 m / s, about 1,505 m / sto about 1,530 m / s, about 1,505 m / s to about 1,535 m / s, about 1,510 m / s to about 1,515 m / s, about 1,510 m / s to about 1,520 m / s, about 1,510 m / s to about 1,525 m / s, about 1,510 m / s to about 1,530 m / s, about 1,510 m / s to about 1,535 m / s, about 1,515 m / s to about 1,520 m / s, about 1,515 m / s to about 1,525 m / s, about 1,515 m / s to about 1,530 m / s, about 1,515 m / s to about 1,535 m / s, about 1,520 m / s to about 1,525 m / s, about 1,520 m / s to about 1,530 m / s, about 1,520 m / s to about 1,535 m / s, about 1,525 m / s to about 1,530 m / s, about 1,525 m / s to about 1,535 m / s, or about 1,530 m / s to about 1,535 m / s. In some embodiments, the hydrogel comprises a specific sound speed of about 1,505 m / s, about 1,510 m / s, about 1,515 m / s, about 1,520 m / s, about 1,525 m / s, about 1,530 m / s, or about 1,535 m / s. In some embodiments, the hydrogel comprises a specific sound speed of at least about 1,505 m / s, about 1,510 m / s, about 1,515 m / s, about 1,520 m / s, about 1,525 m / s, or about 1,530 m / s. In some embodiments, the hydrogel comprises a specific sound speed of at most about 1,510 m / s, about 1,515 m / s, about 1,520 m / s, about 1,525 m / s, about 1,530 m / s, or about 1,535 m / s.

[0091] In some embodiments, the hydrogel comprises physical crosslinks. In some embodiments, the hydrogel comprises chemical crosslinks. The crosslinking may include hydrophobic interactions, charge interactions, polyelectrolyte complexes, physical mixtures, and hydrogen bonding, stereocomplexation, supramolecular chemistry, covalent crosslinking, or interpenetrating networks. In some embodiments, the physical crosslinks are reversible.

[0092] In some embodiments, the hydrogel comprises an ultrasonic reflectivity of at most about -260 cB. In some embodiments, the hydrogel comprises an ultrasonic reflectivity of about -800 cB to about -260 cB. In some embodiments, the hydrogel comprises an ultrasonic reflectivity of about -800 cB to about -700 cB, about -800 cB to about -600 cB, about -800 cB to about -500 cB, about -800 cB to about -400 cB, about -800 cB to about -300 cB, about - 800 cB to about -260 cB, about -700 cB to about -600 cB, about -700 cB to about -500 cB, about -700 cB to about -400 cB, about -700 cB to about -300 cB, about -700 cB to about -260 cB, about -600 cB to about -500 cB, about -600 cB to about -400 cB, about -600 cB to about - 300 cB, about -600 cB to about -260 cB, about -500 cB to about -400 cB, about -500 cB to about -300 cB, about -500 cB to about -260 cb cB about -400 cB to about -300 cB, about - 400 cB to about -260 cB, or about -300 cB to about -260 cB. In some embodiments, the hydrogel comprises an ultrasonic reflectivity of about -800 cB, about -700 cB, about -600 cB, about -500 cB, about -400 cB, about -300 cB, or about -260 cB. In some embodiments, the hydrogel comprises an ultrasonic reflectivity of at least about -800 cB, about -700 cB, about - 600 cB, about -500 cB, about -400 cB, or about -300 cB. In some embodiments, the hydrogelcomprises an ultrasonic reflectivity of at most about -700 cB, about -600 cB, about -500 cB, about -400 cB, about -300 cB, or about -260 cB.

[0093] In some embodiments, the hydrogel comprises a shear force of at least about 0.45 Ibf. In some embodiments, the hydrogel comprises a shear force of about 0.45 Ibf to about 2 Ibf. In some embodiments, the hydrogel comprises a shear force of about 0.45 Ibf to about 0.5 Ibf, about 0.45 Ibf to about 0.6 Ibf, about 0.45 Ibf to about 0.7 Ibf, about 0.45 Ibf to about 0.8 Ibf, about 0.45 Ibf to about 0.9 Ibf, about 0.45 Ibf to about 1 Ibf, about 0.45 Ibf to about 1.2 Ibf, about 0.45 Ibf to about 1.4 Ibf, about 0.45 Ibf to about 1.6 Ibf, about 0.45 Ibf to about 2 Ibf, about 0.5 Ibf to about 0.6 Ibf, about 0.5 Ibf to about 0.7 Ibf, about 0.5 Ibf to about 0.8 Ibf, about 0.5 Ibf to about 0.9 Ibf, about 0.5 Ibf to about 1 Ibf, about 0.5 Ibf to about 1.2 Ibf, about 0.5 Ibf to about 1.4 Ibf, about 0.5 Ibf to about 1.6 Ibf, about 0.5 Ibf to about 2 Ibf, about 0.6 Ibf to about 0.7 Ibf, about 0.6 Ibf to about 0.8 Ibf, about 0.6 Ibf to about 0.9 Ibf, about 0.6 Ibf to about 1 Ibf, about 0.6 Ibf to about 1.2 Ibf, about 0.6 Ibf to about 1.4 Ibf, about 0.6 Ibf to about 1.6 Ibf, about 0.6 Ibf to about 2 Ibf, about 0.7 Ibf to about 0.8 Ibf, about 0.7 Ibf to about 0.9 Ibf, about 0.7 Ibf to about 1 Ibf, about 0.7 Ibf to about 1.2 Ibf, about 0.7 Ibf to about 1.4 Ibf, about 0.7 Ibf to about 1.6 Ibf, about 0.7 Ibf to about 2 Ibf, about 0.8 Ibf to about 0.9 Ibf, about 0.8 Ibf to about 1 Ibf, about 0.8 Ibf to about 1.2 Ibf, about 0.8 Ibf to about 1.4 Ibf, about 0.8 Ibf to about 1.6 Ibf, about 0.8 Ibf to about 2 Ibf, about 0.9 Ibf to about 1 Ibf, about 0.9 Ibf to about 1.2 Ibf, about 0.9 Ibf to about 1.4 Ibf, about 0.9 Ibf to about 1.6 Ibf, about 0.9 Ibf to about 2 Ibf, about 1 Ibf to about 1.2 Ibf, about 1 Ibf to about 1.4 Ibf, about 1 Ibf to about 1.6 Ibf, about 1 Ibf to about 2 Ibf, about 1.2 Ibf to about 1.4 Ibf, about 1.2 Ibf to about 1.6 Ibf, about 1.2 Ibf to about 2 Ibf, about 1.4 Ibf to about 1.6 Ibf, about 1.4 Ibf to about 2 Ibf, or about 1.6 Ibf to about 2 Ibf. In some embodiments, the hydrogel comprises a shear force of about 0.45 Ibf, about 0.5 Ibf, about 0.6 Ibf, about 0.7 Ibf, about 0.8 Ibf, about 0.9 Ibf, about 1 Ibf, about 1.2 Ibf, about 1.4 Ibf, about 1.6 Ibf, or about 2 Ibf. In some embodiments, the hydrogel comprises a shear force of at least about 0.45 Ibf, about 0.5 Ibf, about 0.6 Ibf, about 0.7 Ibf, about 0.8 Ibf, about 0.9 Ibf, about 1 Ibf, about 1.2 Ibf, about 1.4 Ibf, or about 1.6 Ibf. In some embodiments, the hydrogel comprises a shear force of at most about 0.5 Ibf, about 0.6 Ibf, about 0.7 Ibf, about 0.8 Ibf, about 0.9 Ibf, about 1 Ibf, about 1.2 Ibf, about 1.4 Ibf, about 1.6 Ibf, or about 2 Ibf.

