阅读说明：本技术 用于超声成像中的半硬质声耦合介质的水凝胶组合物 (Hydrogel compositions for semi-rigid acoustic coupling media in ultrasound imaging ) 是由 Z.斯泰布勒 A.韦格纳 于 2020-02-13 设计创作，主要内容包括：公开了用于为超声诊断和治疗技术提供声耦合介质的半硬质水凝胶材料的组合物和制品。在一方面中,用于声耦合介质的水凝胶材料包括海藻酸钠嵌段共聚物、二甲基丙烯酰胺单体和水。在一些实施中,基于水凝胶组合物的总重量,海藻酸钠嵌段共聚物以约0.5重量％至约25重量％的量存在,二甲基丙烯酰胺单体以约1重量％至约40重量％的量存在,并且水以至少约50重量％的量存在。(Compositions and articles of manufacture of semi-rigid hydrogel materials for providing acoustic coupling media for ultrasound diagnostic and therapeutic techniques are disclosed. In one aspect, a hydrogel material for an acoustic coupling medium includes a sodium alginate block copolymer, a dimethylacrylamide monomer, and water. In some implementations, the sodium alginate block copolymer is present in an amount of about 0.5 wt% to about 25 wt%, the dimethylacrylamide monomer is present in an amount of about 1 wt% to about 40 wt%, and the water is present in an amount of at least about 50 wt%, based on the total weight of the hydrogel composition.)

1. A hydrogel composition comprising:

sodium alginate block copolymer (P (SA)), dimethylacrylamide monomer (DMAm) and water, wherein

The P (SA) is present in an amount of about 0.5 wt% to about 25.00 wt%, based on the total weight of the hydrogel composition,

the DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%, and

the water is present in an amount of at least about 50.00 wt%.

2. The hydrogel composition of claim 1, wherein the DMAm is present in an amount from about 3.3 wt% to about 14.8 wt%.

3. The hydrogel composition of claim 1, wherein the DMAm is present in an amount from about 8.3 wt% to about 9.8 wt%.

4. The hydrogel composition of claim 1, wherein the p (sa) is present in an amount of about 0.5% to about 5.5% by weight.

5. The hydrogel composition of claim 1, wherein the water is present in an amount of at least about 75.6 weight percent of the total weight of the hydrogel composition.

6. The hydrogel composition of any one of claims 1 to 5, further comprising:

n, N '-Methylenebisacrylamide (MBA), N', N, N-Tetramethylethylenediamine (TMED), calcium sulfate (CA), and Ammonium Persulfate (APS).

7. The hydrogel composition of claim 6, wherein the MBA is present in an amount of about 0.04 wt% to about 10.00 wt% of the total weight of the hydrogel composition.

8. The hydrogel composition of claim 6 or 7, wherein TMED is present in an amount of 0.004 wt% to about 1.00 wt% of the total weight of the hydrogel composition.

9. The hydrogel composition of any one of claims 6 to 8, wherein CA is present in an amount of about 0.01 wt% to about 1.00 wt% of the total weight of the hydrogel composition.

10. The hydrogel composition of any one of claims 6 to 9, wherein the APS is present in an amount of about 0.01 weight percent to about 1.00 weight percent of the total weight of the hydrogel composition.

11. A semi-rigid acoustic coupling medium comprising a hydrogel material, the hydrogel material comprising: sodium alginate block copolymer (P (SA)), dimethylacrylamide monomer (DMAm), and water.

12. The semi-rigid acoustic coupling medium of claim 11, wherein

The P (SA) is present in an amount of about 0.5 wt.% to about 25.00 wt.%, based on the total weight of the hydrogel composition,

the DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%, and

the water is present in an amount of at least about 50.00 wt%.

13. The semi-rigid acoustic coupling medium of claim 11, wherein

The P (SA) is present in an amount of about 0.5 wt.% to about 5.5 wt.%, based on the total weight of the hydrogel composition,

the DMAm is present in an amount of about 3.3 wt% to about 14.8 wt%, and

the water is present in an amount of at least about 75.6 wt%.

14. The semi-rigid acoustic coupling medium of any one of claims 11 to 13, wherein the semi-rigid acoustic coupling medium has a sound velocity of 1480-1700 m/s.

15. The semi-rigid acoustic coupling medium of any one of claims 11 to 14, wherein the semi-rigid acoustic coupling medium has an acoustic impedance of about 1.00-2.00 MRayls.

16. The semi-rigid acoustic coupling medium of any one of claims 11 to 15, wherein the semi-rigid acoustic coupling medium has an acoustic attenuation of about 0.001-1.00 dB/cm/MHz.

17. The semi-rigid acoustic coupling medium of any one of claims 11-16, wherein the semi-rigid acoustic coupling medium has a young's modulus of about 500.00kPa or less.

18. The semi-rigid acoustic coupling medium of any one of claims 11-17, wherein the hydrogel has an engineering compression and elastic strain of greater than or equal to 50%.

19. The semi-rigid acoustic coupling medium of any one of claims 11 to 18, wherein the hydrogel material further comprises:

n, N '-Methylenebisacrylamide (MBA), N', N, N-Tetramethylethylenediamine (TMED), calcium sulfate (CA), and Ammonium Persulfate (APS).

20. A hydrogel composition comprising:

sodium alginate block copolymer (P (SA)), dimethylacrylamide monomer (DMAm) and water, wherein

The P (SA) is present in an amount of about 0.5 wt.% to about 5.5 wt.%, based on the total weight of the hydrogel composition,

the DMAm is present in an amount of about 3.3 wt% to about 14.8 wt%, and

the water is present in an amount of at least about 75.6 wt%.

21. The hydrogel composition of claim 20, wherein the DMAm is present in an amount from about 8.3 wt% to about 9.8 wt%.

22. The hydrogel composition of claim 20 or 21, further comprising:

n, N '-Methylenebisacrylamide (MBA), N', N, N-Tetramethylethylenediamine (TMED), calcium sulfate (CA), and Ammonium Persulfate (APS).

23. The hydrogel composition of claim 22, wherein the MBA is present in an amount of about 0.04 wt% to about 3.4 wt% of the total weight of the hydrogel composition.

24. The hydrogel composition of claim 22 or 23, wherein TMED is present in an amount of 0.004 wt% to about 0.082 wt% of the total weight of the hydrogel composition.

25. The hydrogel composition of any one of claims 22 to 24, wherein CA is present in an amount of about 0.13 wt% to about 0.23 wt% of the total weight of the hydrogel composition.

26. The hydrogel composition of any one of claims 22 to 25, wherein the APS is present in an amount of about 0.02 wt% to about 0.24 wt% of the total weight of the hydrogel composition.

27. A hydrogel composition comprising dimethylacrylamide monomer (DMAm), wherein the DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%.

28. The hydrogel composition of claim 27, wherein the DMAm is present in an amount from about 3.3 wt% to about 14.8 wt%.

29. A hydrogel composition comprising a sodium alginate block copolymer (p (sa)), wherein said p (sa) is present in an amount of about 0.5% to about 25% by weight.

30. The hydrogel of claim 29, wherein the p (sa) is present in an amount of about 0.5% to about 5.5% by weight.

31. A flat hydrogel comprising dimethylacrylamide monomer (DMAm), wherein the DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%.

32. The flat hydrogel of claim 31, wherein the DMAm is present in an amount of about 3.3 wt% to about 14.8 wt%.

33. The flat hydrogel of any one of claims 31 or 32, wherein the flat hydrogel exhibits brittleness when: the flat hydrogel experiences significant loading with or without elastic strain and then fails as a result of the formation and propagation of cracks or fissures across the flat material.

34. A flat hydrogel comprising a sodium alginate block copolymer (p (sa)), wherein said p (sa) is present in an amount of about 0.5% to about 25% by weight.

35. The flat hydrogel of claim 34, wherein the p (sa) is present in an amount of about 0.5% to about 5.5% by weight.

36. The flat hydrogel of any one of claims 34 or 35, wherein the flat hydrogel exhibits brittleness when: the flat hydrogel experiences significant loading with or without elastic strain and then fails as a result of the formation and propagation of cracks or fissures across the flat material.

Technical Field

This patent document relates to compositions, articles, and methods of acoustic coupling media useful for ultrasound imaging.

Background

Acoustic imaging is an imaging mode that takes the property of an acoustic wave passing through a medium to present a visible image. High frequency acoustic imaging has been used as an imaging modality in a wide variety of biomedical fields for decades to view internal structures and functions of animals and humans. High frequency sound waves used in biomedical imaging may operate at different frequencies, for example, between 1 and 20MHz, or even higher frequencies, and are often referred to as ultrasound. Using conventional ultrasound imaging techniques, several factors, including insufficient spatial resolution and tissue differentiation, can result in unsatisfactory image quality, which can limit its use for many clinical indications or applications.

Disclosure of Invention

Compositions and articles of manufacture of semi-rigid hydrogel materials for providing acoustic coupling media for ultrasound diagnostic and therapeutic techniques are disclosed. In some aspects, the semi-rigid hydrogel material includes a sodium alginate block copolymer and a dimethylacrylamide monomer.

In some aspects according to the disclosed technology, the semi-rigid acoustic coupling medium comprises a hydrogel material comprising: sodium alginate block copolymer (P (SA)), dimethylacrylamide monomer (DMAm) and water.

In some aspects according to the disclosed technology, the hydrogel composition includes a sodium alginate block copolymer (p (sa)), a dimethylacrylamide monomer (DMAm), and water, wherein p (sa) is present in an amount of about 0.5 wt% to about 25.00 wt%, DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%, and water is present in an amount of at least about 50.00 wt%, based on the total weight of the hydrogel composition.

In some aspects in accordance with the disclosed technology, the hydrogel composition includes a sodium alginate block copolymer (p (sa)), a dimethylacrylamide monomer (DMAm), and water, wherein p (sa) is present in an amount of about 0.5 wt% to about 5.5 wt%, DMAm is present in an amount of about 3.3 wt% to about 14.8 wt%, and water is present in an amount of at least about 75.6 wt%, based on the total weight of the hydrogel composition.

In some aspects according to the disclosed technology, the hydrogel composition includes dimethylacrylamide monomer (DMAm), wherein DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%.

In some aspects according to the disclosed technology, the hydrogel composition includes a sodium alginate block copolymer (p (sa)), where p (sa) is present in an amount of about 0.5 wt% to about 25 wt%.

The subject matter described in this patent document can be implemented in a specific manner to provide one or more of the following features.

Drawings

Fig. 1A and 1B show diagrams illustrating conventional acoustic couplants that exhibit a lack of conformability (fit) to the skin of a patient.

