Device, system and method for controlled use of a species utilizing functionalized scaffolds or hydrogels

Abstract

The present disclosure relates to a system for controlled use of a first species. The system (100) comprising a scaffold and / or a hydrogel (130) and an outlet (113), wherein said outlet (113) exits into an inner region (135) enclosed by said scaffold and / or hydrogel (130). The outlet (113) is arranged to allow the first species (121) into said inner region (135). Said scaffold and / or hydrogel (130) comprises a functionalization of a first region (131) of said scaffold and / or hydrogel (130). Said functionalization of a first region (131) is arranged to reduce movement of said first species (121) between said inner region (135) and the environment outside said scaffold and / or hydrogel (130).

Description

[0001] Title

[0002] Device, system and method for controlled use of a species utilizing functionalized scaffolds or hydrogels

[0003] TECHNICAL FIELD

[0004] The present disclosure relates to molecular release systems, drug release systems, diffusion hindrance or guiding, functionalized hydrogels and scaffolds, electrokinetic transport systems, ion exchange membranes, secure and reliable drug release.

[0005] BACKGROUND ART lontronic devices allow for on-demand diffusional drug delivery and drug delivery systems with electronic precision and control. Typically, an actively transported species is delivered to a location to then reach and interact with a target species in the environment. Typically, once devices actively transport species into the environment the control of said species is lost. In the case of a device or reservoir rupture, all species may leak into the surrounding environment and potentially causing devastating side effects with no technological solution to contain or handle the leaked species. Solutions in the field of bioorthogonal chemistry aim to regain some of said lost control and reduce risks in biological environments by utilizing species designed to selectively react with a type of corresponding species. For solutions utilizing bioorthogonal chemistry, as well as in several other release or activation systems, it is often of critical importance that species configured to trigger a reaction arrive at the corresponding target species at the right time, place, and concentration.

[0006] Such control is of great importance in the case of highly potent drugs that could cause a severe health risk in case of an uncontrolled release. This uncontrollable release may occur if the device or reservoir is ruptured, and the entire potent drug content, or corresponding species thereof, is released at once or if passive leakage of a species over time leads to dangerous concentrations of either the species itself and / or products produced as it reacts. There is a demand for better control and reliability in release systems in order for them to safely operate at their full potential. SUMMARY OF THE INVENTION

[0007] One object of the invention is to provide improved control of species and protection from species in the environment surrounding a scaffold or hydrogel, such as controlling concentration of ionic species in space and time beyond the limited concentration range of traditional iontronic delivery.

[0008] This has in accordance with the present disclosure been achieved by means of a system for controlled use of a first species. The system comprises a scaffold and / or a hydrogel and an outlet, wherein said outlet exits into an inner region enclosed by said scaffold and / or hydrogel, wherein the outlet is arranged to allow the first species into said inner region, and wherein said scaffold and / or hydrogel comprises a functionalization of a first region of said scaffold and / or hydrogel, wherein said functionalization of a first region is arranged to reduce movement of said first species between said inner region and the environment outside said scaffold and / or hydrogel.

[0009] This has the advantage of allowing the functionalized scaffold or hydrogel to control the behaviour of the transported first species after being released into the inner region. This further allows the inner region to be protected from any corresponding first species located the environment outside entering the inner region, while still being fluidly connected to said environment via the scaffold or hydrogel.

[0010] In some embodiments, the functionalization in the first region comprises a first capture species, wherein said first capture species is arranged to chemically interact with the first species, and wherein said interaction causes binding of the first species to the first capture species.

[0011] This has the advantage of allowing first species to be outright captured and immobilized in parts of the scaffold or hydrogel where first species moving through is not desired, such as between the inner region and the environment outside. This further has the advantage of allowing parts of the scaffold or hydrogel to be functionalized with large amounts of capture species to increase the probability of capture, thereby improving control of movement of the first species. Typically, the capture species is covalently bound to the captured first species and the scaffold or hydrogel, such that the probability of bound first species escaping is very low. In some embodiments, said scaffold and / or hydrogel comprises a functionalization of a second region of said scaffold and / or hydrogel with a first target species, wherein the first target species is arranged to chemically interact with the first species, and wherein interaction causes release of a first releasable species from the first target species.

[0012] This has the advantage of allowing the first species to trigger a release of a releasable species in a part of scaffold or hydrogel. The second region with the first target species combined with the first region being arranged to reduce movement of said first species, allows for designing the system to control the probability of individual first species reaching parts of the scaffold or hydrogel as well as the type of releasable species that may be released upon reaching said part of the scaffold or hydrogel.

[0013] In some embodiments, the functionalization of said first region comprises a covalently bound inactivating species arranged to chemically interact with the first species, wherein interaction causes chemically inactivating the first species from performing said interaction with said first target species.

[0014] This has the advantage of allowing first species to be inactivated in parts of the scaffold or hydrogel where first species moving through intact is not desired, such as between the inner region and the environment outside. This further has the advantage of allowing parts of the scaffold or hydrogel to be functionalized with large amounts of inactivating species to increase the probability of inactivating the first species, thereby improving control of movement of non-inactivated first species. Functionalization with inactivating species and capture species represent two options for making the first species chemically react such that it is unable to react at other locations, either by being immobilized or being chemically altered.

[0015] In some embodiments, the reactions between the first species and first capture species are bioorthogonal, and / or wherein the reactions between the first species and inactivating species are bioorthogonal, and / or wherein the reactions between the first species and first target species are bioorthogonal.

[0016] This has the advantage of allowing the scaffold or hydrogel to be fluidly connected to a biological environment where biological processes are occurring, such as an environment comprising microorganisms or a cell culture, without interfering with or being interfered by compounds and biomolecules in or from the biological environment. In some embodiments, the system comprises a device comprising said outlet, wherein the device comprises one or more reservoirs arranged to hold said first species, and transport means arranged to transport the first species from the reservoir out into said inner region via the outlet.

[0017] This has the advantage of allowing control by active transport of the first species to the inner region. This further has the advantage of allowing the amount of the first species entering the inner region to be controlled in time by utilizing a schedule with transport rate over time.

[0018] In some embodiments, the device comprises one or more reservoirs that are arranged to hold at least the first species and a second species, and the transport means are arranged to transport said first species and to transport said second species to the outlet, wherein the scaffold and / or hydrogel is functionalized with the first target species and a second target species each arranged to chemically interact with a corresponding first and second species and upon interacting cause release of corresponding first and second releasable species, wherein the first region is functionalized with capture species and / or inactivating species arranged to bind and / or inactivate said first and second species, and wherein said interactions of the first and second species are bioorthogonal and orthogonal to each other.

[0019] This has the advantage of allowing the device to transport two species arranged to each interact with corresponding target species to release corresponding releasable species. This further has the advantage of allowing, by functionalizing different parts of the scaffold or hydrogel with different amounts of the first and second target species, control of the release of releasable species in said different parts of the scaffold or hydrogel. This further has the advantage of allowing an object intended to be exposed to the releasable species to be exposed by the first and second releasable species with different concentrations and timing. Control of timing and concentration may allow for optimal therapeutic approaches for individual patients that comprise not just one drug but a plurality of drugs that need to be precisely tuned in respect to their spatiotemporal release and also relative concentrations to each other. Such complex choreographed (concentration, time, sequence) cascade processes aiming to achieve individually programmable release of multiple compounds with distinct concentration / time profiles are not feasible using existing methods. In some embodiments, said first region encloses the device.

[0020] This has the advantage of allowing a system to be designed to avoid the environment accessing the inner region via any gaps between the device and the scaffold or hydrogel, such as along the outside of the transport means. This further has the advantage of allowing any first species inadvertently leaving the device via other paths than the outlet to be captured or inactivated before reaching the environment, such as in a scenario where the reservoir or the device ruptures.

[0021] In some embodiments, the hydrogel surrounds or partially surrounds an object to be exposed to the first species and / or the first target species, and the hydrogel is functionalized to reduce movement of the first species and / or the corresponding releasable species in the hydrogel at said object to the environment outside said hydrogel.

[0022] The present disclosure further relates to device for controlled use of a first species. Said device comprises a reservoir arranged to hold a first species inside a body of the device, an outlet extending into the environment, and transport means arranged to transport the first species from the reservoir out via the outlet, the device further comprising a scaffold and / or a hydrogel surrounding the body of the device, wherein said scaffold and / or hydrogel comprises a functionalization arranged to reduce movement of said first species between said body of the device and the environment outside said scaffold and / or hydrogel.