[0094] In some embodiments, the hydrogel maintains at least about 90% of its original mass for at least about 5 minutes in an aqueous environment at about 30 °C to about 45 °C. In some embodiments, the hydrogel is durable for about 5 min to about 60 min. In some embodiments, the hydrogel is durable for about 5 min to about 10 min, about 5 min to about15 min, about 5 min to about 20 min, about 5 min to about 25 min, about 5 min to about 30 min, about 5 min to about 45 min, about 5 min to about 60 min, about 10 min to about 15 min, about 10 min to about 20 min, about 10 min to about 25 min, about 10 min to about 30 min, about 10 min to about 45 min, about 10 min to about 60 min, about 15 min to about 20 min, about 15 min to about 25 min, about 15 min to about 30 min, about 15 min to about 45 min, about 15 min to about 60 min, about 20 min to about 25 min, about 20 min to about 30 min, about 20 min to about 45 min, about 20 min to about 60 min, about 25 min to about 30 min, about 25 min to about 45 min, about 25 min to about 60 min, about 30 min to about 45 min, about 30 min to about 60 min, or about 45 min to about 60 min in an aqueous environment. In some embodiments, the hydrogel is durable for about 5 min, about 10 min, about 15 min, about 20 min, about 25 min, about 30 min, about 45 min, or about 60 min in an aqueous environment. In some embodiments, the hydrogel is durable for at least about 5 min, about 10 min, about 15 min, about 20 min, about 25 min, about 30 min, or about 45 min in an aqueous environment. In some embodiments, the hydrogel is durable for at most about 10 min, about 15 min, about 20 min, about 25 min, about 30 min, about 45 min, or about 60 min in an aqueous environment.

[0095] In some embodiments, the hydrogel maintains at least about 90% of its original mass for at least about 5 minutes when submerged into an aqueous environment at about 30 °C to about 45 °C. In some embodiments, the hydrogel maintains about 75 % to about 95 % of its original mass for at least about 5 minutes when submerged into an aqueous environment. In some embodiments, the hydrogel maintains about 75 % to about 80 %, about 75 % to about 85 %, about 75 % to about 90 %, about 75 % to about 95 %, about 80 % to about 85 %, about 80 % to about 90 %, about 80 % to about 95 %, about 85 % to about 90 %, about 85 % to about 95 %, or about 90 % to about 95 % of its original mass for at least about 5 minutes when submerged into an aqueous environment. In some embodiments, the hydrogel maintains about 75 %, about 80 %, about 85 %, about 90 %, or about 95 % of its original mass for at least about 5 minutes when submerged into an aqueous environment. In some embodiments, the hydrogel maintains at least about 75 %, about 80 %, about 85 %, or about 90 % of its original mass for at least about 5 minutes when submerged into an aqueous environment. In some embodiments, the hydrogel maintains at most about 80 %, about 85 %, about 90 %, or about 95 % of its original mass for at least about 5 minutes when submerged into an aqueous environment.