Fig. 2 shows a diagram illustrating a conventional acoustic couplant, which may be composed of a polymer that creates a hard gap between the interface of the coupling medium and the patient's skin.

Fig. 3A-3D depict the chemical structure of exemplary components of a Hydrogel Interface Pad (HIP) according to example embodiments of the present disclosure.

FIGS. 4A-4C depict the chemical structure of the polymer chains of a HIP according to example embodiments of the present disclosure.

FIG. 4D depicts an exemplary polymer network highlighting the ion-ion junctions between polymer chains of HIPs according to example embodiments of the present disclosure.

FIG. 5A shows a schematic diagram depicting an exemplary HIP of the present disclosure undergoing a crack propagation test at stress regions #1, #2, and # 3.

FIGS. 5B-5D show more detailed schematic diagrams of an exemplary HIP at stress regions #1, #2, and #3 of FIG. 5A, respectively.

Fig. 6A and 6B show diagrams depicting super aggregate (super aggregate) hydrogels.

Fig. 7A and 7B show diagrams depicting a weak, brittle hydrogel.

FIG. 8 shows a schematic diagram illustrating acoustic transmission through an example HIP into a heterogeneous substrate comprising a homogeneous body.

FIG. 9 shows an image of an example acoustic couplant including an example HIP according to the present technology used in an example implementation for evaluating acoustic and mechanical properties of the couplant.

FIGS. 10A-10F show images of an example HIP under mechanical stress.

FIG. 11 shows an image of an example ion crosslinked example HIP.

FIG. 12 shows an illustrative diagram depicting an example embodiment of a method for synthesizing a hydrogel composition (which can be used to produce HIPs) in accordance with the present techniques.

Figure 13 depicts a hydrogel network comprising 95% water and corresponding electron microscope images.

Detailed Description

Acoustic imaging can be performed by: acoustic waveforms (e.g., pulses) are emitted within a physically elastic medium, such as a biological medium (including tissue). Acoustic waveforms are transmitted from transducer elements (e.g., of an array of transducer elements) toward a target volume of interest (VOI). The propagation of an acoustic waveform in a medium towards a target volume may encounter the following structure: which causes the acoustic waveform to become partially reflected and partially transmitted from the boundary between the two media (e.g., different biological tissue structures). The reflection of the transmitted acoustic waveform may depend on the acoustic impedance difference between the two media (e.g., at the interface between the two different biological tissue types). For example, some of the acoustic energy of the transmitted acoustic waveform may be scattered back to the transducer at the interface to be received and processed to extract information, while the remainder may continue on and reach the next medium. In some cases, scattering of the reflection may occur due to two or more impedances contained in the reflective medium that acts as a scattering center. Additionally, acoustic energy may be refracted, diffracted, delayed, and/or attenuated based on the properties of the medium and/or the nature of the acoustic wave, for example.

For propagation of the acoustic waveform toward the target volume, acoustic velocity and acoustic impedance differences may exist at the interface between the transducer and the medium used to receive the acoustic waveform (e.g., referred to as the receiving medium), which may interfere with the transmission of acoustic signals for imaging, range-doppler measurements, tissue characterization (e.g., acoustic radiation force impulse-ARFI), or therapeutic applications. Due to the material properties (e.g., material density) and acoustic wave velocity of the two different media, a difference in acoustic impedance results such that a significant amount of the emitted acoustic energy will be reflected at the interface, rather than being transmitted entirely across the interface. In a typical acoustic (e.g., ultrasound) imaging or therapy application, for example, a transmitting gel is applied to a receiving medium (i.e., the subject's skin) at the interface where the transducer will contact to improve the transmission of acoustic waveforms from the transducer to the body and the reception of acoustic waveforms back from the body to the transducer. In such applications without ultrasound gel, the interface may include air as a component of the medium between the receiving medium (e.g., living skin tissue) and the transducer, and the acoustic impedance mismatch in terms of transducer-to-air and air-to-body discontinuities results in scattering (e.g., reflection) of the emitted acoustic energy.

While relatively good success at reducing acoustic impedance differences at interfaces, when dispensed over a VOI, acoustic transmission gels can contain tiny pockets of air that can interfere with the transmission of acoustic signals. In addition, many patients complain of discomfort with respect to the use of gels dispensed on their skin, such as, for example, temperature, tackiness, or others. However, of more concern, the sound-transmitting gel may become contaminated during production or storage, which has led to infection in some patients. For subjects with hair on their skin at the location where the transducer is to be placed, these subjects typically must shave off or otherwise remove external hair that exacerbates the entrapment of air between the skin and the gel.

For non-normal (abnormal) angles of incidence of the acoustic wave with respect to the interface, the difference in acoustic wave velocity may cause refraction of the acoustic wave. The difference in acoustic wave velocity at the interface causes the propagation path of the longitudinal acoustic wave to refract or change direction as a function of the angle of incidence and the acoustic wave velocity on either side of the interface according to Snell's law. The accumulation of an infinitesimal amount of refraction as the wave propagates in the heterogeneous material causes a flexing or bending of the path of the acoustic wave.

Since conventional Ultrasound (US) imaging assumes that an acoustic wave travels in a straight line, refraction along the acoustic path causes degradation and distortion of the resulting image due to its uncertainty as to the arrival time and location of the acoustic waveform in space for both transmission and reception. Materials that match the acoustic wave velocity at the interface significantly reduce the refraction effect, resulting in a clearer and less blurred image. In addition, a semi-rigid material with uniform acoustic wave velocity throughout (all of) the material will minimize the likelihood of bending of the acoustic wave path within the material.

Ultrasound imaging has gained interest in the medical imaging community due to portability, multiple anatomical target patterns, safety, and relatively low cost when compared to X-ray, Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) techniques. Some modes focus entirely on cardiology and can produce 4D images of a beating heart chamber. Another model is a dedicated calculator that calculates fluid flow through tiny corpuscular (cellular) capillaries in the liver and spleen, while another model simply uses US as a general purpose machine. Regardless of the narrow or wide application, all US machines suffer from the same limitations resulting from conventional ultrasound designs, namely loss of image quality at depth and low near-field resolution. Although the image depth depends primarily on the array design and transducer frequency, the blurred near field is the result of large impedance mismatch differences between the transducer interface and the patient interface and the focal point of the transducer.

Near field convolution is an annoyance encountered in many US diagnostic techniques, especially for synovial joints that are bundles of tendons, fluids, bones, and muscles that are tightly bound together under thin, robust skin and tissue coverings. This is a common problem, and many clinicians have taken to fill nitrile rubber gloves with tap water to act as a portable quasi-water bath that doubles as a stand (standoff), e.g., any acoustic coupling material that provides a distance between the transducer interface and the patient interface. This technique, which is simple, cost-effective, and fast to implement, is a good enough solution to produce fast non-visceral US images with linear arrays.

Fig. 1A and 1B show diagrams illustrating acoustic couplants, such as conventional water-ball couplants, which exhibit a lack of conformity to the skin of a patient. As shown in fig. 1A, in this example, the water sphere couplant includes a polymer sphere outer membrane that surrounds degassed water (e.g., degassed Deionized (DI) water) within the polymer outer membrane. The degassed water trapped within the outer membrane provides pressure on the inner surface of the outer membrane such that the shape of the water ball couplant is defined by an external force exerted on the water ball — in this example, the external force comprises a normal force (F) exerted by a flat surface in contact with the water ball couplant_N) And external force (F) from the external environment_L). The outer membrane of the water ball couplant is typically flexible and can bend in an attempt to conform to a curved surface, as shown by the illustration in fig. 1B. However, such bending typically creates entrained air and wrinkles at turning points (inflection points) along the outer membrane and in the fluidic interior of the water balloon couplant.

Furthermore, for non-linear arrays and non-planar surfaces, the technical problem becomes too challenging to solve for simple water spheres. A semicircular array for Acoustic Coherence Tomography (ACT) is exemplified, which has several array elements that need to be bonded to a diverse sheet of patient interface geometry during a multiple VOI examination. A first challenge with water balloons is to distort the tubular geometry to bond to the transducer interface without wrinkling on the patient interface, as shown in fig. 1. Wrinkles will capture air that looks like comets in the US image with bright spots, which obscure (shadow out) anatomical features and create artifacts (artifacts). Even if some mil thick (e.g., 0.001 inch thick) polymer films were designed to accommodate the array without wrinkling, the water globules were still lacking in the single layerThe conformity required for scanning multiple anatomical targets in an examination, since water is a semi-incompressible fluid (k 46.4 × 10)^-6atm^-1) And the principle of volume conservation is applied.

For polymers with thick walls, high young's modulus, and low strain-to-failure, the load on the transducer side of the water ball is transmitted directly to the patient interface without spreading the load over a larger surface area and without conforming to asymmetric patient geometry. Low modulus of elasticity, high pre-failure strain, and thin-walled polymers can deform more, but are not sufficiently compliant, cannot bridge large gaps between rigid, symmetric transducer interfaces and asymmetric, deformable patient interfaces, and are more prone to bursting and rolling during examination, as shown in fig. 2.

Fig. 2 shows a diagram illustrating a conventional acoustic couplant, such as a water-ball couplant, which is composed of a polymer that creates a rigid gap between the interface of the coupling medium and the patient's skin. Diagram 200A shows an example hydroacoustic couplant in contact with a surface, illustrating the force from the surface in contact with the couplant applied externally (normal force F)_N) And force from the surroundings (F)_L) The maximum compression on the water ball couplant in between. Diagram 200B shows an example hydrospheric acoustic coupler comprising ridges in the outer polymer film that create gaps between the contacting surfaces, and also shows the example hydrospheric acoustic coupler at maximum expansion (swell). Diagram 200C shows an example water-ball couplant in contact with a target volume (e.g., skin of a body part of a patient), illustrating how the water-ball couplant may have a gap between the couplant and the target volume due to variations and/or fragments in the contour of the target.

A more conformable and durable stent is needed, and therefore thin, semi-solid hydrogel puck shaped blocks (pucks) or sheets (e.g., -1.0 to 1.5cm) have been developed to accommodate traditional US imaging in the near field. These hydrogel puck or patch mounts aim to minimize impedance mismatch between a rigid, symmetric transducer interface and an asymmetric, conformal patient interface for a linear array. A thin hydrogel sheet, more conformable than a water ball, can be filled in segments (divot) and steep slopes (escarpment) along a flat surface and form a curved topography that combines. In addition, depending on the hydrogel chemistry (composition) and morphology, the hydrogel can be adhesive for long static US diagnostic scans or produce a lubricious layer via syneresis when short dynamic scans are performed under pressure.