[0023] The present disclosure further relates to a method for controlled use of a first species. The method comprises

[0024] - providing a scaffold and / or a hydrogel comprising a functionalization in a first region of the scaffold and / or hydrogel, wherein said functionalization is arranged to reduce movement of the first species through the first region;

[0025] - arranging the scaffold and / or hydrogel to enclose an inner region of the scaffold and / or hydrogel; and

[0026] - transporting the first species into said inner region utilizing transport means, wherein said scaffold and / or hydrogel comprises a functionalization arranged to reduce movement of the first species between said inner region and the environment. In some embodiments, the transport means are enclosed by said scaffold and / or hydrogel.

[0027] This has the advantage of allowing reduced access of the environment to the inner region via any gaps between the transport means and the scaffold or hydrogel.

[0028] The present disclosure further relates to a scaffold and / or hydrogel for release of a bound releasable species, the scaffold and / or hydrogel comprising a first functionalization of a first region of the scaffold and / or hydrogel; and a second functionalization of a second region of the scaffold and / or hydrogel, wherein the first functionalization comprises a covalently bound species configured to bind, and / or chemically inactivate a first species, and wherein the second functionalization comprises said covalently bound releasable species configured to be released upon interaction with said first species.

[0029] In some embodiments, the first region encloses at least part of the second region.

[0030] This has the advantage of allowing the first region to control the behaviour of any first species in the second region. This further allows the second region to be protected by the first region from any corresponding first species located the environment outside entering the second region, while still being fluidly connected to said environment via the scaffold or hydrogel.

[0031] BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Fig. 1a-b show schematically a functionalized hydrogel.

[0033] Fig. 2a-d illustrates schematically systems for controlled use of a species.

[0034] Fig. 3 illustrates schematically a device for controlled use of a first species.

[0035] Fig. 4 shows schematically a method for controlled use of a first species.

[0036] DETAILED DESCRIPTION Throughout the figures, same reference numerals refer to same parts, concepts, and / or elements. Consequently, what will be said regarding a reference numeral in one figure applies equally well to the same reference numeral in other figures unless not explicitly stated otherwise.

[0037] Terms and expressions

[0038] The expression “controlled use of a species” relates to limiting the species from freely and intactly diffusing from and / or to a location. Typically, the species is actively transported to, and set free at, a location that is fluidly connected to a volume of fluid, wherein the species is controlled by one or more functionalization at or around the location that are arranged to hinder diffusion of intact species away from the location. Typically, the functionalization at or around the location is a functionalization of a scaffold and / or a hydrogel that is permeated by fluid that is fluidly connected to the volume of fluid. For example, “controlled use of a species” may relate to surrounding a location with a functionalized hydrogel to reducing the diffusion of the species from the location to the environment outside the functionalized hydrogel. For some examples, “controlled use of a species” may relate to utilizing a scaffold or a hydrogel functionalized to capture the species and / or to alter the species, thereby controlling the species by reducing diffusion of intact species through the scaffold or the hydrogel.

[0039] The expression “reduce movement of a species between an inner hydrogel region and the environment outside the hydrogel” relates to delaying or substantially stopping diffusion of the species through the hydrogel, capture the first species, and / or chemically inactivating the species such that it no longer has the properties of the species. Typically, the expression relates to reducing the probability or rate of the species diffusing between an inner hydrogel region and the environment outside the hydrogel in an intact state.

[0040] The term scaffold relates to a structure that can be used to attach molecules in a specific orientation or pattern. Typically, scaffolds are made of materials that are compatible with water, such as polymers, and may be designed to have specific chemical and / or mechanical properties that allow them to interact with the molecules being attached. Typically, scaffolds for functionalizing molecules in an aqueous environment are structures that can be used to attach molecules in a specific orientation or pattern. These scaffolds are typically made of materials that are compatible with water, such as polymers or hydrogels. They can be designed to have specific chemical properties that allow them to interact with the molecules being attached, such as through covalent bonding, hydrogen bonding or electrostatic interactions. Typically, the scaffold is configured to allow fluid connections through said scaffold, such as being porous.

[0041] The term hydrogel relates to a polymer network that that can be functionalized, or loaded, with molecules. For example, the hydrogel may be functionalized with crosslinking agents to reduce pore size, covalently bound fixed charge groups for electrostatic repulsion and / or attraction, or covalently bound activatable and / or releasable species, drugs, and / or bioactive molecules thus functioning as a reservoir of inactive species, drugs, and / or biomolecules.

[0042] The expression “functionalization of a hydrogel region” relates to changing the hydrogel and / or adding molecules to at least part of the hydrogel. For example, the hydrogel may be functionalized with increased crosslinking, covalently bound charge groups, activatable and / or releasable species, drugs, and / or bioactive molecules thus functioning as a reservoir of inactive species, drugs, and / or biomolecules.

[0043] The term enclosed relates to blocking paths between the enclosed entity and the environment. Herein the expression “A enclosed by B” is to be understood as B completely surrounding A, or, if a part of the outer surface of A is already blocked, blocking the paths between the remaining outer surface of A and the environment. The expression “hydrogel region in the form of a layer”. For examples, the expression “enclosed by a hydrogel” may relate to covering, encompassing, engulfing an object with the hydrogel. The functionalization of a scaffold region is defined correspondingly.

[0044] The term a first species relates to an ion or molecule. Typically, the first species is a species arranged to interact with a corresponding target species. The interaction can be a direct biological response, or a chemical interaction that sequentially leads to another interaction, such as a biological response or multistep reaction cascade. Typically, the first species is introduced or actively transported to a location. Herein the terms second species, third species, etc relate to other species that may be used in parallel with the first species, typically each of said species is arranged to interact with a corresponding target, such as a target species arranged to release a compound on interaction.

[0045] The term “target species” relates to a species arranged to release a releasable species upon interaction with a corresponding species. Typically, the first target species relates to an intended interaction partner for the first species, such as releasing a releasable species.

[0046] The expression “binding a species to a capture species” relates to a covalent reaction of the species with the capture species. For example, a covalent reaction of the species with the capture species that binds the species covalently to the capture species that is itself covalently bound to the hydrogel thus rendering the species immobile.

[0047] The term capturing relates to a covalent reaction of a capture species with a species configured to trigger another reaction that binds the species covalently to the capture species, wherein the capture species itself is covalently bound to the hydrogel thus rendering the species inert and / or immobile. Typically, capturing relates to making the trigger species become inert and / or immobile before performing said intended other reaction. It is to be understood that term capturing is not used when describing a reaction leading to the release of a releasable species, such as the first species reacting with a corresponding target species, even though such a reaction may result in the first species being bound to the corresponding target species. Correspondingly, the term inactivating is not used when describing a reaction leading to the release of a releasable species from a target species.

[0048] The term inactivating relates to a reaction of the first species with an inactivating species arranged to render the first species inert and unable to performing its intended function. For example, a chemical reaction may result in the first species being chemically altered to become unable to interact with the corresponding target species such that a releasable species is released. It is to be understood that term inactivating is not used when describing a reaction leading to capturing the first species and immobilizing it, such as the first species reacting with a corresponding capture species bound to a hydrogel, even though such a reaction may result in the first species being altered. The term “transport means” relates to a system or device for controlled delivery of a first species from a reservoir into a desired volume. Typically, the purpose of such a delivery if for the first species to interact with a target in said volume. For example, the transport means may be controlled by a computer arranged to provide spatio-temporal dose control of the first species. For example, the transport means may be of electrokinetic nature such as an ion pump, or a fluidic pump.

[0049] The term bioorthogonal chemistry relates to a class of reactions that are intrinsically selective transformations not commonly found in biology. Bioorthogonal reactions are intrinsically chemoselective. For example, bioorthogonal reactions typically proceed rapidly and selectively in biological environments with little or no reactivity towards endogenous functional groups. Typically, bioorthogonal chemistry is configured to readily proceed in aqueous environments at biocompatible pH and temperature.

[0050] The term bioorthogonal bond cleavage reaction (BBCR) or click-to-release (C2R) or bioorthogonal uncaging relates to release or activation of biomolecules, such as drugs, proteins, toxins, based on a bioorthogonal reaction that leads to the liberation of a released species.