[0096] In some embodiments, the hydrogel maintains at least about 90% of its original mass for at least about 5 minutes when submerged into an aqueous environment comprising atemperature of about 30 °C to about 45 °C. In some embodiments, the aqueous environment comprises a temperature of about 30 °C to about 45 °C. In some embodiments, the aqueous environment comprises a temperature of about 30 °C to about 35 °C, about 30 °C to about 36 °C, about 30 °C to about 37 °C, about 30 °C to about 38 °C, about 30 °C to about 39 °C, about 30 °C to about 40 °C, about 30 °C to about 41 °C, about 30 °C to about 42 °C, about 30 °C to about 43 °C, about 30 °C to about 44 °C, about 30 °C to about 45 °C, about 35 °C to about 36 °C, about 35 °C to about 37 °C, about 35 °C to about 38 °C, about 35 °C to about 39 °C, about 35 °C to about 40 °C, about 35 °C to about 41 °C, about 35 °C to about 42 °C, about 35 °C to about 43 °C, about 35 °C to about 44 °C, about 35 °C to about 45 °C, about 36 °C to about 37 °C, about 36 °C to about 38 °C, about 36 °C to about 39 °C, about 36 °C to about 40 °C, about 36 °C to about 41 °C, about 36 °C to about 42 °C, about 36 °C to about 43 °C, about 36 °C to about 44 °C, about 36 °C to about 45 °C, about 37 °C to about 38 °C, about 37 °C to about 39 °C, about 37 °C to about 40 °C, about 37 °C to about 41 °C, about 37 °C to about 42 °C, about 37 °C to about 43 °C, about 37 °C to about 44 °C, about 37 °C to about 45 °C, about 38 °C to about 39 °C, about 38 °C to about 40 °C, about 38 °C to about 41 °C, about 38 °C to about 42 °C, about 38 °C to about 43 °C, about 38 °C to about 44 °C, about 38 °C to about 45 °C, about 39 °C to about 40 °C, about 39 °C to about 41 °C, about 39 °C to about 42 °C, about 39 °C to about 43 °C, about 39 °C to about 44 °C, about 39 °C to about 45 °C, about 40 °C to about 41 °C, about 40 °C to about 42 °C, about 40 °C to about 43 °C, about 40 °C to about 44 °C, about 40 °C to about 45 °C, about 41 °C to about 42 °C, about 41 °C to about 43 °C, about 41 °C to about 44 °C, about 41 °C to about 45 °C, about 42 °C to about 43 °C, about 42 °C to about 44 °C, about 42 °C to about 45 °C, about 43 °C to about 44 °C, about 43 °C to about 45 °C, or about 44 °C to about 45 °C. In some embodiments, the aqueous environment comprises a temperature of about 30 °C, about 35 °C, about 36 °C, about 37 °C, about 38 °C, about 39 °C, about 40 °C, about 41 °C, about 42 °C, about 43 °C, about 44 °C, or about 45 °C. In some embodiments, the aqueous environment comprises a temperature of at least about 30 °C, about 35 °C, about 36 °C, about 37 °C, about 38 °C, about 39 °C, about 40 °C, about 41 °C, about 42 °C, about 43 °C, or about 44 °C. In some embodiments, the aqueous environment comprises a temperature of at most about 35 °C, about 36 °C, about 37 °C, about 38 °C, about 39 °C, about 40 °C, about 41 °C, about 42 °C, about 43 °C, about 44 °C, or about 45 °C.

[0097] In some embodiments, the hydrogel has a viscosity of 1 cp to about 5,000,000 cps. In some embodiments, the hydrogel has a viscosity of about 10 cp to about 5,000,000 cp. In some embodiments, the hydrogel has a viscosity of about 10 cp to about 10,000 cp, about 10cp to about 50,000 cp, about 10 cp to about 100,000 cp, about 10 cp to about 250,000 cp, about 10 cp to about 500,000 cp, about 10 cp to about 750,000 cp, about 10 cp to about 1,000,000 cp, about 10 cp to about 5,000,000 cp, about 10,000 cp to about 50,000 cp, about 10,000 cp to about 100,000 cp, about 10,000 cp to about 250,000 cp, about 10,000 cp to about 500,000 cp, about 10,000 cp to about 750,000 cp, about 10,000 cp to about 1,000,000 cp, about 10,000 cp to about 5,000,000 cp, about 50,000 cp to about 100,000 cp, about 50,000 cp to about 250,000 cp, about 50,000 cp to about 500,000 cp, about 50,000 cp to about 750,000 cp, about 50,000 cp to about 1,000,000 cp, about 50,000 cp to about 5,000,000 cp, about 100,000 cp to about 250,000 cp, about 100,000 cp to about 500,000 cp, about 100,000 cp to about 750,000 cp, about 100,000 cp to about 1,000,000 cp, about 100,000 cp to about 5,000,000 cp, about 250,000 cp to about 500,000 cp, about 250,000 cp to about 750,000 cp, about 250,000 cp to about 1,000,000 cp, about 250,000 cp to about 5,000,000 cp, about 500,000 cp to about 750,000 cp, about 500,000 cp to about 1,000,000 cp, about 500,000 cp to about 5,000,000 cp, about 750,000 cp to about 1,000,000 cp, about 750,000 cp to about 5,000,000 cp, or about 1,000,000 cp to about 5,000,000 cp. In some embodiments, the hydrogel has a viscosity of about 10 cp, about 10,000 cp, about 50,000 cp, about 100,000 cp, about 250,000 cp, about 500,000 cp, about 750,000 cp, about 1,000,000 cp, or about 5,000,000 cp. In some embodiments, the hydrogel has a viscosity of at least about 10 cp, about 10,000 cp, about 50,000 cp, about 100,000 cp, about 250,000 cp, about 500,000 cp, about 750,000 cp, or about 1,000,000 cp. In some embodiments, the hydrogel has a viscosity of at most about 10,000 cp, about 50,000 cp, about 100,000 cp, about 250,000 cp, about 500,000 cp, about 750,000 cp, about 1,000,000 cp, or about 5,000,000 cp.

[0098] In some embodiments, the hydrogel has a thickness of about 10 mm to about 50 mm. In some embodiments, the hydrogel has a thickness of about 10 mm to about 20 mm, about 10 mm to about 25 mm, about 10 mm to about 30 mm, about 10 mm to about 35 mm, about10 mm to about 40 mm, about 10 mm to about 45 mm, about 10 mm to about 50 mm, about20 mm to about 25 mm, about 20 mm to about 30 mm, about 20 mm to about 35 mm, about20 mm to about 40 mm, about 20 mm to about 45 mm, about 20 mm to about 50 mm, about25 mm to about 30 mm, about 25 mm to about 35 mm, about 25 mm to about 40 mm, about25 mm to about 45 mm, about 25 mm to about 50 mm, about 30 mm to about 35 mm, about30 mm to about 40 mm, about 30 mm to about 45 mm, about 30 mm to about 50 mm, about35 mm to about 40 mm, about 35 mm to about 45 mm, about 35 mm to about 50 mm, about40 mm to about 45 mm, about 40 mm to about 50 mm, or about 45 mm to about 50 mm. In some embodiments, the hydrogel has a thickness of about 10 mm, about 20 mm, about 25mm, about 30 mm, about 35 mm, about 40 mm, about 45 mm, or about 50 mm. In some embodiments, the hydrogel has a thickness of at least about 10 mm, about 20 mm, about 25 mm, about 30 mm, about 35 mm, about 40 mm, or about 45 mm. In some embodiments, the hydrogel has a thickness of at most about 20 mm, about 25 mm, about 30 mm, about 35 mm, about 40 mm, about 45 mm, or about 50 mm.Methods of Preparation