However, despite greater conformability than water spheres, hydrogels on the market today have a large bulk modulus, which increases hydrogel stiffness as thickness increases. In combination with low fracture toughness and paraben (paraben) preservatives, the ambiguity of hardness and brittleness, ease of crack propagation, and health safety make hydrogel scaffolds useless in the following applications: where thick (e.g., >2cm), tough, and conformable semi-rigid scaffolds are required for non-linear arrays, like the aforementioned ACT semicircular arrays.

Compositions and articles of manufacture of semi-rigid hydrogel materials for providing an acoustic coupling medium for ultrasound techniques are disclosed. The use of hydrogel coupling media according to embodiments disclosed herein provides advantages over conventional coupling media such as water baths and stents like water bags and puck or sheet hydrogels, for example, including, but not limited to, providing superior acoustic and mechanical properties, as well as achieving low manufacturing costs, fast production speeds, and minimal redundancy.

In some aspects, the disclosed semi-rigid hydrogels include an engineered polymer network with the ability to form fine geometries and trap water to a high percentage (e.g., 85% or more) that provides acoustic impedance matching between an ultrasound transducer element and a target biological volume. The disclosed hydrogels provide additional advantages in their way of manufacture, distribution (assignment) and application based on their low cost manufacture, simultaneous sterilization and curing steps, stable storage and biocompatibility.

Also disclosed are compositions and articles for a rigid hydrogel material that provides an acoustic coupling medium that can be used in some ultrasound techniques and applications, for example, particularly as an acoustic coupling agent between a planar transducer array and a planar surface of a target volume for imaging.

Example hydrogel compositions

In some embodiments according to the present techniques, the composition of the hydrogel includes a monomer, a block copolymer, a dispersed phase, a covalent crosslinking agent, a cationic crosslinking agent, a catalyst, and/or a free radical initiator.

The monomer functions as the primary structural network of the hydrogel. In some embodiments, the monomer is acrylamide. Non-limiting examples of acrylamide monomers include Dimethylacrylamide (DMA), Diethylacrylamide (DEAA), phenylacrylamide, t-butylacrylamide, octadecylacrylamide, isopropylacrylamide, or diphenylmethacrylamide.

In some embodiments, the monomer is present in an amount of about 1 wt% to about 40 wt%, about 10 wt% to about 40 wt%, about 20 wt% to about 40 wt%, about 30 wt% to about 40 wt%, about 1 wt% to about 10 wt%, about 1 wt% to about 5 wt%, about 1 wt% to about 15 wt%, about 1 wt% to about 20 wt%, about 1 wt% to about 30 wt%, about 10 wt% to about 20 wt%, about 10 wt% to about 30 wt%, about 10 wt% to about 15 wt%, about 15 wt% to about 20 wt%, about 15 wt% to about 30 wt%, about 15 wt% to about 15 wt%, about 15 wt% to about 40 wt%, about 20 wt% to about 30 wt%, or about 20 wt% to about 40 wt% of the total weight of the hydrogel composition. In some embodiments, the monomer is DMA, which is present in an amount of about 1 wt% to about 40 wt% of the total weight of the hydrogel composition.

In some embodiments, the monomer is present in an amount of about 1 wt% to about 10 wt%, about 1 wt% to about 15 wt%, about 2 wt% to about 10 wt%, about 2 wt% to about 15 wt%, about 3 wt% to about 10 wt%, about 3 wt% to about 15 wt%, about 4 wt% to about 10 wt%, about 4 wt% to about 15 wt%, about 5 wt% to about 10 wt%, about 5 wt% to about 15 wt%, about 6 wt% to about 10 wt%, about 6 wt% to about 15 wt%, about 7 wt% to about 10 wt%, about 7 wt% to about 15 wt%, about 8 wt% to about 10 wt%, about 8 wt% to about 15 wt%, about 9 wt% to about 10 wt%, or about 9 wt% to about 15 wt% of the total weight of the hydrogel composition. In some embodiments, the monomer is DMA and is present in an amount of about 3.3 wt% to about 14.83 wt% of the total weight of the hydrogel composition.

The function of the block copolymer is to provide a secondary grafted sacrificial network of the hydrogel. In some embodiments, the block copolymer is an alginate. Non-limiting examples of alginates include Sodium Alginate (SA), potassium alginate, calcium alginate, ammonium alginate, low acetylated gellan, high acetylated gellan, modified starch, agar, k-carrageenan, I-carrageenan, low methoxy pectin, high methoxy pectin, methyl cellulose, hydroxypropyl methyl cellulose, cellulose/gelatin, or propylene glycol alginate.

In some embodiments, the block copolymer is present in an amount from about 0.5 wt% to about 25 wt%, from about 0.5 wt% to about 20 wt%, from about 0.5 wt% to about 15 wt%, from about 0.5 wt% to about 10 wt%, from about 0.5 wt% to about 5 wt%, from about 0.5 wt% to about 1 wt%, from about 1 wt% to about 25 wt%, from about 1 wt% to about 20 wt%, from about 5 wt% to about 15 wt%, from about 5 wt% to about 10 wt%, from about 10 wt% to about 25 wt%, from about 10 wt% to about 20 wt%, from about 10 wt% to about 15 wt%, from about 15 wt% to about 25 wt%, or from about 15 wt% to about 20 wt% of the total weight of the hydrogel composition. In some embodiments, the block copolymer is SA and is present in an amount from about 0.5 wt% to about 25 wt% of the total weight of the hydrogel composition.

In some embodiments, the block copolymer is present in an amount from about 0.1 to about 10 wt%, from about 0.1 to about 8 wt%, from about 0.1 wt% to about 6 wt%, from about 0.1 wt% to about 4 wt%, from about 0.1 wt% to about 2 wt%, from about 0.2 wt% to about 10 wt%, from about 0.2 wt% to about 8 wt%, from about 0.2 wt% to about 6 wt%, from about 0.2 wt% to about 4 wt%, from about 0.2 wt% to about 2 wt%, from about 0.3 wt% to about 10 wt%, from about 0.3 wt% to about 8 wt%, from about 0.3 wt% to about 6 wt%, from about 0.3 wt% to about 4 wt%, from about 0.3 wt% to about 2 wt%, from about 0.4 wt% to about 10 wt%, from about 0.4 wt% to about 8 wt%, from about 0.4 wt% to about 4 wt%, from about 4 wt% to about 4 wt%, from about 4.4 wt% to about 2 wt%, from about 4 wt% to about 2 wt%, based on the total weight of the hydrogel composition, Present in an amount of about 0.5 wt% to about 10 wt%, about 0.5 wt% to about 8 wt%, about 0.5 wt% to about 6 wt%, about 0.5 wt% to about 4 wt%, or about 0.5 wt% to about 2 wt%. In some embodiments, the block copolymer is SA and is present in an amount from about 0.51 wt% to about 5.53 wt% of the total weight of the hydrogel composition.

In some embodiments, the dispersed phase is water (e.g., deionized water). In some embodiments, the dispersed phase is present in an amount of at least about 40 weight percent, at least about 50 weight percent, at least about 60 weight percent, 70 weight percent, at least about 75 weight percent, at least about 80 weight percent, at least about 85 weight percent, at least about 90 weight percent, or at least about 95 weight percent of the total weight of the hydrogel composition. In some embodiments, the dispersed phase is water and is present in an amount of at least about 50 weight percent of the total weight of the hydrogel composition. In some embodiments, the dispersed phase is water and is present in an amount of about 75.65 weight% to about 95.98 weight% of the total weight of the hydrogel composition.

In some embodiments, the covalent crosslinking agent is acrylamide. Non-limiting examples of acrylamide covalent crosslinking agents include N ', N' -Methylene Bisacrylamide (MBA), bisacrylamide, ethylene bisacrylamide, piperazine bisacrylamide, or ethylene glycol bisacrylamide.

In some embodiments, the covalent crosslinking agent is present in an amount of about 0.04 wt% to about 10 wt%, about 0.04 wt% to about 9 wt%, about 0.04 wt% to about 8 wt%, about 0.04 wt% to about 7 wt%, about 0.04 wt% to about 6 wt%, about 0.04 wt% to about 5 wt%, about 0.04 wt% to about 4 wt%, about 0.04 wt% to about 3 wt%, about 0.04 wt% to about 1 wt%, about 1 wt% to about 10 wt%, about 2 wt% to about 10 wt%, about 3 wt% to about 10 wt%, about 4 wt%, to about 10 wt%, about 5 wt% to about 10 wt%, about 6 wt% to about 10 wt%, about 7 wt% to about 10 wt%, about 8 wt% to about 10 wt%, or about 9 wt% to about 10 wt% of the total weight of the hydrogel composition. In some embodiments, the covalent crosslinking agent is MBA and is present in an amount of about 0.04 wt% to about 10 wt% of the total weight of the hydrogel composition.

In some embodiments, the covalent crosslinking agent is present in an amount of about 0.01 wt% to about 5 wt%, about 0.01 wt% to about 4 wt%, about 0.1 wt% to about 3 wt%, about 0.02 wt% to about 5 wt%, about 0.02 wt% to about 4 wt%, about 0.02 wt% to about 3 wt%, about 0.02 wt% to about 2 wt%, about 0.03 wt% to about 5 wt%, about 0.03 wt% to about 4 wt%, about 0.03 wt% to about 3 wt%, about 0.3 wt% to about 2 wt%, about 0.04 wt% to about 5 wt%, about 0.04 wt% to about 4 wt%, about 0.04 wt% to about 3 wt%, about 0.04 wt% to about 2 wt%, about 0.05 wt% to about 5 wt%, about 0.05 wt% to about 4 wt%, about 0.05 wt% to about 3 wt%, about 0.05 wt% to about 2 wt%, about 0.05 wt% to about 5 wt%, about 0.05 wt% to about 2 wt%, based on the total weight of the hydrogel composition, Present in an amount of about 0.05 wt% to about 4 wt%, about 0.05 wt% to about 3 wt%, or about 0.05 wt% to about 2 wt%. In some embodiments, the covalent crosslinking agent is MBA and is present in an amount of about 0.041 wt% to about 3.43 wt% of the total weight of the hydrogel composition.

In some embodiments, the cationic crosslinking agent is a monovalent, divalent, or trivalent metal. For example, the cationic crosslinker can be a transition metal, an alkali metal, or an alkaline earth metal, wherein the metal is 1⁺、2⁺Or 3⁺Oxidation state. In some embodiments, the cationic crosslinker is lithium, sodium,Potassium, magnesium, calcium, zinc, zirconium, iron, cobalt, nickel, titanium, or copper. In some embodiments, the cationic crosslinking agent is in the form of any monovalent, divalent, or trivalent salt. For example, in some embodiments, the cationic crosslinker is any sulfate, phosphate, chloride, bromide, triflate, amine, or carboxylate. In some embodiments, the cationic crosslinker is calcium sulfate (CA), calcium phosphate, calcium chloride, calcium bromide, or calcium triflate.