[0051] The term orthogonal bioorthogonal relates to a plurality of sets of interacting species interacting in a bioorthogonal manner, wherein each set of interacting species interacts mutually orthogonal to other sets. For example, a first species and a corresponding first target species interacting independently of a second species and a corresponding second target species, despite being in proximity.

[0052] It is to be understood that the figures are schematic representations aimed at highlighting the novel features of the examples. Shown parts may not be to scale and some parts may not be depicted for readability, such as the polymer of hydrogels or parts of a scaffold. Typically, the examples shown are in an aqueous and / or biological environment.

[0053] Throughout the examples, relating to figures the term hydrogel is used for a structure that is functionalized. It is to be understood that said functionalized structure may be a scaffold and / or a hydrogel. Examples describing a hydrogel correspond to corresponding examples describing a scaffold, and combinations thereof. In some examples, the scaffold comprises ureido-pyrimidinones, polyethylene glycol, poly(lactic-co-glycolic acid), poly(ethylene oxide), poly(vinyl alcohol), alginate, chitosan, and / or hyaluronic acid. In some examples, the scaffold comprises a porous structure.

[0054] In some examples, the hydrogel and / or scaffold comprises linear, branched or hyperbranched hydrogels, self-assembling peptide hydrogels, UV curable crosslinked, or non-crosslinked hydrogels, RGD-modified hydrogels, polyethylene glycol), polyethylene oxide (PEO), poly(ethylene glycol) diacrylate, alginate, cellulose, poly(acrylic acid), hyaluronic acid (HA), Carrageenan, Agarose, Collagen, or derivatives thereof.

[0055] Fig. 1a-b show schematically an example hydrogel. Fig. 1a shows a hydrogel functionalized in a region of the hydrogel. Fig. 1 b shows a functionalized hydrogel with a first species entering the hydrogel via an outlet arranged in the hydrogel.

[0056] Fig. 1a shows schematically an example hydrogel 130 functionalized in a first hydrogel region 131. Said example hydrogel 130 has an oval form that is filled with said hydrogel 130. Fig. 1a shows a cross section of the 3D geometry, wherein the functionalized first hydrogel region 131 is of the form of an outer layer enclosing an inner hydrogel region 135 with an oval shape. Thus, the example hydrogel 130 being configured such that any path between the inner hydrogel region 135 and the environment outside the hydrogel 130 must pass through the functionalized first hydrogel region 131 .

[0057] It is to be understood that the expression “the first hydrogel region 131 encloses the inner hydrogel region 135” relates to surrounding the inner hydrogel region 135, which is straightforward when the hydrogel 130 is free in the environment. For situations when the inner hydrogel region 135 is arranged against a solid material, or a material a species of interest cannot readily diffuse through, then the expression “the first hydrogel region 131 encloses the inner hydrogel region 135” is to be understood as the first hydrogel region surrounding the outer surface of the inner hydrogel region 135 that is not blocked by the solid material, such that the typical movement path for a species from the inner hydrogel region 135 to the environment outside the hydrogel would go via the first hydrogel region 131. Correspondingly, the typical movement path for a species from the environment outside the hydrogel to the inner hydrogel region 135 would go via the first hydrogel region 131 .

[0058] It is to be understood that the first hydrogel region 131 may be the region of the whole hydrogel 130 or any part(s) thereof.

[0059] The functionalization of the first hydrogel region 131 is arranged to reduce movement of a first species 121 between the inner hydrogel region 135 and the environment outside said hydrogel 130. In fig. 1a-b, the functionalization comprises a first capture species 141 arranged to chemically interact with the first species 121 , wherein said interaction causes binding of the first species 121 to the first capture species 141 . The first capture species 141 serves to stop movement / diffusion of the first species 121 between the environment and the interior of the hydrogel 130.

[0060] It is to be understood that to reduce movement of a first species 121 between the inner hydrogel region 135 and the environment outside said hydrogel 130, also is to reduce movement of a first species 121 between the environment outside said hydrogel 130 and the inner hydrogel region 135. It is to be understood that the term “movement” in this context relates to the first species 121 going from one side of the hydrogel 130 through said hydrogel 130 and to the other side of the hydrogel 130 while intact and unbound, the term is not about the velocity of species. Thereby the functionalized hydrogel 130 acts as a barrier for the first species 121 .

[0061] In some examples, the first species 121 is arranged to function as a trigger species that interacts with another species to activate said species or cause a part of said species to be released, such as interacting to cause a chemical reaction, or a drug release, as exemplified in fig. 2a-c. In some of these examples, the chemical reaction or drug release causes a biological response. In some examples, the first species 121 is arranged to interact with cells, microorganisms, tissue and / or parts thereof to cause a biological response. In some of these examples, the hydrogel is arranged at and / or around said cells and / or tissue. In some examples, the hydrogel is arranged to be inside a non-human animal and / or a human.

[0062] The example functionalized first hydrogel region allows for making the inner hydrogel region 135 protected against the first species 121 entering from the environment via an undesired way, such as by leakage and / or reservoir rupture, such that improved control over the amount of said first species 121 in the inner hydrogel region 135 may be achieved. Furthermore, the functionalized first hydrogel region 131 reduces the risk of any first species 121 inside the inner hydrogel region 135 escaping out into the environment. This may allow for increased safety in case of reservoir / implant rupture of the device and / or from adjacent devices utilizing said first species 121 .

[0063] In some examples, said functionalized hydrogel 130 comprises said first capture species 141 covalently bound within and / or to the hydrogel 130.

[0064] In some examples, at least some first capture species 141 are arranged to each capture a plurality of said first species 121 , such as by comprising a plurality of active sites arranged to chemically interact with said first species 121 .

[0065] Fig. 1 b shows schematically the example hydrogel 130 from fig. 1a with an outlet 113 probing into the inner hydrogel region 135. The first species 121 being transported into the inner hydrogel region 135 via said outlet 113. Individual first species 121 travelling through the first hydrogel region 131 towards the environment outside the hydrogel 130 may interact with the first capture species 141 and become a bound first species 12T. Correspondingly, first species 121 in the environment entering the hydrogel 130 may interact with the first capture species 141 and become a bound first species 12T.

[0066] In some examples, the interaction between the first capture species 141 and the first species 121 is bioorthogonal. This has the advantage of allowing for an encapsulated volume with access to the environment via the hydrogel 130 in which the first species 121 may be introduced for a primary interaction, such as the release of a drug, while having a reduced risk that the first species 121 travels into the environment, and correspondingly a reduced risk that any first species 121 in the environment travels into the hydrogel 130.

[0067] The probability of the first species 121 diffusing between the inner hydrogel region 135 and the environment may be controlled by adjusting the concentration of the capture species 141 in the first hydrogel region 131 , and arranging the hydrogel 130 to obtain a minimum travel path distance between the environment and the inner hydrogel region 135 through the first hydrogel region 131 . Typically, the first hydrogel region is functionalized with a high concentration of first capture species 141 , such as to increase the probability of capture of a first species 121 . Typically, the first capture species 141 is bound to the hydrogel 130.

[0068] In some examples, the hydrogel 130 is arranged to enclose material, such that the hydrogel 130 encloses at least one volume not containing said hydrogel 130. In some of these examples, the inner hydrogel region 135 is in the volume enclosed by the hydrogel 130. In some of these examples, the inner hydrogel region 135 does not comprise said hydrogel 130. In some of these examples, the outlet 113 is arranged to lead the first species 121 into said at least one enclosed volume.

[0069] In some examples, the hydrogel 130 is one continuous hydrogel, and / or a plurality of separate hydrogels. It is to be understood that the first hydrogel region 131 may comprise a plurality of separate regions of hydrogel.

[0070] It is to be understood that the term “inner hydrogel region 135” relates to any region inside the outer bounds of the hydrogel 130 towards the environment. Typically, the inner hydrogel region relates to a region defined such that expected travel paths between said inner hydrogel region and the environment outside the hydrogel has a probability of interaction between the first species 121 and the first capture species 141 above some threshold probability value corresponding to a measurable reduction in movement of the first species 121 . The inner hydrogel region may contain a part of the hydrogel 130; a part of the hydrogel 130 and non-hydrogel material; or nonhydrogel material, wherein the non-hydrogel material is material that is not the hydrogel and enclosed by the outer surface of said hydrogel. It is to be understood that the hydrogel 130 may be arranged to surround one or more objects, such as chemical actuators, chemical transducers, microorganisms, and / or cells or tissue samples to be studied under controlled conditions. In some examples, the first species 121 is arranged to interact with an object surrounded by the hydrogel. In some of these examples, said object comprises a microorganism, a cell sample and / or tissue sample.