[0099] In an aspect of the present disclosure is a method of preparing a hydrogel composition comprising adding a polysaccharide and a synthetic polymer crosslinker to a reaction vessel, mixing the polysaccharide and the synthetic polymer crosslinker into a mixture with high shear mixing at a temperature of about 40 °C to about 100 °C, degassing the mixture, and pouring the mixture into a mold.

[0100] In some embodiments, the hydrogel composition comprises the hydrogel of the present disclosure.

[0101] In some embodiments, the polysaccharide and the synthetic polymer are disclosed elsewhere herein. In some embodiments, the polysaccharide is a powder. In some embodiments, the synthetic polymer is a powder.

[0102] In some embodiments, the polysaccharide is dissolved in a first solution. In some embodiments, the first solution is an aqueous solution. In some embodiments, the first solution is deionized water. In some embodiments, the first solution is a buffer. In some embodiments, the first solution is heated. In some embodiments, the first solution is heated prior to addition of the polysaccharide. In some embodiments, the first solution is heated after addition of the polysaccharide. In some embodiments, the polysaccharide is added to a heated first solution at a rate sufficient to avoid clumping.

[0103] In some embodiments, the synthetic polymer crosslinker is dissolved in a second solution. In some embodiments, the second solution is an aqueous solution. In some embodiments, the second solution is deionized water. In some embodiments, the second solution is a buffer. In some embodiments, the second solution is heated. In some embodiments, the second solution is heated prior to addition of the synthetic polymer crosslinker. In some embodiments, the second solution is heated after addition of the polysaccharide. In some embodiments, the synthetic polymer crosslinker is added to a heated second solution at a rate sufficient to avoid clumping.

[0104] In some embodiments, a second polysaccharide is added to the reaction vessel. In some embodiments, a second synthetic crosslinker is added to the reaction vessel.

[0105] In some embodiments, the polysaccharide, the synthetic polymer crosslinker, the second polysaccharide, and / or the second crosslinker are added to the reaction vessel. In some embodiments, the polysaccharide and the second polysaccharide are added to the reaction vessel before the synthetic crosslinker and / or the second crosslinker. In some embodiments, the synthetic crosslinker and / or the second crosslinker are added to the reaction vessel before the polysaccharide and / or the second polysaccharide.

[0106] In some embodiments, the polysaccharide, the synthetic polymer crosslinker, the second polysaccharide, and / or the second crosslinker are a mixture.

[0107] In some embodiments, the polysaccharide is added to the reaction vessel before the synthetic polymer crosslinker is added to the reaction vessel. In some embodiments, the synthetic polymer crosslinker is added to the reaction vessel before the polysaccharide.

[0108] In some embodiments, the polysaccharide is added to the reaction vessel and mixed under high shearing prior to adding the synthetic polymer crosslinker. In some embodiments, the synthetic polymer crosslinker is added to the reaction vessel and mixed under high shearing prior to adding the polysaccharide.

[0109] In some embodiments, the high shear mixing comprises a range of 20-30 m / s for rotor speed and 15,000-25,000 s'1shear rate. In some embodiments, the high shear mixing comprises a rotor speed of about 20 m / s to about 30 m / s. In some embodiments, the high shear mixing comprises a rotor speed of about 20 m / s to about 22 m / s, about 20 m / s to about 24 m / s, about 20 m / s to about 26 m / s, about 20 m / s to about 28 m / s, about 20 m / s to about 30 m / s, about 22 m / s to about 24 m / s, about 22 m / s to about 26 m / s, about 22 m / s to about 28 m / s, about 22 m / s to about 30 m / s, about 24 m / s to about 26 m / s, about 24 m / s to about 28 m / s, about 24 m / s to about 30 m / s, about 26 m / s to about 28 m / s, about 26 m / s to about 30 m / s, or about 28 m / s to about 30 m / s. In some embodiments, the high shear mixing comprises a rotor speed of about 20 m / s, about 22 m / s, about 24 m / s, about 26 m / s, about 28 m / s, or about 30 m / s. In some embodiments, the high shear mixing comprises a rotor speed of at least about 20 m / s, about 22 m / s, about 24 m / s, about 26 m / s, or about 28 m / s. In some embodiments, the high shear mixing comprises a rotor speed of at most about 22 m / s, about 24 m / s, about 26 m / s, about 28 m / s, or about 30 m / s. In some embodiments, the high shear mixing comprises a shear rate of about 15,000 s-1 to about 25,000 s-1. In some embodiments, the high shear mixing comprises a shear rate of about 15,000 s-1 to about 17,500 s-1, about 15,000 s-1 to about 20,000 s-1, about 15,000 s-1 to about 22,500 s-1, about 15,000 s-1 to about 25,000 s-1, about 17,500 s-1 to about 20,000 s-1, about 17,500 s-1 to about 22,500 s-1, about 17,500 s-1 to about 25,000 s-1, about 20,000 s-1 to about 22,500 s-1, about 20,000 s-to about 25,000 s-1, or about 22,500 s-1 to about 25,000 s-1. In some embodiments, the high shear mixing comprises a shear rate of about 15,000 s-1, about 17,500 s-1, about 20,000 s-1, about 22,500 s-1, or about 25,000 s-1. In some embodiments, the high shear mixing comprises a shear rate of at least about 15,000 s-1, about 17,500 s-1, about 20,000 s-1, or about 22,500 s-1. In some embodiments, the high shear mixing comprises a shear rate of at most about 17,500 s-1, about 20,000 s-1, about 22,500 s-1, or about 25,000 s-1.