In some embodiments, the cationic crosslinking agent is present in an amount of about 0.1 wt% to about 0.5 wt%, about 0.1 wt% to about 0.6 wt%, about 0.1 wt% to about 0.7 wt%, about 0.01 wt% to about 0.8 wt%, about 0.01 wt% to about 0.9 wt%, or about 0.01 wt% to about 1 wt% of the total weight of the hydrogel composition. In some embodiments, the cationic crosslinking agent is CA and is present in an amount of about 0.14 wt% to about 0.23 wt% of the total weight of the hydrogel composition.

The catalyst functions to promote and/or increase the rate of chemical reactions that form the hydrogel composition. In some embodiments, the catalyst is an amine. Non-limiting examples of amine catalysts include aliphatic amines, N', N, N-Tetramethylethylenediamine (TMED), benzyldimethylamine, methylamine, or triethylamine.

In some embodiments, the catalyst is present in an amount from about 0.004 wt% to about 1.00 wt%, from about 0.004 wt% to about 0.9 wt%, from about 0.004 wt% to about 0.8 wt%, from about 0.004 wt% to about 0.7 wt%, from about 0.004 wt% to about 0.6 wt%, from about 0.004 wt% to about 0.5 wt%, from about 0.004 wt% to about 0.4 wt%, from about 0.004 wt% to about 0.3 wt%, from about 0.004 wt% to about 0.2 wt%, from about 0.004 wt% to about 1 wt%, from 0.01 wt% to about 1 wt%, from about 0.1 wt% to about 1 wt%, from about 0.2 wt% to about 1 wt%, from about 0.3 wt% to about 1 wt%, from about 0.4 wt% to about 1 wt%, from about 0.5 wt% to about 1 wt%, from about 0.6 wt% to about 1 wt%, from about 0.7 wt% to about 1 wt%, from about 0.8 wt% to about 1 wt%, or from about 0.9 wt% to about 1 wt%. In some embodiments, the catalyst is TMED and is present in an amount of about 0.004 wt% to about 1 wt% of the total weight of the hydrogel composition.

In some embodiments, the catalyst is present in an amount of about 0.001 wt% to about 0.05 wt%, about 0.001 wt% to about 0.06 wt%, about 0.001 wt% to about 0.07 wt%, about 0.001 wt% to about 0.08 wt%, about 0.001 wt% to about 0.09 wt%, or about 0.001 wt% to about 0.1 wt% of the total weight of the hydrogel composition. In some embodiments, the catalyst is TMED and is present in an amount of about 0.004 wt% to about 0.08 wt% of the total weight of the hydrogel composition.

The function of the free radical initiator is to generate free radicals that initiate the formation of the polymer network of the hydrogel composition. Non-limiting examples of free radical initiators include Ammonium Persulfate (APS), riboflavin-5 '-phosphate (salt), riboflavin-5' -sodium phosphate, peroxides such as dialkyl peroxides, hydroperoxides, diacyl peroxides, or azo compounds (i.e., -N ═ N-moieties). In some embodiments, the initiator is a photoinitiator. Non-limiting examples of photoinitiators include ethyl (2,4, 5-trimethylbenzoyl) phenylphosphinate (TPO-L), bisacylphosphine oxide (BAPO), 2-hydroxy-2-methylpropiophenone, methyl benzoylformate, isoamyl 4- (dimethylamino) benzoate, 2-ethylhexyl 4- (dimethylamino) benzoate, or diphenyl (2,4, 6-Trimethylbenzoyl) Phosphine Oxide (TPO). Additional non-limiting examples of suitable photoinitiators include 1-hydroxycyclohexyl phenyl ketone (Irgacure 184), 2-dimethoxy-2-phenylacetophenone (Irgacure 651), and 2-methyl-1- [4- (methylthio) phenyl ] -2- (4-morpholinyl) -1-propanone (Irgacure 907), hydroxyacetophenones, phosphine oxides, benzophenones, and lithium phenyl-2, 4, 6-trimethylbenzoylphosphinate (LAP).

In some embodiments, the initiator is present in an amount of about 0.01% to about 1%, about 0.01% to about 0.9%, about 0.01% to about 0.8%, about 0.01% to about 0.7%, about 0.01% to about 0.6%, about 0.01% to about 0.5%, about 0.01% to about 0.4%, about 0.01% to about 0.3%, about 0.01% to about 0.2%, about 0.01% to about 0.1%, from about 0.02 wt% to about 1 wt%, from about 0.03 wt% to about 1 wt%, from about 0.04 wt% to about 1 wt%, from about 0.05 wt% to about 1 wt%, from about 0.06 wt% to about 1 wt%, from about 0.07 wt% to about 1 wt%, from about 0.08 wt% to about 1 wt%, from about 0.09 wt% to about 1 wt%, or from about 0.1 wt% to about 1 wt%. In some embodiments, the initiator is APS and is present in an amount from about 0.01 wt% to about 1 wt% of the total weight of the hydrogel composition.

In some embodiments, the initiator is present in an amount from about 0.01 wt% to about 0.05 wt%, from about 0.01 wt% to about 0.06 wt%, from about 0.01 wt% to about 0.07 wt%, from about 0.01 wt% to about 0.08 wt%, from about 0.01 wt% to about 0.09 wt%, from about 0.01 wt% to about 0.1 wt%, from 0.02 wt% to about 0.15 wt%, from about 0.02 wt% to about 0.16 wt%, from about 0.02 wt% to about 0.17 wt%, from about 0.02 wt% to about 0.18 wt%, from about 0.02 wt% to about 0.19 wt%, from about 0.01 wt% to about 0.2 wt%, or from about 0.02 wt% to about 0.25 wt% of the total weight of the hydrogel composition. In some embodiments, the initiator is APS and is present in an amount from about 0.02 wt% to about 0.24 wt% of the total weight of the hydrogel composition.

In some embodiments, the hydrogel includes dimethylacrylamide monomer (DMAm), sodium alginate block copolymer (p (sa)), and water. In some embodiments, the hydrogel composition further comprises MBA, TMED, CA, and APS. In some embodiments, the DMAm is present in an amount of about 3.3 wt% to about 14.83 wt% of the total weight of the hydrogel composition; and in some embodiments, the DMAm is present in an amount of about 8.3 wt% to about 9.8 wt%. For example, the DMA concentration may be designed to affect elasticity and conformability. In some embodiments, the p (sa) is present in an amount from about 0.52 wt% to about 5.53 wt% of the total weight of the hydrogel composition. In some embodiments, the MBA is present in an amount from about 0.041 wt% to about 3.44 wt% of the total weight of the hydrogel composition. In some embodiments, the TMED is present in an amount of about 0.004 wt% to about 0.02 wt% of the total weight of the hydrogel composition. In some embodiments, the CA is present in an amount of about 0.14 wt% to about 0.23 wt% of the total weight of the hydrogel composition. In some embodiments, the APS is present in an amount from about 0.0198 wt% to about 0.235 wt% of the total weight of the hydrogel composition. In some embodiments, the hydrogel further comprises water (e.g., degassed water) in an amount of about 75.65 weight% to about 95.98 weight% of the total weight of the hydrogel composition.

In some embodiments, the hydrogel includes dimethylacrylamide monomer (DMAm), sodium alginate block copolymer (p (sa)), and water. In some embodiments, MBA, TMED, CA, and APS. In some embodiments, the DMAm is present in an amount of about 3.3 wt% to about 14.83 wt% of the total weight of the hydrogel composition; and in some embodiments, the DMAm is present in an amount of about 1 wt% to about 40 wt%. For example, the DMA concentration may be designed to affect elasticity and conformability. In some embodiments, the p (sa) is present in an amount from about 0.5 wt% to about 25 wt% of the total weight of the hydrogel composition. In some embodiments, the MBA is present in an amount from about 0.04 wt% to about 10 wt% of the total weight of the hydrogel composition. In some embodiments, the TMED is present in an amount of about 0.004 wt% to about 1 wt% of the total weight of the hydrogel composition. In some embodiments, the CA is present in an amount from about 0.01 wt% to about 1 wt% of the total weight of the hydrogel composition. In some embodiments, the APS is present in an amount from about 0.01 wt% to about 1 wt% of the total weight of the hydrogel composition. In some embodiments, the hydrogel further comprises water (e.g., degassed water) in an amount of at least about 50 weight percent of the total weight of the hydrogel composition.

In some example embodiments, the hydrogel composition may be formed into a hydrogel interface pad that includes more than 91% by weight water at the expense of other ingredients (e.g., p (sa) or DMAm) to produce a more fragile hydrogel pad, e.g., a hydrogel interface pad that includes 95% by weight water.

Example embodiments of Hydrogel Interface Pads (HIPs)

In various embodiments, an example hydrogel composition can be configured as a semi-rigid pad, referred to herein as a Hydrogel Interface Pad (HIP). In some exemplary embodiments of the present disclosure, the HIP is comprised of two water-soluble polymer networks: primary (1 °) scaffold (scaffold) and secondary (2 °) sacrificial grafts.

FIGS. 3A-3D depict the chemical structures of the components of an example HIP. Fig. 3A is the chemical structure of DMA, and fig. 3B is the chemical structure of MBA. The 1 ° scaffold consists of DMA monomers as shown in figure 3C polymerized via free radical vinyl addition and crosslinked by MBA monomers (MBAm) as shown in figure 3D. DMA monomers are used instead of DMA terminated (terminated) polymers to produce widely cross-linked polymers with long chain lengths for strength and elasticity. Terminated poly (DMAm) chains that crosslink via a vinyl addition reaction produce polymers with shorter chain lengths, resulting in brittle, rigid hydrogels. The extensive degree of crosslinking and polymerization in the 1 ° network increases the elasticity and conformability of the poly (DMAm) hydrogel while increasing the burst pressure. Additional strength is achieved by intramolecular interactions such as H-bonding and polymer entanglement.

FIGS. 4A-4C depict the chemical structure of the polymer chains of an example HIP. The 2 ° network consists of capped chains of p (sa) block copolymers further consisting of linear β -d-mannuronate (M) (see fig. 4A) and kinked α -l-guluronic acid (guluronate) (G) (see fig. 4B) homogeneous block polymers as well as heterogeneous curved poly (MG) (see fig. 4C) block polymers.