[0071] In some examples, the first hydrogel region 131 is functionalized with a concentration of capture species 141 of at least 10 pM . In some of these examples, the concentration of capture species 141 is at least 100 pM, at least 1 mM, or at least 10 mM. It is to be understood that the minimum concentrations of capture species 141 may be dependent on the geometry of the hydrogel 130, the first hydrogel region 131 , the amount of said first species 121 expected to be introduced into the inner region of the hydrogel 135, and a set of criteria relating to a minimum acceptable amount and / or concentration of said first species 121 outside the hydrogel 130. Correspondingly the minimum concentrations of capture species 141 may be dependent on an amount of said first species 121 expected to be in the environment outside the hydrogel 130 and a set of criteria relating to a minimum acceptable amount and / or concentration of said first species 121 entering the inner hydrogel region from outside the hydrogel 130.

[0072] In some examples, a hydrogel 130 may be functionalized with significantly larger amounts of capture species 141 compared to the amounts of first species 121 expected to be delivered into the hydrogel 130, therefore the concentration of capture species 141 during use may be assumed to be substantially constant in the hydrogel. Correspondingly, in some examples, the hydrogel 130 may be functionalized with significantly larger amounts of target species 142 compared to the amounts of first species 121 that are expected to interact with the target species 142, such that the concentration of target species 142 may be assumed to be substantially unchanged in the hydrogel. By sufficiently functionalizing the hydrogel 130 with target species 142 a robust relationship between the amount of transported first species 121 and amount of interactions between target species and the first species may be achieved.

[0073] It is to be understood that hydrogel 130 functionalized with said target species 142 may represent a safe reservoir of inactive releasable species, such as pro-drugs or activatable biomolecules.

[0074] For hydrogels 130 with a bioorthogonal reaction between the first species 121 and the capture species 141 , it may be desirable to functionalize the first hydrogel region 131 to achieve the highest possible concentration of capture species 141 . In some examples, the amount of capture species 141 in the hydrogel 130 is at least one hundred times the amount of first species 121 expected to be introduced into the hydrogel 130 via said outlet 113.

[0075] Fig. 2a-d show schematically systems for controlled use of a first species. Fig. 2a shows an example system with a device arranged to transport one species 121 into a hydrogel 130 comprising a first functionalization in a first region 131 and a second functionalization in a second region 132, wherein the first region 131 is arranged to surround the second region 132 and is functionalized with a first capture species 141 arranged to bind a first species 121 . Fig. 2b shows an example system with a device 110 arranged to transport the first species 121 and a second species 122 into a hydrogel 130. Fig. 2c shows an example system with a device 110 enclosed by the hydrogel 130 functionalized with the first capture species 141 , thus providing protection in case of rupture or leakage of first species 121 from the device 110. Fig. 2d show an example system 100 wherein the hydrogel 130 surrounds or partially surrounds an object 160 to be exposed to the first species 121 .

[0076] Fig. 2a shows schematically an example system 100 comprising a device 110 and a hydrogel 130. The device comprises a reservoir 111 , transport means 112 and an outlet 113 extending out from the body of the device 110 and exiting into an inner hydrogel region. The reservoir 111 is arranged to hold a first species 121 . The transport means 112 is arranged to transport the first species 121 from the reservoir 111 into said inner hydrogel region via the outlet 113. The example hydrogel 130 comprises a first functionalized hydrogel region 131 that encloses a second functionalized hydrogel region 132. The hydrogel 130 is arranged to enclose or fill said inner hydrogel region at the outlet 113. In this example, said inner hydrogel region may be the volume of the second hydrogel region 132.

[0077] In the example system 100 shown in fig. 2a, the device 110 is arranged to transport the first species 121 from the reservoir 111 into the second hydrogel region 132. The first hydrogel region 131 is functionalized to reduce movement of said first species 121 between the second hydrogel region 132 and the environment outside said hydrogel 130. In the example shown in fig. 2a, the first hydrogel region 131 is functionalized with a first capture species 141 arranged to bind the first species 121 , thereby reducing movement of the first species 121 by making it a bound first species 12T. In some of these examples, the first capture species 141 is arranged to covalently bind the first species 121 .

[0078] The system 100 comprising the functionalized first hydrogel region 131 reduces the probability of first species 121 moving through the second hydrogel 132 and moving outside the hydrogel 130, thus preventing possible undesired effects of the first species 121 in the environment, such as toxic side effects of a high concentration of the first species or any corresponding releasable species in an organism. Furthermore, the functionalized first hydrogel region 131 reduces the probability of any first species 121 in the environment outside the hydrogel 130 moving into the second hydrogel region 132, such as a leakage from the device 110 of the system 100 or another device comprising the first species 121 .

[0079] In the example system 100 shown in fig. 2a, the hydrogel 130 is functionalized with a target species 142 in the second hydrogel region 132. The target species 142 being arranged to, upon interaction with the first species 121 , release a releasable species 143. In some examples, the releasable species 143 is a drug or bioactive compound. In some examples, the releasable species 143 and the hydrogel 130 are configured to allow the releasable species 143 to exit the hydrogel 130 into the environment. In fig. 2a a bioorthogonal bond-cleavage reaction sequence of a first species 121 interacting with a target species 142 in the second hydrogel region 132 is shown, wherein depicted reaction intermediate 142’ represents a non-thermodynamically stable compound.

[0080] It is to be understood that the first hydrogel region 131 and the second hydrogel region 132 may overlap fully, overlap partially, or not overlap at all. In some examples the first hydrogel region 131 and / or second hydrogel region 132 is the volume of the whole hydrogel 130.

[0081] In some examples, the scaffold and / or the hydrogel 130 is comprised in a vessel. In some examples, the scaffold and / or the hydrogel 130 is in a region within 100 mm of the outlet 113. In some of these examples, the scaffold and / or the hydrogel is in a region within 50 mm, 30 mm, 20 mm, 10 mm, 5 mm, or 2 mm of the outlet 113.

[0082] In some examples, the releasable species 143 and the hydrogel 130 are configured to retain the releasable species 143 within an inner hydrogel region, such as to obtain a high concentration of releasable species 143 in a specific region.

[0083] In some examples, the first species 121 and the target species 142 interact by bioorthogonal chemistry. In some of these examples, said interaction comprises a click-to-release reaction and / or bioorthogonal bond-cleavage reaction. In some of these examples, the target species 142 is a click-activatable species, such that said releasable species 143 is released and becomes biologically active upon interaction between the first species 121 and the target species 142. In some examples, the first species 121 is arranged to react with the corresponding target species 142, wherein said rection comprises bioorthogonal bond-cleavage reaction (BBCR), click-to-release (C2R), and / or bioorthogonal uncaging.

[0084] In some examples, the hydrogel 130 is functionalized with an inactivating species 144 in the first hydrogel region 131 , wherein the inactivating species 144 is arranged to chemically react with the first species 121 to modify the first species 121 into an inactivated first species 121” unable to perform said interaction with the target species 142. In some of these examples, the inactivating species 144 is arranged to repeatedly chemically react with multiple first species 121 , and thus allowing a plurality of fist species 121 to be inactivated by one inactivating species 144.

[0085] In some examples, the hydrogel 130 is functionalized with the inactivating species 144 in a third hydrogel region, such that some parts of the hydrogel 130 may be functionalized with the capture species 141 but not the inactivating species 144, and vice versa.

[0086] In some examples, for each first species 121 , any corresponding capture species 141 , target species 142 and inactivating species 144 are different species. For some combinations of species, the target species 142 will irreversibly bind the trigger species 121 upon interacting, however, for said examples it is clarified that a hydrogel 130 with only target species 142 would not be interpreted as an inner region with target species 142 surrounded by a region of “capture species” where the target species 142 are considered to act as capture species 141 .

[0087] In some examples, the hydrogel 130 is functionalized with a repelling species and / or an attracting species (not shown) in the first hydrogel region 131 , wherein the repelling species and / or the attracting species are arranged to repel or attract the first species 121 to reduce movement of said first species 121 between said inner hydrogel region 135 and the environment outside said hydrogel 130. Typically, the repelling species and / or the attracting species comprise moieties that are permanently charged in buffered aqueous solution under physiologically relevant conditions. In some examples, the repelling species and / or the attracting species comprise permanently charged moieties such as sulfonates, phosphonium moieties, protonated amines, quaternary ammonium groups, and / or carboxylic acid groups. In some examples, the repelling species and / or the attracting species comprise protonated guanidines, imidazoles, acidic phenols, boronic acids, and / or N-heterocycles such as protonated pyridines.