[0110] In some embodiments, the mixture is mixed with high shear mixing at a temperature of about 40 °C to about 100 °C. In some embodiments, the mixture is mixed with high shear mixing at a temperature of about 40 °C to about 100 °C. In some embodiments, the mixture is mixed with high shear mixing at a temperature of about 40 °C to about 50 °C, about 40 °C to about 60 °C, about 40 °C to about 70 °C, about 40 °C to about 80 °C, about 40 °C to about 90 °C, about 40 °C to about 100 °C, about 50 °C to about 60 °C, about 50 °C to about 70 °C, about 50 °C to about 80 °C, about 50 °C to about 90 °C, about 50 °C to about 100 °C, about 60 °C to about 70 °C, about 60 °C to about 80 °C, about 60 °C to about 90 °C, about 60 °C to about 100 °C, about 70 °C to about 80 °C, about 70 °C to about 90 °C, about 70 °C to about 100 °C, about 80 °C to about 90 °C, about 80 °C to about 100 °C, or about 90 °C to about 100 °C. In some embodiments, the mixture is mixed with high shear mixing at a temperature of about 40 °C, about 50 °C, about 60 °C, about 70 °C, about 80 °C, about 90 °C, or about 100 °C. In some embodiments, the mixture is mixed with high shear mixing at a temperature of at least about 40 °C, about 50 °C, about 60 °C, about 70 °C, about 80 °C, or about 90 °C. In some embodiments, the mixture is mixed with high shear mixing at a temperature of at most about 50 °C, about 60 °C, about 70 °C, about 80 °C, about 90 °C, or about 100 °C.[OHl] In some embodiments, the mixture is degassed. In some embodiments, the mixture is degassed for about 1 minute. In some embodiments, the mixture is degassed at least about 1 min, about 2 min, about 5 min, about 10 min, about 20 min, or about 30 min. In some embodiments, the mixture is degassed at most about 2 min, about 5 min, about 10 min, about 20 min, about 30 min, or about 60 min. In some embodiments, the mixture is not degassed.

[0112] In some embodiments, the mixture is poured into a mold. In some embodiments, the mixture is poured into a mold and cooled at room temperature. In some embodiments, the mixture is cooled at below room temperature. In some embodiments, the mixture is cooled at about 30 °C, about 20 °C, about 10 °C, about 0 °C, about -10 °C, or about -20 °C. In some embodiments, the mixture is cooled at least about 30 °C, about 20 °C, about 10 °C, about 0 °C, or about -10 °C. In some embodiments, the mixture is cooled at most about 20 °C, about10 °C, about 0 °C, about -10 °C, or about -20 °C.

[0113] In some embodiments, the mold is shaped to receive a breast-shaped tissue volume.

[0114] The hydrogel's structure and the material composition of the hydrogel's precursors determine its properties. Precursor factors include properties such as biocompatibility, water solubility, hydrophilicity, molecular weight, arm length, number of arms, functional groups, distance between crosslinks, degradability, and the like. The choice of reaction conditions also affects the hydrogel's structure and properties, including choices of solvents, reaction schemes, reactant concentrations, solids content, and the like. There can be a variety of ways to achieve certain properties, or combination of properties. On the other hand some properties are in tension with each other, for instance brittleness may increase as a distance between crosslinks or solids content increases. Strength may be increased by increasing the number of crosslinks, but swelling may thereby be reduced.

[0115] In some embodiments, the hydrogel is formed by cross-linking of complementary chemical reactive groups, condensation reactions, free radical polymerization, high energy radiation, or addition reactions.Gel Pad

[0116] In an aspect of the present disclosure is a gel pad comprising the hydrogel composition of the disclosure. For example, gel pads disclosed herein may comprise an embodiment, variation, or example of interface pad 156 or pad (e.g., toroidal pad, or another shape such as described herein above) 132 disclosed herein with respect to Figs. 1 A to 7G. Disclosed herein are gel pads (e.g., for use in an imaging system, a medical device, etc.) based on hybrid natural and synthetic crosslinking polymers. Such a hybrid gel pad may have the advantage over natural only or synthetic only crosslinked polymers for this use. Advantageous properties may include specific sound speed (1505-1535 m / s), low ultrasonic reflectivity to avoid artifacts in the image, durability in body temperature aqueous environments for extended time as measured by shear force, and combinations thereof. For example, a sound speed within a range similar to tissue to be imaged may allow for an interface pad which is acoustically transparent and / or which has a reduced acoustic impedance difference between the tissue and the interface pad. For example, durability may be particularly important in the example imaging systems described herein with where the interface pad is used in connection with a tissue manipulation system to aid in breast imaging.

[0117] In an aspect of the present disclosure is a gel pad for use in an imaging system wherein the gel pad comprises a hydrogel comprising a natural polysaccharide and asynthetic polymer crosslinker. In some embodiments, the imaging system is an ultrasound imaging system.

[0118] In some embodiments, the gel pad comprises a center aperture configured to fluidically couple to a low-pressure source of a tissue positioning system. In some embodiments, a vacuum circuit is configured to be closed or completed when a tissue volume makes contact and seals the center aperture of the gel pad. In some embodiments, the gel pad is configured to releasably couple to the tissue positioning system. In some embodiments, the gel pad comprises a frustoconical portion configured to receive a tissue volume. In some embodiments, the frustoconical portion can have a range of maximum and minimum radii, e.g., for different breast sizes and shapes. In some embodiments, the tissue volume is a breast. In some embodiments, the frustoconical portion is configured to receive an areola of the breast. In some embodiments, the gel pad is configured to receive the tissue volume without obstructing ultrasound energy directed radially through the gel pad from an ultrasound imaging apparatus.