FIG. 4D depicts a polymer network highlighting the ion-ion junctions between the polymer chains of an example HIP. The resulting polymer is a series of amorphous regions joined to a series of ordered regions in an ion-ion junction mesh having a configuration similar to an egg carton, as shown in fig. 4D. High molecular weight chains generally have higher viscosities, which increases SA hydrogel strength and haze by more chain entanglements and ion-ion junctions, while low molecular weight chains have lower viscosities, which improves gel clarity (clarity) at the expense of gel strength due to fewer ion-ion junctions and entanglements.

The mechanical properties of SA hydrogels can also be tuned by adjusting the p (SA) block polymer composition of the G and M blocks. High G-block concentrations increase SA hydrogel haze, stiffness and strength by increasing chain ion-ion junction density, while low G-block concentrations increase SA hydrogel clarity, elasticity and brittleness by decreasing chain ion-ion junction density.

Under tension, DMAm hydrogels undergo significant elastic deformation before plastic deformation and rapidly fail shortly thereafter. Low fracture toughness leads to rapid failure in the plastic region, with the result that the poly (DMAm) chains and covalently crosslinked precipitation fractures around localized stress sites, such as small cracks and fissures, propagate (propagate) as large cracks.

Under compression, the SA hydrogel will undergo plastic deformation by: the G blocks are released (decompressed) around the divalent cations to dissipate the stress that causes strain hardening as the polymer structure compresses. Once the compressive load is removed, the G block will reform or "recompress" (re-zip) around the divalent cation. Like DMAm hydrogels, SA alginate hydrogels have low fracture toughness because the ion-ion junctions break easily at localized stress regions.

Because both poly (DMAm) and p (sa) hydrogels have low fracture toughness, neither can be used as acoustically transparent scaffolds and acoustic couplants amenable to clinical use. However, in combination, the mechanical properties of the HIP Dual Interpenetrating Network (DIN) are greater than the sum of its parts. Grafting p (sa) to poly (DMAm) by covalent bonds dissipates local stress across the bulk of the material while maintaining the poly (DMAm) backbone.

FIGS. 5A-5D show a set of graphs of 1 and 2 network morphology and strain (λ) for crack propagation under tensile load_c) The following correlation with local stress dispersion and fracture toughness is shown in the crack initiated HIP specimens. Specifically, FIG. 5A is a schematic representation (labeled 500A) of a HIP undergoing a crack propagation test in which stress occurs at three circular regions, referred to as region (#1) represented by 500B, region (#2) represented by 500C, and region (#3) represented by 500D. Region 500B refers to a low stress region of hydrogel 500E, region 500C refers to a crack propagation region of hydrogel 500E, and finally, region 500D refers to a hydrogel fission (mission) line of hydrogel 500E. When hydrogel 500E is placed between clamps 500F and a force 500G is applied to hydrogel 500E, stress occurs, resulting in stress regions 500B, 500C, and 500D. Fig. 5B-5D are enlargements of depictions of stress regions #1, #2, and #3, respectively.

Fig. 5B represents the low stress region #1 depicted in fig. 5A (labeled 500B). In the diagram of fig. 5B, 502B represents a1 ° network, where 503B represents the terminated end of the 1 ° network. 505B represents a 2 ° network. 501B is a covalent bond between 1 ° network 502B and 2 ° network 505B. 504B represents covalent bonding between the 1 ° networks 502B. 506B represents the entanglement between the 1 ° network 502 and the 2 ° network 505B, and 507B represents the ion-ion junction formed between the 2 ° networks in the case of an interposed divalent cation 508B.

In this example implementation, at zero or minimum stress, the 1 ° network and 2 ° network ion-ion junctions are below the covalent and ionic crosslink burst pressures, shown in the minimum stress region (#1) in fig. 5B. Covalent bonds between several 1 ° networks give the polymer mesh size (#), which determines the hydrogel swelling and mechanical properties. Long crosslinks between the 1 ° network (1 ° -1 °) produced soft, compliant, elastic gels, while short 1 ° -1 ° crosslinks had firm, elastic and hard gels. The additional strength is achieved by entanglement of the 1 ° network, which gives the HIP additional strength. Emphasis on 1 ° network radical quenching is presented by showing radical termination of 1 ° network chains. Divalent ion-ion junctions (2 ° -2 °) were also shown to involve (influence) p (sa) G-block compression and release, while dispersing local stress.

Fig. 5C represents a local stress region #2 (labeled 500C) at the crack but prior to crack propagation. In fig. 5C, 503C represents a tensile force flow applied to a 2 ° network ionic junction that releases and dissipates the load from tensile force flow 503C. Tensile force flow 503C causes the 2 ° network to travel as shown at 501C, also causing dissociation of divalent cations 504C. This together minimizes the loading on the intact crosslinks 505C.

At the local stress site (#2) in fig. 5C, the 1 ° network elongates and the majority of the stress concentrated at the crack focus is redirected by the force flow (arrows) from the 1 ° network to the 2 ° network. Upon overloading, the 2 ° -2 ° junctions dissociate and the stored energy is dispersed throughout the medium, maintaining a covalently bonded 1 ° network. The 2 ° graft is mobile like the 1 ° network chain and newly forms 2 ° to 2 ° junctions, providing additional shear resistance. Thus, by bridging cracks through the sacrifice and regeneration of 2 ° -2 ° junctions, a1 ° network can achieve the maximum polymer chain elongation that was previously hindered by poor fracture toughness.

Cyclically elongating and relaxing the HIP without time recovery causes mechanical hysteresis, but for the same mechanical phenomena, a lesser degree of P (SA) stress-strain hysteresis is observed. Because hysteresis is observed as follows: the 2-2 knots break, after which they can reform, yielding a more ductile HIP with a wider elastic zone and lower fracture toughness. Healing can be accelerated as follows: low heat is used to increase the G block and divalent cation mobility to reform the 2 ° -2 ° junctions. Finally, when healed for one day under humid conditions, nearly all 2 ° -2 ° junctions recover and mitigate (improve) the compromised HIP fracture toughness.

FIG. 5D represents crack propagation and 1 ° network cracking at z region #3 (labeled 500D). In fig. 5D, the stress causes dissociation of the cation 501D and breaks the 1 ° network bond 502E. The t.f.s. flow 502G along the 1 ° network is under tensile load and once the material is at rest (at rest), the 2 ° -2 ° ionic junction 502H recovers. 502F represents hydrogel fission.

For applications, creating a tough, compliant, malleable HIP with a desired set of acoustic properties requires tuning of 1 ° and 2 ° networks, as well as the concentration of initiator. Therefore, it is of utmost importance to understand the effect of the concentrations of the ingredients on the mechanical properties of the HIP and to limit the impact to avoid unfavourable brittleness and hardness of the HIP.

Fig. 6A and 6B show diagrams depicting a super aggregate hydrogel. For example, sodium alginate is an anionic polysaccharide and block copolymer that is crosslinked via ion-ion junctions in the presence of divalent cations and is a HIP sacrificial secondary network grafted to a primary network. Excess divalent cations create super aggregates; dispersing energy across an insufficiently dense crosslinked network in the bulk material during plastic deformation, but improving the yield stress of the material at the expense of fracture toughness. In the super-aggregate, all G blocks in p (sa) are occupied by divalent ion 600B to form an ion-ion junction, while additional divalent ion 600A dissociates in the aqueous dispersion medium, as shown in fig. 6A. For an infinitesimal divalent ion concentration, few G blocks are occupied by divalent cation 600B to create ion-ion junctions, forming a weak, brittle hydrogel, as shown in fig. 6B. Few ion-ion junctions are insufficient in dispersing local stresses, easily "relaxing" and rapidly propagating cracks through the material.

Fig. 7A and 7B show diagrams depicting a weak, brittle hydrogel. Long poly (DMAm) polymers are composed of reactive allylamide monomers polymerized by free radical vinyl addition and constitute the HIP primary structural network. Upon propagation, the MBA crosslinker reacts with the free radical (DMAm) chain, bonding the two poly (DMAm) chains together. As more crosslinker is added to the solution, the crosslink length decreases, as shown by the circled region 700A in fig. 7A. Low molecular weight crosslinks break more easily under stress, resulting in brittle high modulus poly (DMAm) hydrogels. Too little crosslinker also produces a brittle poly (DMAm) hydrogel. Adding a trace amount of cross-linking agent to the solution reduces the amount of cross-linking, as shown in the shaded area 700B in fig. 7B; as a result, there are fewer crosslinks to dissipate the force from the local stress sites across the bulk material, resulting in fewer crosslinks to overload and blow out.

Fracture toughness was also optimized by adjusting the concentration of 1 ° network monomer relative to 2 ° network block copolymer. Decreasing the concentration of DMAm versus p (sa) increases the elastic modulus while decreasing the fracture toughness and critical elongation (critical stretch). HIPs with more P (SA) exhibit greater shear resistance from more ion-ion junction interactions, reducing HIP plasticity and fracture toughness. For example, increasing the ratio of DMAm to p (sa) decreases the critical elongation, fracture toughness, and elastic modulus. More poly (DMAm) reduces p (sa) graft density and resistance to material shear; however, with less p (sa) grafting, less sacrificial bonds are available to dissipate localized forces, reducing HIP fracture toughness.

Eventually enough of the sacrificial network is destroyed and approaches (approaches) the 1 ° network maximum elongation, which concentrates the force flow along the 1 ° network. These forces build up and irreversibly break the 1 ° -1 ° crosslinks, chain entanglements, and the 1 ° chains themselves, in a morphology similar to that exhibited at the cleavage line (#3) where the hydrogel is cut off as shown in fig. 5D. After rupture, the 1 ° and 2 ° chains are pulled apart from each other under tensile load (indicated by the dashed lines) and relax after failure. Once relaxed, the 2-2 knot reforms and allows half of the HIP to heal; however, HIPs cannot be recovered along the fission.

In various embodiments, the hydrogels of the present disclosure are configured to produce a polymer matrix with ionic junctions for the sacrificial network to dissipate concentrated stress regions and covalent bonds for the structural network to provide elasticity and strength. The 1 ° network is produced via a radical vinyl addition reaction, which dominates the elasticity and strength of the HIP.