[0088] It is to be understood that selecting the repelling species and / or the attracting species is based on the relevant conditions under which they are expected to carry charges, such as under physiological conditions for microorganisms or other cells.

[0089] In some examples, the device 110 comprises an energy source 114 arranged to power the transport means 112. In some of these examples, the energy source 114 is a battery. In some examples, the battery 114 is connected to at least two electrodes (not shown) of the transport means 112 arranged to generate electric fields in the transport path of the first species 121 between the reservoir 111 and the outlet 113, such as an ion pump.

[0090] In some examples, the transport means 112 comprise electrokinetic transport means. In some of these examples, the transport means 112 comprise an ion pump. In some examples, the transport means 112 utilize electrophoretic transport to transport said first species 121 . In some examples, the transport means 112 comprise an ion selective membrane.

[0091] In some examples, the transport means 112 in an idle state passively leak an amount of first species 121 from said reservoir 111 out via the outlet 113, wherein the hydrogel 130 is configured to at most allow a predetermined amount and / or fraction of said leaked amount of first species 121 to reach the environment.

[0092] In some examples, the device 110 comprises a computer 115 arranged to control the transport means. In some of these examples, the device 110 comprises a sensor (not shown) connected to the computer, wherein the computer 115 controls the transport means based on sensor signals obtained from said sensor. In some of these examples, the sensor is arranged at the outlet 113. In some examples, the sensor is arranged in the inner hydrogel region and / or in the environment outside the hydrogel 130 or the device 110.

[0093] Fig. 2a shows the body of the device 110 outside the hydrogel 130, the transport means 112 penetrating the hydrogel 130, and the outlet 130 surrounded by the hydrogel 130. In some examples, the body of the device 110 is at or partially inside the hydrogel 130. In some examples, the body of the device 100 is inside the hydrogel 130.

[0094] In some examples, a fourth hydrogel region (not shown) is functionalized with a zwitterionic species (not shown) arranged to reduce foreign body reactions that the system 100 causes when inside or in contact with an organism. In some of these examples, the system 100 is arranged to be implanted into said organism. Typically, the fourth hydrogel region comprises at least some parts of the outer bounds of the hydrogel 130 facing the environment.

[0095] Fig. 2a further relates to an example hydrogel for release of a bound releasable species 143. The hydrogel 130 comprising a first functionalization of a first hydrogel region 131 and a second functionalization of a second hydrogel region 132, wherein the first functionalization comprises a covalently bound species 141 configured to bind, and / or chemically inactivate a first species 121 , and wherein the second functionalization comprises said covalently bound releasable species 143 configured to be released upon interaction with said first species 121 .

[0096] In some examples, the second functionalization comprises said covalently bound target species 142 comprising the releasable species 143, wherein the target species 142 is configured to upon interaction with said first species 121 release the releasable species 143.

[0097] Fig. 2b shows a schematic example system 100 according to the system 100 described in fig. 2a, wherein the reservoir 111 is further arranged to hold the second species 122, wherein the device 100 is arranged to utilize the transport means 112 to transport said second species 122 to the outlet 113. In fig. 2b, the second species 122 is depicted as having a “U” shaped active site, while the first species 121 has a “V” shaped active site.

[0098] In the example in fig. 2b, the first hydrogel region 131 is further functionalized to reduce movement of said second species 122 between the second hydrogel region 132 and the environment outside said hydrogel 130. In this example, the first hydrogel region 131 is functionalized with a capture species 141 arranged to bind the first species 121 , thereby reducing movement of the first species 121 by making it a bound first species 12T, and functionalized with a second capture species 145 arranged to bind the second species 122, thereby reducing movement of the second species 122 by making it a bound second species 122’. In some of these examples, the interactions between the first species 121 and the capture species 141 and between the second species 122 and the second capture species 145 are mutually orthogonal, independent bioorthogonal reactions. In some examples, the first capture species 141 is arranged to covalently bind the first species 121 ; and / or the second capture species 145 is arranged to covalently bind the second species 122.

[0099] It is to be understood that the hydrogel 130 may be functionalized to reduce the movement of said second species 122, such as with the second capture species 145, in another hydrogel region of the hydrogel 130. For example, the concentration of functionalized first and second capture species 141 ,145 may differ such that different sized regions of functionalization would be required to achieve a similar reduction of the movement of corresponding species 121 ,122.

[0100] In some examples, one or more reservoirs 111 are arranged to hold the first and second species 121 ,122. For example, the transport means 112 may be arranged to transport each species 121 , 122 individually from the one or more reservoirs 111 , such as transporting each species 121 ,122 from a specific reservoir 111. In some examples, each species 121 ,122 is arranged in an individual reservoir 111 , and the transport means 112 are arranged to transport each species 121 ,122 individually from said reservoir 111 to a corresponding outlet 113. In some examples, one reservoir 111 is arranged to hold at least the first and second species 121 , 122. In some of these examples, the transport means 112 are arranged to transport each species 121 ,122 individually from said reservoir 111 to a corresponding outlet 113.

[0101] Fig. 2a-d depicts a single outlet 113 connected to a single reservoir 111 , however, it should be understood that the device 110 may comprise a plurality of outlets 113 at the hydrogel 130 each connected to one or more reservoirs 111 via the transport means 112. In some examples, the device 110 comprises two or more outlets 113. In some of these examples, said outlets 113 are arranged at different positions at the hydrogel 130. Releasing the first species 121 at different positions at the hydrogel 130 may result in a different release of releasable species 143,147.

[0102] The example in fig. 2b represents embodiments with two or more types of species 121 ,122, and / or two or more corresponding types of capture species 141 ,145, and / or two or more corresponding types of target species 142,146 that may allow for individually controlled release of releasable species 143,147.

[0103] In some examples, the first and second species 121 ,122 are arranged to be captured by one capture species 141 ,145.

[0104] In some examples, for at least one first species 121 ,122, the corresponding capture species 141 ,145 is the corresponding target species 142,146 without its releasable species 143,147 or precursor thereof.

[0105] The second hydrogel region 132 is functionalized with a second target species 146 arranged to, upon interaction with the second species 122, release a second releasable species 147. In some examples, the first releasable species 143 and / or the second releasable species 147 is a drug, and / or toxin. In some examples, the second releasable species 147 and the hydrogel 130 are configured to allow the second releasable species 147 to exit the hydrogel 130. In some examples, the second releasable species 147 and the hydrogel 130 are configured to retain the second releasable species 147 within an inner hydrogel region. Fig. 2b shows a sequence of a second species 122 interacting with a second target species 146 in the second hydrogel region 132, wherein depicted reaction intermediate 146’ represents a non- thermodynamically stable compound.

[0106] It is to be understood that the hydrogel 130 may be functionalized with the second target species 146 in another hydrogel region of the hydrogel 130. Typically, such a hydrogel region functionalized with the second target species 146 would be enclosed by a hydrogel region functionalized to reduce the movement of said second species 122, such as functionalization with the second capture species 145.

[0107] In some examples, each target species 142,146 comprises a stoichiometric distribution of a set of releasable species 143,147. For an example scenario, a large number of the first target species 142 each have one of three possible releasable species 143, 50% have A, 30% have B, and 20% have C, such that transporting a large number of copies of the first species 121 that react randomly with a large number of said first target species 142, may upon reacting, release a distribution of releasable species 143 consisting of 50% of releasable species A, 30% of releasable species B, and 20% of releasable species C. Thus, the system 100 may be designed such that transporting multiple copies of one type of species 121 , 122 arranged to trigger the corresponding target species 142,146 may cause release of a plurality of different releasable species 143,147 in a known distribution. In some examples, at least one target species 142,146 comprises a stoichiometric distribution of at least two different releasable species 143,147, or precursors thereof. For these examples, it is to be understood that if the first target species comprises a stoichiometric distribution of a set of releasable species it would herein still be referred to as the first target species by its ability to react with the first species even though its releasable payload can vary.