[0119] In some aspects of the present disclosure is an imaging system, wherein the imaging system comprises a tissue interface, wherein the tissue interface comprises the gel pad of the present disclosure. In some embodiments, the imaging system is an ultrasound imaging system. In some embodiments, the gel pad is configured to replaceably attach to an upper surface of an interface plate of a tissue positioning system of the imaging system. In some embodiments, the gel pad comprises a center aperture which fluidly couples to a low pressure source of the tissue positioning system via at least one perforation in a center region of the interface plate when the gel pad is replaceably attached to the upper surface of the interface plate. In some embodiments, the gel pad is configured to receive a tissue volume without obstructing ultrasound energy directed radially through the gel pad from an ultrasound imaging apparatus coupled to the tissue positioning system. In some embodiments, a vacuum circuit is configured to be closed or completed when the tissue volume makes contact and seals a center aperture of the gel pad. In some embodiments, the interface plate is mounted on a support column of the tissue positioning system. In some embodiments, the gel pad is releasable from the interface plate without disassembly of the interface plate from the support column.

[0120] Embodiments of the system, methods, and protocols of the present disclosure and variations thereof can be embodied and / or implemented at least in part by a machine configured to receive a computer-readable medium storing computer-readable instructions. The instructions are preferably executed by computer-executable components preferablyintegrated with the system and one or more portions of a processor and / or a controller. The computer-readable medium can be stored on any suitable computer-readable media such as RAMs, ROMs, flash memory, EEPROMs, optical devices (CD or DVD), hard drives, floppy drives, or any suitable device. The computer-executable component is preferably a general or application specific processor, but any suitable dedicated hardware or hardware / firmware combination device can alternatively or additionally execute the instructions.

[0121] The FIGURES illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to preferred embodiments, example configurations, and variations thereof. In this regard, each block in a flowchart or block diagram may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block can occur out of the order noted in the FIGURES. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and / or flowchart illustration, and combinations of blocks in the block diagrams and / or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.

[0122] As a person skilled in the art will recognize from the previous detailed description and from the figures and claims, modifications and changes can be made to the preferred embodiments of the disclosure without departing from the scope of this disclosure defined in the following claims.EXAMPLESExample 1: Preparation of a hydrogel gel pad

[0123] A stock solution of a polysaccharide was prepared by dissolving the polysaccharide (e.g., carrageenan) in deionized water at an elevated temperature (e.g., 90 °C). The polysaccharide was added into a reaction vessel with high shear mixing at an elevated temperature (e.g., 90 °C). The synthetic polymer crosslinker (e.g., PEG) and optionally, EDTA and a bactericide (e.g., Sporicidin, methylparaben) were added into the reaction vessel and allowed to mix with high shear mixing at an elevated temperature (e.g., 90 °C). The contents of the reaction vessel were optionally degassed for about 1 minute. The resulting solution was poured into molds and allowed to cure into a hydrogel at a cool temperature re(e.g., 10 °C). The resulting hydrogel was tested for specific sound speed (SS), ultrasonic reflectivity (Ref), and shear force (SF) as shown in Table 2.TABLE 2. FORMULATIONS AND PROPERTIES OF HYDROGELS

[0124] While preferred embodiments of the present disclosure have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed in practicing the disclosure. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A hydrogel composition comprising a polysaccharide and a synthetic polymer crosslinker, wherein the composition comprises one or more characteristics selected from the group consisting of:(a) an ultrasound reflectivity of at most about -260 cB;(b) a specific sound speed of about 1505 m / s to about 1535 m / s; and(c) a shear force of at least about 0.45 Ibf.

2. The composition of claim 1, wherein the hydrogel comprises two characteristics selected from the group consisting of:(a) an ultrasound reflectivity of at most about -260 cB;(b) a specific sound speed of about 1505 m / s to about 1535 m / s; and(c) a shear force of at least about 0.45 Ibf.

3. The composition of claim 1, wherein the hydrogel comprises three characteristics selected from the group consisting of:(a) an ultrasound reflectivity of at most about -260 cB;(b) a specific sound speed of about 1505 m / s to about 1535 m / s; and(c) a shear force of at least about 0.45 Ibf.

4. The composition of any one of claims 1-3, wherein the synthetic polymer is a synthetic polymer crosslinker.

5. The composition of any one of claims 1-4, wherein the polysaccharide is a natural polysaccharide.

6. The composition of claim 5, wherein the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, and hyaluronic acid.

7. The composition of claim 6, wherein the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, and agar.

8. The composition of any one of claims 1-7, the hydrogel composition comprises a natural polysaccharide and a synthetic polymer crosslinker.

9. The composition of claim 8, wherein the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, and hyaluronic acid.

10. The composition of claim 9, wherein the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, and agar.

11. The composition of any one of claims 1-10, wherein the hydrogel composition comprises carrageenan and a synthetic polymer crosslinker.

12. The composition of any one of claims 1-11, wherein the polysaccharide has a molecular weight of about 50,000 Da to about 500,000 Da.

13. The composition of any one of claims 1-12, wherein the polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 10: 1.

14. The composition of any one of claims 1-13, wherein the polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 5: 1.

15. The composition of any one of claims 1-14, wherein the polysaccharide is included at about 1 % w / w to about 10 % w / w.

16. A hydrogel composition comprising carrageenan and a synthetic polymer crosslinker.

17. The composition of claim 16, wherein the composition comprises one or more characteristics selected from the group consisting of:(a) an ultrasound reflectivity of at most about -260 cB;(b) a specific sound speed of about 1505 m / s to about 1535 m / s; and(c) a shear force of at least about 0.45 Ibf.

18. The composition of claim 16, wherein the hydrogel comprises two characteristics selected from the group consisting of:(a) an ultrasound reflectivity of at most about -260 cB;(b) a specific sound speed of about 1505 m / s to about 1535 m / s; and(c) a shear force of at least about 0.45 Ibf.