The free radical vinyl addition chain reaction is initiated when the initiator produces a free radical monomer or a free radical chain intermediate which subsequently produces another free radical monomer or chain intermediate. This process continues until most of the free radicals react, while the remaining free radicals are unable to react due to the physical forces that limit their reaction. The process is summarized as follows.

a) And (3) initiation:

v_i＝k_i[I] (3)

b) growth (propagation):

c) and (4) terminating:

the initiation step is a fast step of the reaction, in which the initiator (I) dissociates and generates free radicalsFree radicalFurther generating free radical monomers or chainsRate of initiation (v)_i) To initiate a reaction constant (k)_i) And initiator concentration. During the propagation step, the free radical chain is linked with other chains (M)_n) Reaction of the other chain (M)_n) And become free-radically reacted. Increased steady state rateThe product of the rate initiation constant, the concentration of initiator, and the fraction of successful free radical chain initiation (f) for both terminal chain ends to react with the other chain, which in turn generates new free radical terminal ends. The successful radical chain initiation fraction depends on solution temperature, viscosity, and steric hindrance.

Termination can result in one of three ways: reciprocal termination, disproportionation, and chain transfer. Mutual termination results in longer chain lengths and is therefore a desirable termination step. Disproportionation leads to termination of free radicals on both chains and to shorter chain lengths. Chain transfer results in shorter chain lengths for the radical donor, while the radical acceptor becomes chemically active. Steady State Rate of termination by assuming that chain transfer and disproportionation are minimalBecomes two radical terminal ends of the reaction, terminating the reaction constant (k)_t) And the concentration of free radical chains.

From the initiation, propagation, and termination steps, a net steady state response is generated.

d) The net reaction:

net rate of growth (v)_p) Is the total growth reaction constant (k)_r) The initiator concentration, and the concentration of chain or monomer present in the solution. Since this isStage reaction, the monomer concentration (first stage) will experience an exponential decay in concentration, while the initiator concentration will decay at half the rate of the monomer concentration. Since the free radical chains are less stable than the free radical initiator, the free radical chains react with each other faster than the initiator reacts with the free radical chains. In addition, the mutually reactive free radical initiators will produce more free radical initiators that will eventually quench as the reaction rate decreases.

From the rate of growth, the degree of polymerization (< N >) and the kinetic chain length (v) can be calculated.

e) Degree of polymerization

<N>＝2v (18)

Kinetic chain length is the ratio of the rate of chain growth to the rate of radical generation; thus, increasing the concentration of free radicals relative to the concentration of monomer chains will increase kinetic chain length. The degree of polymerization of a linear chain is directly proportional to the kinetic chain length. Thus, an increase in kinetic chain length results in a two-fold increase in the degree of polymerization.

Since the 1 ° network polymerizes via vinyl addition reactions, the composition of the ingredients will have a significant impact on the mechanical and acoustic properties of the hydrogel. Too much initiator will produce HIP with very short chains, which increases the viscosity of the solution, but will not produce a semi-solid material. On the other hand, too little initiator reduces the reaction rate to slowly progress (creep) and can result in higher concentrations of residual monomer if the radical vinyl addition reaction is quenched before completion.

In a similar manner, too much catalyst enhances the rate of initiation and propagation, which results in shorter chain lengths, resulting in brittle, inelastic HIP. Conversely, a small amount of catalyst may increase the reaction duration from hours to days. While longer reaction durations may theoretically result in longer chain lengths, the increase in solution viscosity during gelation will frequently terminate and grow less and increase the likelihood that oxygen will quench the vinyl addition reaction, resulting in HIP with significant concentrations of residual monomers and free radicals and greater variability in mechanical properties.

The excess amount of monomer for the 1 ° network gives HIP long chain length and strength, but also retains a significant amount of residual monomer as the reaction proceeds towards gelation which increases with increasing solution viscosity. At the other extreme, an infinitesimal amount of monomer will reduce the growth rate and residual monomer concentration, but produce a hard and brittle HIP with small kinetic chain length, because there is not enough monomer in solution to produce a long polymer chain.

Environmental factors such as temperature, humidity and oxygen content should be controlled for consistent mechanical and acoustic properties. Increasing the temperature increases the reaction rate and decreases the average polymer chain length, which makes HIP brittle and hard. High Relative Humidity (RH) can degrade the initiator and catalyst prior to reaction in solution, and reduce the degree of polymerization and increase the amount of residual monomer in the HIP. In addition, O in solution₂Can be quenchedThe radical vinyl groups are quenched and harmful radicals and residual monomers are left on the surface of the HIP. Furthermore, the mold container has an impact on the surface morphology and chemistry, which in turn affects the swelling properties and biocompatibility of the HIP.

As discussed above, the disclosed hydrogel compositions and articles are designed to provide certain mechanical and acoustic properties, including, for example, fracture toughness, elasticity, transparency, mechanical tunability, and acoustic tunability, which makes the disclosed hydrogels suitable for three-dimensional tomographic ultrasound applications, including ultrasound imaging and doppler distance diagnostic studies.

Water is an effective acoustic transmission medium that makes up the majority of the HIP composition to negligibly attenuate the US waves propagating from the transducer. DIN is a continuous phase consisting of 1 ° and 2 ° networks, while water is the dispersed phase in HIP, resulting in a low bulk modulus semisolid material that can compress and expand (swell) without significant resistance, doubling as an effective US wave transmission medium.

FIG. 8 shows a simple illustration (labeled 800) of acoustic transmission by an example HIP into a heterogeneous substrate containing a homogeneous body. As shown in the diagram, the arrows represent the trajectory of the US wave propagating in the medium. Transmitted energy (T) may be refracted (T) and reflected (R) when interacting with material interfaces. Transmitted and refracted energy may be refracted and reflected several times in a medium that scatters energy. The energy (E) of the transmitted signal is also lost as heat and wave diffraction, which is added to all the refraction and scattering energy (power) through the medium to yield the total energy loss (Δ E) of the transmitted signal.

At the HIP, substrate/target volume interface, some of the propagating waves are reflected back to the transducer, while the rest of the acoustic energy is transmitted into the substrate. The impedance mismatch between the transducer matching layer and the skin interface is minimized, refracting the US waves only slightly. Inevitably, the transmitted signal encounters the homogeneous body, refracting, diffracting, absorbing and scattering the transmitted US wave; in summary, the total energy loss (Δ Ε) of the transmitted signal is dispersed throughout (is dispersed throughout) the surrounding medium. For each body in the substrate, the transmitted US waves will be reflected at the material interface and lose energy as described above. There are multiple interfaces, thus reducing the initial curvature of the US wave propagating through the acoustically transparent HIP increases the number of reflections and improves the received reflected signal strength.

Acoustic transmission is illustrated in FIG. 8, where the signal is represented by 800A (T)₁) The energy represented is transmitted from transducer 800B and through HIP 800C. From 800A (T)₁) Some of the energy of (c) is reflected back to the transducer 800B at the substrate surface 800D, as by 800E (R)₁) Shown. From 800F (T)₂) The remaining energy represented is transferred to the homogeneous material 800E. Once energy 800F (T)₂) Is transmitted to the homogeneous material 800G, energy 800F (T)₂) Transmitted through the homogeneous material 800G and reflected back to the transducer 800B. For example, energy 800F (T)₂) Is refracted at an angle (theta) upon entering homogeneous material 800G, with the resulting refractive energy being represented as 800H (T'₂₃). Refractive energy 800H (T'₂₃) Then propagates through the homogeneous material 800G and is refracted at an angle (θ) upon exiting the homogeneous material 800G, such as by 800I (T)₃) Shown. However, energy 800F (T)₂) Once propagating through the homogeneous material 800G and contacting the surface of the homogeneous material 800G, is reflected back to the transducer, as by 800K (R)₃) And (4) showing. Finally, energy 800F (T)₂) Does not enter the homogeneous material 800D, but is reflected back to the transducer 800B upon contact with the surface of the homogeneous material 800G, as by 800J (R)₂) Shown. The total energy loss from the process, as represented by 800L (Δ E), is dispersed throughout the homogeneous material 800G (throughout the homogeneous material 800G).

Table 1 shows the tested acoustic and mechanical properties of the example hydrogel compositions of various embodiments of semi-rigid HIP in accordance with the present technology (hydrogel samples 902, 903, and 904) and the example control hydrogel sample (901). Note that in table 1, "SOS" represents a sound speed (sound velocity); "Z" is acoustic impedance, "ATTN" is attenuation, "E" is Young's modulus, and "ε" is engineering strain. Pictures of sample hydrogels 901, 902, 903, and 904 are shown in fig. 9.

TABLE 1

Example implementation of hydrogel interface pad

The composition of HIP has been adjusted to produce a soft, compliant hydrogel that is conformable and encompasses the target site to bridge the air acoustic impedance boundary and is tough for clinical applications, as demonstrated in fig. 10A-10F. By adjusting the HIP composition-covalent and ionic cross-linkers, amount and type of 1 ° network monomers and 2 ° network block copolymers, and reaction rate-a range of different mechanical properties can be achieved while maintaining relatively constant sound velocity (SOS), acoustic impedance (Z), and Attenuation (ATTN), as shown in table 1.

Fig. 10A-10F show images of the flexibility, stretchability, and robustness of an example hydrogel interface pad 903. In particular, FIG. 10A shows the HIP before localized compression, in contrast to FIG. 10B, which shows the HIP after localized compression. Similarly, FIG. 10C shows the HIP before the handshake (squeezing), in contrast to FIG. 10D, which shows the HIP after the handshake. Finally, FIG. 10E shows the conformability characteristics of the HIP, and FIG. 10F shows the HIP under full (full) compression. Taken together, these demonstrations show that HIP903 is fracture resistant due to its toughness and elasticity.

In example implementations, example HIP 901 was used as a control hydrogel, consisting of a poly (acrylamide) (poly (aa)) and low viscosity p (sa)2 ° network possessing good elastic, conformability, and transparency properties. The waviness on the exposed surface of the HIP 901 is due to the surface tension difference during the gelling process. Example HIP903 was configured to have the same composition as HIP 901 without surface corrugation. Example HIP 904 is configured to have the same composition as the poly (aa) and p (sa) components of HIP 901 and HIP 903; however, example HIP 904 complements low viscosity p (sa) with high viscosity p (sa). Example HIP 902 was configured to have the same composition as p (sa) of HIP 901 and HIP903, while replacing poly (aa) with poly (dmam). In these implementations, all example HIPs are shown to have similar acoustic properties, with only differences in elastic modulus (E) and Ultimate Tensile Strength (UTS).