[0108] In some examples, the interaction between the first target species 142 and the first species 121 is bioorthogonal. In some examples, the interaction between the second target species 146 and the second species 122 is bioorthogonal. In some of these examples, the pairwise interactions are all mutually orthogonal. This allows for the system 100 to function as an orthogonal bioorthogonal release system, wherein each set of interacting species interact bioorthogonal and wherein each set of interacting species interacts orthogonal to other sets, such as the interaction between the first species 121 and the first target species 142 being orthogonal to the interaction between the second species 122 and the second target species 146.

[0109] Fig. 2b illustrates the first and second species 121 ,122 interacting with their corresponding capture species 141 ,145 and corresponding target species 142,146 via the same active site. It is to be understood that the interaction with the corresponding capture species 141 ,145 may occur at a functional group that is different from the functional group for interacting with the corresponding target species 142,146. That being said, a natural choice for the capture species 141 ,145 is typically to use a molecule similar to the target species 142,146 that does not comprise the releasable species 143,146, or having the functionality to release the releasable species 143,146.

[0110] In some examples, the first and / or second capture species 141 ,145 comprises the active site of the corresponding target species 142,146. In some examples, the first and / or second target species 142,146 comprises, or is a derivative of, the corresponding capture species 141 ,145.

[0111] In some examples, the first hydrogel region 131 is functionalized with a second inactivating species (not shown) arranged to chemically react with the second species 122 to modify the second species 122 into an inactivated second species unable to perform said interaction with the second target species 146. The second inactivating species corresponds to the first inactivating species 144. In some of these examples, the second inactivating species is arranged to repeatedly chemically react with a plurality of the second species 122.

[0112] In some examples, the first hydrogel 130 is functionalized with the second inactivating species (not shown) in a region separating the hydrogel functionalized with the second target species 146 and the environment outside said first hydrogel 130.

[0113] In some examples, the device 110 comprises two or more reservoirs 111 , wherein said two or more reservoirs 111 are arranged to hold two or more species 121 ,122. In some of these examples, each of said two or more reservoirs 111 is arranged to hold one individual species 121 ,122.

[0114] In some examples, the device 110 is arranged to independently transport a first species 121 and a second species 122 utilizing said transport means 112. In some examples, the device 110 is arranged to transport a first species 121 and a second species 122 at at least two different relative rates, such as transporting more of the first species 121 during a first mode of operation, and more of the second species 122 during a second mode of operation.

[0115] In an example scenario, the transport means 112 are arranged to transport Tetrazine at a rate of 5 pmol / min. Depending on transported molecule and choice of transport means 112 the rate may be in a range between attomol per minute to micromol per minute. In some examples, the transport means 112 are arranged to transport at least the first species 112 at 1 femtomol per minute to 1 nanomol per minute.

[0116] It is to be understood that the term transport means 112 may relate to one or more individual species transport solutions, such as two separate ion pumps each arranged to transport species from a different reservoir 111.

[0117] In some examples, the device 110 is arranged to hold a first and second species 121 ,122 of opposite charge in the reservoir 110, and the transport means 112 is arranged to select the species 121 ,122 to be transported by utilizing electrokinetic transport means. In some examples, the device comprises a computer 115 arranged to control the amount of a first species 121 and a second species 122 being transported.

[0118] It is to be understood that the example in fig. 2b of a system 100 further comprising a second species 122, a second capture species 145, a second target species 146 may be extended to example systems with a third species or more, and corresponding third capture species and third target species.

[0119] In some examples, the device 110 is arranged to hold and transport at least a first, second and third species and the hydrogel is functionalized with corresponding third capture species and third target species. In some of these examples, the device 110 is further arranged to hold and transport at least a fourth species and the hydrogel 130 is functionalized with corresponding fourth capture species and fourth target species. In some of these examples, the device 110 is further arranged to hold and transport at least a fifth species and the hydrogel 130 is functionalized with corresponding fifth capture species and fifth target species.

[0120] It is to be understood that the first species, the second species, the third species, the fourth species, and the fifth species are different species.

[0121] In some examples, the at least first species 121 and / or second species 122 is arranged to react with a corresponding target species 142,146, wherein said reaction comprises bioorthogonal bond-cleavage reaction ,BBCR, click-to-release, C2R, and / or bioorthogonal uncaging.

[0122] In some examples, the at least first species 121 and / or second species 122 each comprise tetrazine, Tz, bicyclo[6.1 ,0]non-4-yn-9-ylmethanol, BCN, cyclooctyne cycloalkynes, fluoride, and / or trans-cyclooctene, TCO, or derivatives thereof.

[0123] In some examples, the at least one target species 142,146 comprises trans-cyclooctene, TCO, iminosydnone, mesoionic compounds, ortho-carbamoylmethylene silyl-phenolic ethers, tetrazine, Tz, or derivatives thereof.

[0124] Target species 142,146 comprising ortho-carbamoylmethylene silyl-phenolic ethers may allow for desilylation induced release using silyl ether groups. For example, silyl ether may be cleaved by reacting with fluoride to release a phenol, which may further collapse to release other functional groups if a self-immolative linkers / spacers is used.

[0125] In some examples, each species 121 ,122 and corresponding target species 142,146 comprises respectively tetrazine, Tz, and trans-cyclooctene, TCO; bicyclo[6.1 ,0]non-4-yn-9-ylmethanol, BCN, and iminosydnone; fluoride, and ortho-carbamoylmethylene silyl-phenolic ether; trans-cyclooctene, TCO, and tetrazine, Tz; or derivatives thereof.

[0126] In some examples, the at least one target species 142,146 comprises chlorinated iminosydnone.

[0127] In some examples, the at least first and second species 121 ,122 each comprise at least one of the following moieties: tetrazine ,Tz, fluoride, trans-cyclooctene, TCO, cyclooctyne, and bicyclononyne, BCN. In some of these examples, two or more of the at least first and second species 121 ,122 comprise different moieties.

[0128] It is to be understood that in order to transport species, such as BCN or Tz, with an ion pump it may be necessary to form charged derivatives thereof. Charged derivatives may be formed by introducing amino-functionalized Tz or BCN scaffolds and / or carboxylic functionalized Tz or BCN scaffolds to facilitate permanent positive and / or negative charges at the pH used, such as physiological pH.

[0129] In some examples, the first and / or second capture species 141 ,145 comprises the active site of the corresponding target species 142,146. In some examples, the first and / or second target species 142,146 comprises, or is a derivative of, the corresponding capture species 141 ,145.

[0130] In some examples, the first and / or second capture species 141 ,145 each comprise trans-cyclooctene, TCO, iminosydnone, mesoionic compounds, ortho-carbamoylmethylene silyl-phenolic ethers, tetrazine, Tz, or derivatives thereof.

[0131] Fig. 2c show schematically an example system 100 according to the system 100 described in fig. 2a, wherein the first hydrogel region 131 surrounds the device 110.

[0132] The example in fig. 2c represents embodiments arranged to reduce the release of species from leakages at the body of the device.

[0133] In some examples, the device 110 is enclosed by the second hydrogel region 132.

[0134] In some examples, the outlet 113 is enclosed by the second hydrogel region 132, and the remainder of the device 110 is enclosed by the first hydrogel region 131 , such as represented by the schematic illustration in fig. 2c. An advantage of surrounding the device 110 with the first hydrogel region 131 is that an occurrence of a leakage from the reservoir 111 out into the environment outside the device may be reduced by the capture species 141 in the first hydrogel region 131 . If the system 100 suffers a leakage, or unintended transport, moving the first species 121 from the reservoir 111 to the outlet 113 then the first hydrogel region 131 would at least reduce the spread of first species 121 outside of the hydrogel 130. The increased control over the first species 121 allows for a reduced risk of unintended release of the corresponding releasable species 143.

[0135] It is to be understood that the example system 100 in fig. 2c further relates to a system wherein the device body is surrounded by one hydrogel corresponding to the first hydrogel region 131 and the outlet is at and / or surrounded by another hydrogel corresponding to the first and second hydrogel region 131 ,132, wherein said hydrogels are separate. Such an embodiment may be envisioned by starting from fig. 2c and removing a slice of the first hydrogel region 131 from a plane separating the body of the device 110 and the second hydrogel region 132; alternatively starting from fig. 2a and replacing the device 110 with a hydrogel surrounded device as depicted in fig. 3.