19. The composition of claim 16, wherein the hydrogel comprises three characteristics selected from the group consisting of:(a) an ultrasound reflectivity of at most about -260 cB;(b) a specific sound speed of about 1505 m / s to about 1535 m / s; and(c) a shear force of at least about 0.45 Ibf.

20. The composition of any one of claims 16-19, wherein the composition further comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, and hyaluronic acid.

21. The composition of any one of claims 16-20, wherein the composition further comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, and agar.

22. The composition of any of one of claims 16-21, wherein the carrageenan has a molecular weight of about 50,000 Da to about 500,000 Da.

23. The composition of any of one of claims 16-22, wherein the carrageenan and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 10: 1.

24. The composition of any of one of claims 16-23, wherein the carrageenan and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 5: 1.

25. The composition of any of one of claims 16-24, wherein the carrageenan is included at about 1 % w / w to about 10 % w / w.

26. The composition of any preceding claim, wherein the synthetic polymer crosslinker is selected from the group consisting of poly(ethylene glycol) (PEG), PEG derivatives, poly(acrylamide) (PAM), PVA, PLA, and PCL.

27. The composition of any preceding claim, wherein the synthetic polymer crosslinker is selected from the group consisting of poly(ethylene glycol) (PEG) and PEG derivatives.

28. The composition of claim 27, wherein PEG derivatives are selected from the group consisting of PEGDA, PEGMA, EDGA, and Pluronics.

29. The composition of any preceding claim, wherein the hydrogel comprises an additional synthetic polymer crosslinker.

30. The composition of any preceding claim, wherein the synthetic polymer crosslinker is included at about 0.1 % w / w to about 5 % w / w.

31. The composition of any preceding claim, wherein the hydrogel comprises physical crosslinks.

32. The composition of any preceding claim, wherein the hydrogel comprises chemical crosslinks.

33. The composition of any preceding claim, wherein the hydrogel comprises both physical and chemical crosslinks.

34. The composition of any preceding claim, wherein the synthetic polymer crosslinker comprises polyethylene glycol, or a derivative thereof.

35. The composition of claim 34, wherein the polyethylene glycol has a molecular weight from about 300 Da to about 5000 Da.

36. The composition of any preceding claim, wherein the hydrogel has a specific sound speed of about 1505 m / s to about 1535 m / s.

37. The composition of any preceding claim, wherein the hydrogel has an ultrasonic reflectivity of at most about -260 cB.

38. The composition of claim 37, wherein the hydrogel has an ultrasonic reflectivity of about -800 cB to about -260 cB.

39. The composition of any preceding claim, wherein the hydrogel has a shear force of at least about 0.45 Ibf.

40. The composition of claim 39, wherein the hydrogel has a shear force of about 0.45 Ibf to about 2.0 Ibf.

41. The composition of any preceding claim, wherein the hydrogel maintains at least about 90% of its original mass when submerged in an aqueous environment at about 30 °C to about 45 °C for at least about 5 minutes.

42. The composition of any preceding claim, wherein the hydrogel further comprises a second polysaccharide.

43. The composition of any preceding claim, wherein the hydrogel further comprises a bactericide.

44. The composition of claim 43, wherein the bactericide is sporocidin or methylparaben.

45. The composition of claim 43, wherein the bactericide is included at about 0.01 % w / w to about 2 % w / w.

46. The composition of claim 43, wherein the bactericide is included at about 0.05 % w / w.

47. The composition of any preceding claim, wherein the hydrogel further comprises ED TA.

48. The composition of claim 47, wherein the EDTA is included at about 0.01 % w / w to about 0.1 % w / w.

49. The composition of claim 47, wherein the EDTA is included at about 0.025 % w / w.

50. A gel pad for use in an imaging system, the gel pad comprising the hydrogel composition of any preceding claim.

51. The gel pad of claim 50, wherein the imaging system is an ultrasound imaging system.

52. An imaging system, wherein the imaging system comprises a tissue interface, wherein the tissue interface comprises a gel pad, wherein the gel pad comprises the hydrogel composition of any preceding claim.

53. The imaging system of claim 52, wherein the imaging system is an ultrasound imaging system.

54. A gel pad for use in an imaging system, wherein the gel pad comprises a hydrogel comprising a natural polysaccharide and a synthetic polymer crosslinker.

55. The gel pad of claim 54, wherein the imaging system is an ultrasound imaging system.

56. The gel pad of claim 54 or 55, wherein the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, guar, agar, chitosan, cellulose, and hyaluronic acid.

57. The gel pad of claim 56, wherein the natural polysaccharide comprises one or more members selected from the group consisting of carrageenan, konjac, xanthan, and agar.

58. The gel pad of any one of claims 54-57, wherein natural polysaccharide comprises carrageenan.

59. The gel pad of any one of claims 54-58, wherein the natural polysaccharide has a molecular weight of about 50,000 Da to about 500,000 Da.

60. The gel pad of any one of claims 54-59, wherein the natural polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 10: 1.

61. The gel pad of any one of claims 54-60, wherein the natural polysaccharide and the synthetic polymer crosslinker are included at a mass ratio of about 1 : 1 to about 5: 1.

62. The gel pad of any one of claims 54-61, wherein the natural polysaccharide is included at about 1 % w / w to about 10 % w / w.

63. The gel pad of any one of claims 54-62, wherein the composition comprises one or more characteristics selected from the group consisting of:(a) an ultrasound reflectivity of at most about -260 cB;(b) a specific sound speed of about 1505 m / s to about 1535 m / s; and(c) a shear force of at least about 0.45 Ibf.

64. The gel pad of any one of claims 54-62, wherein the hydrogel comprises two characteristics selected from the group consisting of:(a) an ultrasound reflectivity of at most about -260 cB;(b) a specific sound speed of about 1505 m / s to about 1535 m / s; and(c) a shear force of at least about 0.45 Ibf.