For example, the waviness of HIP 901 on the transducer side is due to interfacial tension between the air and solution boundaries during gelation, resulting in buckling and warping of the gel surface. HIP903 reduces the interfacial surface tension during gelation, eliminating all rippling. HIP 904 is supplemented with a high viscosity p (sa) and a low viscosity p (sa), which results in a significant reduction in the modulus of elasticity, resulting in a softer, more flexible HIP. The most flexible is HIP 902, which has the lowest modulus of elasticity while exhibiting similar toughness and acoustic energy transmission properties. By further adjusting the crosslinking reaction rate, process variables, and concentration and type of ingredients of HIP 902, a wide variety of different mechanical properties can be achieved for a wide variety of US inspection applications without sacrificing good acoustic transmission. As an extreme example, the deformation of HIP 902 (HIP 902') has the same SOS, ATTN, and Z as HIP 902, is excessively crosslinked to give a stiff and bendable hydrogel, as shown in fig. 11. The addition of excess divalent ionic crosslinker did not affect SOS (e.g., 1549m/s), ATTN (e.g., 0.07dB/cm MHz), and transparency, while exhibiting a significantly different elastic modulus (e.g., 302kPa) than HIP 902.

In some implementations, the example hydrogel interface pad can be coupled to an acoustic transducer probe (probe) device (e.g., an ultrasound scanner). Details of an example implementation of an ACOUSTIC transducer detection device that can be connected AND utilize an example HIP are described in U.S. publication No.2016/0242736A1, entitled "Acoustic Signal Transmission coatings AND coating media," the entire contents of which are incorporated by reference as part of the disclosure of this patent document for all purposes.

Example methods for making hydrogel compositions and articles

Fig. 12 shows an example embodiment of a method for making a hydrogel interface pad in accordance with the present techniques. The exemplary method, labeled 1200, includes process 1201, where DMAm is dissolved in Deionized (DI) water at Standard Temperature and Pressure (STP). The addition of DMAm to deionized water is an endothermic mixing process in which DMAm rapidly dissolves. Process 1201 then includes introducing SA to the DMAm solution. When SA is added to DMAm solution, the solution swells (expands), resulting inAggregate/fisheye formation, wherein gelled p (sa) encapsulates dry p (sa) powder (enclosing dry p (sa) powder inside). In some implementations, process 1201 of the method, e.g., DMAm-SA, is used to form a "stock solution" for subsequent reactions and maintain stability for an extended period of time (e.g., greater than 30 minutes). The method then includes process 1202, where gaseous argon (Ar), nitrogen (N) are used₂) Helium (He) or mixtures thereof to bubble and degas the DMAm-SA solution to remove traces of oxygen (O)₂). Next, the method includes a process 2013 in which the solution is placed in a vacuum chamber under reduced pressure to remove all external source gases. The degassed solution of N, N '-Methylenebisacrylamide (MBA) and N', N-Tetramethylethylenediamine (TMED) is then introduced to the DMAm-SA solution to make a "primed solution" ready for the subsequent polymerization treatment step as shown by process 2014. All solutions need to be O-free₂Otherwise radical quenching and catalyst oxidation will occur. Finally, the method includes a process 1205 in which a degassed solution of APS and CA is added to the priming solution to initiate an exothermic polymerization and crosslinking reaction, thereby forming a "gel-solvent" or "gel-sol" solution. After addition of the APS and CA solutions, the gel-sol was cast and cured in a mold for less than 8 hours to form HIP.

Table 2 shows example weight percent ratios (w/w) of each of the components added during the treatment step, along with their corresponding functions to the hydrogel.

TABLE 2

In some embodiments, the resulting gel-sol exhibits a longer propagation reaction step (i.e., has an increased pot life). Pot life is of great importance for small and large scale manufacture of HIP and for mitigating and/or preventing premature polymerization of the ingredients. For example, increasing the pot life of the gel-sol increases the time for entrapped air bubbles to escape from the gel-sol after casting the HIP, minimizing the risk of entrapped air in the cured HIP. This characteristic is significant because failure to remove and/or prevent bubble formation results in poor acoustic transmission-increased attenuation, less reflection, unwanted scattering and blurred ultrasound images-and impaired mechanical properties-local stress areas, lower tear strength and lower burst pressure.

The mesh size of the hydrogel depends on various parameters such as reaction rate, chain length, stereochemistry, intramolecular interactions and reaction conditions such as temperature, pressure and atmosphere.

Figure 13 depicts a mesh and corresponding electron microscope image of an example poly (DMA) hydrogel network comprising 95% water. The mesh of the hydrogel affects the balance of transparency, density, SOS, impedance, stiffness, strength, and swelling.

For example, in some implementations of method 1200, important considerations in making HIPs involve judicious selection of the amounts of both cationic and covalent crosslinking agents. For example, in the present exemplary method of making HIP, adding too much CA (i.e., cationic crosslinker) results in the formation of super aggregates, while too little CA results in the formation of super dispersions. The balance of too little CA (e.g., super dispersion) and too much CA (i.e., super aggregate) is depicted in fig. 4D. Similarly, too much MBAm (i.e., covalent crosslinker) results in a tiny mesh size, while too little MBAm results in a too large mesh size. Thus, 0.1382-0.23234 wt% CA and 8.290-9.815 wt% MBAm used in the manufacture of HIP903 of the present disclosure provide the best degree of aggregation and mesh size.

An additional consideration important to making flexible and strong HIPs is the degree of grafting that occurs when the secondary grafting sacrificial network component (e.g., sodium alginate) reacts with the primary structural network component (e.g., DMAm). Grafting provides the impact strength, energy dissipation, self-healing properties, mechanical hysteresis, and thermal hysteresis of HIPs. The exemplary HIPs of the present disclosure exhibit an optimal degree of grafting between SA and DMAm that provides the above characteristics.

However, for some acoustic signal propagation applications, it may be advantageous to utilize an acoustic couplant with acoustic impedance matching characteristics that is more rigid and less flexible than at least some of the earlier embodiments described above. For example, such a rigid acoustic couplant may include a hydrogel composition useful for: some ultrasound techniques and applications, for example, ultrasound imaging techniques that specifically utilize a flat transducer array and a flat surface of a target volume, where conformability of the couplant to the receiver is not a major challenge.

In some embodiments, the rigid acoustic coupling medium comprises a hydrogel composition comprising dimethylacrylamide monomer (DMAm), wherein DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%. In some embodiments of the hydrogel composition, DMAm is present in an amount from about 3.3 wt% to about 14.8 wt%.

In some embodiments, the rigid acoustic coupling medium comprises a hydrogel composition comprising sodium alginate block copolymer (p (sa)), wherein p (sa) is present in an amount of about 0.5% to about 25% by weight. In some embodiments of the hydrogel composition, p (sa) is present in an amount of about 0.5 wt.% to about 5.5 wt.%.

In some embodiments, the flat acoustic coupling medium comprises a hydrogel composition comprising dimethylacrylamide monomer (DMAm), wherein DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%. In some embodiments of the hydrogel composition, DMAm is present in an amount from about 3.3 wt% to about 14.8 wt%. In such embodiments, the flat acoustic coupling medium may exhibit brittle and/or weak mechanical properties, for example, where the material is subjected to significant loading with or without significant elastic strain, followed by abrupt failure as small cracks suddenly appear and propagate across the material. Significant loads may include compressive and tensile stresses. For example, the compressive stress before failure of a flat hydrogel comprising DMAm may comprise a range of about 100kPa to about 250kPa at 50-80% compression. For example, a flat hydrogel comprising DMAm may have a tensile stress prior to failure in a range from about 12.0kPa to about 20.0kPa at 25-50% elongation. Furthermore, flat hydrogels comprising DMAm can suddenly fail, for example, under elastic deformation.

However, DMAm hydrogels, while exhibiting potentially brittle and/or weak mechanical properties, can be durable for some conditions and useful in some applications. For example, if tensile or shear loads are applied to DMAm hydrogels, these hydrogels can suddenly fail between 25-50% strain; however, under compression, DMAm hydrogels can experience over 50% strain before bursting. In addition, DMAm hydrogels are typically viscous, which is desirable for applications where the gel must bond to a surface, such as in long-term static ultrasound examinations. Further, for example, for lumbar surgery using a laparoscopic ultrasound guided instrument, a large sheet of DMAm hydrogel may be deployed while the patient is prone to cover the thoracic and lumbar vertebrae of the patient. Because the gel is easily punctured, a laparoscopic tool lubricated with sterile water can puncture into the hydrogel and then the tissue, forming a sterile acoustically transparent cover (blanket) to guide the instrument to the VOI. During surgery, DMAm hydrogel adheres to the flat topography of the back while the ultrasound device transmits data about other vessels and organs adjacent to the tool. Notably, more conformable hydrogel interface pads can also be used with equal success, but will provide significantly greater tensile and shear strength.

In some embodiments, the flat acoustic coupling medium comprises a hydrogel composition comprising sodium alginate block copolymer (p (sa)), wherein p (sa) is present in an amount of about 0.5% to about 25% by weight. In some embodiments of the hydrogel composition, p (sa) is present in an amount of about 0.5 wt.% to about 5.5 wt.%. In some embodiments, a flat acoustic coupling medium may exhibit brittle and/or weak mechanical properties. In such embodiments, the flat acoustic coupling medium exhibits brittleness as follows: it experiences significant loading with or without elastic strain and then fails as a result of the formation and propagation of cracks or fissures across the hydrogel material as a result of the significant loading. Significant loads may include compressive and tensile stresses. For example, the compressive stress before failure of the hydrogel comprising alginate may comprise a range of about 200kPa to about 500kPa at 20-60% compression. For example, the tensile stress before failure of the hydrogel comprising alginate may comprise a range of about 4.5kPa to about 10.0kPa at 2-20% elongation. Furthermore, for example, hydrogels comprising alginate may suddenly fail under elastic deformation.

For example, there are practical applications where a more rigid p (sa) hydrogel may be applied to scan a flat area of the body in a linear array. In particular, since p (sa) hydrogel is non-adhesive, the p (sa) stent can easily slide on the skin of the patient, which is ideal for dynamic ultrasound examinations. For example, a patient with broken ribs may be scanned with a linear array of rigid p (sa) stents to scan the ribs near the surface of the skin. If the probe is used without a stent, the rib surface may not be distinguishable from other tissues because the rib is in close proximity to the transducer. In the case of stents, the ultrasound beam can be focused through the skin surface onto the bone, producing a sharp image of the bone beneath the cortex, fat layer, and ligament layer. Thus, rib fractures can be readily identified with medical ultrasound equipment instead of more expensive and cumbersome CT and MRI scans. A more conformal HIP can also be used in this case, but the additional conformality provides little additional benefit because the array is linear and the patient topography around the ribs is relatively flat.

Examples of the invention

The following examples illustrate several embodiments of the present technology. Other exemplary embodiments of the present technology may be provided before, or after, the examples listed below.