[0136] In some examples, at least part of the hydrogel 130 is arranged inside the body of the device 100. Fig. 2d show schematically an example system 100 wherein the hydrogel 130 surrounds or partially surrounds an object 160 to be exposed to the first species 121 . The hydrogel 130 comprises a functionalization of a first hydrogel region 131 arranged to reduce movement of said first species 121 between said inner hydrogel region and the environment outside said hydrogel 130. In some examples, hydrogel 130 comprises a functionalization of a first hydrogel region 131 arranged to reduce movement of said first species 121 and / or said corresponding releasable species 143 in the hydrogel 130 at said object 160 to the environment outside said hydrogel 130. In some of these examples, the hydrogel 130 comprises a functionalization of a first hydrogel region 131 arranged to, upon continuous transport of said first species 121 and / or release of said releasable species 143, retain said first species 121 and / or said corresponding releasable species 143 in the hydrogel 130 at said object 160, thereby increasing concentration of said first species 121 and / or said corresponding releasable species 143 in the hydrogel 130 at said object 160 and increasing the probability of interactions with said object 160.

[0137] In the example system 100 in fig. 2d, the first species 121 is positively charged and the first hydrogel region 131 comprises functionalization with a positively charged species 149 arranged to electrostatically repulse the first species 121. The first hydrogel region 131 is configured to utilize electrostatically repulsion to reduce the movement of the first species 121 through the first hydrogel region 131 . The electrostatic repulsion may allow a higher concentration of the first species 121 to accumulate at the object 160 compared to a first hydrogel region 131 that is functionalized to bind the first species 121 , such as in the example in fig. 2a.

[0138] It is to be understood that the depicted positively charged species 149 may be a negatively charged species 149. In some examples, the charged species 149 comprises a plurality of charged groups. It is to be understood that charged species 149 are expected to be charged under operational conditions.

[0139] The ability to better control the first species 121 after pumping and building up a concentration of a first species 121 in a region surrounded by the hydrogel 130 can have multiple applications in different technical fields. Typically, controlling a concentration of a species in a small region is advantageous to pumping a species into a larger volume. In some example, the building up of first species concentration is utilized to form a deposit of the first species for a slow release of the first species. In some example, the building up of first species concentration is utilized for a step in a chemical process. In some example, the building up of first species concentration is utilized for stimulating microorganisms. In some examples, the building up of first species concentration is utilized for exposing tissue to the first species.

[0140] In some examples, the hydrogel 130 arranged at the outlet 113 is configured dilute the first species as an effect of distance, whereby a diffusion gradient decay is formed. In some of these examples, the hydrogel 130 arranged between the outlet 113 and the object 160 is configured to form a diffusion gradient decay.

[0141] In some examples, the object 160 to be exposed to the first species 121 comprises a target species 142.

[0142] In some examples, the object 160 to be exposed to the first species 121 comprise at least one microorganism and / or tissue.

[0143] In some examples, the hydrogel 130 is arranged between the outlet 113 and the object 160 to be exposed to the first species 121 , and the hydrogel 130 forms a continuous connection between the outlet 113 and the object 160 to be exposed to the first species 121 .

[0144] It is to be understood that the functionalization for the first hydrogel region 131 is not limited to functionalizations that chemically react or electrostatically interact with the first species 121 .

[0145] In some examples, the first hydrogel region 131 is functionalized to reduce pore size and / or water content of the hydrogel in the first hydrogel region 131 , whereby the movement of the first species 121 through the first hydrogel region 131 is reduced.

[0146] The example system in fig. 2d represents embodiments where the functionalization of the first hydrogel region 131 is arranged to reduce movement of said first species 121 between said inner hydrogel region and the environment outside said hydrogel 130 based on stopping or slowing movement of the first species 121 , as opposed to the approach of capturing and inactivating the first species 121 shown in fig. 2a-c. In some examples, the hydrogel 130 comprises an electrochemical material configured to change its concentration of charge groups upon being electrochemically switched. In some examples, the device 110 is arranged to electrochemically switch at least part of said electrochemical material. In some examples, the first hydrogel region 131 and / or the second hydrogel region 132 comprises said electrochemical material.

[0147] By electrochemically switching the state of at least part of the hydrogel 130 the properties of the hydrogel may be altered, and thereby may impact the behaviour and diffusion of the different species.

[0148] It is to be understood that the example hydrogel functionalizations in fig. 2a-d may be combined.

[0149] In some examples, the first hydrogel region 131 functionalization comprises at least one of

[0150] - a functionalization reducing pore size and / or water content to reduce the movement of the first species 121 and / or

[0151] - a charged species 149 arranged to electrostatically repulse or attract the first species 121 ;

[0152] - a covalently bound species 141 configured to bind, and / or chemically inactivate a first species 121 ; and / or

[0153] - an inactivating species 144 is arranged to chemically react with the first species 121 to modify the first species 121 into an inactivated fist species 121” unable to perform said interaction with the target species 142.

[0154] In some examples, the functionalization in the first hydrogel region 131 and / or the second hydrogel region 132 comprises a charged species 149, wherein said charged species 149 is arranged to electrostatically interact with the first species 121 , wherein said interaction causes repulsion of the first species 121 , thereby reducing movement of the first species 121 by reducing the concentration of first species 112 in the corresponding part of the hydrogel 130. Thus allowing for a reduced leakage from the outlet 113 to the environment by forming depletion zones in the hydrogel 130.

[0155] In some examples, the functionalization in the first hydrogel region 131 and / or the second hydrogel region 132 comprises a charged species 149, wherein said charged species 149 is arranged to electrostatically interact with the first species 121 , wherein said interaction causes attraction of the first species 121 , thereby reducing movement of the first species in one area of the hydrogel 130 by increasing the concentration of first species 121 another area in the hydrogel 130. Thus, allowing the first species 121 to be guided towards a desired area.

[0156] In some examples, the functionalization in the first hydrogel region 131 and / or the second hydrogel region 132 comprises an obstructing species (not shown), wherein said obstructing species is arranged to sterically interact with the first species 121 , wherein said interaction causes reduced permeability of the first species 121 into said region 131 ,132, thereby reducing movement of the first species 121 by controlling the permeability of first species in the hydrogel 130.

[0157] It is to be understood that at least some examples described for fig. 2d may be combined with the examples described for fig. 2b, whereby the system is arranged to expose the object 160 to the first species 121 and / or a corresponding releasable species 143. In some of these examples, the system 100 is arranged to expose the object 160 to at least a second species 122 and / or a corresponding second releasable species 146.

[0158] The examples described for fig. 2a-d may be combined.

[0159] In some examples, the system 100 is configured to be arranged at and / or around cells, microorganisms and / or tissue, such as in being configured to be in fluid contact with a cell culture via a culture medium.

[0160] In some examples, the system 100 is configured to be arranged inside a non-human animal and / or a human, such as the hydrogel 130 being injectable and the device 110 being implantable.

[0161] Fig. 3 illustrates schematically a device for controlled use of a first species. The device 110 comprises a reservoir 111 , transport means 112 and an outlet 113. The device further comprises a hydrogel 130 surrounding a body of the device 110 comprising the reservoir 111. The outlet 113 extends out from the body of the device 110. The reservoir 111 is arranged to hold a first species 121 . The transport means 112 is arranged to transport the first species 121 from the reservoir 111 to outside said device 110 via the outlet 113. The hydrogel 130 is functionalized to reduce movement of said first species 121 between the body of the device 110 and the environment outside said hydrogel 130.

[0162] The device 110 depicted in fig. 3 provides a protection from the first species 121 moving intact from the device 110 to the environment via paths other than the outlet. A device may be required to be fluidly connected to the environment in order to perform sensor measurements, while also having a considerable risk of leaking trigger species out via the body of the device. For such a device, a solution may be to surround the device with functionalized hydrogel.

[0163] In some examples, the first hydrogel 130 is functionalized with a first capture species 141 arranged to bind the first species 121 , thereby reducing movement of the first species 121 by making it a bound first species 12T. In some of these examples, the first capture species 141 is arranged to covalently bind the first species 121 .

[0164] In some examples, the first hydrogel 130 is functionalized with a first inactivating species 144 arranged to modify the first species 121 into an inactivated fist species 121” unable to perform said interaction with the target species 142.

[0165] In some examples, the hydrogel 130 surrounding the body of the device 110 is arranged at the body of the device 110. In some examples, at least part of the hydrogel 130 is arranged inside the body of the device 100.

[0166] The example device 110 provides protection from leakages from the reservoir 111 out via the body of the device 110 and into the environment. The example device 110 further allows the body of the device 110 to be in indirect contact with the environment via the hydrogel 130, as opposed to surrounding the body of the device with a hermetic seal.