65. The gel pad of any one of claims 54-62, wherein the hydrogel comprises three characteristics selected from the group consisting of:(a) an ultrasound reflectivity of at most about -260 cB;(b) a specific sound speed of about 1505 m / s to about 1535 m / s; and(c) a shear force of at least about 0.45 Ibf.

66. The gel pad of any preceding claim, wherein the synthetic polymer crosslinker is selected from the group consisting of polyethylene glycol) (PEG), PEG derivatives, poly(acrylamide) (PAM), PVA, PLA, and PCL.

67. The gel pad of any preceding claim, wherein the synthetic polymer crosslinker is selected from the group consisting of poly(ethylene glycol) (PEG) and PEG derivatives.

68. The gel pad of claim 67, wherein PEG derivatives are selected from the group consisting of PEGDA, PEGMA, EDGA, and Pluronics.

69. The gel pad of any preceding claim, wherein the hydrogel comprises an additional synthetic polymer crosslinker.

70. The gel pad of any preceding claim, wherein the synthetic polymer crosslinker is included at about 0.1 % w / w to about 5 % w / w.

71. The gel pad of any preceding claim, wherein the hydrogel comprises physical crosslinks.

72. The gel pad of any preceding claim, wherein the hydrogel comprises chemical crosslinks.

73. The gel pad of any preceding claim, wherein the hydrogel comprises both physical and chemical crosslinks.

74. The gel pad of any preceding claim, wherein the synthetic polymer crosslinker comprises polyethylene glycol, or a derivative thereof.

75. The gel pad of claim 74, wherein the polyethylene glycol has a molecular weight from about 300 Da to about 5000 Da.

76. The gel pad of any preceding claim, wherein the hydrogel has a specific sound speed of about 1505 m / s to about 1535 m / s.

77. The gel pad of any preceding claim, wherein the hydrogel has an ultrasonic reflectivity of at most about -260 cB.

78. The gel pad of claim 77, wherein the hydrogel has an ultrasonic reflectivity of about -800 cB to about -260 cB.

79. The gel pad of any preceding claim, wherein the hydrogel has a shear force of at least about 0.45 Ibf.

80. The gel pad of claim 79, wherein the hydrogel has a shear force of about 0.45 Ibf to about 2.0 Ibf.

81. The gel pad of any preceding claim, wherein the hydrogel maintains at least about 90% of its original mass when submerged in an aqueous environment at about 30 °C to about 45 °C for at least about 5 minutes.

82. The gel pad of any preceding claim, wherein the hydrogel further comprises a second polysaccharide.

83. The gel pad of any preceding claim, wherein the hydrogel further comprises a bactericide.

84. The gel pad of claim 83, wherein the bactericide is sporocidin or methylparaben.

85. The gel pad of claim 83, wherein the bactericide is included at about 0.01 % w / w to about 2 % w / w.

86. The gel pad of claim 83, wherein the bactericide is included at about 0.05 % w / w.

87. The gel pad of any preceding claim, wherein the hydrogel further comprises EDTA.

88. The gel pad of claim 87, wherein the EDTA is included at about 0.01 % w / w to about 0.1 % w / w.

89. The gel pad of claim 87, wherein the EDTA is included at about 0.025 % w / w.

90. The gel pad of any of claims 50, 51, or 54-89, wherein the gel pad comprises a center aperture configured to fluidically couple to a low-pressure source of a tissue positioning system.

91. The gel pad of claim 90, wherein a vacuum circuit is configured to be closed or completed when a tissue volume makes contact and seals the center aperture of the gel pad.

92. The gel pad of claim 90 or 91, wherein the gel pad is configured to releasably couple to the tissue positioning system.

93. The gel pad of any of claims 50, 51, or 54-92, wherein the gel pad comprises a frustoconical portion configured to receive a tissue volume.

94. The gel pad of claim 93, wherein the tissue volume is a breast.

95. The gel pad of claim 94, wherein the frustoconical portion is configured to receive an areola of the breast.

96. The gel pad of any one of claims 93-95, wherein the gel pad is configured to receive the tissue volume without obstructing ultrasound energy directed radially through the gel pad from an ultrasound imaging apparatus.

97. An imaging system, wherein the imaging system comprises a tissue interface, wherein the tissue interface comprises the gel pad of any preceding claim.

98. The imaging system of claim 97, wherein the imaging system is an ultrasound imaging system.

99. The imaging system of claim 97 or 98, wherein gel pad is configured to replaceably attach to an upper surface of an interface plate of a tissue positioning system of the imaging system.

100. The imaging system of claim 99, wherein the gel pad comprises a center aperture which fluidly couples to a low pressure source of the tissue positioning system via at least one perforation in a center region of the interface plate when the gel pad is replaceably attached to the upper surface of the interface plate.

101. The imaging system of claim 99 or 100, wherein the gel pad is configured to receive a tissue volume without obstructing ultrasound energy directed radially through the gel pad from an ultrasound imaging apparatus coupled to the tissue positioning system.

102. The imaging system of claim 101, wherein a vacuum circuit is configured to be closed or completed when the tissue volume makes contact and seals a center aperture of the gel pad.

103. The imaging system of any one of claims 99-102, wherein the interface plate is mounted on a support column of the tissue positioning system.

104. The imaging system of any one of claims 99-103, wherein the gel pad is releasable from the interface plate without disassembly of the interface plate from the support column.

105. A method of preparing a hydrogel composition comprising: a. adding a polysaccharide and a synthetic polymer crosslinker to a reaction vessel, b. mixing the polysaccharide and the synthetic polymer crosslinker into a mixture with high shear mixing at a temperature of about 40 °C to about 100 °C, c. degassing the mixture; and d. pouring the mixture into a mold.

106. The method of claim 105, wherein the hydrogel comprises the hydrogel of any one of claims 1-51.

Images