In some embodiments according to the present technology (example 1), the hydrogel composition includes a sodium alginate block copolymer (p (sa)), a dimethylacrylamide monomer (DMAm), and water, wherein p (sa) is present in an amount of about 0.5 wt% to about 25.00 wt%, DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%, and water is present in an amount of at least about 50.00 wt%, based on the total weight of the hydrogel composition.

Example 2 includes the hydrogel composition of any of examples 1-10, wherein DMAm is present in an amount from about 3.3 wt% to about 14.8 wt%.

Example 3 includes the hydrogel composition of any of examples 1-10, wherein DMAm is present in an amount from about 8.3 wt% to about 9.8 wt%.

Example 4 includes the hydrogel composition of any one of examples 1-10, wherein p (sa) is present in an amount of about 0.5 wt% to about 5.5 wt%.

Example 5 includes the hydrogel composition of any one of examples 1-10, wherein the water is present in an amount of at least about 75.6 weight percent of the total weight of the hydrogel composition.

Example 6 includes the hydrogel composition of any of examples 1-10, wherein the hydrogel composition further comprises N, N '-Methylenebisacrylamide (MBA), N', N-Tetramethylethylenediamine (TMED), calcium sulfate (CA), and Ammonium Persulfate (APS).

Example 7 includes the hydrogel composition of any one of examples 1-10, wherein the MBA is present in an amount of about 0.04 wt% to about 10.00 wt% of the total weight of the hydrogel composition.

Example 8 includes the hydrogel composition of any of examples 1-10, wherein the TMED is present in an amount of 0.004 weight% to about 1.00 weight% of the total weight of the hydrogel composition.

Example 9 includes the hydrogel composition of any one of examples 1-10, wherein the CA is present in an amount of about 0.01 weight% to about 1.00 weight% of the total weight of the hydrogel composition.

Example 10 includes the hydrogel composition of any one of examples 1-19, wherein the APS is present in an amount of about 0.01 wt% to about 1.00 wt% of the total weight of the hydrogel composition.

In some embodiments according to the present technology (example 11), the semi-rigid acoustic coupling medium comprises a hydrogel material comprising: sodium alginate block copolymer (P (SA)), dimethylacrylamide monomer (DMAm), and water.

Example 12 includes the semi-rigid acoustic coupling medium of any of examples 11-19, wherein p (sa) is present in an amount of about 0.5 wt% to about 25.00 wt%, DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%, and water is present in an amount of at least about 50.00 wt%, based on the total weight of the hydrogel composition.

Example 13 includes the semi-rigid acoustic coupling medium of any of examples 11-19, wherein p (sa) is present in an amount of about 0.5 wt% to about 5.5 wt%, DMAm is present in an amount of about 3.3 wt% to about 14.8 wt%, and water is present in an amount of at least about 75.6 wt%, based on the total weight of the hydrogel composition.

Example 14 includes the semi-rigid acoustic coupling medium of any of examples 11-19, wherein the semi-rigid acoustic coupling medium has a sound velocity of 1480-.

Example 15 includes the semi-rigid acoustic coupling medium of any of examples 11-19, wherein the semi-rigid acoustic coupling medium has an acoustic impedance of about 1.00-2.00 MRayls.

Example 16 includes the semi-rigid acoustic coupling medium of any of examples 11-19, wherein the semi-rigid acoustic coupling medium has an acoustic attenuation of about 0.001-1.00 dB/cm/MHz.

Example 17 includes the semi-rigid acoustic coupling medium of any of examples 11-19, wherein the semi-rigid acoustic coupling medium has a young's modulus of about 500.00kPa or less.

Example 18 includes the semi-rigid acoustic coupling medium of any of examples 11-19, wherein the hydrogel has an engineering compression and elastic strain greater than or equal to 50%.

Example 19 includes the semi-rigid acoustic coupling medium of any of examples 11-18, wherein the hydrogel material further comprises N, N '-Methylenebisacrylamide (MBA), N', N-Tetramethylethylenediamine (TMED), calcium sulfate (CA), and Ammonium Persulfate (APS).

In some embodiments according to the present technology (example 20), the hydrogel composition comprises sodium alginate block copolymer (p (sa)), dimethylacrylamide monomer (DMAm), and water, wherein p (sa) is present in an amount of about 0.5 wt% to about 5.5 wt%, DMAm is present in an amount of about 3.3 wt% to about 14.8 wt%, and water is present in an amount of at least about 75.6 wt%, based on the total weight of the hydrogel composition.

Example 21 includes the hydrogel composition of any of examples 20-26, wherein DMAm is present in an amount from about 8.3 wt% to about 9.8 wt%.

Example 22 includes the hydrogel composition of any one of examples 20-26, wherein the hydrogel composition further comprises N, N '-Methylenebisacrylamide (MBA), N', N-Tetramethylethylenediamine (TMED), calcium sulfate (CA), and Ammonium Persulfate (APS).

Example 23 includes the hydrogel composition of any one of examples 20-26, wherein the MBA is present in an amount of about 0.04 wt% to about 3.4 wt% of the total weight of the hydrogel composition.

Example 24 includes the hydrogel composition of any of examples 20-26, wherein the TMED is present in an amount of 0.004 weight% to about 0.082 weight% of the total weight of the hydrogel composition.

Example 25 includes the hydrogel composition of any one of examples 20-26, wherein the CA is present in an amount of about 0.13 wt% to about 0.23 wt% of the total weight of the hydrogel composition.

Example 26 includes the hydrogel composition of any one of examples 20-25, wherein the APS is present in an amount of about 0.02 wt% to about 0.24 wt% of the total weight of the hydrogel composition.

In some embodiments according to the present technology (example 27), the hydrogel composition includes dimethylacrylamide monomer (DMAm), wherein DMAm is present in an amount of about 1.0 wt% to about 40.00 wt%.

Example 28 includes the hydrogel composition of example 27, wherein DMAm is present in an amount from about 3.3 wt% to about 14.8 wt%.

In some embodiments according to the present technology (example 29), the hydrogel composition comprises a sodium alginate block copolymer (p (sa)), wherein p (sa) is present in an amount of about 0.5% to about 25% by weight.

Example 30 includes the hydrogel of example 29, wherein p (sa) is present in an amount of about 0.5% to about 5.5% by weight.

In some embodiments according to the present technology (example 31), the flat hydrogel includes dimethylacrylamide monomer (DMAm), wherein DMAm is present in an amount of about 1.00 wt% to about 40.00 wt%.

Example 32 includes the flat hydrogel of example 31, wherein DMAm is present in an amount from about 3.3 wt% to about 14.8 wt%.

Example 33 includes the flat hydrogel of any one of examples 31 or 32, wherein the flat hydrogel exhibits brittleness when: flat hydrogels experience significant loading with or without elastic strain and then fail as a result of the formation and propagation of cracks or fissures across the flat material. Significant loads may include compressive and tensile stresses. For example, the compressive stress before failure of a flat hydrogel comprising DMAm may comprise a range of about 100kPa to about 250kPa at 50-80% compression. For example, the tensile stress before failure of a flat hydrogel comprising DMAm may comprise a range of about 12.0kPa to about 20.0kPa at 25-50% elongation. Furthermore, flat hydrogels comprising DMAm can suddenly fail, for example, under elastic deformation.

In some embodiments according to the present technology (example 34), the flat hydrogel comprises a sodium alginate block copolymer (p (sa)), wherein p (sa) is present in an amount of about 0.5% to about 25% by weight.

Example 35 includes the flat hydrogel of example 34, wherein p (sa) is present in an amount of about 0.5 wt% to about 5.5 wt%.

Example 36 includes the flat hydrogel of any one of examples 34 or 35, wherein the flat hydrogel exhibits brittleness as follows: flat hydrogels experience significant loading with or without elastic strain and then fail as a result of the formation and propagation of cracks or fissures across the flat material. Significant loads may include compressive and tensile stresses. For example, the compressive stress before failure of a flat hydrogel comprising alginate may comprise a range of about 200kPa to about 500kPa at 20-60% compression. For example, the tensile stress before failure of a flat hydrogel comprising alginate may comprise a range of about 4.5kPa to about 10.0kPa at 2-20% elongation. Furthermore, flat hydrogels comprising alginate may suddenly fail, for example, under elastic deformation.

All numerical expressions such as pH, temperature, time, concentration and molecular weight (including ranges) are approximations that vary (+) or (-) by increments of 1.0 or 0.1, or alternatively +/-15%, or alternatively 10%, or alternatively 5%, or alternatively 2%, as appropriate. It will be understood that, although not always explicitly stated, all numerical values are preceded by the term "about". It is to be understood that such a range format is used for convenience and brevity, and should be interpreted flexibly to include numerical values explicitly recited as the limits of the range, and to include all the individual numerical values and sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a ratio within the range of about 1 to about 200 should be understood to include the explicitly recited limits of about 1 and about 200, but also to include individual ratios such as about 2, about 3, and about 4, as well as sub-ranges such as about 10 to about 50, about 20 to about 100, and the like. It will also be understood that, although not always explicitly stated, the reagents described herein are exemplary only and equivalents thereof are known in the art.

The term "about" as used herein, when referring to a measurable value such as an amount or concentration, etc., is intended to encompass a change of 20%, 10%, 5%, 1%, 0.5%, or even 0.1% of the specifically recited amount.

The term or "acceptable", "effective" or "sufficient" when used to describe the selection of any component, range, dosage form, etc. disclosed herein is intended that the component, range, dosage form, etc. is suitable for the purposes disclosed.

The word "comprising" is intended to mean that the compositions and methods include the recited elements, but not exclude others. "consisting essentially of … …" when used to define compositions and methods is meant to exclude other elements having any substantial meaning for combination for the purpose stated. Thus, a composition consisting essentially of the elements as defined herein shall not exclude other materials or steps that do not materially affect the basic and novel characteristics of the claimed invention. "consisting of … …" shall mean more than trace elements and substantial method steps excluding other ingredients. Embodiments defined by each of these transition terms are within the scope of the present invention.

It is intended that the specification, together with the drawings, be considered exemplary only, with the examples being meant to be exemplary. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. In addition, use of "or" is intended to include "and/or" unless the context clearly indicates otherwise.

While this patent document contains many specifics, these should not be construed as limitations on the scope of any invention or of what may be claimed, but rather as descriptions of features that may be specific to particular embodiments of particular inventions. Some of the features described in this patent document may also be implemented in combination in a single embodiment, in the context of separate embodiments. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a subcombination or variation of a subcombination.

Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. Moreover, the separation of various system components in the embodiments described in this patent document should not be understood as requiring such separation in all embodiments.

Only a few implementations and examples have been described, and other implementations, enhancements, and variations can be made based on what is described and illustrated in this patent document.