[0167] It is to be understood that a hydrogel 130 functionalized with capture species 141 and / or inactivating species 144 that irreversibly binds or modifies the first species 121 acts as a barrier for the first species 121 . This type of barrier may be used to surround target species 142 or to surround a reservoir 111 of first species 121 , with the goal of avoiding uncontrolled and unplanned interactions between the first species 121 and the target species 142. In some cases, the first species 121 may be undesirable to have released into the environment should the reservoir 111 of first species 121 rupture. The functionalized hydrogel 130 may be considered a safety gel aimed at controlling the first species 121 , while allowing other species to pass.

[0168] In some examples, the transport 112 means of the device 110 comprise and utilizes an ion pump.

[0169] The example device 110 in fig. 3 may be the device 110 and a part of the hydrogel 130 comprised in the example system 100 in fig. 2c.

[0170] In some examples, the device 110 is configured to be arranged at and / or around cells, microorganisms and / or tissue, such as in being configured to be in fluid contact with a cell culture via a culture medium.

[0171] In some examples, the device 110 is configured to be arranged inside a non-human animal and / or a human, such as the device 110 being implantable.

[0172] Fig. 4 shows schematically a method for controlled use of a first species. The method 300 comprises

[0173] - providing 310 a hydrogel comprising a functionalization in a first hydrogel region of the hydrogel, wherein said functionalization is arranged to reduce movement of a first species through the first hydrogel region,

[0174] - arranging 320 the hydrogel, wherein the first hydrogel region is arranged to enclose an inner hydrogel region,

[0175] - transporting 330 the first species into said inner hydrogel region via an outlet exiting into said inner hydrogel region.

[0176] It is to be understood that the hydrogel may be arranged and then functionalized.

[0177] In some examples, transporting 330 the first species into said inner hydrogel region via an outlet comprises transporting the first species from a reservoir to the outlet utilizing transport means.

[0178] In some examples, the method further comprises monitoring a state 340 of the transport of first species utilizing at least one sensor, and wherein transporting 330 the first species is based on said monitored state and at least one criterion. In some of these examples, the method repeatedly monitors the state 340 and transports 330 the first species based on said monitoring.

[0179] In some examples, the hydrogel is arranged 320 to surround or partially surround an object to be exposed to the first species and / or the first target species, and wherein the hydrogel is functionalized to, upon transporting 330 the first species into said inner hydrogel region, reduce movement of the first species and / or a corresponding releasable species in the hydrogel at said object to the environment outside said hydrogel.

[0180] In some examples, the method 300 is a non-therapeutic method.

[0181] In some examples, the method 300 is used to control the exposure of samples or microorganisms to the first species or the corresponding first releasable species.

[0182] In some examples, the method 300 is for performing treatment of a human or nonhuman animal with controlled exposure of the first species and / or the corresponding first releasable species. In some of these examples, the method 300 further comprises introducing the hydrogel into a human or a non-human animal. In some of these examples, transporting 330 the first species into said inner hydrogel region comprises implanting the outlet and / or a device comprising said outlet into a human or a non- human animal.

Claims

CLAIMS1. A system for controlled use of a first species, the system (100) comprising a scaffold and / or a hydrogel (130) and an outlet (113), wherein said outlet (113) exits into an inner region (135) enclosed by said scaffold and / or hydrogel (130), wherein the outlet (113) is arranged to allow the first species (121 ) into said inner region (135), and wherein said scaffold and / or hydrogel (130) comprises a functionalization of a first region (131 ) of said scaffold and / or hydrogel (130), wherein said functionalization of a first region (131 ) is arranged to reduce movement of said first species (121 ) between said inner region (135) and the environment outside said scaffold and / or hydrogel (130).

2. The system according to claim 1 , wherein the functionalization in the first region (131 ) comprises a first capture species (141 ), wherein said first capture species (141 ) is arranged to chemically interact with the first species (121 ), and wherein said interaction causes binding of the first species (121 ) to the first capture species (141 ).

3. The system according to claim 1 or 2, wherein said scaffold and / or hydrogel (130) comprises a functionalization of a second region (132) of said scaffold and / or hydrogel (130) with a first target species (142), wherein the first target species (142) is arranged to chemically interact with the first species (121 ), and wherein interaction causes release of a first releasable species (143) from the first target species (142).

4. The system according to claim 3, wherein the functionalization of said first region (131 ) comprises a covalently bound inactivating species (144) arranged to chemically interact with the first species (121 ), wherein interaction causes chemically inactivating the first species (121 ) from performing said interaction with said first target species (142).

5. The system according to any of claims 2-4, wherein the reactions between the first species (121 ) and first capture species (141 ) are bioorthogonal, and / or wherein the reactions between the first species (121 ) and inactivating species (144) are bioorthogonal, and / or wherein the reactions between the first species (121 ) and first target species (142) are bioorthogonal.

6. The system according to any preceding claim, wherein the system (100) comprises a device (110) comprising said outlet (113), wherein the device (110) comprises one or more reservoirs (111 ) arranged to hold said first species (121 ), and transport means (112) arranged to transport the first species (121 ) from the reservoir (111 ) out into said inner region (135) via the outlet (113).

7. The system according to claim 6, wherein the device (110) comprises one or more reservoirs (111 ) that are arranged to hold at least the first species (121 ) and a second species (122), and the transport means (112) are arranged to transport said second species (122) to the outlet (113), wherein the scaffold and / or hydrogel (130) is functionalized with the first target species (142) and a second target species (146) each arranged to chemically interact with the corresponding first and second species (121 ,122) and upon interacting cause release of corresponding first and second releasable species (143,147), wherein the first region (131 ) is functionalized with capture species (141 ,145) and / or inactivating species (144) arranged to bind and / or inactivate said first and second species (121 ,122), and wherein said interactions of the first and second species (121 ,122) are bioorthogonal and orthogonal to each other.

8. The system according to claim 6 or 7, wherein the transport means (112) comprise electrokinetic transport means.

9. The system according to any of claims 6-8, wherein said first region (131 ) encloses the device (110).

10. The system according to any preceding claim, wherein the hydrogel (130) surrounds or partially surrounds an object (160) to be exposed to the first species (121 ) and / or the first target species (142), and wherein the hydrogel (130) is functionalized to reduce movement of the first species (121 ) and / or the corresponding releasable species (143) in the hydrogel (130) at said object (160) to the environment outside said hydrogel (130).

11. A device for controlled use of a first species, said device (110) comprising a reservoir (111 ) arranged to hold a first species (121 ) inside a body of the device (110), an outlet (113) extending out from the body of the device 110, and transport means (112) arranged to transport the first species (121 ) from thereservoir (111 ) out via the outlet (113), the device (110) further comprising a scaffold and / or a hydrogel (130) surrounding the body of the device (110), wherein said scaffold and / or hydrogel (130) comprises a functionalization arranged to reduce movement of said first species (121 ) between said body of the device (110) and the environment outside said scaffold and / or hydrogel (130).

12. A method for controlled use of a first species, the method (300) comprises- providing (310) a scaffold and / or a hydrogel (130) comprising a functionalization in a first region (131 ) of the scaffold and / or hydrogel (130), wherein said functionalization is arranged to reduce movement of the first species (121 ) through the first region (131 );- arranging (320) the scaffold and / or hydrogel (130) to enclose an inner region (135) of the scaffold and / or hydrogel (130); and- transporting (330) the first species (121 ) into said inner region (135) utilizing transport means (112), wherein said scaffold and / or hydrogel comprises a functionalization arranged to reduce movement of the first species (121 ) between said inner region (135) and the environment.

13. The method according to claim 12, wherein the transport means (112) are enclosed by said scaffold and / or hydrogel (130).

14. A scaffold and / or hydrogel for release of a bound releasable species (143), the scaffold and / or hydrogel (130) comprising a first functionalization of a first region (131 ) of the scaffold and / or hydrogel (130); and a second functionalization of a second region (132) of the scaffold and / or hydrogel (130), wherein the first functionalization comprises a covalently bound species (141 ) configured to bind, and / or chemically inactivate a first species (121 ), and wherein the second functionalization comprises said covalently bound releasable species (143) configured to be released upon interaction with said first species (121 ).

15. The scaffold and / or hydrogel according to claim 14, wherein the first region (220) encloses at least part of the second region (230).

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